Teratological studies of DTPA-CaNa3, DTPA-ZnNa3 and quinamic acid in mice

International Nuclear Information System (INIS)

Luo Meichu; Ruan Tianming; Tong Shungao

1989-01-01

DTPA-CaNa 3 , DTPA-ZnNa 3 and quinamic acid are effective chelating agents for removing actinide elements from the body. In this experiment, different doses of DTPA-CaNa 3 , DTPA-ZnNa 3 and quinamic acid were given to mice on gestation days 6-10. Eight groups of mice received 0.8 and 2.0 mM/kg of DTPA-CaNa 3 , 3.8, 7.6, and 11.4 mM/kg of DTPA-ZnNa 3 and 0.42, 2.1, and 4.2 mM/kg of quinamic acid. Hypetonic saline and isotonic saline were given to two control groups. DTPA-CaNa 3 and quinamidic acid were found to be much more toxic to fetus of mice than DTPA-ZnNa 3 . When the doses of DTPA-CaMa 3 and quinamidic acid were 20 times higher than the human dose, the number of resorbed fetus was increased and the number and weight of live fetus were reduced. The result of injection with 7.6 mM/kg (200 times of human dose)DTPA-ZnNa 3 and that of injection with isotonic saline are the same. Therefore, we suggest that the DTPA-CaNa 3 and quinamidic acid should not be given to pregnant woman, if chelation therapy is needed, while the much safer DTPA-ZnNa 3 could be used

Ursolic acid inhibits superoxide production in activated neutrophils and attenuates trauma-hemorrhage shock-induced organ injury in rats.

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Tsong-Long Hwang

Full Text Available Neutrophil activation is associated with the development of organ injury after trauma-hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma-hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma-hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma-hemorrhagic shock-induced organ injury in rats.

Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

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Anjaneyulu K

2018-04-01

Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice

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Hsu Cheng-chin

2009-08-01

Full Text Available Abstract Background Caffeic acid (CA and ellagic acid (EA are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined. Methods Diabetic mice were divided into three groups (15 mice per group: diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured. Results The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p p p p p p p Conclusion These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.

Lactose behaviour in the presence of lactic acid and calcium.

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Wijayasinghe, Rangani; Vasiljevic, Todor; Chandrapala, Jayani

2016-08-01

Physical properties of lactose appeared influenced by presence of lactic acid in the system. Some other components such as Ca may further attenuate lactose behaviour and impact its phase transition. A model-based study was thus implemented with varying concentrations of Ca (0·12, 0·072 or 0·035% w/w) and lactic acid (0·05, 0·2, 0·4 or 1% w/w) in establishing the effects of these two main acid whey constituents on lactose phase behaviour. Concentrated solutions (50% w/w) containing lactose, lactic acid and Ca were analysed for thermal behaviour and structural changes by Differential Scanning Colorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR), respectively. Presence of 1% (w/w) lactic acid and 0·12% (w/w) Ca in lactose solution significantly increased the evaporation enthalpy of water, delayed and increased the energy required for lactose crystallisation as compared to pure lactose. FTIR analysis indicated a strong hydration layer surrounding lactose molecules, restricting water mobility and/or inducing structural changes of lactose, hindering its crystallisation. The formation of calcium lactate, which restricts the diffusion of lactose molecules, is also partly responsible. It appears that Ca removal from acid whey may be a necessary step in improving the processability of acid whey.

CaCO3 supplementation alleviates the inhibition of formic acid on acetone/butanol/ethanol fermentation by Clostridium acetobutylicum.

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Qi, Gaoxiang; Xiong, Lian; Lin, Xiaoqing; Huang, Chao; Li, Hailong; Chen, Xuefang; Chen, Xinde

2017-01-01

To investigate the inhibiting effect of formic acid on acetone/butanol/ethanol (ABE) fermentation and explain the mechanism of the alleviation in the inhibiting effect under CaCO 3 supplementation condition. From the medium containing 50 g sugars l -1 and 0.5 g formic acid l -1 , only 0.75 g ABE l -1 was produced when pH was adjusted by KOH and fermentation ended prematurely before the transformation from acidogenesis to solventogenesis. In contrast, 11.4 g ABE l -1 was produced when pH was adjusted by 4 g CaCO 3 l -1 . The beneficial effect can be ascribed to the buffering capacity of CaCO 3 . Comparative analysis results showed that the undissociated formic acid concentration and acid production coupled with ATP and NADH was affected by the pH buffering capacity of CaCO 3 . Four millimole undissociated formic acid was the threshold at which the transformation to solventogenesis occurred. The inhibiting effect of formic acid on ABE fermentation can be alleviated by CaCO 3 supplementation due to its buffering capacity.

Random poly(amino acid)s synthesized by ring opening polymerization as additives in the biomimetic mineralization of CaCO3

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Dmitrovic, V.; Habraken, G.J.M.; Hendrix, M.M.R.M.; Habraken, W.J.E.M.; Heise, A.; With, de G.; Sommerdijk, N.A.J.M.

2012-01-01

Biominerals such as bones, teeth and seashells, very often have advanced material properties and are a source of inspiration for material chemists. As in biological systems acidic proteins play an important role in regulating the formation of CaCO3 biominerals, we employ poly(amino acid)s to mimic

Acute treatment with 17beta-estradiol attenuates astrocyte-astrocyte and astrocyte-neuron communication.

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Rao, Shilpa P; Sikdar, Sujit Kumar

2007-12-01

Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control. (c) 2007 Wiley-Liss, Inc.

Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

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Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

1995-02-06

EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores.

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Kim, Hee Jung; Yum, Keun Sang; Sung, Jong-Ho; Rhie, Duck-Joo; Kim, Myung-Jun; Min, Do Sik; Hahn, Sang June; Kim, Myung-Suk; Jo, Yang-Hyeok; Yoon, Shin Hee

2004-02-01

Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.

Measurement of the mass attenuation coefficients and electron densities for BiPbSrCaCuO superconductor at different energies

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Çevik, U.; Baltaş, H.

2007-03-01

The mass attenuation coefficients for Bi, Pb, Sr, Ca, Cu metals, Bi2O3, PbO, SrCO3, CaO, CuO compounds and solid-state forms of Bi1.7Pb0.3Sr2Ca2Cu3O10 superconductor were determined at 57.5, 65.2, 77.1, 87.3, 94.6, 122 and 136 keV energies. The samples were irradiated using a 57Co point source emitted 122 and 136 keV γ-ray energies. The X-ray energies were obtained using secondary targets such as Ta, Bi2O3 and (CH3COO)2UO22H2O. The γ- and X-rays were counted by a Si(Li) detector with a resolution of 0.16 keV at 5.9 keV. The effect of absorption edges on electron density, effective atomic numbers and their variation with photon energy in composite superconductor samples was discussed. Obtained values were compared with theoretical values.

Blockade of acid sensing ion channels attenuates the augmented exercise pressor reflex in rats with chronic femoral artery occlusion.

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Tsuchimochi, Hirotsugu; Yamauchi, Katsuya; McCord, Jennifer L; Kaufman, Marc P

2011-12-15

We found previously that static contraction of the hindlimb muscles of rats whose femoral artery was ligated evoked a larger reflex pressor response (i.e. exercise pressor reflex) than did static contraction of the contralateral hindlimb muscles which were freely perfused. Ligating a femoral artery in rats results in blood flow patterns to the muscles that are remarkably similar to those displayed by humans with peripheral artery disease. Using decerebrated rats, we tested the hypothesis that the augmented exercise pressor reflex in rats with a ligated femoral artery is attenuated by blockade of the acid sensing ion channel (ASIC) 3. We found that femoral arterial injection of either amiloride (5 and 50 μg kg(-1)) or APETx2 (100 μg kg(-1)) markedly attenuated the reflex in rats with a ligated femoral artery. In contrast, these ASIC antagonists had only modest effects on the reflex in rats with freely perfused hindlimbs. Tests of specificity of the two antagonists revealed that the low dose of amiloride and APETx2 greatly attenuated the pressor response to lactic acid, an ASIC agonist, but did not attenuate the pressor response to capsaicin, a TRPV1 agonist. In contrast, the high dose of amiloride attenuated the pressor responses to lactic acid, but also attenuated the pressor response to capsaicin. We conclude that ASIC3 on thin fibre muscle afferents plays an important role in evoking the exercise pressor reflex in rats with a compromised arterial blood supply to the working muscles.

Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

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Takeda, Atsushi; Itagaki, Kosuke; Ando, Masaki; Oku, Naoto

2012-03-01

Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. Copyright © 2011 Wiley Periodicals, Inc.

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

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Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca(2+).

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Dubinin, Mikhail V; Samartsev, Victor N; Astashev, Maxim E; Kazakov, Alexey S; Belosludtsev, Konstantin N

2014-11-01

The article examines the molecular mechanism of the Ca(2+)-dependent cyclosporin A (CsA)-insensitive permeability transition in rat liver mitochondria induced by α,ω-dioic acids. The addition of α,ω-hexadecanedioic acid (HDA) to Ca(2+)-loaded liver mitochondria was shown to induce a high-amplitude swelling of the organelles, a drop of membrane potential and the release of Ca(2+) from the matrix, the effects being insensitive to CsA. The experiments with liposomes loaded with sulforhodamine B (SRB) revealed that, like palmitic acid (PA), HDA was able to cause permeabilization of liposomal membranes. However, the kinetics of HDA- and PA-induced release of SRB from liposomes was different, and HDA was less effective than PA in the induction of SRB release. Using the method of ultrasound interferometry, we also showed that the addition of Ca(2+) to HDA-containing liposomes did not change the phase state of liposomal membranes-in contrast to what was observed when Ca(2+) was added to PA-containing vesicles. It was suggested that HDA/Ca(2+)- and PA/Ca(2+)-induced permeability transition occurs by different mechanisms. Using the method of dynamic light scattering, we further revealed that the addition of Ca(2+) to HDA-containing liposomes induced their aggregation/fusion. Apparently, these processes result in a partial release of SRB due to the formation of fusion pores. The possibility that this mechanism underlies the HDA/Ca(2+)-induced permeability transition of the mitochondrial membrane is discussed.

Study of mixed Ca-Zn hydroxyapatite surface modified by lactic acid

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Turki, Thouraya; Aissa, Abdallah; Bac, Christophe Goze; Rachdi, Férid; Debbabi, Mongi

2012-07-01

The new hybrid inorganic-organic composites, Ca(10-x)Znx(PO4)6(OH)2-lactic acid, at different amounts of zinc and lactic acid were prepared by dissolution of the organic compound in an hydroxyapatite suspension. They were characterized by XRD, IR, MAS NMR (13C and 1H) and chemical analysis. The crystallinity was slightly affected by the presence of organic fragments. IR and (13C and 1H) MAS NMR measurements indicate that the carboxylic groups of the acid interact with calcium and zinc ions of hydroxyapatite surface. Chemical analysis displays that zinc promotes the acid grafting. A mechanism of surface modification is proposed based on the obtained results.

Study of mixed Ca-Zn hydroxyapatite surface modified by lactic acid

International Nuclear Information System (INIS)

Turki, Thouraya; Aissa, Abdallah; Bac, Christophe Goze; Rachdi, Férid; Debbabi, Mongi

2012-01-01

The new hybrid inorganic-organic composites, Ca (10-x) Zn x (PO 4 ) 6 (OH) 2 -lactic acid, at different amounts of zinc and lactic acid were prepared by dissolution of the organic compound in an hydroxyapatite suspension. They were characterized by XRD, IR, MAS NMR ( 13 C and 1 H) and chemical analysis. The crystallinity was slightly affected by the presence of organic fragments. IR and ( 13 C and 1 H) MAS NMR measurements indicate that the carboxylic groups of the acid interact with calcium and zinc ions of hydroxyapatite surface. Chemical analysis displays that zinc promotes the acid grafting. A mechanism of surface modification is proposed based on the obtained results.

Effect of amino acids on the precipitation kinetics and Ca isotopic composition of gypsum

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Harouaka, Khadouja; Kubicki, James D.; Fantle, Matthew S.

2017-12-01

Stirred gypsum (CaSO4 · 2H2O) precipitation experiments (initial Ωgypsum = 2.4 ± 0.14, duration ≈ 1.0-1.5 h) were conducted in the presence of the amino acids glycine (190 μM), L-alanine (190 μM), D- and L-arginine (45 μM), and L-tyrosine (200 μM) to investigate the effect of simple organic compounds on both the precipitation kinetics and Ca isotopic composition of gypsum. Relative to abiotic controls, glycine, tyrosine, and alanine inhibited precipitation rates by ∼22%, 27%, and 29%, respectively, while L- and D-arginine accelerated crystal growth by ∼8% and 48%, respectively. With the exception of tyrosine, amino acid induced inhibition resulted in fractionation factors (αs-f) associated with precipitation that were no more than 0.3‰ lower than amino acid-free controls. In contrast, the tyrosine and D- and L-arginine experiments had αs-f values associated with precipitation that were similar to the controls. Our experimental results indicate that Ca isotopic fractionation associated with gypsum precipitation is impacted by growth inhibition in the presence of amino acids. Specifically, we propose that the surface-specific binding of amino acids to gypsum can change the equilibrium fractionation factor of the bulk mineral. We investigate the hypothesis that amino acids can influence the growth of gypsum at specific crystal faces via adsorption and that different faces have distinct fractionation factors (αface-fluid). Accordingly, preferential sorption of amino acids at particular faces changes the relative, face-specific mass fluxes of Ca during growth, which influences the bulk isotopic composition of the mineral. Density functional theory (DFT) calculations suggest that the energetic favorability of glycine sorption onto gypsum crystal faces occurs in the order: (1 1 0) > (0 1 0) > (1 2 0) > (0 1 1), while glycine sorption onto the (-1 1 1) face was found to be energetically unfavorable. Face-specific fractionation factors constrained by

The effect of gallic acid on cytotoxicity, Ca(2+) homeostasis and ROS production in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes.

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Hsu, Shu-Shong; Chou, Chiang-Ting; Liao, Wei-Chuan; Shieh, Pochuen; Kuo, Daih-Huang; Kuo, Chun-Chi; Jan, Chung-Ren; Liang, Wei-Zhe

2016-05-25

Gallic acid, a polyhydroxylphenolic compound, is widely distributed in various plants, fruits and foods. It has been shown that gallic acid passes into blood brain barrier and reaches the brain tissue of middle cerebral artery occlusion rats. However, the effect of gallic acid on Ca(2+) signaling in glia cells is unknown. This study explored whether gallic acid affected Ca(2+) homeostasis and induced Ca(2+)-associated cytotoxicity in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes. Gallic acid (20-40 μM) concentration-dependently induced cytotoxicity and intracellular Ca(2+) level ([Ca(2+)]i) increases in DBTRG-05MG cells but not in CTX TNA2 cells. In DBTRG-05MG cells, the Ca(2+) response was decreased by half by removal of extracellular Ca(2+). In Ca(2+)-containing medium, gallic acid-induced Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (2-APB, econazole and SKF96365). In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin abolished gallic acid-induced [Ca(2+)]i increases. Conversely, incubation with gallic acid also abolished thapsigargin-induced [Ca(2+)]i increases. Inhibition of phospholipase C with U73122 abolished gallic acid-induced [Ca(2+)]i increases. Gallic acid significantly caused cytotoxicity in DBTRG-05MG cells, which was partially prevented by prechelating cytosolic Ca(2+) with BAPTA-AM. Moreover, gallic acid activated mitochondrial apoptotic pathways that involved ROS production. Together, in DBTRG-05MG cells but not in CTX TNA2 cells, gallic acid induced [Ca(2+)]i increases by causing Ca(2+) entry via 2-APB, econazole and SKF96365-sensitive store-operated Ca(2+) entry, and phospholipase C-dependent release from the endoplasmic reticulum. This Ca(2+) signal subsequently evoked mitochondrial pathways of apoptosis that involved ROS production. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury

International Nuclear Information System (INIS)

Domitrović, Robert; Cvijanović, Olga; Šušnić, Vesna; Katalinić, Nataša

2014-01-01

Highlights: • Chlorogenic acid attenuated cisplatin-induced renal oxidative stress by reducing the expression of 4-HNE, HO-1 and CYP2E1. • The inhibition of inflammatory response was achieved through the reduction of TNF-α and COX-2 expression. • The expression of p53, Bax, active caspase-3 and LC3B was suppressed, suggesting the inhibition of apoptosis and autophagy. • Attenuation of Mrp1 and Mrp2 expression and the increase in Oct2 expression indicated reduced burden of tubular cells. • The recovery of kidneys form cisplatin injury was accompanied by the suppression of cyclin D1 and augmented PCNA expression. - Abstract: The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30 mg/kg for two successive days, 48 h after intraperitoneal injection of CP (13 mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery

Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

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da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

2015-07-15

We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. Copyright © 2015 the American Physiological Society.

SYNTHESIS, CHARACTERIZATION AND ANTITUMOR ACTIVITY OF A Ca (II COORDINATION POLYMER BASED ON 3-AMINO-2-PYRAZINECARBOXYLIC ACID

Directory of Open Access Journals (Sweden)

XI-SHI TAI

2015-10-01

Full Text Available A new Ca(II coordination polymer has been obtained by reaction of Ca(ClO42·H2O with 3-amino-2-pyrazinecarboxylic acid in CH3CH2OH/H2O. It was characterized by IR, 1HNMR, thermal analysis and X-ray single crystal diffraction analysis. X-ray analysis reveals that each Ca(II center is seven-coordination with a N2O5 distorted pentagonal bipyramidal coordination environment. The Ca(II ions are linked through the O atoms of 3-amino-2-pyrazinecarboxylic acid ligands to form 1D chain structure. And then a 3D network structure is constructed by hydrogen bonds and π-π stacking. The antitumor activity of 3-amino-2-pyrazinecarboxylic acid ligand and its Ca(II coordination polymer against human intestinal adenocarcinoma HCT-8 cells, lung adenocarcinoma HCT-116 cells and human lung adenocarcinoma A549 cells line have been investigated.

Attenuated RANKL-induced cytotoxicity by Portulaca oleracea ethanol extract enhances RANKL-mediated osteoclastogenesis.

Science.gov (United States)

Erkhembaatar, Munkhsoyol; Choi, Eun-Joo; Lee, Hak-Yong; Lee, Choong Hun; Lee, Young-Rae; Kim, Min Seuk

2015-07-14

Portulaca oleracea (PO) has been widely used as traditional medicine because of its pharmacological activities. However, the effects of PO on osteoclasts that modulate bone homeostasis are still elusive. In this study, we examined the effects of PO ethanol extract (POEE) on receptor activator of nuclear factor-κB ligand (RANKL)-mediated Ca(2+) mobilization, nuclear factor of activated T-cell c1 (NFATc1) amplification, tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cell (MNC) formation, and cytotoxicity. Our results demonstrated that POEE suppressed RANKL-induced Ca(2+) oscillations by inhibition of Ca(2+) release from internal Ca(2+) stores, resulting in reduction of NFATc1 amplification. Notably, POEE attenuated RANKL-mediated cytotoxicity and cleavage of polyadenosine 5'-diphosphate-ribose polymerase (PARP), resulted in enhanced formation of TRAP+ MNCs. These results present in vitro effects of POEE on RANKL-mediated osteoclastogenesis and suggest the possible use of PO in treating bone disorders, such as osteopetrosis.

Study of mixed Ca-Zn hydroxyapatite surface modified by lactic acid

Energy Technology Data Exchange (ETDEWEB)

Turki, Thouraya; Aissa, Abdallah [Laboratoire de Physico-Chimie des Materiaux, Faculte des Sciences de Monastir, 5019 Monastir (Tunisia); Bac, Christophe Goze [Laboratoire Charles Coulomb, UMR 5221 CNRS/UM2, Universite Montpellier 2, Place E. Bataillon, 34095 Montpellier (France); Rachdi, Ferid, E-mail: Ferid.Rachdi@univ-montp2.fr [Laboratoire Charles Coulomb, UMR 5221 CNRS/UM2, Universite Montpellier 2, Place E. Bataillon, 34095 Montpellier (France); Debbabi, Mongi [Laboratoire de Physico-Chimie des Materiaux, Faculte des Sciences de Monastir, 5019 Monastir (Tunisia)

2012-07-01

The new hybrid inorganic-organic composites, Ca{sub (10-x)}Zn{sub x}(PO{sub 4}){sub 6}(OH){sub 2}-lactic acid, at different amounts of zinc and lactic acid were prepared by dissolution of the organic compound in an hydroxyapatite suspension. They were characterized by XRD, IR, MAS NMR ({sup 13}C and {sup 1}H) and chemical analysis. The crystallinity was slightly affected by the presence of organic fragments. IR and ({sup 13}C and {sup 1}H) MAS NMR measurements indicate that the carboxylic groups of the acid interact with calcium and zinc ions of hydroxyapatite surface. Chemical analysis displays that zinc promotes the acid grafting. A mechanism of surface modification is proposed based on the obtained results.

Studies on the Protective Effects of Scutellarein against Neuronal Injury by Ischemia through the Analysis of Endogenous Amino Acids and Ca2+ Concentration Together with Ca2+-ATPase Activity

Directory of Open Access Journals (Sweden)

Hao Tang

2015-01-01

Full Text Available Scutellarin, which is extracted from the dried plant of Erigeron breviscapus, has been reported to protect the neural injury against excitotoxicity induced by ischemia. However, there are a few studies on the protective effects of scutellarein, which is the main metabolite of scutellarin in vivo. Thus, this study investigated the neuroprotective effects of scutellarein on cerebral ischemia/reperfusion in rats by bilateral common carotid artery occlusion (BCCAO model, through the analysis of endogenous amino acids using HILIC-MS/MS, and evaluation of Ca2+ concentration together with Ca2+-ATPase activity. The results showed that scutellarein having good protective effects on cerebral ischemia/reperfusion might by decreasing the excitatory amino acids, increasing the inhibitory amino acids, lowing intracellular Ca2+ level, and improving Ca2+-ATPase activity, which suggested that scutellarein might be a promising potent agent for the therapy of ischemic cerebrovascular disease.

Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice.

Science.gov (United States)

Kim, Ja Kyung; Lee, Kwan Sik; Lee, Dong Ki; Lee, Su Yeon; Chang, Hye Young; Choi, Junjeong; Lee, Jung Il

2014-12-19

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

Regulation of phenylacetic acid uptake is sigma54 dependent in Pseudomonas putida CA-3.

LENUS (Irish Health Repository)

O' Leary, Niall D

2011-10-13

Abstract Background Styrene is a toxic and potentially carcinogenic alkenylbenzene used extensively in the polymer processing industry. Significant quantities of contaminated liquid waste are generated annually as a consequence. However, styrene is not a true xenobiotic and microbial pathways for its aerobic assimilation, via an intermediate, phenylacetic acid, have been identified in a diverse range of environmental isolates. The potential for microbial bioremediation of styrene waste has received considerable research attention over the last number of years. As a result the structure, organisation and encoded function of the genes responsible for styrene and phenylacetic acid sensing, uptake and catabolism have been elucidated. However, a limited understanding persists in relation to host specific regulatory molecules which may impart additional control over these pathways. In this study the styrene degrader Pseudomonas putida CA-3 was subjected to random mini-Tn5 mutagenesis and mutants screened for altered styrene\\/phenylacetic acid utilisation profiles potentially linked to non-catabolon encoded regulatory influences. Results One mutant, D7, capable of growth on styrene, but not on phenylacetic acid, harboured a Tn5 insertion in the rpoN gene encoding σ54. Complementation of the D7 mutant with the wild type rpoN gene restored the ability of this strain to utilise phenylacetic acid as a sole carbon source. Subsequent RT-PCR analyses revealed that a phenylacetate permease, PaaL, was expressed in wild type P. putida CA-3 cells utilising styrene or phenylacetic acid, but could not be detected in the disrupted D7 mutant. Expression of plasmid borne paaL in mutant D7 was found to fully restore the phenylacetic acid utilisation capacity of the strain to wild type levels. Bioinformatic analysis of the paaL promoter from P. putida CA-3 revealed two σ54 consensus binding sites in a non-archetypal configuration, with the transcriptional start site being resolved by

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression.

Science.gov (United States)

Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

2012-01-01

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA(A)) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus.

Mechanism of cytotoxic action of perfluorinated acids. III. Disturbance in Ca2+ homeostasis

International Nuclear Information System (INIS)

Kleszczynski, Konrad; Skladanowski, Andrzej C.

2011-01-01

The global distribution of perfluorinated acids (PFAs) in industry and in household is well known. Their increasing environmental occurrence and biomagnification in the living organisms have drawn growing interests in efforts to describe precisely the mechanisms of action in vitro and in vivo. Our previous investigations widely described lipophilicity-dependent cytotoxicity of PFAs as well as the effect of perfluorination of carbon chain on depolarization of plasma membrane potential, acidification or mitochondrial dysfunctions. In this study we presented in dose- and time-dependent manner the impact of PFAs on calcium homeostasis in HCT116 cells. Comparative analysis of cytosolic [Ca 2+ ] c and mitochondrial calcium [Ca 2+ ] m carried out by flow cytometry revealed distinct uptake of calcium into mitochondria in correlation to increasing lipophilicity of PFAs. Massive accumulation of [Ca 2+ ] m was not accompanied by equivalent loss of [Ca 2+ ] c . Indeed, moderate changes of [Ca 2+ ] c were observed after incubation with 400 μM PFDoDA reaching 29.83% and 49.17% decrease at 4th and 72nd hour, respectively. At the same time, mitochondrial calcium uptake increased from 2- to more than 4-fold comparing with non-treated cells. Incubation with non-fluorinated decanoic acid (DA) did not cause any changes in calcium homeostasis. Presented data show that PFAs-induced perturbations in calcium distribution seem to be a missing link related to mitochondria dysfunction playing a crucial role in determination of apoptotic cell death. Complete scheme for the mechanism of cytotoxic action of PFAs has been included.

An iso-α-acid-rich extract from hops (Humulus lupulus) attenuates acute alcohol-induced liver steatosis in mice.

Science.gov (United States)

Hege, Marianne; Jung, Finn; Sellmann, Cathrin; Jin, Chengjun; Ziegenhardt, Doreen; Hellerbrand, Claus; Bergheim, Ina

2018-01-01

Results of in vitro and in vivo studies suggest that consumption of beer is less harmful for the liver than consumption of spirits. It also has been suggested that secondary plant compounds derived from hops such as xanthohumol or iso-α-acids may have beneficial effects on the development of liver diseases of various etiologies. The aim of this study was to determine whether iso-α-acids consumed in doses achieved by "normal" beer consumption have beneficial effects on health. Female C57 Bl/6 J mice, pretreated for 4 d with an iso-α-acid-rich extract (∼30% iso-α-acids from hops, 0.75 mg/kg body weight), were fed one bolus of ethanol (6 g/kg body weight intragastric) or an iso-caloric maltodextrin solution. Markers of liver damage, toll-like receptor-4 signaling, and lipid peroxidation were determined. Furthermore, the effect of isohumulone on the lipopolysaccharide-dependent activation of J774 A.1 macrophages, used as a model of Kupffer cells, was determined. In the liver, acute ethanol administration led to a significant accumulation of fat (∼10-fold), which was accompanied by significantly higher inducible nitric oxide synthase protein level, elevated nitric oxide production, and increased plasminogen activator inhibitor 1 protein concentration when compared to controls. In mice pretreated with iso-α-acids, these effects of alcohol were markedly attenuated. Pretreatment of J774 A.1 macrophages with isohumulone significantly attenuated lipopolysaccharide-induced mRNA expression of inducible nitric oxide synthase and interleukin-6 as well as the release of nitric oxide. Taken together, iso-α-acids markedly attenuated the development of acute alcohol-induced damage in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard-induced cell death by inhibiting the lipoxygenase pathway.

Science.gov (United States)

Kim, Shin; Jeong, Kwang-Joon; Cho, Sung Kweon; Park, Joo-Won; Park, Woo-Jae

2016-11-01

Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM‑induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM‑induced cell death. Among several antioxidants, CA partially alleviated SM‑induced cell death in a dose‑dependent manner. Although CA treatment decreased the phosphorylation of p38 mitogen‑activated protein (MAP) kinase and p53, p38 MAP kinase inhibition by SB203580 did not affect SM‑induced cell death. As CA has also been reported as a 15‑lipoxygenase (15‑LOX) inhibitor, the role of 15‑LOX in SM‑induced cytotoxicity was also examined. Similar to the results observed with CA, treatment with PD146176, a specific 15‑LOX inhibitor, decreased SM‑induced cytotoxicity, accompanied by decreases in the production of tumor necrosis factor‑α and 15‑hydroxyeicosatetraenoic acid. Furthermore, the present study investigated the protective effects of two natural 15‑LOX inhibitors, morin hydrate and quercetin, in SM‑induced cytotoxicity. As expected, these inhibitors had similar protective effects against SM‑induced cytotoxicity. These antioxidants also reduced the generation of ROS and nitrate/nitrite. Therefore, the results of the present study indicated that the natural products, CA, quercetin and morin hydrate, offer potential as adjuvant therapeutic agents for SM‑induced toxicity, not only by reducing inflammation mediated by the p38 and LOX signaling pathways, but also by decreasing the generation of ROS and nitrate/nitrite.

Na+/Ca2+ exchange inhibitor, KB-R7943, attenuates contrast-induced acute 
kidney injury.

Science.gov (United States)

Yang, Dingwei; Yang, Dingping; Jia, Ruhan; Tan, Jin

2013-01-01

Intracellular Ca2+ overload is considered to be a key factor in contrast-induced acute kidney injury (CI-AKI). The Na+/Ca2+ exchanger (NCX) system is one of the main pathways of intracellular Ca2+ overload. We investigated the effects of KB-R7943, an inhibitor of the reverse mode of NCX, on CI-AKI in a rat model. Rats were divided into control group, CI-AKI group and pretreatment groups (with KB-R7943 dose of 5 or 10 mg/kg). CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks. Renal function and renal hemodynamics were determined 1 day following contrast medium administration. Renal histopathology was observed by light microscope. Renal tubular apoptosis was examined by TUNEL. Renal endothelin-1 (ET-1) was measured by radioimmunoassay. Renal malondialdehyde (MDA) and catalase (CAT) were measured as oxidative markers. Levels of serum creatinine (Scr), renal ET-1, MDA and CAT, and resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats. The 
increases in Scr and RI of renal blood vessels induced by diatrizoate were suppressed significantly and 
dose-dependently by pretreatment with KB-R7943. Histopathological and TUNEL results showed that 
the contrast medium-induced severe renal tubular 
necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943. KB-R7943 significantly suppressed the increment of renal ET-1 content and MDA and CAT level induced by contrast medium administration. Activation of the reverse mode of NCX, followed by ET-1 overproduction and increased oxidative stress, seems to play an important role in the pathogenesis of CI-AKI. The inhibitor of the reverse mode of NCX, KB-R7943, has renoprotective effects on CI-AKI.

Synthesis of Fluorite (CaF2 Crystal from Gypsum Waste of Phosphoric Acid Factory in Silica Gel

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Mohammad Misbah Khunur

2012-06-01

Full Text Available This paper report the synthesis and characterization of fluorite single crystal prepared from gypsum waste of phosphoric acid production in silica gel. Instead of its high calcium, gypsum was used to recycle the waste which was massively produces in the phosphoric acid production. The gypsum waste, the raw material of CaCl2 supernatant, was dissolved in concentrated HCl and then precipitated as calcium oxalate (CaC2O4 by addition of ammonium oxalate. The CaCl2 was obtained by dissolving the CaC2O4 with HCl 3M. The crystals were grown at room temperature in silica gel and characterized by AAS, FTIR and powder XRD. The optimum crystal growth condition, which is pH of gel, CaCl2 concentration and growth time, were investigated. The result shows that at optimum condition of pH 5.80, CaCl2 concentrations of 1.2 M, and growth time of 144 hours, colorless crystals with the longest size of 3 mm, were obtained (72.57%. Characterization of the synthesized crystal by AAS indicates that the obtained crystal has high purity. Meanwhile, analysis by FTIR spectra shows a Ca–F peak at 775 cm-1, and powder-XRD analysis confirms that the obtained crystal was fluorite (CaF2. © 2012 BCREC UNDIP. All rights reservedReceived: 11st April 2012; Revised: 4th June 2012; Accepted: 13rd June 2012[How to Cite: M.M. Khunur, A. Risdianto, S. Mutrofin, Y.P. Prananto. (2012. Synthesis of Fluorite (CaF2 Crystal from Gypsum Waste of Phosphoric Acid Factory in Silica Gel. Bulletin of Chemical Reaction Engineering & Catalysis, 7 (1: 71-77.  doi:10.9767/bcrec.7.1.3171.71-77 ][How to Link / DOI: http://dx.doi.org/10.9767/bcrec.7.1.3171.71-77 ] | View in 

Application of natural attenuation to ground water contaminated by phenoxy acid herbicides at an old landfill in Sjoelund

DEFF Research Database (Denmark)

Tuxen, Nina; Ejlskov, P.; Albrechtsen, Hans-Jørgen

2003-01-01

Investigations of geology, hydrogeology, and ground water chemistry in the aquifer downgradient from Sjoelund Landfill, Denmark, formed the basis for an evaluation of natural attenuation as a remediation technology for phenoxy acid herbicides at the site. Concentrations of phenoxy acids were up......, such as specific metabolites, changes in enantiomeric fractions, compound-specific stable carbon isotope ratios, or microbial fingerprints....

PMR spectroscopy of Ca(II) complexes of ethylenediamine-N,N,N',N' - tetraacetic acid

International Nuclear Information System (INIS)

Novomesky, P.; Balgavy, P.; Majer, J.

1977-01-01

Proton magnetic resonance spectra for the EDTA complexes of Ca(II) were measured in aqueous solutions as a function of solution pH. It follows from the analysis of chemical shift changes that the nitrogen atoms rather than the carboxylate groups are protonated (as the pH is lowered) in the tetraanion of EDTA. The same conclusion follows for the protonization of the [CaEDTA] 2- complex in the acid pH range where the hydrogen complex [CaH(EDTA)] - is formed. The formation of [Ca(OH)EDTA] 3- was not observed at pH less than 12.6, at [CaEDTA] 2- concentration of 0.5 mol/l. In solutions with a metal-to-ligand molar ratio 1:1.5 two sets of resonance signals appear in the pH range from 12.8 to 6.0, the former for the free ligand and the latter for the stable [CaEDTA] 2- complex. However, from pH 6.0 to 4.35 only one set of broadened signals was observed, which indicates that an exchange process between free ligand, normal [CaEDTA] 2- complex and [CaH(EDTA)] - takes place. (author)

Advanced glycation end-products (AGEs acutely impair Ca2+ signalling in bovine aortic endothelial cells

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Nadim eNaser

2013-03-01

Full Text Available Post-translational modification of proteins in diabetes, including formation of advanced glycation end products (AGEs are believed to contribute to vascular dysfunction and disease. Impaired function of the endothelium is an early indicator of vascular dysfunction in diabetes and as many endothelial cell processes are dependent upon intracellular [Ca2+] and Ca2+ signalling, the aim of this study was to examine the acute effects of AGEs on Ca2+ signalling in bovine aortic endothelial cells (BAEC. Ca2+ signalling was studied using the fluorescent indicator dye Fura2-AM. AGEs were generated by incubating bovine serum albumin with 0 - 250 mM glucose or glucose-6-phosphate for 0 to 120 days at 37ºC. Under all conditions, the main AGE species generated was carboxymethyl lysine (CML as assayed using both GC-MS and HPLC. In Ca2+-replete solution, exposure of BAEC to AGEs for 5 min caused an elevation in basal [Ca2+] and attenuated the increase in intracellular [Ca2+] caused by ATP (100 µM. In the absence of extracellular Ca2+, exposure of BAEC to AGEs for 5 min caused an elevation in basal [Ca2+] and attenuated subsequent intracellular Ca2+ release caused by ATP, thapsigargin (0.1 µM and ionomycin (3 µM, but AGEs did not affect extracellular Ca2+ entry induced by the re-addition of Ca2+ to the bathing solution in the presence of any of these agents. The anti-oxidant α-lipoic acid (2 µM and NAD(PH oxidase inhibitors apocynin (500 µM and diphenyleneiodonium (DPI, 1 µM abolished these effects of AGEs on BAECs, as did the IP3 receptor antagonist xestospongin C (1 µM. In summary, AGEs caused an acute depletion of Ca2+ from the intracellular store in BAECs, such that the Ca2+ signal stimulated by the subsequent application other agents acting upon this store is reduced. The mechanism may involve generation of ROS from NAD(PH oxidase and possible activation of the IP3 receptor.

Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

Science.gov (United States)

Stein, T. P.; Schluter, M. D.; Leskiw, M. J.; Boden, G.

1999-01-01

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P BCAA supplementation attenuates the N loss during short-term bed rest.

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

Directory of Open Access Journals (Sweden)

Chung-Hsiang Liu

2012-01-01

Full Text Available Uncaria rhynchophylla (UR, which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA- induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

Science.gov (United States)

Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

2013-01-01

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. © 2013 Published by Elsevier Ltd.

Evaluation of the substitution of PMMA plates by PLA 3D printed in TL response of CaSO{sub 4}:Dy; Avaliacao da substituicao de placas de PMMA por PLA impresso 3D na resposta TL do CaSO{sub 4}:Dy

Energy Technology Data Exchange (ETDEWEB)

Almeida, Shirlane Barbosa de; Valeriano, Caio Cesar Santos; Campos, Leticia Lucente, E-mail: caio144fisicamedica@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2016-07-01

The CaSO{sub 4}:Dy is a dosimetric material that is nationally produced, which presents high sensibility but a high energy dependence of its thermoluminescent (TL) response at the photoelectric effect region. This study aims to compare the TL response of the CaSO{sub 4}:Dy when irradiated, with different energies, at the presence of 3D printed plates of polylactic acid (PLA) and polymethylmethacrylate (PMMA). Results show that the PLA has a different attenuation of the radiation, when compared to PMMA, indicating that it should be taken into account the quality of the print used on PLA plates manufacture. (author)

Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

Science.gov (United States)

Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

2010-08-01

Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning.

Science.gov (United States)

Andrienko, Tatyana; Pasdois, Philippe; Rossbach, Andreas; Halestrap, Andrew P

2016-01-01

Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(P)H and flavoproteins on reperfusion (detected using autofluorescence) was rapid (t0.5 ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2-3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA) and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1) increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2-3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that IP may inhibit initial mPTP opening by alternative mechanisms such as prevention of hexokinase 2 dissociation from mitochondria during ischemia.

Oral Uncaria rhynchophylla (UR) reduces kainic acid-induced epileptic seizures and neuronal death accompanied by attenuating glial cell proliferation and S100B proteins in rats.

Science.gov (United States)

Lin, Yi-Wen; Hsieh, Ching-Liang

2011-05-17

Epilepsy is a common clinical syndrome with recurrent neuronal discharges in cerebral cortex and hippocampus. Here we aim to determine the protective role of Uncaria rhynchophylla (UR), an herbal drug belong to Traditional Chinese Medicine (TCM), on epileptic rats. To address this issue, we tested the effect of UR on kainic acid (KA)-induced epileptic seizures and further investigate the underlying mechanisms. Oral UR successfully decreased neuronal death and discharges in hippocampal CA1 pyramidal neurons. The population spikes (PSs) were decreased from 4.1 ± 0.4 mV to 2.1 ± 0.3 mV in KA-induced epileptic seizures and UR-treated groups, respectively. Oral UR protected animals from neuronal death induced by KA treatment (from 34 ± 4.6 to 191.7 ± 48.6 neurons/field) through attenuating glial cell proliferation and S100B protein expression but not GABAA and TRPV1 receptors. The above results provide detail mechanisms underlying the neuroprotective action of UR on KA-induced epileptic seizure in hippocampal CA1 neurons. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

Science.gov (United States)

Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

2018-01-01

Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

Ursodeoxycholic and deoxycholic acids: Differential effects on intestinal Ca(2+) uptake, apoptosis and autophagy of rat intestine.

Science.gov (United States)

Rodríguez, Valeria A; Rivoira, María A; Pérez, Adriana del V; Marchionatti, Ana M; Tolosa de Talamoni, Nori G

2016-02-01

The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca(2+) uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca(2+) uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca(2+) uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca(2+) absorption occur by decreasing the Ca(2+) uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca(2+) uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca(2+) pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

MEMANTINE ATTENUATES THE OKADAIC ACID INDUCED SHORT-TERM SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS IN RATS.

Science.gov (United States)

Dashniani, M; Chighladze, M; Burjanadze, M; Beselia, G; Kruashvili, L

2016-03-01

In the present study, the possible beneficial effect of memantine on the Okadaic Acid (OA) induced spatial short-term memory impairment was examined in spatial alternation task, and the neuroprotective potential of memantine on OA-induced structural changes in the hippocampus was evaluated by Nissl staining. OA was dissolved in artificial cerebrospinal fluid (aCSF) and injected intracerebroventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into 2 subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline were given daily for 13 days starting from the day of OA injection. Behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory. Nissl staining in the present study showed that the ICV microinjection of OA significantly decreased the number of surviving pyramidal neurons in the CA1 region of the hippocampus. Chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment and the OA-induced neuropathological changes in the hippocampus. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutics targets for AD pathology.

Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

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Chih-Cheng Lai

2014-08-01

Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

Influence of Ca/Mg ratio on phytoextraction properties of Salix viminalis. II. Secretion of low molecular weight organic acids to the rhizosphere.

Science.gov (United States)

Magdziak, Z; Kozlowska, M; Kaczmarek, Z; Mleczek, M; Chadzinikolau, T; Drzewiecka, K; Golinski, P

2011-01-01

A hydroponic experiment in a phytotron was performed to investigate the effect of two different Ca/Mg ratios (4:1 and 1:10) and trace element ions (Cd, Cu, Pb and Zn) in solution on the efficiency of low molecular weight organic acid (LMWOA) formation in Salix viminalis rhizosphere. Depending on the Ca/Mg ratio and presence of selected trace elements at 0.5mM concentration, the amount and kind of LMWOAs in the rhizosphere were significantly affected. In physiological 4:1 Ca/Mg ratio the following complex of acids was observed: malonic (Pb, Zn), citric, lactic, maleic and succinic (Zn) acids. Under 1:10 Ca/Mg ratio, citric (Cd, Zn), maleic and succinic (Cd, Cu, Pb, Zn) acids were seen. Additionally, high accumulation of zinc and copper in all systems was observed, with the exception of those where one of the metals was at higher concentration. Summing up, the results indicate a significant role of LMWOAs in Salix phytoremediation abilities. Both effects can be modulated depending on the mutual Ca/Mg ratio. Copyright © 2010 Elsevier Inc. All rights reserved.

Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.

Science.gov (United States)

Swietach, Pawel; Youm, Jae-Boum; Saegusa, Noriko; Leem, Chae-Hun; Spitzer, Kenneth W; Vaughan-Jones, Richard D

2013-05-28

Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one end of a myocyte evoked a local [Ca(2+)]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca(2+) transport into the acidic zone via Ca(2+)/H(+) exchange on diffusible HDPs and ATP molecules, energized by the [H(+)]i gradient. Ca(2+) recruitment to a localized acid microdomain was greatly reduced during intracellular Mg(2+) overload or by ATP depletion, maneuvers that reduce the Ca(2+)-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca(2+)/H(+) coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca(2+)/H(+) coupling is likely to be of general importance in cell signaling.

Mast cell mediators in citric acid-induced airway constriction of guinea pigs

International Nuclear Information System (INIS)

Lin, C.-H.; Lai, Y.-L.

2005-01-01

We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H 1 receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C 4 (LTC 4 ) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV 0.1 ) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV 0.1 , indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC 4 and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction

Behaviour of lactose with the presence of lactic acid and Ca as affected by pH.

Science.gov (United States)

Chandrapala, Jayani; Gauthier, Claire; Vasiljevic, Todor

2017-11-01

Contradictory statements about the effects of pH change on crystallisation behaviour of lactose exist in the literature. Considering the importance of addressing the processability issue of acid whey, a systematic study is required to establish lactose crystallisation behaviour in the presence of LA and Ca at concentrations present in real acid whey waste streams emphasising impact of pH. Structural modifications of lactose were evident at elevated, more neutral pH in the presence of 1% w/w LA and 0·12% w/w Ca. These structural changes led to changes in the anomeric equilibrium of lactose, which manipulated the water-lactose behaviour and increased the crystallinity. Therefore, altering pH to 6·5 may be the solution to proper industrial processing of acid whey, enhancing the ability of lactose to crystallise properly.

Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

Science.gov (United States)

Stein, T. P.; Schluter, M. D.; Leskiw, M. J.; Boden, G.

1999-01-01

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest.

Evaluation of the substitution of PMMA plates by PLA 3D printed in TL response of CaSO_4:Dy

International Nuclear Information System (INIS)

Almeida, Shirlane Barbosa de; Valeriano, Caio Cesar Santos; Campos, Leticia Lucente

2016-01-01

The CaSO_4:Dy is a dosimetric material that is nationally produced, which presents high sensibility but a high energy dependence of its thermoluminescent (TL) response at the photoelectric effect region. This study aims to compare the TL response of the CaSO_4:Dy when irradiated, with different energies, at the presence of 3D printed plates of polylactic acid (PLA) and polymethylmethacrylate (PMMA). Results show that the PLA has a different attenuation of the radiation, when compared to PMMA, indicating that it should be taken into account the quality of the print used on PLA plates manufacture. (author)

Utilization of Encapsulated CaCO_3 in Liquid Core Capsules for Improving Lactic Acid Fermentation

International Nuclear Information System (INIS)

Boon-Beng, Lee; Nurul Ainina Zulkifli

2016-01-01

Lactic acid bacteria (LAB) have been used for food fermentation due to its fermentative ability to improve and enhance the quality of the end food products. However, the performance of LAB is affected as fermentation time elapsed because the microbial growth is inhibited by its end product, for example lactic acid. In this study, a new approach was introduced to reduce the product inhibition effect using CaCO_3 which is encapsulated in spherical liquid core capsules of diameter 3.5 mm and 3.6 mm produced through extrusion dripping method. The results showed that the pH and lactic acid concentration of LAB fermentation was well maintained by the capsules. The results of the fermentation conducted to control pH and lactic acid concentration using the capsules were better than those of the control set and comparable with that of the free CaCO_3 set. In addition, the viable cell concentration of L. casei shirota was high at the end of fermentation when the fermentation was conducted using the capsules. The results of this study suggested that the capsules have high potential to be applied for pH and lactic acid level control in LAB fermentation for various productions. (author)

Fabrication of superhydrophobic surfaces via CaCO3 mineralization mediated by poly(glutamic acid)

Science.gov (United States)

Cao, Heng; Yao, Jinrong; Shao, Zhengzhong

2013-03-01

Surfaces with micrometer and nanometer sized hierarchical structures were fabricated by an one-step in situ additive controlled CaCO3 mineralization method. After chemical modification, the surfaces with various morphologies showed superhydrophobicity in different states, which could be easily adjusted by the initial supersaturation of the mineralization solution (concentration of calcium ion and poly(glutamic acid)). Generally, the "lotus state" surface which was covered by a thick layer of tetrahedron-shaped CaCO3 particles to exhibit a contact angle (CA) of 157±1° and a very low contact angle hysteresis (CAH) (roll-off angle=1°) was produced under high supersaturation. On the other hands, the petal-like surface with flower-shaped calcite spherulites was obtained in a relative low supersaturation, which showed both high CA (156±2°) and CAH (180°) in a "Cassie impregnating wetting state".

Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

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H. M. N. Iqbal

2015-09-01

Full Text Available We have developed novel composites by grafting caffeic acid (CA onto the P(3HB-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB-EC i.e., P(3HB-EC (control, 5CA-g-P(3HB-EC, 10CA-g-P(3HB-EC, 15CA-g-P(3HB-EC and 20CA-g-P(3HB-EC. FT-IR (Fourier-transform infrared spectroscopy was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics.

Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

International Nuclear Information System (INIS)

Liu, Hao; Rose, Marie E.; Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward; Graham, Steven H.

2016-01-01

Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

Energy Technology Data Exchange (ETDEWEB)

Liu, Hao; Rose, Marie E. [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States); Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurosurgery, University of Pittsburgh, PA 15216 (United States); Department of Critical Care Medicine, University of Pittsburgh, PA 15216 (United States); Graham, Steven H., E-mail: Steven.Graham@va.gov [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States)

2016-04-15

Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells

DEFF Research Database (Denmark)

Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle

2007-01-01

Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning.

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Tatyana Andrienko

Full Text Available Mitochondrial permeability transition pore (mPTP opening is critical for ischemia / reperfusion (I/R injury and is associated with increased [Ca2+] and reactive oxygen species (ROS. Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(PH and flavoproteins on reperfusion (detected using autofluorescence was rapid (t0.5 < 15 s and significantly slower following ischemic preconditioning (IP. This argues against superoxide production from reduced Complex 1 being a critical mediator of initial mPTP opening during early reperfusion. Furthermore, MitoPY1 (a mitochondria-targeted H2O2-sensitive fluorescent probe and aconitase activity measurements failed to detect matrix ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2-3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1 increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2-3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that

Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

Science.gov (United States)

Jin, Li; Piao, Zhe Hao; Sun, Simei; Liu, Bin; Ryu, Yuhee; Choi, Sin Young; Kim, Gwi Ran; Kim, Hyung-Seok; Kee, Hae Jin; Jeong, Myung Ho

2017-12-01

Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Ca2+ and aminoguanidine on γ-aminobutyric acid accumulation in germinating soybean under hypoxia–NaCl stress

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Runqiang Yang

2015-06-01

Full Text Available Gamma-aminobutyric acid (GABA, a nonproteinous amino acid with some benefits on human health, is synthesized by GABA-shunt and the polyamine degradation pathway in plants. The regulation of Ca2+ and aminoguanidine on GABA accumulation in germinating soybean (Glycine max L. under hypoxia-NaCl stress was investigated in this study. Exogenous Ca2+ increased GABA content significantly by enhancing glutamate decarboxylase gene expression and its activity. Addition of ethylene glycol tetra-acetic acid into the culture solution reduced GABA content greatly due to the inhibition of glutamate decarboxylase activity. Aminoguanidine reduced over 85% of diamine oxidase activity, and 33.28% and 36.35% of GABA content in cotyledon and embryo, respectively. Under hypoxia–NaCl stress, the polyamine degradation pathway contributed 31.61–39.43% of the GABA formation in germinating soybean.

Hydrogeochemical and mineralogical characteristics related to heavy metal attenuation in a stream polluted by acid mine drainage:A case study in Dabaoshan Mine, China

Institute of Scientific and Technical Information of China (English)

Huarong Zhao; Beicheng Xia; Jianqiao Qin; Jiaying Zhang

2012-01-01

Dabaoshan Mine,the largest mine in south China,has been developed since the 1970s.Acid mine drainage (AMD) discharged from the mine has caused severe environmental pollution and human health problems.In this article,chemical characteristics,mineralogy of ocher precipitations and heavy metal attenuation in the AMD are discussed based on physicochemical analysis,mineral analysis,sequential extraction experiments and hydrogeochemistry.The AMD chemical characteristics were determined from the initial water composition,water-rock interactions and dissolved sulfide minerals in the mine tailings.The waters,affected and unaffected by AMD,were Ca-SO4 and Ca-HCO3 types,respectively.The affected water had a low pH,high SO42- and high heavy metal content and oxidation as determined by the Fe2+/Fe3+ couple.Heavy metal and SO42- contents of Hengshi River water decreased,while pH increased,downstream.Schwertmannite was the major mineral at the waste dump,while goethite and quartz were dominant at the tailings dam and streambed.Schwertmannite was transformed into goethite at the tailings dam and streambed.The sulfate ions of the secondary minerals changed from bidentate- to monodentate-complexes downstream.Fe-Mn oxide phases of Zn,Cd and Pb in sediments increased downstream.However,organic matter complexes of Cu in sediments increased further away from the tailings.Fe3+ mineral precipitates and transformations controlled the AMD water chemistry.

Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

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Honglei Guo

2016-01-01

Full Text Available Aldosterone (Aldo is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA, and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.

Neutralization and attenuation of metal species in acid mine drainage and mine leachates using magnesite: a batch experimental approach

CSIR Research Space (South Africa)

Masindi, Vhahangwele

2014-08-01

Full Text Available International Mine Water Association Conference – An Interdisciplinary Response to Mine Water Challenges, China University of Mining and Technogy, China, China, 18-22 August 2014 Neutralization and Attenuation of Metal Species in Acid Mine Drainage and Mine...

Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways.

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Ying, Tsung-Ho; Chen, Chia-Wei; Hsiao, Yu-Ping; Hung, Sung-Jen; Chung, Jing-Gung; Yang, Jen-Hung

2013-10-01

Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro.

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Jia, Zhanwei; He, Qiang; Shan, Chunguang; Li, Fengyi

2018-09-15

Gentamycin is one of the most clinically used aminoglycoside antibiotics which induce intrinsic apoptosis of hair cells. Tauroursodeoxycholic acid (TUDCA) is known as safe cell-protective agent in disorders associated with apoptosis. We aimed to investigate the protective effects of TUDCA against gentamicin-induced ototoxicity. House Ear Institute-Organ of Corti 1(HEI-OC1) cells and explanted cochlear tissue were treated with gentamicin and TUDCA, followed by serial analyses including cell viability assay, hair cell staining, qPCR, ELISA and western blotting to determine the cell damage by the parameters relevant to cell apoptosis and endoplasmic reticulum stress. TUDCA significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and explanted cochlear hair cells. TUDCA alleviated gentamicin-induced cell apoptosis, supported by the decreased Bax/Bcl2 ratio compared with that of gentamicin treated alone. TUDCA decreased gentamicin-induced nitric oxide production and protein nitration in both models. In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of pertussis and cholera toxins administered supraspinally on CA3 hippocampal neuronal cell death and the blood glucose level induced by kainic acid in mice.

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Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Sharma, Naveen; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-12-01

The effect of cholera toxin (CTX) or pertussis toxin (PTX) administered supraspinally on hippocampal neuronal cell death in CA3 region induced by kainic acid (KA) was examined in mice. After the pretreatment with either PTX or CTX intracerebroventricularly (i.c.v.), mice were administered i.c.v. with KA. The i.c.v. treatment with KA caused a neuronal cell death in CA3 region and PTX, but not CTX, attenuated the KA-induced neuronal cell death. In addition, i.c.v. treatment with KA caused an elevation of the blood glucose level. The i.c.v. PTX pretreatment alone caused a hypoglycemia and inhibited KA-induced hyperglycemic effect. However, i.c.v. pretreatment with CTX did not affect the basal blood glucose level and KA-induced hyperglycemic effect. Moreover, KA administered i.c.v. caused an elevation of corticosterone level and reduction of the blood insulin level. Whereas, i.c.v. pretreatment with PTX further enhanced KA-induced up-regulation of corticosterone level. Furthermore, i.c.v. administration of PTX alone increased the insulin level and KA-induced hypoinsulinemic effect was reversed. In addition, PTX pretreatment reduces the KA-induced seizure activity. Our results suggest that supraspinally administered PTX, exerts neuroprotective effect against KA-induced neuronal cells death in CA3 region and neuroprotective effect of PTX is mediated by the reduction of KA-induced blood glucose level. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

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Chang, Shih-Sheng; Lee, Viola S. Y.; Tseng, Yu-Lun; Chang, Kuan-Cheng; Chen, Kuen-Bao; Chen, Yuh-Lien; Li, Chi-Yuan

2012-01-01

Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid. PMID:22811749

Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

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Shih-Sheng Chang

2012-01-01

Full Text Available Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid.

Changes in the content of fatty acids in CA1 and CA3 areas of the hippocampus of Krushinsky-Molodkina rats after single and fivefold audiogenic seizures.

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Savina, Tatyana; Aripovsky, Alexander; Kulagina, Tatyana

2017-09-01

Audiogenic seizures (AS) are generalized seizures evoked by high frequency sounds. Since the hippocampus is involved in the generation and maintenance of seizures, the effect of AS on the composition and content of fatty acids in the CA1 and CA3 hippocampal areas of AS-susceptible Krushinsky-Molodkina (KM) rats on days 1, 3, and 14 after single and fivefold seizures were examined. The total content of all fatty acids in field СА1 was found to be lower compared with the control at all times of observation after both a single seizure or fivefold seizures. The total content of fatty acids in field СА3 decreased at all times of examination after a single seizure, whereas it remained unchanged on days 3 and 14 following five AS. The content of omega-3 fatty acids in both fields at all times of observation after a single seizure and fivefold AS did not significantly differ from that in intact animals. The absence of significant changes in the content of stearic and α-linolenic acids and a considerable decrease in the levels of palmitic, oleic, and eicosapentaenoic acids were common to both fields at all times after both a single seizure or fivefold AS. The changes in the content of fatty acids in the СА3 and СА1 fields of the brain of AS-susceptible rats indicate that fatty acids are involved in both the development of seizure activity and neuroprotective anticonvulsive processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Salicylic acid failed to increase the efficacy of Ca-DTPA in the decorporation of plutonium and americium

International Nuclear Information System (INIS)

Jones, C.W.; Lloyd, R.D.; Mays, C.W.

1979-01-01

Male and female C57BL/Do mice were each given a single i.p. injection of 237+239 Pu + 241 Am as the citrate complex at 45 days of age. Twice weekly i.p. injecctions of either 500 μmol/kg Ca-DTPA or 500 μmol/kg Ca-DTPA, mixed just before injection with 2000 μmol/kg salicylic acid (SA), were begun 3 days after nuclide administration and continued for 5 weeks. Control mice were injected each time with isotonic saline. Nuclide retention was determined by in vivo counting using NaI(T1) spectrometry. At the end of treatment, total-body retention of Pu or Am in the mice given Ca-DTPA was significantly lower (P < 0.001) than in the control animals. Mice treated with Ca-DTPA + SA were statistically indistinguishable from mice treated with Ca-DTPA

Inorganic contaminants attenuation in acid mine drainage by fly ash and fly ash-ordinary Portland cement (OPC) blends : column experiments

International Nuclear Information System (INIS)

Gitari, W.M.; Petrik, L.F.; Etchebers, O.; Key, D.L.; Okujeni, C.

2010-01-01

The infiltration of acid mine drainage (AMD) material into mine voids is one of the environmental impacts of underground coal mining. In this study, the mitigation of AMD in a mine void was simulated in laboratory conditions. Various mixtures of fly ash, solid residues, and Portland cement were added to packed columns over a 6-month period. The fly ash additions generated near-neutral to alkaline pH levels, which in turn induced precipitation, co-precipitation, and adsorption contaminant attenuation mechanisms. A modelling study demonstrated that the precipitation of ferrihydrite, Al-hydroxides, Al-oxyhydroxysulphates, gypsum, ettringite, manganite, and rhodochrosite lowered contaminant levels. Results of the study indicated that the pH regime and acidity level of the AMD strongly influenced both the leaching of the toxic trace elements as well as the attenuation of the AMD. 3 refs., 2 figs.

Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

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Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

2016-01-01

Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

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Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

2008-01-01

The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

Cu2+ and Ca2+ adsorption to goethite in the presence of fulvic acids

NARCIS (Netherlands)

Weng, L.P.; Riemsdijk, van W.H.; Hiemstra, T.

2008-01-01

The interaction between copper ions (Cu2+), Strichen fulvic acid (FA), and goethite has been studied with batch experiments in the pH range of 3¿11. Similar systems with Ca2+ have been studied previously and are used here for comparison. Depending on the pH and Cu2+ loading, the binding of Cu ions

Catalytic oxidation of methanol on Pt/X (X = CaTP, NaTP electrodes in sulfuric acid solution

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Said Benmokhtar

2013-10-01

Full Text Available In this paper, we report the synthesis and characterization of electrodes based on NASICON type phosphates. The study of the electrochemical oxidation of methanol at ambient temperature on electrodes based on NASICON type Ca0,5Ti2(PO43 (CaTP and Na5Ti(PO43 (NaTP compared to that of the platinum electrode model has been conducted by cyclic voltammetry in acidic medium. The results showed a significant increase of current density on the electro oxidation of methanol on the material developed based NASICON structure CaTP, cons deactivation of the electro oxidation is observed the closed structure type NaTP.

Mechanisms of Vanadium Recovery from Stone Coal by Novel BaCO3/CaO Composite Additive Roasting and Acid Leaching Technology

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Zhenlei Cai

2016-03-01

Full Text Available In this report, the vanadium recovery mechanisms by novel BaCO3/CaO composite additive roasting and acid leaching technology, including the phase transformations and the vanadium leaching kinetics, were studied. The purpose of this manuscript is to realize and improve the vanadium recovery from stone coal using BaCO3/CaO as the composite additive. The results indicated that during the composite additive BaCO3/CaO roasting process, the monoclinic crystalline structure of muscovite (K(Al,V2[Si3AlO10](OH2 was converted into the hexagonal crystalline structure of BaSi4O9 and the tetragonal crystalline structure of Gehlenite (Ca2Al2SiO7, which could, therefore, facilitate the release and extraction of vanadium. Vanadium in leaching residue was probably in the form of vanadate or pyrovanadate of barium and calcium, which were hardly extracted during the sulfuric acid leaching process. The vanadium leaching kinetic analysis indicated that the leaching process was controlled by the diffusion through a product layer. The apparent activation energy could be achieved as 46.51 kJ/mol. The reaction order with respect to the sulfuric acid concentration was 1.1059. The kinetic model of vanadium recovery from stone coal using novel composite additive BaCO3/CaO could be finally established.

Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

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Tanaka Mika

2013-01-01

Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line.

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Chandrasekhar, Y; Phani Kumar, G; Ramya, E M; Anilakumar, K R

2018-04-18

Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson's disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

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Panchal, Sunil K; Ward, Leigh; Brown, Lindsay

2013-03-01

Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome. Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised. High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1. Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

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Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

2015-08-15

Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

Remediation of groundwater contaminated with arsenic through enhanced natural attenuation: Batch and column studies.

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Hafeznezami, Saeedreza; Zimmer-Faust, Amity G; Jun, Dukwoo; Rugh, Megyn B; Haro, Heather L; Park, Austin; Suh, Jae; Najm, Tina; Reynolds, Matthew D; Davis, James A; Parhizkar, Tarannom; Jay, Jennifer A

2017-10-01

Batch and column laboratory experiments were conducted on natural sediment and groundwater samples from a contaminated site in Maine, USA with the aim of lowering the dissolved arsenate [As(V)] concentrations through chemical enhancement of natural attenuation capacity. In batch factorial experiments, two levels of treatment for three parameters (pH, Ca, and Fe) were studied at different levels of phosphate to evaluate their impact on As(V) solubility. Results illustrated that lowering pH, adding Ca, and adding Fe significantly increased the sorption capacity of sediments. Overall, Fe amendment had the highest individual impact on As(V) levels. To provide further evidence for the positive impact of Ca on As(V) adsorption, isotherm experiments were conducted at three different levels of Ca concentrations. A consistent increase in adsorption capacity (26-37%) of sediments was observed with the addition of Ca. The observed favorable effect of Ca on As(V) adsorption is likely caused by an increase in the surface positive charges due to surface accumulation of Ca 2+ ions. Column experiments were conducted by flowing contaminated groundwater with elevated pH, As(V), and phosphate through both uncontaminated and contaminated sediments. Potential in-situ remediation scenarios were simulated by adding a chemical amendment feed to the columns injecting Fe(II) or Ca as well as simultaneous pH adjustment. Results showed a temporary and limited decrease in As(V) concentrations under the Ca treatment (39-41%) and higher levels of attenuation in Fe(II) treated columns (50-91%) but only after a certain number of pore volumes (18-20). This study illustrates the importance of considering geochemical parameters including pH, redox potential, presence of competing ions, and sediment chemical and physical characteristics when considering enhancing the natural attenuation capacity of sediments to mitigate As contamination in natural systems. Copyright © 2017 Elsevier Ltd. All rights

Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses.

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Vengust, M; Stämpfli, H; De Moraes, A N; Teixeiro-Neto, F; Viel, L; Heigenhauser, G

2010-11-01

Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl(-) and HCO(3)(-) exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses. To determine the effects of Carbonic anhydrase inhibition on CO(2) output and ionic exchange between erythrocytes and plasma and their influence on acid-base balance in the pulmonary circulation (across the lung) in exercising horses with and without CA inhibition. Six horses were exercised to exhaustion on a treadmill without (Con) and with CA inhibition (AczTr). CA inhibition was achieved with administration of acetazolamide (10 mg/kg bwt t.i.d. for 3 days and 30 mg/kg bwt before exercise). Arterial, mixed venous blood and CO(2) output were sampled at rest and during exercise. An integrated physicochemical systems approach was used to describe acid base changes. AczTr decreased the duration of exercise by 45% (P changes across the lung with exception of lactate. CO(2) and chloride changes in erythrocytes across the lung seem to be the major contributors to acid-base and ions balance in pulmonary circulation in exercising horses. © 2010 EVJ Ltd.

Comparison of Monte Carlo simulation of gamma ray attenuation coefficients of amino acids with XCOM program and experimental data

Science.gov (United States)

Elbashir, B. O.; Dong, M. G.; Sayyed, M. I.; Issa, Shams A. M.; Matori, K. A.; Zaid, M. H. M.

2018-06-01

The mass attenuation coefficients (μ/ρ), effective atomic numbers (Zeff) and electron densities (Ne) of some amino acids obtained experimentally by the other researchers have been calculated using MCNP5 simulations in the energy range 0.122-1.330 MeV. The simulated values of μ/ρ, Zeff, and Ne were compared with the previous experimental work for the amino acids samples and a good agreement was noticed. Moreover, the values of mean free path (MFP) for the samples were calculated using MCNP5 program and compared with the theoretical results obtained by XCOM. The investigation of μ/ρ, Zeff, Ne and MFP values of amino acids using MCNP5 simulations at various photon energies when compared with the XCOM values and previous experimental data for the amino acids samples revealed that MCNP5 code provides accurate photon interaction parameters for amino acids.

Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation

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Dongdong Sun

2017-07-01

Full Text Available Traumatic brain injury (TBI is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA, a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI device. Using western blotting, we first examined TBI-induced changes in the expression levels of GRP78, an ER stress marker, p-PERK, PERK, p-eIF2a, eIF2a, ATF4, p-Akt, Akt, Pten, Bax, Bcl-2, Caspase-12 and CHOP, as well as changes in the mRNA levels of Akt, GRP78, Caspase-12 and CHOP using RT-PCR. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end-labeling (TUNEL assay, and CHOP expression in neuronal cells was detected by double-immunofluorescence staining. Neurological and motor deficits were assessed by modified neurological severity scores (mNSS and beam balance and beam walking tests, and brain water content was also assessed. Our results indicated that ER stress peaked at 72 h after TBI and that TUDCA abolished ER stress and inhibited p-PERK, p-eIF2a, ATF4, Pten, Caspase-12 and CHOP expression levels. Moreover, our results show that TUDCA also improved neurological function and alleviated brain oedema. Additionally, TUDCA increased p-Akt expression and the Bcl-2/Bax ratio. However, the administration of the Akt inhibitor MK2206 or siRNA targeting of Akt abolished the beneficial effects of TUDCA. Taken together, our results indicate that TUDCA may attenuate early brain injury via Akt pathway activation.

Novel Intriguing Strategies Attenuating to Sarcopenia

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Kunihiro Sakuma

2012-01-01

Full Text Available Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA or ursolic acid, etc. for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant.

Significant effect of Ca2+ on improving the heat resistance of lactic acid bacteria.

Science.gov (United States)

Huang, Song; Chen, Xiao Dong

2013-07-01

The heat resistance of lactic acid bacteria (LAB) has been extensively investigated due to its highly practical significance. Reconstituted skim milk (RSM) has been found to be one of the most effective protectant wall materials for microencapsulating microorganisms during convective drying, such as spray drying. In addition to proteins and carbohydrate, RSM is rich in calcium. It is not clear which component is critical in the RSM protection mechanism. This study investigated the independent effect of calcium. Ca(2+) was added to lactose solution to examine its influence on the heat resistance of Lactobacillus rhamnosus ZY, Lactobacillus casei Zhang, Lactobacillus plantarum P8 and Streptococcus thermophilus ND03. The results showed that certain Ca(2+) concentrations enhanced the heat resistance of the LAB strains to different extents, that is produced higher survival and shorter regrowth lag times of the bacterial cells. In some cases, the improvements were dramatic. More scientifically insightful and more intensive instrumental study of the Ca(2+) behavior around and in the cells should be carried out in the near future. In the meantime, this work may lead to the development of more cost-effective wall materials with Ca(2+) added as a prime factor. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Properties of Ca2+ release induced by clofibric acid from the sarcoplasmic reticulum of mouse skeletal muscle fibres

Science.gov (United States)

Ikemoto, Takaaki; Endo, Makoto

2001-01-01

To characterize the effect of clofibric acid (Clof) on the Ca2+ release mechanism in the sarcoplasmic reticulum (SR) of skeletal muscle, we analysed the properties of Clof-induced Ca2+ release under various conditions using chemically skinned skeletal muscle fibres of the mouse.Clof (>0.5 mM) released Ca2+ from the SR under Ca2+-free conditions buffered with 10 mM EGTA (pCa >8).Co-application of ryanodine and Clof at pCa >8 but not ryanodine alone reduced the Ca2+ uptake capacity of the SR. Thus, Ca2+ release induced by Clof at pCa >8 must be a result of the activation of the ryanodine receptor (RyR).At pCa >8, (i) Clof-induced Ca2+ release was inhibited by adenosine monophosphate (AMP), (ii) the inhibitory effect of Mg2+ on the Clof-induced Ca2+ release was saturated at about 1 mM, and (iii) Clof-induced Ca2+ release was not inhibited by procaine (10 mM). These results indicate that Clof may activate the RyR-Ca2+ release channels in a manner different from Ca2+-induced Ca2+ release (CICR).In addition to this unique mode of opening, Clof also enhanced the CICR mode of opening of RyR-Ca2+ release channels.Apart from CICR, a high concentration of Ca2+ might also enhance the unique mode of opening by Clof.These results suggest that some features of Ca2+ release activated by Clof are similar to those of physiological Ca2+ release (PCR) in living muscle cells and raise the possibility that Clof may be useful in elucidating the mechanism of PCR in skeletal muscle. PMID:11606311

Ca2+-induced uncoupling of Aplysia bag cell neurons.

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Dargaei, Zahra; Standage, Dominic; Groten, Christopher J; Blohm, Gunnar; Magoski, Neil S

2015-02-01

Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons of Aplysia are a group of electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during a prolonged period of synchronous firing called the afterdischarge. Accompanying the afterdischarge is an increase in intracellular Ca2+ and the activation of protein kinase C (PKC). We used whole cell recording from paired cultured bag cell neurons to demonstrate that electrical coupling is regulated by both Ca2+ and PKC. Elevating Ca2+ with a train of voltage steps, mimicking the onset of the afterdischarge, decreased junctional current for up to 30 min. Inhibition was most effective when Ca2+ entry occurred in both neurons. Depletion of Ca2+ from the mitochondria, but not the endoplasmic reticulum, also attenuated the electrical synapse. Buffering Ca2+ with high intracellular EGTA or inhibiting calmodulin kinase prevented uncoupling. Furthermore, activating PKC produced a small but clear decrease in junctional current, while triggering both Ca2+ influx and PKC inhibited the electrical synapse to a greater extent than Ca2+ alone. Finally, the amplitude and time course of the postsynaptic electrotonic response were attenuated after Ca2+ influx. A mathematical model of electrically connected neurons showed that excessive coupling reduced recruitment of the cells to fire, whereas less coupling led to spiking of essentially all neurons. Thus a decrease in electrical synapses could promote the afterdischarge by ensuring prompt recovery of electrotonic potentials or making the neurons more responsive to current spreading through the network. Copyright © 2015 the American Physiological Society.

Intracellular alkalinization induces cytosolic Ca2+ increases by inhibiting sarco/endoplasmic reticulum Ca2+-ATPase (SERCA.

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Sen Li

Full Text Available Intracellular pH (pHi and Ca(2+ regulate essentially all aspects of cellular activities. Their inter-relationship has not been mechanistically explored. In this study, we used bases and acetic acid to manipulate the pHi. We found that transient pHi rise induced by both organic and inorganic bases, but not acidification induced by acid, produced elevation of cytosolic Ca(2+. The sources of the Ca(2+ increase are from the endoplasmic reticulum (ER Ca(2+ pools as well as from Ca(2+ influx. The store-mobilization component of the Ca(2+ increase induced by the pHi rise was not sensitive to antagonists for either IP(3-receptors or ryanodine receptors, but was due to inhibition of the sarco/endoplasmic reticulum Ca(2+-ATPase (SERCA, leading to depletion of the ER Ca(2+ store. We further showed that the physiological consequence of depletion of the ER Ca(2+ store by pHi rise is the activation of store-operated channels (SOCs of Orai1 and Stim1, leading to increased Ca(2+ influx. Taken together, our results indicate that intracellular alkalinization inhibits SERCA activity, similar to thapsigargin, thereby resulting in Ca(2+ leak from ER pools followed by Ca(2+ influx via SOCs.

Attenuation of abnormalities in the lipid metabolism during experimental myocardial infarction induced by isoproterenol in rats: beneficial effect of ferulic acid and ascorbic acid.

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Yogeeta, Surinder Kumar; Hanumantra, Rao Balaji Raghavendran; Gnanapragasam, Arunachalam; Senthilkumar, Subramanian; Subhashini, Rajakannu; Devaki, Thiruvengadam

2006-05-01

The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.

The Distribution of Charged Amino Acid Residues and the Ca2+ Permeability of Nicotinic Acetylcholine Receptors: A Predictive Model

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Sergio Fucile

2017-05-01

Full Text Available Nicotinic acetylcholine receptors (nAChRs are cation-selective ligand-gated ion channels exhibiting variable Ca2+ permeability depending on their subunit composition. The Ca2+ permeability is a crucial functional parameter to understand the physiological role of nAChRs, in particular considering their ability to modulate Ca2+-dependent processes such as neurotransmitter release. The rings of extracellular and intracellular charged amino acid residues adjacent to the pore-lining TM2 transmembrane segment have been shown to play a key role in the cation selectivity of these receptor channels, but to date a quantitative relationship between these structural determinants and the Ca2+ permeability of nAChRs is lacking. In the last years the Ca2+ permeability of several nAChR subtypes has been experimentally evaluated, in terms of fractional Ca2+ current (Pf, i.e., the percentage of the total current carried by Ca2+ ions. In the present study, the available Pf-values of nAChRs are used to build a simplified modular model describing the contribution of the charged residues in defined regions flanking TM2 to the selectivity filter controlling Ca2+ influx. This model allows to predict the currently unknown Pf-values of existing nAChRs, as well as the hypothetical Ca2+ permeability of subunit combinations not able to assemble into functional receptors. In particular, basing on the amino acid sequences, a Pf > 50% would be associated with homomeric nAChRs composed by different α subunits, excluding α7, α9, and α10. Furthermore, according to the model, human α7β2 receptors should have Pf-values ranging from 3.6% (4:1 ratio to 0.1% (1:4 ratio, much lower than the 11.4% of homomeric α7 nAChR. These results help to understand the evolution and the function of the large diversity of the nicotinic receptor family.

Effects of Bronsted acidity in the mechanism of selective oxidation of propane to acetone on CaY zeolite at room temperature.

NARCIS (Netherlands)

Xu, J.; Mojet, Barbara; van Ommen, J.G.; Lefferts, Leonardus

2005-01-01

The importance of Brønsted acid sites for partial oxidation of propane to acetone in CaY was investigated by in situ FTIR spectroscopy. With an increasing number of protons in Ca-Y, Volcano plots were observed for (1) amount of adsorbed propane; (2) initial acetone formation rate; (3) total amount

Amino Acids Attenuate Insulin Action on Gluconeogenesis and Promote Fatty Acid Biosynthesis via mTORC1 Signaling Pathway in trout Hepatocytes

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Weiwei Dai

2015-06-01

Full Text Available Background/Aims: Carnivores exhibit poor utilization of dietary carbohydrates and glucose intolerant phenotypes, yet it remains unclear what are the causal factors and underlying mechanisms. We aimed to evaluate excessive amino acids (AAs-induced effects on insulin signaling, fatty acid biosynthesis and glucose metabolism in rainbow trout and determine the potential involvement of mTORC1 and p38 MAPK pathway. Methods: We stimulated trout primary hepatocytes with different AA levels and employed acute administration of rapamycin to inhibit mTORC1 activation. Results: Increased AA levels enhanced the phosphorylation of ribosomal protein S6 kinase (S6K1, S6, and insulin receptor substrate 1 (IRS-1 on Ser302 but suppressed Akt and p38 phosphorylation; up-regulated the expression of genes related to gluconeogenesis and fatty acid biosynthesis. mTORC1 inhibition not only inhibited the phosphorylation of mTORC1 downstream targets, but also blunted IRS-1 Ser302 phosphorylation and restored excessive AAs-suppressed Akt phosphorylation. Rapamycin also inhibited fatty acid biosynthetic and gluconeogenic gene expression. Conclusion: High levels of AAs up-regulate hepatic fatty acid biosynthetic gene expression through an mTORC1-dependent manner, while attenuate insulin-mediated repression of gluconeogenesis through elevating IRS-1 Ser302 phosphorylation, which in turn impairs Akt activation and thereby weakening insulin action. We propose that p38 MAPK probably also involves in these AAs-induced metabolic changes.

Ca and S K-edge XANES studies of calcite-acid mine water interactions

International Nuclear Information System (INIS)

Myneni, S.C.B.; Perera, R.C.C.

1997-01-01

Heavy metal-rich acidic waters (SO 4 2- , AsO 4 3- , SeO 4 2- , Fe 2+ , Fe 3+ , Al 3+ , Cu 2+ , Zn 2+ , Cd 2+ ) and related ochreous coatings are common around abandoned sulfide and coal mine sites. This is mainly caused by the natural weathering of pyrite (FeS 2 ), arsenopyrite (FeAsS), and other metal sulfide containing shales. Acid generation in the case of pyrite can be explained by a general reaction: FeS 2 + 3.5 O 2 + H 2 O ↔ Fe 2+ + SO 4 2- + 2H + . Also, these low pH waters interact with the soils, and mobilize their soluble elements. One of the common remediation strategies is to allow these acid waters to react with limestone (CaCO 3 -rich rock) and neutralize the pH and precipitate out soluble metals. Yet, the associated problem is the precipitation of Fe and Al oxides and hydroxy sulfate coatings on limestone surfaces, which block calcite reactive sites, and make them ineffective a few hours after initiation of treatment. The main objectives of this research are to examine: (1) the chemistry of limestone surface coatings, and (2) their toxic metal uptake and the conditions that inhibit their formation. Previous molecular studies using X-ray diffraction, and vibrational spectroscopy on limestone surface coatings (sampled from Athens, OH) indicate that the surface-most layer (the layer in contact with water) is composed of schwertmannite (Fe(III)-hydroxy sulfate) like phases. However, white, X-ray amorphous; Al-, sulfate- and carbonate-rich; and Ca-poor phases appeared at the interface between the limestone and the iron oxide coatings. The structure, morphology, and coordination chemistry of component major and trace elements of these white precipitate phases have not previously been examined

The effect of CaCl2 on growth rate, wood decay and oxalic acid accumulation in Serpula lacrymans and related brown-rot fungi

DEFF Research Database (Denmark)

Hastrup, Anne Christine Steenkjær; Jensen, Bo; Clausen, Carol. A.

2006-01-01

The dry rot fungus, Serpula lacrymans, is one of the most destructive copper-tolerant fungi causing timber decay in buildings in temperate regions. Calcium and oxalic acid have been shown to play important roles in the mechanism of wood decay. The effect of calcium on growth and decay was evaluated...... for 12 strains of S. lacrymans and compared to five brown-rot fungi. This was done by treating copper citrate (CC)-treated Southern yellow pine (SYP) wood with a CaCl2 solution and estimating the decay rate and amount of soluble oxalic acid in an ASTM soil block test. Decay by S. lacrymans was found....... In summary, a marked decrease was observed in the decay capacity of S. lacrymans in pine treated with CC+CaCl2. The amount of soluble oxalic acid was measured in CC-treated blocks and blocks also treated with CaCl2. Of the comparative brown-rot fungi, both Antrodia vaillantii (TFFH 294) and Postia placenta...

Adsorption of endotoxins on Ca2+ -iminodiacetic acid by metal ion affinity chromatography.

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Lopes, André Moreni; Romeu, Jorge Sánchez; Meireles, Rolando Páez; Perera, Gabriel Marquez; Morales, Rolando Perdomo; Pessoa, Adalberto; Cárdenas, Lourdes Zumalacárregui

2012-11-01

Endotoxins (also known as lipopolysaccharides (LPS)) are undesirable by-products of recombinant proteins, purified from Escherichia coli. LPS can be considered stable under a wide range of temperature and pH, making their removal one of the most difficult tasks in downstream processes during protein purification. The inherent toxicity of LPS makes their removal an important step for the application of these proteins in several biological assays and for a safe parenteral administration. Immobilized metal affinity chromatography (IMAC) enables the affinity interactions between the metal ions (immobilized on the support through the chelating compound) and the target molecules, thus enabling high-efficiency separation of the target molecules from other components present in a mixture. Affinity chromatography is applied with Ca2+ -iminodiacetic acid (IDA) to remove most of the LPS contaminants from the end product (more than 90%). In this study, the adsorption of LPS on an IDA-Ca2+ was investigated. The adsorption Freundlich isotherm of LPS-IDA-Ca2+ provides a theoretical basis for LPS removal. It was found that LPS is bound mainly by interactions between the phosphate group in LPS and Ca2+ ligands on the beads. The factors such as pH (4.0 or 5.5) and ionic strength (1.0 mol/L) are essential to obtain effective removal of LPS for contaminant levels between endotoxin' concentration values less than 100 EU/mL and 100 000 EU/mL. This new protocol represents a substantial advantage in time, effort, and production costs.

Study of variation in thermal width of nematic and induced smectic ordering phase of citric acid (CA) and 4-heptyloxybenzoic acid (7OBA) hydrogen bonded liquid crystal complexes

Science.gov (United States)

Sundaram, S.; Jayaprakasam, R.; Praveena, R.; Rajasekaran, T. R.; Senthil, T. S.; Vijayakumar, V. N.

2018-01-01

Hydrogen-bonded liquid crystals (HBLCs) have been derived from nonmesogenic citric acid (CA) and mesogenic 4-heptyloxybenzoic acid (7OBA) yielding a highly ordered smectic C (Sm C) phase along with the new smectic X (Sm X) phase which has been identified as fingerprint-type texture. Optical (polarizing optical microscopy), thermal (differential scanning calorimetry) and structural (Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy) properties are studied. A noteworthy observation is that the intermolecular H-bond (between CA and 7OBA) influences on its melting point and clearing temperature of the HBLCs which exhibits lower value than those of the individual compounds. A typical extended mesophase region has been observed in the present complex while varying the mixture ratio (1:1 to 1:3) than those of individual compounds. The change in the ratio of the mesogenic compound in the mixture alters thermal properties such as enthalpy value and thermal span width in nematic (N) region of HBLC complex. Optical tilt angle measurement of CA+7OBA in Sm C phase has been discussed to identify the molecular position in the mesophase.

Fatty Acids Composition and Antibacterial Activity of Aristolochia longa L. and Bryonia dioïca Jacq. Growing Wild in Tunisia.

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Dhouioui, Mouna; Boulila, Abdennacer; Jemli, Maroua; Schiets, Fréderic; Casabianca, Hervé; Zina, Mongia Saïd

2016-08-01

The composition of the fatty acids of the roots and aerial parts of Aritolochia longa (Aristolacheae) and Bryonia dioïca (Cucurbutaceae) was analyzed by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The oils extracted from the aerial parts of both species were rich in polyunsaturated fatty acids with the essential linolenic and linoleic acids being the most prominent compounds. Oleic and linoleic acids were the majors fatty acids in the roots of both species. Whatever the plant part analyzed and the species, the saturated fatty acids were predominantly composed of palmitic and stearic acids. The antibacterial activity, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the lipid extracts were determined against a panel of five bacterial strains. The results showed that the sensitivity to the lipid extracts was different for the test bacterial strains, and the susceptibility of gram positive bacteria was found to be greater than gram negative bacteria. The antibacterial activity of the root lipid extracts was particularly important against Enterococcus feacium (CMI value of 125 µg/mL; CMB values > 250 µg/mL) and Streptococcus agalactiae (CMI value of 125 µg/mL; CMB values 250 µg/mL for A. longa roots). These results indicate that A. longa and B. dioïca could be considered as good sources of essential fatty acids which can act as natural antibacterial agents.

Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

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Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

2011-08-01

Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

Arabidopsis Glutamate Receptor Homolog3.5 Modulates Cytosolic Ca2+ Level to Counteract Effect of Abscisic Acid in Seed Germination1[OPEN

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Kong, Dongdong; Ju, Chuanli; Parihar, Aisha; Kim, So; Cho, Daeshik; Kwak, June M.

2015-01-01

Seed germination is a critical step in a plant’s life cycle that allows successful propagation and is therefore strictly controlled by endogenous and environmental signals. However, the molecular mechanisms underlying germination control remain elusive. Here, we report that the Arabidopsis (Arabidopsis thaliana) glutamate receptor homolog3.5 (AtGLR3.5) is predominantly expressed in germinating seeds and increases cytosolic Ca2+ concentration that counteracts the effect of abscisic acid (ABA) to promote germination. Repression of AtGLR3.5 impairs cytosolic Ca2+ concentration elevation, significantly delays germination, and enhances ABA sensitivity in seeds, whereas overexpression of AtGLR3.5 results in earlier germination and reduced seed sensitivity to ABA. Furthermore, we show that Ca2+ suppresses the expression of ABSCISIC ACID INSENSITIVE4 (ABI4), a key transcription factor involved in ABA response in seeds, and that ABI4 plays a fundamental role in modulation of Ca2+-dependent germination. Taken together, our results provide molecular genetic evidence that AtGLR3.5-mediated Ca2+ influx stimulates seed germination by antagonizing the inhibitory effects of ABA through suppression of ABI4. These findings establish, to our knowledge, a new and pivotal role of the plant glutamate receptor homolog and Ca2+ signaling in germination control and uncover the orchestrated modulation of the AtGLR3.5-mediated Ca2+ signal and ABA signaling via ABI4 to fine-tune the crucial developmental process, germination, in Arabidopsis. PMID:25681329

Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS–Ca{sup 2+}–JNK mitochondrial pathways

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yuanyuan; Han, Lirong [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China); Qi, Wentao [Academy of State Administration of Grain, No.11 Baiwanzhuang Avenue, Xicheng District, Beijing, 100037 (China); Cheng, Dai; Ma, Xiaolei; Hou, Lihua [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China); Cao, Xiaohong, E-mail: caoxh@tust.edu.cn [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China); Wang, Chunling, E-mail: wangchunling@tust.edu.cn [Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457 (China)

2015-01-24

Highlights: • EPA evoked ROS formation, [Ca{sup 2+}]{sub c} accumulation, the opening of MPTP and the phosphorylation of JNK. • EPA-induced [Ca{sup 2+}]{sub c} elevation was depended on production of ROS. • EPA-induced ROS generation, [Ca{sup 2+}]{sub c} increase, and JNK activated caused MPTP opening. • The apoptosis induced by EPA was related to release of cytochrome C through the MPTP. • EPA induced HepG2 cells apoptosis through ROS–Ca{sup 2+}–JNK mitochondrial pathways. - Abstract: Eicosapentaenoic acid (EPA), a well-known dietary n−3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. EPA inhibited proliferation of HepG2 cells in a dose-dependent manner and had no significant effect on the cell viability of humor normal liver L-02 cells. It was found that EPA initially evoked ROS formation, leading to [Ca{sup 2+}]{sub c} accumulation and the mitochondrial permeability transition pore (MPTP) opening; EPA-induced HepG2 cells apoptosis was inhibited by N-acetylcysteine (NAC, an inhibitor of ROS), 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM, a chelator of calcium) and CsA (inhibitor of MPTP). The relationship between ROS production, the increase of cytoplasmic Ca and MPTP opening was detected. It seems that ROS may act as an upstream regulator of EPA-induced [Ca{sup 2+}]{sub c} generation, moreover, generation of ROS, overload of mitochondrial [Ca{sup 2+}]{sub c}, and JNK activated cause the opening of MPTP. Western blotting results showed that EPA elevated the phosphorylation status of JNK, processes associated with the ROS generation. Simultaneously, the apoptosis induced by EPA was related to release of cytochrome C from mitochondria to cytoplasm through the MPTP

Using physical approaches for the attenuation of lactic acid bacteria in an organic rice beverage.

Science.gov (United States)

Bevilacqua, Antonio; Casanova, Francesco Pio; Petruzzi, Leonardo; Sinigaglia, Milena; Corbo, Maria Rosaria

2016-02-01

A wild strain of Lactobacillus plantarum, isolated from an Italian sourdough, was inoculated in an organic rice drink; however, it caused a strong acidification. Thus, it was preliminary processed through homogenization (single or multiple passes) or sonication (US) and then inoculated in the beverage. The samples were stored at 4 °C and analyzed to assess pH, production of lactic acid, viable count and sensory scores. A US-2-step process (power, 80%) could control acidification; viability and sensory traits were never affected by sonication. This result was confirmed on two commercial probiotics (Lactobacillus casei LC01 and Bifidobacterium animalis subsp. lactis Bb12). In the 2nd step samples inoculated with attenuated strains were also stored under thermal abuse conditions (25 or 37 °C for 4 or 24 h, then at 4 °C) and the results showed that US could control acidification for a short thermal abuse. Finally, US-attenuated starter cultures were inoculated in the rice drink containing β-glucans as healthy compounds; the targets did not cause any significant change of prebiotic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age and adaptation to Ca and P deficiencies: 2. Impacts on amino acid digestibility and phytase efficacy in broilers.

Science.gov (United States)

Li, W; Angel, R; Kim, S-W; Jiménez-Moreno, E; Proszkowiec-Weglarz, M; Plumstead, P W

2015-12-01

A total of 1,152 straight-run hatchling Heritage 56M×fast feathering Cobb 500F broiler birds were used to determine Ca, age, and adaptation effects on apparent ileal digestibility of crude protein (AID of CP), amino acids (AID of AA) and phytase efficacy. Twelve treatments with 8 replicates, each were fed from 7 to 9 d (6 birds per replicate), 7 to 21 d (6 birds per replicate) and 19 to 21 d (3 birds per replicate) d of age. Diets were prepared with 3 Ca (0.65, 0.80, and 0.95%) and 2 non-phytate P, (0.20 and 0.40%) concentrations. A 6-phytase was added at 500 or 1,000 FTU/kg to the 0.20% nPP diet at each Ca concentration. The age and adaptation effects were determined by comparing the responses between birds fed from 7 to 9 and 19 to 21 d of age, 19 to 21, and 7 to 21 d of age, respectively. An age effect was observed regardless of Ca, nPP, or phytase concentration, with older birds (19 to 21 d) having greater apparent ileal digestibility (AID) of amino acids (AA) and CP than younger birds (7 to 9 d; Pphytase concentrations. Constant lower AID of CP and AA was seen in adapted birds (7 to 21 d) compared to unadapted bird (19 to 21 d) when 0.20% nPP diets were fed at 0.95% Ca concentrations (PPhytase efficacy was significantly lower in younger (7 to 9 d) compared to older birds (19 to 21 d; PPhytase inclusion increased AID of CP and AA regardless of Ca (P<0.05). In conclusion, the AID of CP and AA can be affected by diet, age, and adaptation. © 2015 Poultry Science Association Inc.

Cadmium induces Ca2+ mediated, calpain-1/caspase-3-dependent apoptosis in primary cultured rat proximal tubular cells.

Science.gov (United States)

Wang, Hong; Zhai, Nianhui; Chen, Ying; Xu, Haibin; Huang, Kehe

2017-07-01

Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca 2+ ] c elevation-mediated apoptosis. The results confirmed the elevation of [Ca 2+ ] c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h. Then we demonstrated that Cd enhanced the protein levels of active calpain-1 and caspase-3 in rPT cells. Pretreatment with a cytosolic Ca 2+ chelator, 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), markedly blocked the up-regulation of active calpain-1 and caspase-3 and inhibited the apoptosis induced by Cd. Further, rPT cells were pretreated with a cell-permeable selective calpain-1 inhibitor, 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and caspase-3 inhibitor, N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), respectively. PD150606 significantly attenuated the up-regulation of active caspase-3 and the apoptosis induced by Cd. As expected, inhibition of active caspase-3 by Ac-DEVD-CHO decreased the apoptosis induced by Cd. Taken together, it could be concluded that [Ca 2+ ] c elevation did act as a pro-apoptotic signal in Cd-induced cytotoxicity of rPT cells, triggered calpain-1 and caspase-3 activation in turn, and induced apoptosis of rPT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Palmitoleic Acid (N-7 Attenuates the Immunometabolic Disturbances Caused by a High-Fat Diet Independently of PPARα

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Camila O. Souza

2014-01-01

Full Text Available Palmitoleic acid (PMA has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD, are PPAR-α dependent. C57BL6 wild-type (WT and PPAR-α-knockout (KO mice fed with a standard diet (SD or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w. or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF B (p65 in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.

Proper balance of omega-3 and omega-6 fatty acid supplements with topical cyclosporine attenuated contact lens-related dry eye syndrome.

Science.gov (United States)

Wang, Ling; Chen, Xi; Hao, Jingfang; Yang, Lu

2016-12-01

Essential fatty acids had been applied in the treatment of dry eye syndrome (DES), but the effects of different combinations of fatty acids have not been investigated. 360 long-term contact lens wearers were included in this double-blinded study. Omega-3 and omega-6 fatty acids were combined in different ratios and supplied to the participants that were randomly divided into six groups, and the effects of different essential fatty acids mixture on DES with or without topical cyclosporine were investigated. More than half of long-term contact lens wearers suffered from DES, which were found to be attenuated by oral supplement of properly balanced O3FA and O6FA fatty acid. The topical cyclosporine treatment considerably inhibited the production of cytokines compared to the cyclosporine negative groups, which further relieved DES. Proper balance of omega-3 and omega-6 fatty acid combination significantly alleviated contact lens-related DES.

Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

DEFF Research Database (Denmark)

Kennedy, Arion; Martinez, Kristina; Chung, Soonkyu

2010-01-01

We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) induced inflammation and insulin resistance in primary human adipocytes by activating nuclear factor kappaB (NFkappaB) and extracellular signal-related kinase (ERK) signaling. In this study, we demonstrated...... that the initial increase in intracellular calcium ([Ca2+]i) mediated by 10,12 CLA was attenuated by TMB-8, an inhibitor of calcium release from the endoplasmic reticulum (ER), by BAPTA, an intracellular calcium chelator, and by D609, a phospholipase C (PLC) inhibitor. Moreover, BAPTA, TMB-8, and D609 attenuated......, and suppression of peroxisome proliferator activated receptor gamma protein levels and insulin-stimulated glucose uptake. These data suggest that 10,12 CLA increases inflammation and insulin resistance in human adipocytes, in part by increasing [Ca2+]i levels, particularly calcium from the ER....

Disorder-derived, strong tunneling attenuation in bis-phosphonate monolayers

Science.gov (United States)

Pathak, Anshuma; Bora, Achyut; Liao, Kung-Ching; Schmolke, Hannah; Jung, Antje; Klages, Claus-Peter; Schwartz, Jeffrey; Tornow, Marc

2016-03-01

Monolayers of alkyl bisphosphonic acids (bisPAs) of various carbon chain lengths (C4, C8, C10, C12) were grown on aluminum oxide (AlO x ) surfaces from solution. The structural and electrical properties of these self-assembled monolayers (SAMs) were compared with those of alkyl monophosphonic acids (monoPAs). Through contact angle (CA) and Kelvin-probe (KP) measurements, ellipsometry, and infrared (IR) and x-ray photoelectron (XPS) spectroscopies, it was found that bisPAs form monolayers that are relatively disordered compared to their monoPA analogs. Current-voltage (J-V) measurements made with a hanging Hg drop top contact show tunneling to be the prevailing transport mechanism. However, while the monoPAs have an observed decay constant within the typical range for dense monolayers, β mono  =  0.85  ±  0.03 per carbon atom, a surprisingly high value, β bis  =  1.40  ±  0.05 per carbon atom, was measured for the bisPAs. We attribute this to a strong contribution of ‘through-space’ tunneling, which derives from conformational disorder in the monolayer due to strong interactions of the distal phosphonic acid groups; they likely form a hydrogen-bonding network that largely determines the molecular layer structure. Since bisPA SAMs attenuate tunnel currents more effectively than do the corresponding monoPA SAMs, they may find future application as gate dielectric modification in organic thin film devices.

Influence of barley grain particle size and treatment with citric acid on digestibility, ruminal fermentation and microbial protein synthesis in Holstein calves.

Science.gov (United States)

Kazemi-Bonchenari, M; Salem, A Z M; López, S

2017-08-01

Chemical and physical treatments of barley grain increase ruminally resistant starch and can improve the rumen fermentation pattern. The objective of the present study was to evaluate the effects of chemical (addition of citric acid, CA) and physical (grinding to two different particle sizes, PS) treatment of barley grain on performance, rumen fermentation, microbial protein yield in the rumen and selected blood metabolites in growing calves. In all, 28 male Holstein calves (172±5.1 kg initial BW) were used in a complete randomised design with a factorial arrangement of 2 barley grain particle sizes×2 levels of citric acid. The diets were as follows: (i) small PS (average 1200 µm) barley grain soaked in water (no CA addition); (ii) small PS barley grain soaked in a CA solution (adding 20 g CA/kg barley); (iii) large PS (average 2400 µm) barley grain soaked in water (no citric acid addition) and (iv) large PS barley grain soaked in a citric acid solution (adding 20 g CA/kg barley). Barley grain was then incorporated at 35% in a total mixed ration and fed to the calves for 11 weeks. Feeding small PS barley decreased feed intake (P=0.02) and average daily weight gain (P=0.01). The addition of CA to barley grain did not affect intake but increased weight gain (P0.05). However, the molar proportion of propionate was increased (P=0.03) when barley was more finely ground, and that of acetate was increased (P=0.04) when CA was added to barley grain. The ruminal concentration of ammonia nitrogen was increased (Pgrain with citric acid increased fibre digestibility of total mixed rations, attenuated the decrease in ruminal pH, and improved weight gain and feed efficiency in male Holstein growing calves fed a high-cereal diet (550 g cereal grain/kg diet).

Ca and S K-edge XANES studies of calcite-acid mine water interactions

Energy Technology Data Exchange (ETDEWEB)

Myneni, S.C.B.; Perera, R.C.C. [Lawrence Berkeley National Lab., CA (United States)

1997-04-01

Heavy metal-rich acidic waters (SO{sub 4}{sup 2{minus}}, AsO{sub 4}{sup 3{minus}}, SeO{sub 4}{sup 2{minus}}, Fe{sup 2+}, Fe{sup 3+}, Al{sup 3+}, Cu{sup 2+}, Zn{sup 2+}, Cd{sup 2+}) and related ochreous coatings are common around abandoned sulfide and coal mine sites. This is mainly caused by the natural weathering of pyrite (FeS{sub 2}), arsenopyrite (FeAsS), and other metal sulfide containing shales. Acid generation in the case of pyrite can be explained by a general reaction: FeS{sub 2} + 3.5 O{sub 2} + H{sub 2}O {leftrightarrow} Fe{sup 2+} + SO{sub 4}{sup 2{minus}} + 2H{sup +}. Also, these low pH waters interact with the soils, and mobilize their soluble elements. One of the common remediation strategies is to allow these acid waters to react with limestone (CaCO{sub 3}-rich rock) and neutralize the pH and precipitate out soluble metals. Yet, the associated problem is the precipitation of Fe and Al oxides and hydroxy sulfate coatings on limestone surfaces, which block calcite reactive sites, and make them ineffective a few hours after initiation of treatment. The main objectives of this research are to examine: (1) the chemistry of limestone surface coatings, and (2) their toxic metal uptake and the conditions that inhibit their formation. Previous molecular studies using X-ray diffraction, and vibrational spectroscopy on limestone surface coatings (sampled from Athens, OH) indicate that the surface-most layer (the layer in contact with water) is composed of schwertmannite (Fe(III)-hydroxy sulfate) like phases. However, white, X-ray amorphous; Al-, sulfate- and carbonate-rich; and Ca-poor phases appeared at the interface between the limestone and the iron oxide coatings. The structure, morphology, and coordination chemistry of component major and trace elements of these white precipitate phases have not previously been examined.

Geochemistry of acid mine drainage from a coal mining area and processes controlling metal attenuation in stream waters, southern Brazil

Directory of Open Access Journals (Sweden)

VERIDIANA P. CAMPANER

2014-06-01

Full Text Available Acid drainage influence on the water and sediment quality was investigated in a coal mining area (southern Brazil. Mine drainage showed pH between 3.2 and 4.6 and elevated concentrations of sulfate, As and metals, of which, Fe, Mn and Zn exceeded the limits for the emission of effluents stated in the Brazilian legislation. Arsenic also exceeded the limit, but only slightly. Groundwater monitoring wells from active mines and tailings piles showed pH interval and chemical concentrations similar to those of mine drainage. However, the river and ground water samples of municipal public water supplies revealed a pH range from 7.2 to 7.5 and low chemical concentrations, although Cd concentration slightly exceeded the limit adopted by Brazilian legislation for groundwater. In general, surface waters showed large pH range (6 to 10.8, and changes caused by acid drainage in the chemical composition of these waters were not very significant. Locally, acid drainage seemed to have dissolved carbonate rocks present in the local stratigraphic sequence, attenuating the dispersion of metals and As. Stream sediments presented anomalies of these elements, which were strongly dependent on the proximity of tailings piles and abandoned mines. We found that precipitation processes in sediments and the dilution of dissolved phases were responsible for the attenuation of the concentrations of the metals and As in the acid drainage and river water mixing zone. In general, a larger influence of mining activities on the chemical composition of the surface waters and sediments was observed when enrichment factors in relation to regional background levels were used.

Geochemistry of acid mine drainage from a coal mining area and processes controlling metal attenuation in stream waters, southern Brazil.

Science.gov (United States)

Campaner, Veridiana P; Luiz-Silva, Wanilson; Machado, Wilson

2014-05-14

Acid drainage influence on the water and sediment quality was investigated in a coal mining area (southern Brazil). Mine drainage showed pH between 3.2 and 4.6 and elevated concentrations of sulfate, As and metals, of which, Fe, Mn and Zn exceeded the limits for the emission of effluents stated in the Brazilian legislation. Arsenic also exceeded the limit, but only slightly. Groundwater monitoring wells from active mines and tailings piles showed pH interval and chemical concentrations similar to those of mine drainage. However, the river and ground water samples of municipal public water supplies revealed a pH range from 7.2 to 7.5 and low chemical concentrations, although Cd concentration slightly exceeded the limit adopted by Brazilian legislation for groundwater. In general, surface waters showed large pH range (6 to 10.8), and changes caused by acid drainage in the chemical composition of these waters were not very significant. Locally, acid drainage seemed to have dissolved carbonate rocks present in the local stratigraphic sequence, attenuating the dispersion of metals and As. Stream sediments presented anomalies of these elements, which were strongly dependent on the proximity of tailings piles and abandoned mines. We found that precipitation processes in sediments and the dilution of dissolved phases were responsible for the attenuation of the concentrations of the metals and As in the acid drainage and river water mixing zone. In general, a larger influence of mining activities on the chemical composition of the surface waters and sediments was observed when enrichment factors in relation to regional background levels were used.

Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

Science.gov (United States)

Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

2016-01-01

Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

Synthesis, structural characterization and antitumor activity of a Ca(II) coordination polymer based on 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide ligands

Energy Technology Data Exchange (ETDEWEB)

Tai, Xi-Shi, E-mail: taixs@wfu.edu.cn [Weifang University, College of Chemistry and Chemical Engineering (China); Wang, Xin [Qinghai Normal University, Department of Chemistry (China)

2017-03-15

A new Ca(II) coordination polymer, ([CaL(H{sub 2}O){sub 4}] · (H{sub 2}O){sub 4}){sub n} (L = 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide) has been prepared by one-pot synthesis method. And it was characterized by elemental analysis, IR and thermal analysis. The result of X-ray single-crystal diffraction analysis shows that the Ca(II) complex molecules form one-dimensional chain structure by the bridging oxygen atoms. The anti-tumor activity of L ligand and the Ca(II) coordination polymer has also been studied.

Phytic acid derived bioactive CaO-P2O5-SiO2 gel-glasses.

Science.gov (United States)

Li, Ailing; Qiu, Dong

2011-12-01

The possibility of using phytic acid as a precursor to synthesize CaO-P(2)O(5)-SiO(2) glasses by sol-gel method has been explored and the pseudo ternary phase diagram has been established. It was shown that gel-glasses over a broader range of compositions could be prepared compared to other phosphorus precursors or melt-quenching method. Furthermore, phytic acid was found to assist calcium being incorporated into glass networks. In vitro tests in simulated body fluid (SBF) were performed on the above gel-glasses and it was found that they were bioactive over a much broader compositional range especially at high phosphate content, thus enabling one to design bioactive materials with various degradation rates by adjusting the phosphate content.

Incorporation of Mg and Ca into nanostructured Fe2O3 improves Fe solubility in dilute acid and sensory characteristics in foods.

Science.gov (United States)

Hilty, Florentine M; Knijnenburg, Jesper T N; Teleki, Alexandra; Krumeich, Frank; Hurrell, Richard F; Pratsinis, Sotiris E; Zimmermann, Michael B

2011-01-01

Iron deficiency is one of the most common micronutrient deficiencies worldwide. Food fortification can be an effective and sustainable strategy to reduce Fe deficiency but selection of iron fortificants remains a challenge. Water-soluble compounds, for example, FeSO(4), usually demonstrate high bioavailability but they often cause unacceptable sensory changes in foods. On the other hand, poorly acid-soluble Fe compounds, for example FePO(4), may cause fewer adverse sensory changes in foods but are usually not well bioavailable since they need to be dissolved in the stomach prior to absorption. The solubility and the bioavailability of poorly acid-soluble Fe compounds can be improved by decreasing their primary particle size and thereby increasing their specific surface area. Here, Fe oxide-based nanostructured compounds with added Mg or Ca were produced by scalable flame aerosol technology. The compounds were characterized by nitrogen adsorption, X-ray diffraction, transmission electron microscopy, and Fe solubility in dilute acid. Sensory properties of the Fe-based compounds were tested in 2 highly reactive, polyphenol-rich food matrices: chocolate milk and fruit yoghurt. The Fe solubility of nanostructured Fe(2)O(3) doped with Mg or Ca was higher than that of pure Fe(2)O(3). Since good solubility in dilute acid was obtained despite the inhomogeneity of the powders, inexpensive precursors, for example Fe- and Ca-nitrates, can be used for their manufacture. Adding Mg or Ca lightened powder color, while sensory changes when added to foods were less pronounced than for FeSO(4). The combination of high Fe solubility and low reactivity in foods makes these flame-made nanostructured compounds promising for food fortification. Practical Application: The nanostructured iron-containing compounds presented here may prove useful for iron fortification of certain foods; they are highly soluble in dilute acid and likely to be well absorbed in the gut but cause less severe

Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

Directory of Open Access Journals (Sweden)

Tzu-Yu Lin

Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

Extraction of Trivalent La, Nd and Eu from Nitric Acid Solution by Ion quest-801 Loaded on Lewatit CA 9221

International Nuclear Information System (INIS)

Nowier, H.G; Metwally, S.S; Abd El-Rehim, S.S; Aly, H.F.

2005-01-01

The extraction of La 3+ , Nd 3+ and Eu 3+ from nitric acid medium by Lewatit CA 9221, Containing 2-ethylhexyl mono -2- ethylhexyl phosphonic acid ester, Ion quest-801, was studied. Batch experiments were carried out to investigate the effect of contact time, V/M ratio, extractant concentration, nitric acid molarity, lanthanide concentration and temperature. The data obtained are discussed in terms of extraction equilibrium and separation factors between the lanthanides as well as certain sorption models. Possible use of column chromatography containing the developed extractant material was assessed

Ecklonia cava Extract and Dieckol Attenuate Cellular Lipid Peroxidation in Keratinocytes Exposed to PM10.

Science.gov (United States)

Lee, Jeong-Won; Seok, Jin Kyung; Boo, Yong Chool

2018-01-01

Airborne particulate matter can cause oxidative stress, inflammation, and premature skin aging. Marine plants such as Ecklonia cava Kjellman contain high amounts of polyphenolic antioxidants. The purpose of this study was to examine the antioxidative effects of E. cava extract in cultured keratinocytes exposed to airborne particulate matter with a diameter of <10  μ m (PM10). After the exposure of cultured HaCaT keratinocytes to PM10 in the absence and presence of E. cava extract and its constituents, cell viability and cellular lipid peroxidation were assessed. The effects of eckol and dieckol on cellular lipid peroxidation and cytokine expression were examined in human epidermal keratinocytes exposed to PM10. The total phenolic content of E. cava extract was the highest among the 50 marine plant extracts examined. The exposure of HaCaT cells to PM10 decreased cell viability and increased lipid peroxidation. The PM10-induced cellular lipid peroxidation was attenuated by E. cava extract and its ethyl acetate fraction. Dieckol more effectively attenuated cellular lipid peroxidation than eckol in both HaCaT cells and human epidermal keratinocytes. Dieckol and eckol attenuated the expression of inflammatory cytokines such as tumor necrosis factor- (TNF-) α , interleukin- (IL-) 1 β , IL-6, and IL-8 in human epidermal keratinocytes stimulated with PM10. This study suggested that the polyphenolic constituents of E. cava , such as dieckol, attenuated the oxidative and inflammatory reactions in skin cells exposed to airborne particulate matter.

Ablation of CaV2.1 Voltage-Gated Ca2+ Channels in Mouse Forebrain Generates Multiple Cognitive Impairments

Science.gov (United States)

Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

2013-01-01

Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels located at the presynaptic membrane are known to control a multitude of Ca2+-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic CaV2.1 mouse models. Global CaV2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of CaV2.1 Ca2+ channels for complex behaviour in adult mice. Consequently we established a forebrain specific CaV2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of CaV2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific CaV2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional CaV2.1 knock-out model that is most suitable for analysing the in vivo functions of CaV2.1 in the adult murine forebrain. PMID:24205277

Detection of Ca2+-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin

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Tigran R Petrosyan

2016-01-01

Full Text Available The study aims to confirm the neuroregenerative effects of bacterial melanin (BM on central nervous system injury using a special staining method based on the detection of Ca2+-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I; n = 12 or unilateral rubrospinal tract transection at the cervical level (C3–4 (group II; n = 12. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup and the remaining six rats were intramuscularly injected with saline (saline subgroup. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca2+-dependent acid phosphatase activity detection in combination with Chilingarian's calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca2+-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.

Colon-specific delivery of 5-aminosalicylic acid from chitosan-Ca-alginate microparticles.

Science.gov (United States)

Mladenovska, K; Raicki, R S; Janevik, E I; Ristoski, T; Pavlova, M J; Kavrakovski, Z; Dodov, M G; Goracinova, K

2007-09-05

Chitosan-Ca-alginate microparticles for colon-specific delivery and controlled release of 5-aminosalicylic acid after peroral administration were prepared using spray drying method followed by ionotropic gelation/polyelectrolyte complexation. Physicochemical characterization pointed to the negatively charged particles with spherical morphology having a mean diameter less than 9 microm. Chitosan was localized dominantly in the particle wall, while for alginate, a homogeneous distribution throughout the particles was observed. (1)H NMR, FTIR, X-ray and DSC studies indicated molecularly dispersed drug within the particles with preserved stability during microencapsulation and in simulated in vivo drug release conditions. In vitro drug release studies carried out in simulated in vivo conditions in respect to pH, enzymatic and salt content confirmed the potential of the particles to release the drug in a controlled manner. The diffusional exponents according to the general exponential release equation indicated anomalous (non-Fickian) transport in 5-ASA release controlled by a polymer relaxation, erosion and degradation. Biodistribution studies of [(131)I]-5-ASA loaded chitosan-Ca-alginate microparticles, carried out within 2 days after peroral administration to Wistar male rats in which TNBS colitis was induced, confirmed the dominant localization of 5-ASA in the colon with low systemic bioavailability.

The amino-terminal 200 amino acids of the plasma membrane Na+,K+-ATPase alpha subunit confer ouabain sensitivity on the sarcoplasmic reticulum Ca(2+)-ATPase.

OpenAIRE

Ishii, T; Takeyasu, K

1993-01-01

Cardiac glycosides such as G-strophanthin (ouabain) bind to and inhibit the plasma membrane Na+,K(+)-ATPase but not the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, whereas thapsigargin specifically blocks the SR Ca(2+)-ATPase. The chimera [n/c]CC, in which the amino-terminal amino acids Met1 to Asp162 of the SR Ca(2+)-ATPase (SERCA1) were replaced with the corresponding portion of the Na+,K(+)-ATPase alpha 1 subunit (Met1 to Asp200), retained thapsigargin- and Ca(2+)-sensitive ATPase activity,...

Natural attenuation of herbicides

DEFF Research Database (Denmark)

Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

2002-01-01

A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

Natural attenuation at a former gas plant site: isotope analyses; Nachweis von Natural Attenuation mittels Isotopenuntersuchungen an einem ehemaligen Kokereistandort

Energy Technology Data Exchange (ETDEWEB)

Nagel, Aglaia; Strauss, Harald; Achten, Christine [Westfaelische Wilhelms-Universitaet Muenster, Institut fuer Geologie und Palaeontologie, Muenster (Germany); Stephan, Manuel [Universitaet Duisburg-Essen, Instrumentelle Analytische Chemie, Essen (Germany)

2011-12-15

Natural attenuation of mono- (BTEX) and polycyclic aromatic hydrocarbons (PAHs) was studied in groundwater at a former gas plant site over a distance of about 500 m. The contamination source was located within a 4-6 m thick succession of interbedded silt and sand (K{sub f} =1,4 .10{sup -7} m/s) at a depth of about 5-6 m below the surface. Groundwater flow times between source and the receiving surface waters were determined on the order of a few hundred years. The main contaminants were found to be benzene and naphthalene with concentrations up to 200,000 and 8,500 {mu}g/l, respectively. Over the past 9 years, concentrations within the contaminant plume have decreased and degradation of benzene was proven by compound specific carbon isotope analyses. In addition, sulphur isotope studies revealed that sulphate reduction has played a significant role. This was supported by ambient sulphate concentrations of 300-1,800 {mu}g/l at the site that are sufficient to sustain a long-term perspective for this process. In agreement with these physico-chemical conditions, no transfer of BTEX or PAHs from the plume into the nearby river has been observed. (orig.) [German] An einem ehemaligen Kokereistandort im Ruhrgebiet wurde das Potenzial von Natural Attenuation (natuerlicher Abbau und Rueckhalt) fuer mono- (BTEX) und polyzyklische aromatische Kohlenwasserstoffe (PAK) im Grundwasser auf einer Fliessstrecke von ca. 500 m untersucht. Das Schadenszentrum befindet sich unter eingeebnetem Bergematerial in ca. 5-6 m Tiefe unter Gelaendeoberkante innerhalb einer ca. 4-6 m maechtigen Schluff-Sand-Wechselfolge (K{sub f} =1,4 .10{sup -7} m/s). Im gesamten Aquifer resultieren Fliesszeiten von wenigen Hundert Jahren vom Schadstoffzentrum bis zur Vorflut. Hauptkontaminanten sind Benzen (bis ca. 200.000 {mu}g/l) und Naphthalen (bis ca. 8.500 {mu}g/l). An der Fahnenspitze liegen seit 9 Jahren schrumpfende Konzentrationen vor, die in Einklang mit einem mittels Kohlenstoffisotopie

Ab initio study of the binding of collagen amino acids to graphene and A-doped (A = H, Ca) graphene

Energy Technology Data Exchange (ETDEWEB)

Cazorla, Claudio, E-mail: c.silva@ucl.ac.u

2010-09-30

We present a theoretical study of the binding of collagen amino acids (AA, namely glycine, Gly; proline, Pro; and hydroxyproline, Hyp) to graphene (Gr), Ca-doped graphene and graphane (Gra) using density functional theory calculations and ab initio molecular dynamics (AIMD) simulations. It is found that binding of Gly, Pro and Hyp to Gr and Gra is thermodynamically favorable yet dependent on the amino acid orientation and always very weak (adsorption energies E{sub ads} range from -90 to -20 meV). AIMD simulations reveal that room-temperature thermal excitations are enough to induce detachment of Gly and Pro from Gr and of all three amino acids from Gra. Interestingly, we show that collagen AA binding to Gr is enhanced dramatically by doping the carbon surface with calcium atoms (corresponding E{sub ads} values decrease by practically two orders of magnitude with respect to the non-doped case). This effect is result of electronic charge transfers from the Ca impurity (donor) to Gr (acceptor) and the carboxyl group (COOH) of the amino acid (acceptor). The possibility of using Gr and Gra as nanoframes for sensing of collagen amino acids has also been investigated by performing electronic density of states analysis. It is found that, whether Gr is hardly sensitive, the electronic band gap of Gra can be modulated by attaching different number and species of AAs onto it. The results presented in this work provide fundamental insights on the quantum interactions of collagen protein components with carbon-based nanostructures and can be useful for developments in bio and nanotechnology fields.

A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster.

Science.gov (United States)

Hoff, Max; Balfanz, Sabine; Ehling, Petra; Gensch, Thomas; Baumann, Arnd

2011-07-01

Rhythmic activity of cells and cellular networks plays an important role in physiology. In the nervous system oscillations of electrical activity and/or second messenger concentrations are important to synchronize neuronal activity. At the molecular level, rhythmic activity can be initiated by different routes. We have recently shown that an octopamine-activated G-protein-coupled receptor (GPCR; DmOctα1Rb, CG3856) from Drosophila initiates Ca(2+) oscillations. Here, we have unraveled the molecular basis of cellular Ca(2+) signaling controlled by the DmOctα1Rb receptor using a combination of pharmacological intervention, site-directed mutagenesis, and functional cellular Ca(2+) imaging on heterologously expressed receptors. Phosphorylation of a single amino acid residue in the third intracellular loop of the GPCR by PKC is necessary and sufficient to desensitize the receptor. From its desensitized state, DmOctα1Rb is resensitized by dephosphorylation, and a new Ca(2+) signal occurs on octopamine stimulation. Our findings show that transient changes of the receptor's surface profile have a strong effect on its physiological signaling properties. We expect that the detailed knowledge of DmOctα1Rb-dependent signal transduction fosters the identification of specific drugs that can be used for GPCR-mediated pest control, since octopamine serves important physiological and behavioral functions in arthropods.

Astragalus Granule Prevents Ca2+ Current Remodeling in Heart Failure by the Downregulation of CaMKII

Directory of Open Access Journals (Sweden)

Sinai Li

2017-01-01

Full Text Available Background. Astragalus was broadly used for treating heart failure (HF and arrhythmias in East Asia for thousands of years. Astragalus granule (AG, extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L in HF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII. Methods. HF mice were induced by thoracic aortic constriction (TAC. After 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte was then isolated and whole-cell patch clamp was used to record action potential (AP and ICa-L. The expressions of L-type calcium channel alpha 1C subunit (Cav1.2, CaMKII, and phosphorylated protein kinase A (p-PKA were examined by western blot. Results. The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition, AG treatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. Conclusion. AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII.

Adsorption of Lysine on Na-Montmorillonite and Competition with Ca(2+): A Combined XRD and ATR-FTIR Study.

Science.gov (United States)

Yang, Yanli; Wang, Shengrui; Liu, Jingyang; Xu, Yisheng; Zhou, Xiaoyun

2016-05-17

Lysine adsorption at clay/aqueous interfaces plays an important role in the mobility, bioavailability, and degradation of amino acids in the environment. Knowledge of these interfacial interactions facilitates our full understanding of the fate and transport of amino acids. Here, X-ray diffraction (XRD) and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) measurements were used to explore the dynamic process of lysine adsorption on montmorillonite and the competition with Ca(2+) at the molecular level. Density functional theory (DFT) calculations were employed to determine the peak assignments of dissolved lysine in the solution phase. Three surface complexes, including dicationic, cationic, and zwitterionic structures, were observed to attach to the clay edge sites and penetrate the interlayer space. The increased surface coverage and Ca(2+) competition did not affect the interfacial lysine structures at a certain pH, whereas an elevated lysine concentration contributed to zwitterionic-type coordination at pH 10. Moreover, clay dissolution at pH 4 could be inhibited at a higher surface coverage with 5 and 10 mM lysine, whereas the inhibition effect was inconspicuous or undetected at pH 7 and 10. The presence of Ca(2+) not only could remove a part of the adsorbed lysine but also could facilitate the readsorption of dissolved Si(4+) and Al(3+) and surface protonation. Our results provide new insights into the process of lysine adsorption and its effects on montmorillonite surface sites.

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

Energy Technology Data Exchange (ETDEWEB)

Li, Ying [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 (China); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 (China); Gu, Tieguang [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia); Yamahara, Johji [Pharmafood Institute, Kyoto 602-8136 (Japan); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia)

2014-06-01

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

International Nuclear Information System (INIS)

Li, Ying; Wang, Jianwei; Gu, Tieguang; Yamahara, Johji; Li, Yuhao

2014-01-01

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

Energy Technology Data Exchange (ETDEWEB)

Krogstad, Daniel V. [Biosystems and; Wang, Dongbo [Biosystems and; Lin-Gibson, Sheng [Biosystems and

2017-08-31

Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.

The Cytoplasmic Carbonic Anhydrases βCA2 and βCA4 Are Required for Optimal Plant Growth at Low CO2.

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DiMario, Robert J; Quebedeaux, Jennifer C; Longstreth, David J; Dassanayake, Maheshi; Hartman, Monica M; Moroney, James V

2016-05-01

Carbonic anhydrases (CAs) are zinc metalloenzymes that interconvert CO2 and HCO3 (-) In plants, both α- and β-type CAs are present. We hypothesize that cytoplasmic βCAs are required to modulate inorganic carbon forms needed in leaf cells for carbon-requiring reactions such as photosynthesis and amino acid biosynthesis. In this report, we present evidence that βCA2 and βCA4 are the two most abundant cytoplasmic CAs in Arabidopsis (Arabidopsis thaliana) leaves. Previously, βCA4 was reported to be localized to the plasma membrane, but here, we show that two forms of βCA4 are expressed in a tissue-specific manner and that the two proteins encoded by βCA4 localize to two different regions of the cell. Comparing transfer DNA knockout lines with wild-type plants, there was no reduction in the growth rates of the single mutants, βca2 and βca4 However, the growth rate of the double mutant, βca2βca4, was reduced significantly when grown at 200 μL L(-1) CO2 The reduction in growth of the double mutant was not linked to a reduction in photosynthetic rate. The amino acid content of leaves from the double mutant showed marked reduction in aspartate when compared with the wild type and the single mutants. This suggests the cytoplasmic CAs play an important but not previously appreciated role in amino acid biosynthesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

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Jianmin Ran

2014-01-01

Full Text Available Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN. Meanwhile, low protein diet (LPD retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ- induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5% and normal protein diet (18%, respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA, creatinine (SCr and 24 h amounts of urinary albumin excretion (UAE, creatintine (UCr, urea nitrogen (UUN, and uric acid (UUA. LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

Disorder-derived, strong tunneling attenuation in bis-phosphonate monolayers

International Nuclear Information System (INIS)

Pathak, Anshuma; Bora, Achyut; Tornow, Marc; Liao, Kung-Ching; Schwartz, Jeffrey; Schmolke, Hannah; Jung, Antje; Klages, Claus-Peter

2016-01-01

Monolayers of alkyl bisphosphonic acids (bisPAs) of various carbon chain lengths (C4, C8, C10, C12) were grown on aluminum oxide (AlO x ) surfaces from solution. The structural and electrical properties of these self-assembled monolayers (SAMs) were compared with those of alkyl monophosphonic acids (monoPAs). Through contact angle (CA) and Kelvin-probe (KP) measurements, ellipsometry, and infrared (IR) and x-ray photoelectron (XPS) spectroscopies, it was found that bisPAs form monolayers that are relatively disordered compared to their monoPA analogs. Current–voltage (J–V) measurements made with a hanging Hg drop top contact show tunneling to be the prevailing transport mechanism. However, while the monoPAs have an observed decay constant within the typical range for dense monolayers, β mono   =  0.85  ±  0.03 per carbon atom, a surprisingly high value, β bis   =  1.40  ±  0.05 per carbon atom, was measured for the bisPAs. We attribute this to a strong contribution of ‘through-space’ tunneling, which derives from conformational disorder in the monolayer due to strong interactions of the distal phosphonic acid groups; they likely form a hydrogen-bonding network that largely determines the molecular layer structure. Since bisPA SAMs attenuate tunnel currents more effectively than do the corresponding monoPA SAMs, they may find future application as gate dielectric modification in organic thin film devices. (paper)

Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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Chen Li

Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

Interventional Vitamin C-A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-2-0064 TITLE: Interventional Vitamin C -A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic...COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Interventional Vitamin C -A Strategy for Attenuation of Coagulopathy and Inflammation in...high dose parenteral vitamin C (VitC) in a swine model of combined hemorrhagic shock and tissue trauma that simulates the course of a combat casualty

Antagonist effects of veratric acid against UVB-induced cell damages.

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Shin, Seoung Woo; Jung, Eunsun; Kim, Seungbeom; Lee, Kyung-Eun; Youm, Jong-Kyung; Park, Deokhoon

2013-05-10

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

Depressing effect of phenoxyl acetic acids on flotation of minerals containing Ca2+/Mg2+ gangues

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Phenoxyl acetic acids were applied to determine their depressing effect on minerals containing Ca2+/Mg2+ gangues. Calcite,mixture of calcite and fluorite, and nickel ore were used in the flotation. And the depression mechanism was studied by the determination of contact angle, zeta potential, adsorptive capacity of collector, and IR analysis as well. It is found that 0.1 mmol/L of phenoxyl acetic acid derived from pyrogallol or gallic acid exhibits strong depressing ability on calcite in almost zero yields at pH value of 9.8, and calcite can be depressed in the flotation of calcite/fluorite mixture for approximate 87% yield of fluorite. The flotation result of practical nickel ore containing serpentine indicates that these two depressants may also show better depression performance to serpentine than traditional depressants such as sodium fluosilicate and carboxylmethyl cellulose. Analysis for the depression mechanism reveals that there exists strong chemical interaction between the depressants and minerals.

Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

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Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

2017-07-01

Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

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Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

2013-01-01

Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.1 mouse models. Global Ca(V)2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V)2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V)2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V)2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V)2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V)2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V)2.1 in the adult murine forebrain.

Molecular cloning of the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease

International Nuclear Information System (INIS)

Imajoh, Shinobu; Aoki, Kazumasa; Ohno, Shigeo; Emori, Yasufumi; Kawasaki, Hiroshi; Sugihara, Hidemitsu; Suzuki, Koichi

1988-01-01

A nearly full-length cDNA clone for the large subunit of high-Ca 2+ -requiring Ca 2+ -activated neutral protease (mCANP) from human tissues has been isolated. The deduced protein, determined for the first time as an mCANP, has essentially the same structural features as those revealed previously for the large subunits of the low-Ca 2+ -requiring form (μCANP). Namely, the protein, comprising 700 amino acid residues, is characterized by four domains, containing a cysteine protease like domain and a Ca 2+ -binding domain. The overall amino acid sequence similarities of the mCANP large subunit with those of human μCANP and chicken CANP are 62% and 66%, respectively. These values are slightly lower than that observed between μCANP and chicken CANP (70%). Local sequence similarities vary with the domain, 73-78% in the cysteine protease like domain and 48-65% in the Ca 2+ -binding domain. These results suggest that CANPs with different Ca 2+ sensitivities share a common evolutionary origin and that their regulatory mechanisms are similar except for the Ca 2+ concentrations required for activation

Mast cells in citric acid-induced cough of guinea pigs

International Nuclear Information System (INIS)

Lai, Y.-L.; Lin, T.-Y.

2005-01-01

It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H 1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C 4 , while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC 4 or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine

Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

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Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

2009-01-01

The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

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Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-08-30

We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

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Kia J Jackson

Full Text Available The influx of Ca(2+ through calcium-permeable nicotinic acetylcholine receptors (nAChRs leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB, which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/- mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

International Nuclear Information System (INIS)

Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

2007-01-01

Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

Science.gov (United States)

Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

2008-02-01

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

Mapping of the mutations present in the genome of the Rift Valley fever virus attenuated MP12 strain and their putative role in attenuation.

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Vialat, P; Muller, R; Vu, T H; Prehaud, C; Bouloy, M

1997-11-01

The MP12 attenuated strain of Rift Valley fever virus was obtained by 12 serial passages of a virulent isolate ZH548 in the presence of 5-fluorouracil (Caplen et al., 1985. Mutagen-directed attenuation of Rift Valley fever virus as a method for vaccine development. J. Gen. Virol., 66, 2271-2277). The comparison of the M segment of the two strains has already been reported by Takehara et al. (Takehara et al., 1989. Identification of mutations in the M RNA of a candidate vaccine strain of Rift Valley fever virus. Virology 169, 452-457). We have completed the comparison and found that altogether a total of nine, 12 and four nucleotides were changed in the L, M and S segments of the two strains, respectively. Three mutations induced amino acid changes in the L protein but none of them was located in the recognized motifs conserved among RNA dependent polymerases. In the S segment, a single change modified an amino acid in the NSs protein and in the M segment, seven of the mutations resulted in amino acid changes in each of the four encoded G1, G2, 14 kDa and 78 kDa proteins. Characterization of the MP12 virus indicated that determinants for attenuation were present in each segment and that they were introduced progressively during the 12 passages in the presence of the mutagen (Saluzzo and Smith, 1990. Use of reassortant viruses to map attenuating and temperature-sensitive mutations of the Rift Valley fever virus MP-12 vaccine. Vaccine 8, 369-375). Passages 4 and 7-9 were found to be essential for introduction of temperature-sensitive lesions and attenuation. In an attempt to correlate some of the mutations with the attenuated or temperature-sensitive phenotypes, we determined by sequencing the passage level at which the different mutations appeared. This work should help to address the question of the role of the viral gene products in Rift Valley fever pathogenesis.

Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness

Science.gov (United States)

Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R.

2015-01-01

In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states. PMID:26056284

Demand for Zn2+ in acid-secreting gastric mucosa and its requirement for intracellular Ca2+.

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JingJing Liu

Full Text Available Recent work has suggested that Zn(2+ plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. Here, we investigate the content, distribution and demand for Zn(2+ in gastric mucosa under baseline conditions and its regulation during secretory stimulation.Content and distribution of zinc were evaluated in sections of whole gastric mucosa using X-ray fluorescence microscopy. Significant stores of Zn(2+ were identified in neural elements of the muscularis, glandular areas enriched in parietal cells, and apical regions of the surface epithelium. In in vivo studies, extraction of the low abundance isotope, (70Zn(2+, from the circulation was demonstrated in samples of mucosal tissue 24 hours or 72 hours after infusion (250 µg/kg. In in vitro studies, uptake of (70Zn(2+ from media was demonstrated in isolated rabbit gastric glands following exposure to concentrations as low as 10 nM. In additional studies, demand of individual gastric parietal cells for Zn(2+ was monitored using the fluorescent zinc reporter, fluozin-3, by measuring increases in free intracellular concentrations of Zn(2+ {[Zn(2+](i} during exposure to standard extracellular concentrations of Zn(2+ (10 µM for standard intervals of time. Under resting conditions, demand for extracellular Zn(2+ increased with exposure to secretagogues (forskolin, carbachol/histamine and under conditions associated with increased intracellular Ca(2+ {[Ca(2+](i}. Uptake of Zn(2+ was abolished following removal of extracellular Ca(2+ or depletion of intracellular Ca(2+ stores, suggesting that demand for extracellular Zn(2+ increases and depends on influx of extracellular Ca(2+.This study is the first to characterize the content and distribution of Zn(2+ in an organ of the gastrointestinal tract. Our findings offer the novel interpretation, that Ca(2+ integrates basolateral demand for Zn(2+ with stimulation of secretion of HCl into the lumen of the gastric

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice.

Science.gov (United States)

Takahara, Ikuko; Akazawa, Yuko; Tabuchi, Maiko; Matsuda, Katsuya; Miyaaki, Hisamitsu; Kido, Youko; Kanda, Yasuko; Taura, Naota; Ohnita, Ken; Takeshima, Fuminao; Sakai, Yusuke; Eguchi, Susumu; Nakashima, Masahiro; Nakao, Kazuhiko

2017-01-01

A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.

Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions.

Science.gov (United States)

Liu, Di; Gao, Yuan; Li, Xiao-Xi; Li, Zheng; Pan, Qiu-Hong

2015-09-17

This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv.) under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A) and 99% (film B) invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA) revealed that (E)-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E)-2-heptenal, styrene, α-phenylethanol, and (Z)-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation.

Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions

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Di Liu

2015-09-01

Full Text Available This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv. under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A and 99% (film B invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA revealed that (E-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E-2-heptenal, styrene, α-phenylethanol, and (Z-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation.

Ablation of Ca(V2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

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Robert Theodor Mallmann

Full Text Available Voltage-gated Ca(V2.1 (P/Q-type Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V2.1 mouse models. Global Ca(V2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V2.1 in the adult murine forebrain.

Fabrication and characterization of novel multilayered structures by stereocomplexion of poly(D-lactic acid/poly(L-lactic acid and self-assembly of polyelectrolytes

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Elena Dellacasa

2016-01-01

Full Text Available The enantiomers poly(D-lactic acid (PDLA and poly(L-lactic acid (PLLA were alternately adsorbed directly on calcium carbonate (CaCO3 templates and on poly(styrene sulfonate (PSS and poly(allylamine hydrochloride (PAH multilayer precursors in order to fabricate a novel layer-by-layer (LBL assembly. A single layer of poly(L-lysine (PLL was used as a linker between the (PDLA/PLLAn stereocomplex and the cores with and without the polymeric (PSS/PAHn/PLL multilayer precursor (PEM. Nuclear magnetic resonance (NMR and gel permeation chromatography (GPC were used to characterize the chemical composition and molecular weight of poly(lactic acid polymers. Both multilayer structures, with and without polymeric precursor, were firstly fabricated and characterized on planar supports. A quartz crystal microbalance (QCM, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR and ellipsometry were used to evaluate the thickness and mass of the multilayers. Then, hollow, spherical microcapsules were obtained by the removal of the CaCO3 sacrificial template. The chemical composition of the obtained microcapsules was confirmed by differential scanning calorimetry (DSC and wide X-ray diffraction (WXRD analyses. The microcapsule morphology was evaluated by scanning electron microscopy (SEM and transmission electron microscopy (TEM measurements. The experimental results confirm the successful fabrication of this innovative system, and its full biocompatibility makes it worthy of further characterization as a promising drug carrier for sustained release.

Fabrication and characterization of novel multilayered structures by stereocomplexion of poly(D-lactic acid)/poly(L-lactic acid) and self-assembly of polyelectrolytes

Science.gov (United States)

Yang, Gesheng; Pastorino, Laura

2016-01-01

Summary The enantiomers poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) were alternately adsorbed directly on calcium carbonate (CaCO3) templates and on poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) multilayer precursors in order to fabricate a novel layer-by-layer (LBL) assembly. A single layer of poly(L-lysine) (PLL) was used as a linker between the (PDLA/PLLA)n stereocomplex and the cores with and without the polymeric (PSS/PAH)n/PLL multilayer precursor (PEM). Nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) were used to characterize the chemical composition and molecular weight of poly(lactic acid) polymers. Both multilayer structures, with and without polymeric precursor, were firstly fabricated and characterized on planar supports. A quartz crystal microbalance (QCM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and ellipsometry were used to evaluate the thickness and mass of the multilayers. Then, hollow, spherical microcapsules were obtained by the removal of the CaCO3 sacrificial template. The chemical composition of the obtained microcapsules was confirmed by differential scanning calorimetry (DSC) and wide X-ray diffraction (WXRD) analyses. The microcapsule morphology was evaluated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) measurements. The experimental results confirm the successful fabrication of this innovative system, and its full biocompatibility makes it worthy of further characterization as a promising drug carrier for sustained release. PMID:26925356

Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle

DEFF Research Database (Denmark)

Pedersen, Line; Holkmann Olsen, Caroline; Pedersen, Bente Klarlund

2012-01-01

Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expres...... in muscle angiogenesis. In conclusion, our data show that overexpression of CXCL1 within a physiological range attenuates diet-induced obesity, likely mediated through a CXCL1-induced improvement of fatty acid oxidation and oxidative capacity in skeletal muscle tissue....

Functional roles of the pepper RING finger protein gene, CaRING1, in abscisic acid signaling and dehydration tolerance.

Science.gov (United States)

Lim, Chae Woo; Hwang, Byung Kook; Lee, Sung Chul

2015-09-01

Plants are constantly exposed to a variety of biotic and abiotic stresses, which include pathogens and conditions of high salinity, low temperature, and drought. Abscisic acid (ABA) is a major plant hormone involved in signal transduction pathways that mediate the defense response of plants to abiotic stress. Previously, we isolated Ring finger protein gene (CaRING1) from pepper (Capsicum annuum), which is associated with resistance to bacterial pathogens, accompanied by hypersensitive cell death. Here, we report a new function of the CaRING1 gene product in the ABA-mediated defense responses of plants to dehydration stress. The expression of the CaRING1 gene was induced in pepper leaves treated with ABA or exposed to dehydration or NaCl. Virus-induced gene silencing of CaRING1 in pepper plants exhibited low degree of ABA-induced stomatal closure and high levels of transpirational water loss in dehydrated leaves. These led to be more vulnerable to dehydration stress in CaRING1-silenced pepper than in the control pepper, accompanied by reduction of ABA-regulated gene expression and low accumulation of ABA and H2O2. In contrast, CaRING1-overexpressing transgenic plants showed enhanced sensitivity to ABA during the seedling growth and establishment. These plants were also more tolerant to dehydration stress than the wild-type plants because of high ABA accumulation, enhanced stomatal closure and increased expression of stress-responsive genes. Together, these results suggest that the CaRING1 acts as positive factor for dehydration tolerance in Arabidopsis by modulating ABA biosynthesis and ABA-mediated stomatal closing and gene expression.

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

Science.gov (United States)

Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

2016-07-01

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Complex formation of calcium with humic acid and polyacrylic acid

Energy Technology Data Exchange (ETDEWEB)

Kirishima, A.; Tanaka, K.; Niibori, Y.; Tochiyama, O. [Dept. of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku Univ., Sendai (Japan)

2002-07-01

In order to understand the migration behavior of radionuclides in the underground, it is also important to estimate the effect of the competing cations originally present in the groundwater. In this connection, the complexation of Ca(II) with Aldrich humic acid has been examined. For the study at trace concentrations ({proportional_to} 10{sup -10} M) of Ca(II), the solvent extraction of {sup 45}Ca with TTA and TOPO in cyclohexane has been used. At macro concentrations (10{sup -4} M) of Ca(II), the measurement of the free Ca{sup 2+} ion concentration with a calcium selective electrode has been conducted. To estimate the polyelectrolyte effect of humic acid separately from its heterogeneous composition effect, polyacrylic acid ([-CH{sub 2}CH(COOH)-]{sub n}) has been selected as a representative of the homogeneous polymeric weak acids and its complexation with Ca(II) has also been examined. The values of log {beta}{sub {alpha}} have been obtained at pH 5 {proportional_to} 7 in 0.1, 0.4 and 1.0 M NaCl, where {beta}{sub {alpha}} is the apparent formation constants defined by {beta}{sub {alpha}} = [ML]/([M][R]). In this definition, [ML] and [M] are the concentrations of bound and free Ca{sup 2+} respectively, [R] is the concentration of dissociated proton exchanging sites. log {beta}{sub {alpha}} of humate decreases from 2.19 {proportional_to} 2.92 (depending on pH and ionic strength 1.0 < I < 0.4) at pCa = 10 to 1.98 {proportional_to} 2.44 at pCa = 4, while the variation of pCa has no appreciable influence on the log {beta}{sub {alpha}} of polyacrylate (1.36 {proportional_to} 3.24 for I = 0.1 {proportional_to} 1.0). For both humate and polyacrylate, log {beta}{sub {alpha}} decreases linearly with log[Na{sup +}], where [Na{sup +}] is the bulk concentration of sodium ion. Their dependences of log {beta}{sub {alpha}} on ionic strength are stronger than those of log {beta} of monomeric carboxylates such as oxalate and EDTA, indicating the large electrostatic effect of

Ketoconazole attenuates radiation-induction of tumor necrosis factor

Energy Technology Data Exchange (ETDEWEB)

Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

1994-07-01

Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

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Jihong Xing

2016-07-01

Full Text Available Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1α in regulating pro-inflammatory cytokines (PICs pathway in the rat hippocampus after cardiac arrest (CA induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR. Those PICs include interleukin-1β (IL-1β, interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α. Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1α and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1β, IL-6 and TNF-α were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1α and the time courses for HIF-1α and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1α by systemic administration of ML228, HIF-1α activator, significantly attenuated the amplified IL-6/IL-6R and TNF-α /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1β and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1β, IL-6 and TNF-α and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1α plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1α improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that

Antagonist Effects of Veratric Acid against UVB-Induced Cell Damages

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Deokhoon Park

2013-05-01

Full Text Available Ultraviolet (UV radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs formation, glutathione (GSH depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

45Ca distribution and transport in saponin skinned vascular smooth muscle

International Nuclear Information System (INIS)

Stout, M.A.; Diecke, F.P.

1983-01-01

45 Ca distribution and transport were studied in chemically skinned strips of caudal artery from Kyoto Wistar rats. Sarcolemmal membranes were made hyperpermeable by exposure for 60 min to solutions containing 0.1 mg/ml of saponin. Skinned helical strips responded with graded contractions to changes in ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid buffered free Ca solutions (10(-7) to 10(-5) M) and were sensitive to the Mg-ATP concentration. Tissues loaded in the presence of 10(-7) M Ca contracted in response to 10 mM caffeine. These experiments indicate the strips are skinned and possess a functional regulatory and contractile system and an intact Ca sequestering system. 45 Ca distributes in three compartments in skinned caudal artery strips. The Ca contents of two components are linear functions of the Ca-ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid concentration and desaturate at rapid rates. They correspond to the extracellular and cytoplasmic spaces. A significantly smaller component releases Ca at comparatively slower rates. 45 Ca uptake by the slow component consists of an ATP-dependent and an ATP-independent fraction. The 45 Ca content of the ATP-dependent fraction is a function of the free Ca concentration and is independent of the Ca-ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid concentration. Its content was enhanced by oxalate and was abolished by Triton X-100 skinning solutions. The ATP-independent component was not affected by Triton X-100 skinning and may represent Ca binding to cytoplasmic molecules and structures. The sequestered Ca was released with caffeine or Ca but not by epinephrine. The observations indicate that the sarcoplasmic reticulum and mitochondria of vascular smooth muscle strips skinned with saponin retain their functional integrity after saponin skinning

Physico-chemical processes in acid mine drainage in coal mining, south Brazil

Energy Technology Data Exchange (ETDEWEB)

Campaner, Veridiana Polvani; Luiz-silva, Wanilson. [Universidade Estadual de Campinas, Campinas (Brazil)

2009-07-01

Acid mine drainage generated from coal mine showed a pH of 3.2, high concentrations of SO{sub 4}{sup 2-}, Al, Fe, Mn, Zn and minor As, Cd, Co, Cr, Cu, Ni and Pb. The major reduction in the concentration occurred for Al, As, Cr, Fe and Pb after the treatment with CaO. The evolution of these acid waters within the tributary stream showed decreasing concentration for all soluble constituents, except Al. This natural attenuation was controlled by pH (6.4 to 10.8) as a result of concurrent mixing with tributary stream and reaction with local bedrock that contains limestone. Aluminum increasing concentration during this evolution seems to be related to an input of Al-enriched waters due to the leaching of silicate minerals in alkaline conditions. 47 refs., 3 figs., 3 tabs.

A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

Science.gov (United States)

A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

Dietary High-Oleic Acid Soybean Oil Dose Dependently Attenuates Egg Yolk Content of n-3 Polyunsaturated Fatty Acids in Laying Hens Fed Supplemental Flaxseed Oil.

Science.gov (United States)

Elkin, Robert G; Kukorowski, Alexandra N; Ying, Yun; Harvatine, Kevin J

2018-02-01

Chickens can hepatically synthesize eicosapentaenoic acid (20:5 n-3) and docosahexaenoic acid (22:6 n-3) from α-linolenic acid (ALA; 18:3 n-3); however, the process is inefficient and competitively inhibited by dietary linoleic acid (LNA; 18:2 n-6). In the present study, the influence of dietary high-oleic acid (OLA; 18:1 n-9) soybean oil (HOSO) on egg and tissue deposition of ALA and n-3 polyunsaturated fatty acids (PUFA) synthesized from dietary ALA was investigated in laying hens fed a reduced-LNA base diet supplemented with high-ALA flaxseed oil (FLAX). We hypothesized that reducing the dietary level of LNA would promote greater hepatic conversion of ALA to very long-chain (VLC; >20C) n-3 PUFA, while supplemental dietary HOSO would simultaneously further enrich eggs with OLA without influencing egg n-3 PUFA contents. Nine 51-week-old hens each were fed 0, 10, 20, or 40 g HOSO/kg diet for 12 weeks. Within each group, supplemental dietary FLAX was increased every 3 weeks from 0 to 10 to 20 to 40 g/kg diet. Compared to controls, dietary FLAX maximally enriched the total n-3 and VLC n-3 PUFA contents in egg yolk by 9.4-fold and 2.2-fold, respectively, while feeding hens 40 g HOSO/kg diet maximally attenuated the yolk deposition of ALA, VLC n-3 PUFA, and total n-3 PUFA by 37, 15, and 32%, respectively. These results suggest that dietary OLA is not neutral with regard to the overall process by which dietary ALA is absorbed, metabolized, and deposited into egg yolk, either intact or in the form of longer-chain/more unsaturated n-3 PUFA derivatives. © 2018 AOCS.

Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans

DEFF Research Database (Denmark)

Cheon, Seon Ah; Bal, Jyotiranjan; Song, Yunkyoung

2012-01-01

p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal...... growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties...

Effect of membrane hyperpolarization induced by a K+ channel opener on histamine-induced Ca2+ mobilization in rabbit arterial smooth muscle.

Science.gov (United States)

Watanabe, Y; Suzuki, A; Suzuki, H; Itoh, T

1996-03-01

1. The role of membrane hyperpolarization on agonist-induced contraction was investigated in intact and alpha-toxin-skinned smooth muscles of rabbit mesenteric artery by use of the ATP-sensitive K+ channel opener, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl-2H-1-benzopyran-3-ol (Y-26763), and either histamine (Hist) or noradrenaline (NA). 2. Hist (3 microM) and NA (10 microM) both produced a phasic, followed by a tonic increase in intracellular Ca2+ concentration ([Ca2+]i) and force. Y-26763 (10 microM) potently inhibited the NA-induced phasic and tonic increase in [Ca2+]i and force. In contrast, Y-26763 attenuated the Hist-induced phasic increase in [Ca2+]i and force but had almost no effect on the tonic response. However, ryanodine-treatment of muscles in order to inhibit the function of intracellular Ca2+ storage sites altered the action of Y-26763 which now attenuated the Hist-induced tonic increase in [Ca2+]i and force in a concentration-dependent manner (at concentrations > 1 microM). Glibenclamide (10 microM) attenuated the inhibitory action of Y-26763. 3. Hist (3 microM) depolarized the smooth muscle cells to the same extent as NA (10 microM). In the absence of either agonist, Y-26763 (over 30 nM) hyperpolarized the membrane and glibenclamide inhibited this hyperpolarization. Y-26763 (10 microM) almost abolished the NA-induced membrane depolarization, but only slightly attenuated the Hist-induced membrane depolarization in which the delta (delta) value (the difference before and after application of Hist) was not modified by any concentration of Y-26763. In ryanodine-treated smooth muscle cells, Y-26763 hyperpolarized the membrane and potently inhibited the membrane depolarization induced by Hist. 4. In ryanodine-treated muscle, Y-26763 had no measurable effect on the Hist-induced [Ca2+]i-force relationship. Y-26763 also had no apparent effect on the myofilament Ca(2+)-sensitivity in the presence of Hist in alpha

The possibility of lactic acid fermentation in the triticale stillage

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MILICA MARKOVIĆ

2011-06-01

Full Text Available Triticale stillage is a by-product of bioethanol production. A research study was conducted in order to see if triticale stillage is adequate for lactic acid bacteria growth and lactic acid fermentation. Three Lactobacillus strains: Lactobacillus fermentum NRRL-B-75624, Lactobacillus fermentum PL-1, and Lactobacillus plantarum PL-4 were taken into consideration. Lactic acid fermentation was monitored by measuring pH value and titratable acidity. Lactobacillus fermentum PL-1 had the greatest decrease of pH values and increase of titratable acidity so it was chosen for future work. During the research, it was investigated how nutrient composition of triticale stillage and CaCO3 can influence lactic acid fermentation and CaCO3 role in cell protection. The nutrient composition of triticale stillage was satisfactory for lactic acid fermentation. The addition of CaCO3 helped in lactic acid fermentation. Although the titratable acidity in the samples with CaCO3 was lower than in the samples without CaCO3, the number of viable cells was higher for the samples with CaCO3, which showed that CaCO3 protected lactic acid cells from inhibition by lactic acid.

Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease.

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Matsumoto, Takayuki; Watanabe, Shun; Kawamura, Ryusuke; Taguchi, Kumiko; Kobayashi, Tsuneo

2014-11-24

There is a growing body of evidence suggesting that epigallocatechin gallate (EGCG), a major catechin isolated from green tea, has several beneficial effects, such as anti-oxidant and anti-inflammatory activities. However, whether treatment with EGCG can suppress the endothelin-1 (ET-1)-induced contraction in carotid arteries from type 2 diabetic rats is unknown, especially at the chronic stage of the disease. We hypothesized that long-term treatment with EGCG would attenuate ET-1-induced contractions in type 2 diabetic arteries. Otsuka Long-Evans Tokushima fatty (OLETF) rats (43 weeks old) were treated with EGCG (200 mg/kg/day for 2 months, p.o.), and the responsiveness to ET-1, phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) was measured in common carotid artery (CA) from EGCG-treated and -untreated OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rats, EGCG attenuated responsiveness to ET-1 in CA compared to untreated groups. However, EGCG did not alter PE-induced contractions in CA from OLETF rats. In endothelium-denuded arteries, EGCG did not affect ET-1-induced contractions in either the OLETF or LETO group. Acetylcholine-induced relaxation was increased by EGCG treatment in CA from the OLETF group. The expressions of ET receptors, endothelial nitric oxide synthase, superoxide dismutases, and gp91(phox) [an NAD(P)H oxidase component] in CA were not altered by EGCG treatment in either group. Our data suggest that, within the timescale investigated here, EGCG attenuates ET-1-induced contractions in CA from type 2 diabetic rats, and one of the mechanisms may involve normalizing endothelial function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Radiolysis of Ca14CO3

International Nuclear Information System (INIS)

Sanchez, M.G.A.

1986-01-01

The partition-ion exclusion chromatography is evaluated to analyse non-ionic organic compounds obtained from radiolysis of high specific activity Ca 14 CO 3 . The Ca 14 CO 3 was irradiated by β - decay of carbon-14 or by γ rays from a cobalt-60 source. The crystals were dissolved for qualitative and quantitative analysis of the radiolytic products. Formic and oxalic acids were produced in high yields. Glyoxylic, acetic and glycolic acids, formaldehyde and methanol were produced in low yields. Quantitative determination was carried out by liquid scintillation spectroscopy and the chemical yields (G-values) were calculated for the products. Mechanisms of product formation are proposed based on thermal annealing experiments. (Author) [pt

Demonstration of the lack of cytotoxicity of unmodified and folic acid modified graphene oxide quantum dots, and their application to fluorescence lifetime imaging of HaCaT cells.

Science.gov (United States)

Goreham, Renee V; Schroeder, Kathryn L; Holmes, Amy; Bradley, Siobhan J; Nann, Thomas

2018-01-24

The authors describe the synthesis of water-soluble and fluorescent graphene oxide quantum dots via acid exfoliation of graphite nanoparticles. The resultant graphene oxide quantum dots (GoQDs) were then modified with folic acid. Folic acid receptors are overexpressed in cancer cells and hence can bind to functionalized graphene oxide quantum dots. On excitation at 305 nm, the GoQDs display green fluorescence with a peak wavelength at ~520 nm. The modified GoQDs are non-toxic to macrophage cells even after prolonged exposure and high concentrations. Fluorescence lifetime imaging and multiphoton microscopy was used (in combination) to image HeCaT cells exposed to GoQDs, resulting in a superior method for bioimaging. Graphical abstract Schematic representation of graphene oxide quantum dots, folic acid modified graphene oxide quantum dots (red), and the use of fluorescence lifetime to discriminate against green auto-fluorescence of HeCaT cells.

A downy mildew effector attenuates salicylic acid-triggered immunity in Arabidopsis by interacting with the host mediator complex.

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Marie-Cécile Caillaud

2013-12-01

Full Text Available Plants are continually exposed to pathogen attack but usually remain healthy because they can activate defences upon perception of microbes. However, pathogens have evolved to overcome plant immunity by delivering effectors into the plant cell to attenuate defence, resulting in disease. Recent studies suggest that some effectors may manipulate host transcription, but the specific mechanisms by which such effectors promote susceptibility remain unclear. We study the oomycete downy mildew pathogen of Arabidopsis, Hyaloperonospora arabidopsidis (Hpa, and show here that the nuclear-localized effector HaRxL44 interacts with Mediator subunit 19a (MED19a, resulting in the degradation of MED19a in a proteasome-dependent manner. The Mediator complex of ∼25 proteins is broadly conserved in eukaryotes and mediates the interaction between transcriptional regulators and RNA polymerase II. We found MED19a to be a positive regulator of immunity against Hpa. Expression profiling experiments reveal transcriptional changes resembling jasmonic acid/ethylene (JA/ET signalling in the presence of HaRxL44, and also 3 d after infection with Hpa. Elevated JA/ET signalling is associated with a decrease in salicylic acid (SA-triggered immunity (SATI in Arabidopsis plants expressing HaRxL44 and in med19a loss-of-function mutants, whereas SATI is elevated in plants overexpressing MED19a. Using a PR1::GUS reporter, we discovered that Hpa suppresses PR1 expression specifically in cells containing haustoria, into which RxLR effectors are delivered, but not in nonhaustoriated adjacent cells, which show high PR1::GUS expression levels. Thus, HaRxL44 interferes with Mediator function by degrading MED19, shifting the balance of defence transcription from SA-responsive defence to JA/ET-signalling, and enhancing susceptibility to biotrophs by attenuating SA-dependent gene expression.

Effect of realgar on extracellular amino acid neurotransmitters in hippocampal CA1 region determined by online microdialysis–dansyl chloride derivatization–high-performance liquid chromatography and fluorescence detection.

Science.gov (United States)

Huo, Taoguang; Zhang, Yinghua; Li, Weikai; Yang, Huilei; Jiang, Hong; Sun, Guifan

2014-09-01

An online microdialysis (MD)–dansyl chloride (Dns) derivatization–high-performance liquid chromatography (HPLC) and fluorescence detection (FD) system was developed for simultaneous determination of eight extracellular amino acid neurotransmitters in hippocampus. The MD probe was implanted in hippocampal CA1 region. Dialysate and Dns were online mixed and derivatized. The derivatives were separated on an ODS column and detected by FD. The developed online system showed good linearity, precision, accuracy and recovery. This online MD-HPLC system was applied to monitor amino acid neurotransmitters levels in rats exposed to realgar (0.3, 0.9 and 2.7 g/kg body weight). The result shows that glutamate concentrations were significantly increased (p<0.05) in hippocampal CA1 region of rats exposed to three doses of realgar. A decrease in γ-aminobutyric acid concentrations was found in rats exposed to medium and high doses of realgar (p<0.05). Elevation of excitotoxic index (EI) values in hippocampal CA1 region of realgar-exposed rats was observed (p<0.05). Positive correlation was found between EI values and arsenic contents in hippocampus of realgar-exposed rats, which indicates that the change in extracellular EI values is associated with arsenic accumulation in hippocampus. The developed online MD–Dns derivatization–HPLC–FD system provides a new experimental method for studying the effect of toxic Chinese medicines on amino acid neurotransmitters.

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake.

Science.gov (United States)

Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

2017-05-01

Mitochondrial calcium ([Ca 2+ ] m ) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca 2+ ] m uptake upon SK channel activation as detected by time lapse mitochondrial Ca 2+ measurements with the Ca 2+ -binding mitochondria-targeted aequorin and FRET-based [Ca 2+ ] m probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca 2+ ] m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.

Omega-3 Polyunsaturated Fatty Acids Attenuate Radiation-induced Oxidative Stress and Organ Dysfunctions in Rats

International Nuclear Information System (INIS)

Abdel Aziz, N.; Yacoub, S.F.

2013-01-01

The Aim of the present study was to determine the possible protective effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) against radiation-induced oxidative stress associated with organ dysfunctions. Omega-3 PUFA was administered by oral gavages to male albino rats at a dose of 0.4 g/ kg body wt daily for 4 weeks before whole body γ-irradiation with 4Gy. Significant increase of serum lipid peroxidation end product as malondialdehyde (MDA) along with the reduction in blood glutathione (GSH) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzyme activities were recorded on 3rd and 8th days post-irradiation. Oxidative stress was associated with a significant increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) enzyme activities, markers of heart damage, significant increases in uric acid, urea and creatinine levels, markers of kidney damage, significant increases of alkaline phosphatase (ALP) and transaminases (ALT and AST) activities, markers of liver damage. Moreover significant increases in total cholesterol and triglycerides levels were recorded. Omega-3 PUFA administration pre-irradiation significantly attenuated the radiation-induced oxidative stress and organ dysfunctions tested in this study. It could be concluded that oral supplementation of omega-3 PUFA before irradiation may afford protection against radiation-induced oxidative stress and might preserve the integrity of tissue functions of the organs under investigations.

Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

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Alpers Charles N

2007-10-01

Full Text Available Abstract Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5. The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Water-chemistry analyses of the mine water reveal: (1 preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2 stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2–3 ‰ heavier in the mine water, relative to those in surface waters; (3 reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA and denaturing gradient gel electrophoresis (DGGE analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures.

Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

Science.gov (United States)

Church, C.D.; Wilkin, R.T.; Alpers, Charles N.; Rye, R.O.; Blaine, R.B.

2007-01-01

Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5). The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB) were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Water-chemistry analyses of the mine water reveal: (1) preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2) stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2-3 ??? heavier in the mine water, relative to those in surface waters; (3) reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM) analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA) and denaturing gradient gel electrophoresis (DGGE) analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures. ?? 2007 Church et al; licensee BioMed Central Ltd.

Reversible high blood CEA and CA19-9 concentrations in a diabetic ...

African Journals Online (AJOL)

dilatation of the main pancreatic duct. Positron emi- ... one of the benign diseases related to CA19-9 elevation. ... The histology of pancreatic islets from type 2 diabetic patients ... This is an Open Access article distributed under the terms of the Creative Commons Attribution- ... Attenuation of endocrine-exocrine pancreatic.

Laboratory evaluation of limestone and lime neutralization of acidic uranium mill tailings solution. Progress report

International Nuclear Information System (INIS)

Opitz, B.E.; Dodson, M.E.; Serne, R.J.

1984-02-01

Experiments were conducted to evaluate a two-step neutralization scheme for treatment of acidic uranium mill tailings solutions. Tailings solutions from the Lucky Mc Mill and Exxon Highland Mill, both in Wyoming, were neutralized with limestone, CaCO 3 , to an intermediate pH of 4.0 or 5.0, followed by lime, Ca(OH) 2 , neutralization to pH 7.3. The combination limestone/lime treatment methods, CaCO 3 neutralization to pH 4 followed by neutralization with Ca(OH) 2 to pH 7.3 resulted in the highest quality effluent solution with respect to EPA's water quality guidelines. The combination method is the most cost-effective treatment procedure tested in our studies. Neutralization experiments to evaluate the optimum solution pH for contaminant removal were performed on the same two tailings solutions using only lime Ca(OH) 2 as the neutralizing agent. The data indicate solution neutralization above pH 7.3 does not significantly increase removal of pH dependent contaminants from solution. Column leaching experiments were performed on the neutralized sludge material (the precipitated solid material which forms as the acidic tailings solutions are neutralized to pH 4 or above). The sludges were contacted with laboratory prepared synthetic ground water until several effluent pore volumes were collected. Effluent solutions were analyzed for macro ions, trace metals and radionuclides in an effort to evaluate the long term effectiveness of attenuating contaminants in sludges formed during solution neutralization. Neutralized sludge leaching experiments indicate that Ca, Na, Mg, Se, Cl, and SO 4 are the only constituents which show solution concentrations significantly higher than the synthetic ground water in the early pore volumes of long-term leaching studies

Ultrasonic study of structural instability of monocrystalline and polycrystalline Bi-Sr-Ca-Cu-O

International Nuclear Information System (INIS)

Wang, Yening; Wu, Jin; Shen, Huimin; Zhu, Jinsong; Chen, Xiaohua; Yan, Yifeng; Zhao, Zhongxian

1990-01-01

Two internal-friction (attenuation) peaks around 95 and 130 K in the polycrystal and single crystal of Bi-Sr-Ca-Cu-O are found to be related to the superconducting transition at 84 and 107 K, respectively. The jump of lattice parameter and shape-memory effect occurring at the peak temperatures reveal the characteristics of a martensitic transition. The velocity and attenuation versus temperature of ultrasonic longitudinal waves propagating along two directions in the a-b plane at 10 degree to the a and b axes and of [010] shear waves with [100] polarization were measured for the Bi 2 Sr 2 CaCu 2 O 8 single crystals. The anisotropic elasticity in the c plane is manifested. Only the longitudinal waves in a direction and the shear waves show an obvious softening minimum of velocity around 250 K, which is associated with an attenuation peak due to a phaselike transition, but other longitudinal waves reveal a monotonic stiffening from room temperature down to T c . The origin of the overall trend of elastic stiffening that appears in the measurements so far for high-T c oxides is discussed

Preparation and characterization of composites based on poly(lactic acid) and CaCO{sub 3} nanofiller

Energy Technology Data Exchange (ETDEWEB)

Moreno, Janaína Fernandes; Silva, Ana Lúcia N. da, E-mail: janamoreno.quim@gmail.com, E-mail: ananazareth@ima.ufrj.br [Instituto de Macromoléculas Professora Eloisa Mano - IMA/UFRJ – Brasil, Rio de Janeiro – RJ (Brazil); Silva, Antonio Henrique Monteiro da Fonseca T. da, E-mail: antoniohmfts@id.uff.br [Departamento Agrícola e Meio Ambiente – UFF – Brasil, Niterói – RJ (Brazil); Sousa, Ana Maria F. de, E-mail: ana.furtado.souza@gmail.com [Instituto de Química da Universidade - IQ/UERJ – Brasil, Rio de Janeiro – RJ (Brazil)

2015-05-22

In recent years, extensive studies have been conducted on the study of the poly(lactic acid) (PLA) properties, because of its being a typical biobased and biodegradable polymer, with good mechanical properties. However, its toughness and gas barrier properties are not satisfactory and can be improved by the addition of nanofillers, such as calcium carbonate (n-CaCO{sub 3}). The present work PLA composites with nano-sized precipitated calcium carbonate (n-NPCC) were prepared by melt extrusion. Thermal, mechanical and flow properties of the composites were evaluated by using a factorial design.The results showed that the addition of the nanofiller in the PLA matrix didn’t improve thethermal and mechanical properties of the matrix significantly. This behavior is probably due to the presence of the stearic acid that is coating on the n-NPCC particles, resulting in a weak polymer-particle interaction. Beyond this, it was also observed a decrease in MFI of the composites when nanofiller was added and at a higher screw speed.

Inhibitory mechanism against oxidative stress of caffeic acid

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Farhan Ahmed Khan

2016-10-01

Full Text Available The purpose of this article is to summarize the reported antioxidant activities of a naturally abundant bioactive phenolic acid, caffeic acid (CA, 3,4-dihydroxycinnamic acid, so that new avenues for future research involving CA can be explored. CA is abundantly found in coffee, fruits, vegetables, oils, and tea. CA is among the most potential and abundantly found in nature, hydroxycinnamic acids with the potential of antioxidant behavior. Reactive oxygen species produced as a result of endogenous processes can lead to pathophysiological disturbances in the human body. Foods containing phenolic substances are a potential source for free radical scavenging; these chemicals are known as antioxidants. This review is focused on CA's structure, availability, and potential as an antioxidant along with its mode of action. A brief overview of the literature published about the prooxidant potential of caffeic acid as well as the future perspectives of caffeic acid research is described. CA can be effectively employed as a natural antioxidant in various food products such as oils.

In-Vitro Radio protective Role of Ferulic Acid in Cultured Lymphocytes

International Nuclear Information System (INIS)

Ahmed, M.M.; Al Fateh, N.M.; Tawfik, S.S.

2010-01-01

Ferulic acid (FA), C 10 H 10 O 4 is the most abundant, ubiquitous hydroxycinnamic acid derived from photochemical phenolic compounds. It is a major constituent of fruits and vegetables such as orange, tomato, carrot, sweet corn and rice bran. Gamma rays generate hydroxyl radicals in cells and cellular DNA damage which leads to genotoxicity and chromosome aberrations. To establish most effective protective support, we used two different concentrations of FA (5 and 10 μg/ ml) and 2 Gy dose of gamma-radiation. Cytogenetic analysis was evaluated using the analysis of structural chromosome aberration (CA) and cytokinesis block micronucleus assay (CBMN). The level of lipid peroxidation analyzed as thiobarbituric acid reactive substances (TBARS), total glutathione (GSH), the enzyme activities of lymphocytes defence mechanism: Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GPx) were determined. The result obtained by all endpoints indicates acceptable toxicity profiles of FA in-vitro when compared with normal lymphocytes; irradiation at 2 Gy increased the MN and CA frequencies. Treatment with FA for 30 min before radiation exposure resulted in a significant decline both of MN and CA yields as FA concentration increased. The levels of TBARS and GSH were altered significantly whereas the levels of the enzymatic antioxidants were decreased in gamma-irradiated lymphocytes. Pretreatment with 10 μg/ ml of FA has attenuated the toxic effects of radiation more than FA (5 μg/ ml) by reduction in the TBARS level, restoration GSH contents and prevented the decreases in the radiation-induced SOD, CAT and GPx activities. These results lead us to the conclusion that FA has antimutagenic effect and benefit as a radio protector against oxidative stress involved by gamma-rays exposure

Excess influx of Zn(2+) into dentate granule cells affects object recognition memory via attenuated LTP.

Science.gov (United States)

Suzuki, Miki; Fujise, Yuki; Tsuchiya, Yuka; Tamano, Haruna; Takeda, Atsushi

2015-08-01

The influx of extracellular Zn(2+) into dentate granule cells is nonessential for dentate gyrus long-term potentiation (LTP) and the physiological significance of extracellular Zn(2+) dynamics is unknown in the dentate gyrus. Excess increase in extracellular Zn(2+) in the hippocampal CA1, which is induced with excitation of zincergic neurons, induces memory deficit via excess influx of Zn(2+) into CA1 pyramidal cells. In the present study, it was examined whether extracellular Zn(2+) induces object recognition memory deficit via excess influx of Zn(2+) into dentate granule cells. KCl (100 mM, 2 µl) was locally injected into the dentate gyrus. The increase in intracellular Zn(2+) in dentate granule cells induced with high K(+) was blocked by co-injection of CaEDTA and CNQX, an extracellular Zn(2+) chelator and an AMPA receptor antagonist, respectively, suggesting that high K(+) increases the influx of Zn(2+) into dentate granule cells via AMPA receptor activation. Dentate gyrus LTP induction was attenuated 1 h after KCl injection into the dentate gyrus and also attenuated when KCl was injected 5 min after the induction. Memory deficit was induced when training of object recognition test was performed 1 h after KCl injection into the dentate gyrus and also induced when KCl was injected 5 min after the training. High K(+)-induced impairments of LTP and memory were rescued by co-injection of CaEDTA. These results indicate that excess influx of Zn(2+) into dentate granule cells via AMPA receptor activation affects object recognition memory via attenuated LTP induction. Even in the dentate gyrus where is scarcely innervated by zincergic neurons, it is likely that extracellular Zn(2+) homeostasis is strictly regulated for cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mobility and natural attenuation of metals and arsenic in acidic waters of the drainage system of Timok River from Bor copper mines (Serbia) to Danube River.

Science.gov (United States)

Đorđievski, Stefan; Ishiyama, Daizo; Ogawa, Yasumasa; Stevanović, Zoran

2018-06-22

Bor, Krivelj, and Bela Rivers belong to the watershed of Timok River, which is a tributary of transboundary Danube River. These rivers receive metal-rich acidic wastewater from metallurgical facilities and acid mine drainage (AMD) from mine wastes around Bor copper mines. The aim of this study was to determine the mobility and natural attenuation of metals and arsenic in rivers from Bor copper mines to Danube River during the year 2015. The results showed that metallurgical facilities had the largest impact on Bor River by discharging about 400 t of Cu per year through highly acidic wastewater (pH = 2.6). The highest measured concentrations of Cu in river water and sediments were 40 mg L -1 and 1.6%, respectively. Dissolution of calcite from limestone bedrock and a high concentration of bicarbonate ions in natural river water (about 250 mg L -1 ) enhanced the neutralization of acidic river water and subsequent chemical precipitation of metals and arsenic. Decreases in the concentrations of Al, Fe, Cu, As, and Pb in river water were mainly due to precipitation on the river bed. On the other hand, dilution played an important role in the decreases in concentrations of Mn, Ni, Zn, and Cd. Chemically precipitated materials and flotation tailings containing Fe-rich minerals (fayalite, magnetite, and pyrite) were transported toward Danube River during the periods of high discharge. This study showed that processes of natural attenuation in catchments with limestone bedrock play an important role in reducing concentrations of metals and arsenic in AMD-bearing river water.

The acidic transformed nano-VO2 causes macrophage cell death by the induction of lysosomal membrane permeabilization and Ca2+ efflux

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Shaohai Xu

2015-01-01

Full Text Available Because of its outstanding thermochromic characteristics and metal-insulator transition (MIT property, nano-vanadium dioxide (abbreviated as nano-VO2 or nVO2 has been applied widely in electrical/optical devices and design of intelligent window. However, the biological effect of nVO2 is not well understood, especially when affected by environmental factors or living organisms. For VO2 is an amphoteric oxide, we simulated pH's influence to nVO2’s physicochemical properties by exposure nVO2 in water of different pH values. We found that nVO2 transformed to a new product after exposure in acidic water for two weeks, as revealed by physicochemical characterization such as SEM, TEM, XRD, and DLS. This transformation product formed in acidic water was referred as (acidic transformed nVO2. Both pristine/untransformed and transformed nVO2 displayed no obvious toxicity to common epithelial cells; however, the acidic transformed nVO2 rapidly induced macrophage cell death. Further investigation demonstrated that transformed nVO2 caused macrophage apoptosis by the induction of Ca2+ efflux and the following mitochondrial membrane permeabilization (MMP process. And a more detailed time course study indicated that transformed nVO2 caused lysosomal membrane permeabilization (LMP at the earlier stage, indicating LMP could be chosen as an earlier and sensitive end point for nanotoxicological study. We conclude that although nVO2 displays no acute toxicity, its acidic transformation product induces macrophage apoptosis by the induction of LMP and Ca2+ efflux. This report suggests that the interplay with environmental factors or living organisms can results in physicochemical transformation of nanomaterials and the ensuing distinctive biological effects.

Individual bile acids have differential effects on bile acid signaling in mice

International Nuclear Information System (INIS)

Song, Peizhen; Rockwell, Cheryl E.; Cui, Julia Yue; Klaassen, Curtis D.

2015-01-01

Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

Individual bile acids have differential effects on bile acid signaling in mice

Energy Technology Data Exchange (ETDEWEB)

Song, Peizhen, E-mail: songacad@gmail.com; Rockwell, Cheryl E., E-mail: rockwelc@msu.edu; Cui, Julia Yue, E-mail: juliacui@uw.edu; Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com

2015-02-15

Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

Science.gov (United States)

Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway.

Science.gov (United States)

da Silva, Luisa Mota; Burci, Ligia de Moura; Crestani, Sandra; de Souza, Priscila; da Silva, Rita de Cássia Melo Vilhena de Andrade Fonseca; Dartora, Nessana; de Souza, Lauro Mera; Cipriani, Thales Ricardo; da Silva-Santos, José Eduardo; André, Eunice; Werner, Maria Fernanda de Paula

2018-04-01

Arctium lappa L., popularly known as burdock, is a medicinal plant used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic extract from roots of Arctium lappa (EET) were already demonstrated. However, the mechanism by which the extract reduces the gastric acid secretion remains unclear. Therefore, this study was designed to evaluate the antisecretory mode of action of EET. The effects of EET on H + , K + -ATPase activity were verified in vitro, whereas the effects of the extract on cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo contractility studies on gastric muscle strips from rats were also employed. The incubation with EET (1000 µg/ml) partially inhibited H + , K + -ATPase activity, and the intraduodenal administration of EET (10 mg/kg) decreased the volume and acidity of gastric secretion stimulated by bethanechol, histamine, and pentagastrin. EET (100-1000 µg/ml) did not alter the gastric relaxation induced by histamine but decreased acetylcholine-induced contraction in gastric fundus strips. Interestingly, EET also reduced the increase in the gastric muscle tone induced by 40 mM KCl depolarizing solution, as well as the maximum contractile responses evoked by CaCl 2 in Ca 2+ -free depolarizing solution, without impairing the effect of acetylcholine on fundus strips maintained in Ca 2+ -free nutritive solution. Our results reinforce the gastric antisecretory properties of preparations obtained from Arctium lappa, and indicate that the mechanisms involved in EET antisecretory effects include a moderate reduction of the H + , K + -ATPase activity associated with inhibitory effects on calcium influx and of cholinergic pathways in the stomach muscle.

Sulfide oxidation and the natural attenuation of arsenic and trace metals in the waste rocks of the abandoned Seobo tungsten mine, Korea

International Nuclear Information System (INIS)

Lee, Pyeong-koo; Kang, Min-Ju; Choi, Sang-Hoon; Touray, Jean-Claude

2005-01-01

Mineralogical examinations were performed to characterize the formation of secondary minerals and natural removal process of dissolved As and trace metals (Pb, Zn and Cu) from sulfide oxidation. Laboratory-based leaching tests were also conducted to determine whether the concentrations of As and trace metals in the leachates from waste-rock materials and contaminated soil could be affected by the presence acids such as acid rainwater or acid mine drainage. Waste-rock materials and contaminated soil were compared by 4-day leaching tests using HNO 3 solutions of increasing acidity (0.00001-0.1mole/L). Mineralogical studies of the waste rocks confirmed the presence of Fe-(oxy)hydroxides (e.g. goethite), jarosite, elemental S, Fe-sulfates, amorphous Fe-As phases, anglesite and covellite as secondary minerals. These secondary minerals act as mineralogical scavengers of dissolved trace metals, SO 4 2- and acidity released by sulfide oxidation. Arsenic was attenuated by the adsorption on Fe-(oxy)hydroxides and/or the formation of an amorphous Fe-As phase, with a Fe/As ratio=1 (maybe scorodite: FeAsO 4 .2H 2 O). Electron probe microanalyses data showed that the Fe-(oxy)hydroxides had high concentrations of Pb (up to 21wt%), with appreciable amounts of As (up to 7.7wt%), Zn (up to 4.6wt%) and Cu (up to 2.5wt%) indicating that dissolved metals were co-precipitated and adsorbed onto Fe-(oxy)hydroxides, Fe(Mn)-hydroxides and Fe-sulfates. The results of the leaching experiments within the pH-range 3.5-5.0 indicated that acidic rainstorms may leach minor amounts of Pb (ca. 1.7-4.0% of total), Zn (ca. 0.8-2.2% of total), Cu (ca. 0.0-0.2% of total) and As (ca. 0.02-0.1% of total) from waste rocks, including the dissolution of soluble secondary minerals previously formed during prolonged dry periods, while dissolution of these elements was negligible from the contaminated soil. In the pH-range 1.0-3.0, the leaching of Pb (ca. 2.4-31% of total) and As (ca. 0.1-5.8% of total) from

How Does the Ca2+-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca2+ Dynamics and Cell Structures in Perfused Rat Hearts—

International Nuclear Information System (INIS)

Mani, Hiroki; Tanaka, Hideo; Adachi, Tetsuya; Ikegawa, Masaya; Dai, Ping; Fujita, Naohisa; Takamatsu, Tetsuro

2015-01-01

The calcium (Ca 2+ )-paradox injury of the heart, induced by restoration of extracellular Ca 2+ after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca 2+ -paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca 2+ dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca 2+ paradox. Under rapid-scanning confocal microscopy, repletion of Ca 2+ following its depletion produced high-frequency Ca 2+ waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl 2 , but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca 2+ influx in the injury. However, saponin-induced membrane permeabilization of Ca 2+ showed no apparent contracture despite the emergence of high-frequency Ca 2+ waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca 2+ paradox. In immunohistochemistry Ca 2+ depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca 2+ influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca 2+ -paradox injury

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro.

Science.gov (United States)

Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

2017-02-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca 2+ -activated K + channel (BK Ca ) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca 2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca 2+ and preventing neuronal apoptosis, and this is mediated by BK Ca channel activation.

Different effects of ursodeoxycholic acid on intrahepatic cholestasis in acute and recovery stages induced by alpha-naphthylisothiocyanate in mice.

Science.gov (United States)

Zhang, Linlin; Su, Huizong; Li, Yue; Fan, Yujuan; Wang, Qian; Jiang, Jian; Hu, Yiyang; Chen, Gaofeng; Tan, Bo; Qiu, Furong

2018-03-01

The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced acute and recovery stage of cholestasis model mice. In the acute stage of model mice, pretreatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 12 days prior to ANIT administration (50 mg·kg -1 , ig) resulted in the dramatic increase in serum biochemistry, with aggrevation of bile infarcts and hepatocyte necrosis. The elevation of beta-muricholic acid (β-MCA), cholic acid (CA), and taurocholic acid (TCA) in serum and liver, and reduction of these bile acids (BAs) in bile was observed. In contrast, in the recovery stage of model mice, treatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 7 days after ANIT administration (50 mg·kg -1 , ig) resulted in the significant decrease in levels of serum alanine aminotransferase (ALT) and total bile acid (TBA). Liver injury was attenuated, and the levels of TBA, CA, TCA, and β-MCA in the liver were significantly decreased. Additionally, UDCA can upregulate expression of BSEP, but it cannot upregulate expression of AE2. UDCA, which induced BSEP to increase bile acid-dependent bile flow, aggravated cholestasis and liver injury when the bile duct was obstructed in the acute stage of injury in model mice. In contrast, UDCA alleviated cholestasis and liver injury induced by ANIT when the obstruction was improved in the recovery stage. Copyright © 2018. Published by Elsevier Inc.

Coniferyl aldehyde attenuates radiation enteropathy by inhibiting cell death and promoting endothelial cell function.

Science.gov (United States)

Jeong, Ye-Ji; Jung, Myung Gu; Son, Yeonghoon; Jang, Jun-Ho; Lee, Yoon-Jin; Kim, Sung-Ho; Ko, Young-Gyo; Lee, Yun-Sil; Lee, Hae-June

2015-01-01

Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function.

Crystal structures of coordination polymers from CaI2 and proline

Directory of Open Access Journals (Sweden)

Kevin Lamberts

2015-06-01

Full Text Available Completing our reports concerning the reaction products from calcium halides and the amino acid proline, two different solids were found for the reaction of l- and dl-proline with CaI2. The enantiopure amino acid yields the one-dimensional coordination polymer catena-poly[[aqua-μ3-l-proline-tetra-μ2-l-proline-dicalcium] tetraiodide 1.7-hydrate], {[Ca2(C5H9NO25(H2O]I4·1.7H2O}n, (1, with two independent Ca2+ cations in characteristic seven- and eightfold coordination. Five symmetry-independent zwitterionic l-proline molecules bridge the metal sites into a cationic polymer. Racemic proline forms with Ca2+ cations heterochiral chains of the one-dimensional polymer catena-poly[[diaquadi-μ2-dl-proline-calcium] diiodide], {[Ca(C5H9NO22(H2O2]I2}n, (2. The centrosymmetric structure is built by one Ca2+ cation that is bridged towards its symmetry equivalents by two zwitterionic proline molecules. In both structures, the iodide ions remain non-coordinating and hydrogen bonds are formed between these counter-anions, the amino groups, coordinating and co-crystallized water molecules. While the overall composition of (1 and (2 is in line with other structures from calcium halides and amino acids, the diversity of the carboxylate coordination geometry is quite surprising.

Utilization of citric acid in wood bonding

Science.gov (United States)

Citric acid (CA) is a weak organic acid. It exists most notably in citrus fruits so that it is named likewise. As a commodity chemical, CA is produced on a large scale by fermentation. In this chapter, we first briefly review the applied research and methods for commercial production of CA. Then we ...

Insulin-Like Growth Factor I (IGF-1) Deficiency Ameliorates Sex Difference in Cardiac Contractile Function and Intracellular Ca2+ Homeostasis

Science.gov (United States)

Ceylan-Isik, Asli F.; Li, Qun; Ren, Jun

2011-01-01

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR90), fura-fluorescence intensity (FFI) and intracellular Ca2+ clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ± dL/dt, longer TPS, TR90 and intracellular Ca2+ clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na+-Ca2+ exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca2+ regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca2+ regulation. PMID:21763763

Insulin-like growth factor I (IGF-1) deficiency ameliorates sex difference in cardiac contractile function and intracellular Ca(2+) homeostasis.

Science.gov (United States)

Ceylan-Isik, Asli F; Li, Qun; Ren, Jun

2011-10-10

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (±dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR(90)), fura-fluorescence intensity (FFI) and intracellular Ca(2+) clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ±dL/dt, longer TPS, TR(90) and intracellular Ca(2+) clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na(+)-Ca(2+) exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca(2+) regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca(2+) regulation. Copyright © 2011 Elsevier Ireland

Arachidonic acid is a chemoattractant for Dictyostelium discoideum

Indian Academy of Sciences (India)

Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells ... Arachidonic acid; chemotaxis; fatty acids; iplA ... Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca2+ concentration by causing the release of Ca2+ from intracellular stores and activating influx of ...

TNF-α as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload

International Nuclear Information System (INIS)

Zhang Ming; Xu Yanjun; Saini, Harjot K.; Turan, Belma; Liu, Peter P.; Dhalla, Naranjan S.

2005-01-01

TNF-α has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-α production in myocardial injury due to intracellular Ca 2+ -overload is available in the literature. The intracellular Ca 2+ -overload was induced in the isolated rat hearts subjected to 5 min Ca 2+ -depletion and 30 min Ca 2+ -repletion (Ca 2+ -paradox). The Ca 2+ -paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-α content. The ratio of cytosolic to homogenate nuclear factor-κB (NFκB) was decreased whereas the ratio of phospho-NFκB to total NFκB was increased in the Ca 2+ -paradox hearts. All these changes due to Ca 2+ -paradox were significantly attenuated upon treating the hearts with 100 μM pentoxifylline. These results suggest that activation of NFκB and increased production of TNF-α may play an important role in cardiac injury due to intracellular Ca 2+ -overload

A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

International Nuclear Information System (INIS)

Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

2008-01-01

The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria

NARCIS (Netherlands)

Kurdi, P; Tanaka, H; van Veen, HW; Asano, K; Tomita, F; Yokota, A

Cholic acid (CA) transport was investigated in nine intestinal Bifidobacterium strains. Upon energization with glucose, all of the bificlobacteria accumulated CA. The driving force behind CA accumulation was found to be the transmembrane proton gradient (DeltapH, alkaline interior). The levels of

Cajaninstilbene acid relaxes rat renal arteries: roles of Ca2+ antagonism and protein kinase C-dependent mechanism.

Directory of Open Access Journals (Sweden)

Dong-Mei Zhang

Full Text Available Cajaninstilbene acid (CSA is a major active component present in the leaves of Cajanus cajan (L. Millsp. The present study explores the underlying cellular mechanisms for CSA-induced relaxation in rat renal arteries. Vascular reactivity was examined in arterial rings that were suspended in a Multi Myograph System and the expression of signaling proteins was assessed by Western blotting method. CSA (0.1-10 µM produced relaxations in rings pre-contracted by phenylephrine, serotonin, 9, 11-dideoxy-9α, 11α-epoxymethanoprostaglandin F(2α (U46619, and 60 mM KCl. CSA-induced relaxations did not show difference between genders and were unaffected by endothelium denudation, nor by treatment with N(G-nitro-L-arginine methyl ester, indomethacin, ICI-182780, tetraethylammonium ion, BaCl(2, glibenclamide, 4-aminopyridine or propranolol. CSA reduced contraction induced by CaCl(2 (0.01-5 mM in Ca(2+-free 60 mM KCl solution and by 30 nM (--Bay K8644 in 15 mM KCl solution. CSA inhibited 60 mM KCl-induced Ca(2+ influx in smooth muscle of renal arteries. In addition, CSA inhibited contraction evoked by phorbol 12-myristate 13-acetate (PMA, protein kinase C agonist in Ca(2+-free Krebs solution. Moreover, CSA reduced the U46619- and PMA-induced phosphorylation of myosin light chain (MLC at Ser19 and myosin phosphatase target subunit 1 (MYPT1 at Thr853 which was associated with vasoconstriction. CSA also lowered the phosphorylation of protein kinase C (PKCδ at Thr505. In summary, the present results suggest that CSA relaxes renal arteries in vitro via multiple cellular mechanisms involving partial inhibition of calcium entry via nifedipine-sensitive calcium channels, protein kinase C and Rho kinase.

Gallic acid attenuates type I diabetic nephropathy in rats.

Science.gov (United States)

Garud, Mayuresh Sudamrao; Kulkarni, Yogesh Anant

2018-02-25

Literature suggests that TGF-β1 has a central role in the progression of diabetic nephropathy and its down regulation can improve the disease condition. Oxidative stress, generation of advanced glycation end products and activation of renin angiotensin system are the connecting links between hyperglycemia and TGF-β1 over expression. Gallic acid is a phytochemical having wide range of biological activities. Gallic acid is reported to have antioxidant and advanced glycation inhibitory activity. It has also shown inhibitory effects on angiotensin converting enzyme. Gallic acid qualifies as a drug candidate to be tested in the diabetic nephropathy, one of the important complication of diabetes. Streptozotocin (55 mg/kg body weight, i.p.) induced diabetic nephropathy was used as an experimental model. Gallic acid was evaluated for its possible effect at the dose of 20 and 40 mg/kg body weight. Gallic acid treatment significantly lowered plasma levels of the creatinine and blood urea nitrogen and elevated the levels of the protein and albumin. Gallic acid also improved creatinine clearance. Determination of oxidative stress parameters showed that the oxidative stress in kidney tissues was reduced significantly in gallic acid treated animals. Results of the plasma, urine and oxidative stress parameters were also reflected in the histopathological evaluation showing improvement in kidney pathophysiology. ELISA assay for circulating TGF-β1 evaluation and immunohistochemical study for determination of kidney expression of TGF-β1 revealed that gallic acid significantly lowered both the circulating and tissue levels of TGF-β1. Results support the hypothesis that gallic acid can be effectively used in the treatment of diabetic nephropathy. Copyright © 2018 Elsevier B.V. All rights reserved.

5-(2-Cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB): correlation of hypnotic and convulsant properties with alterations of synaptosomal 45Ca2+ influx

International Nuclear Information System (INIS)

Chandler, L.J.; Leslie, S.W.; Gonzales, R.

1986-01-01

Male ICR mice were given either 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) alone or CHEB after a 1 h pretreatment with phenobarbital CHEB alone produced excitatory behavior but not convulsive seizures. Higher doses produced convulsive seizures resulting in death. Pretreatment with phenobarbital prevented seizure activity. In vitro, CHEB significantly inhibited 'fast-phase' K + -stimulated 45 Ca 2+ uptake into cerebrocortical synaptosomes. CHEB also significantly increased basal 45 Ca 2+ uptake. The addition of CHEB or pentobarbital to striatal synaptosomes inhibited 'fast-phase' K + -stimulated 45 Ca 2+ uptake and endogenous dopamine release. CHEB, but not pentobarbital, produced a time- and dose-dependent increase in the resulting release of endogenous dopamine from striatal synaptosomes. The results of this study show that CHEB possesses hypnotic activity if its lethal convulsant actions are blocked. The hypnotic actions of CHEB appear to correlate with inhibition of voltage-dependent calcium channels in brain synaptosomes. (Auth.)

The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

Directory of Open Access Journals (Sweden)

Rossner Moritz

2007-10-01

Full Text Available Abstract Background The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD, RNA amplification, and array hybridization. Results Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. Conclusion The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel

Phosphatidic acid accumulation and catecholamine release in adrenal chromaffin cells: stimulation by high potassium and by nicotine, and effect of a diacylglycerol kinase inhibitor R 59 022.

Science.gov (United States)

Owen, P J; Jones, J A; Boarder, M R

1991-09-01

Using primary cultures of bovine adrenal chromaffin cells labelled with 32Pi, we show that stimulation with bradykinin, nicotine, or a depolarising concentration of potassium stimulates the accumulation of [32P]phosphatidic acid. The effects of nicotine and potassium are smaller than the effect of bradykinin, and are dependent entirely on extracellular calcium. The diacylglycerol kinase inhibitor R 59 022 attenuates the formation of phosphatidic acid by nicotine and depolarising concentrations of potassium. This inhibitor also blocks the nicotine and potassium stimulation of noradrenaline release from chromaffin cells. Using 45Ca2+ influx studies, we show that the nicotine-evoked calcium influx is also attenuated by R 59 022. These observations contrast with those in another report in which we showed that bradykinin stimulation of either [32P]phosphatidic acid accumulation or noradrenaline release is not affected by R 59 022. It is likely that the calcium influx produced by nicotine and depolarising potassium is blocked by R 59 022 by a mechanism that is independent of its ability to block diacylglycerol kinase. The nicotine- and potassium-stimulated [32P]phosphatidic acid accumulation is a consequence of this calcium influx and presumably reflects calcium activation of either phospholipase C or phospholipase D.

Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal calcium absorption.

Science.gov (United States)

Rodríguez, Valeria; Rivoira, María; Marchionatti, Ana; Pérez, Adriana; Tolosa de Talamoni, Nori

2013-12-01

The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated with 60 μg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 μg UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+) absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca(2+) absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Pengaruh Kombinasi Senyawa Humik dan CaCO3 terhadap Alumunium dan Fosfat Typic Paleudult Kentrong Banten

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Sugeng Winarso

2009-05-01

Full Text Available Decomposition of organic matter releases humic compounds, that can chelate metals include Al in acidic soils. This chelation of Al is important for decreasing of Al activity and P fixation in acidic soils. This study was aimed to test the effect of humic compounds extracted from rice-straw compost and CaCO3 combination on aluminium activity and phosphate (available P on an Ultisol (Typic Paleudult collected from Kentrong Banten. A laboratory study was conducted by series consentration of CaCO3 (0, 500, 1.000, 2.000, dan 3.000 ppm in 8 grams of acidic soil. The acidic soil had previously been subjected to continuously addition of humic compounds and none. Then, these mix of soil and CaCO3 were added 40 ml contained 5.000 ppm humic compounds to obtain 1:5 soil:suspension ratio and control was made by using aquadest. They were shaked for 2 hours every day and pH was measured. At 11st days incubation Alexch (N KCl and soluble of P (PB and PC were measured. The results showed that liming or addition of CaCO3 to the acidic soils decreased Alexch (precipitated to be Al(OH3 linearly with formula y = -0.778x + 6.108; y = Alexch (Cmol kg-1, x = CaCO3 (M; R² = 0,916. Combination addition of humic compounds and CaCO3 was able to increase pH and Alexch up to not detected. The increased of P-soluble or desorption P untill 384% took place at addition of 0.0016 M CaCO3 and 5000 ppm humic compounds. More desorption of P was observed if the acidic soils has previously been subjected to continuously addition of humic compounds, such us the increased of soluble P up to 739% at addition of CaCO3 0.0008 M.

Renovascular BK(Ca) channels are not activated in vivo under resting conditions and during agonist stimulation

DEFF Research Database (Denmark)

Magnusson, Linda; Sørensen, Charlotte Mehlin; Braunstein, Thomas Hartig

2006-01-01

We investigated the role of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by BK(Ca) of the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation.......3 nmol/min) did not have any effect. Renal injection of ANG II (1-4 ng) or NE (10-40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the BK(Ca) opener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE......, there is no indication for a major role for BK(Ca) channels in the control of basal renal tone in vivo. Furthermore, BK(Ca) channels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular BK(Ca) channels...

The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 mediates environmental stress responses in plants.

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Hong, Jeum Kyu; Hwang, Byung Kook

2009-01-01

The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 was analyzed by an Agrobacterium-mediated transient expression assay in tobacco leaves. Several stress-related cis-acting elements (GT-1, W-box and ABRE) are located within the CaPIMP1 promoter. In tobacco leaf tissues transiently transformed with a CaPIMP1 promoter-beta-glucuronidase (GUS) gene fusion, serially 5'-deleted CaPIMP1 promoters were differentially activated by Pseudomonas syringae pv. tabaci, ethylene, methyl jasmonate, abscisic acid, and nitric oxide. The -1,193 bp region of the CaPIMP1 gene promoter sequence exhibited full promoter activity. The -417- and -593 bp promoter regions were sufficient for GUS gene activation by ethylene and methyl jasmonate treatments, respectively. However, CaPIMP1 promoter sequences longer than -793 bp were required for promoter activation by abscisic acid and sodium nitroprusside treatments. CaPIMP1 expression was activated in pepper leaves by treatment with ethylene, methyl jasmonate, abscisic acid, beta-amino-n-butyric acid, NaCl, mechanical wounding, and low temperature, but not with salicylic acid. Overexpression of CaPIMP1 in Arabidopsis conferred hypersensitivity to mannitol, NaCl, and ABA during seed germination but not during seedling development. In contrast, transgenic plants overexpressing CaPIMP1 exhibited enhanced tolerance to oxidative stress induced by methyl viologen during germination and early seedling stages. These results suggest that CaPIMP1 expression may alter responsiveness to environmental stress, as well as to pathogen infection.

Effects of 45Ca on murine skeletal muscle. 2

International Nuclear Information System (INIS)

Asotra, K.; Katoch, S.S.; Krishan, K.; Malhotra, R.K.

1983-01-01

Swiss albino mice were injected intraperitoneally with 3.7x10 4 Bq and 7.4x10 4 Bq 45 Ca/g body weight. 45 Ca-treated mice were sacrificed on days 1, 3, 5, 7, 14 and 28 and activities of acid phosphatase, alkaline phosphatase and glucose 6-phosphatase bioassayed in diaphragm and gastrocnemius. Activities of acid and alkaline phosphatases decreased after the 1st day of 45 Ca treatment in both the muscles compared with the normal controls. These two enzymes apparently do not contribute to myofiber necrosis in irradiated skeletal muscle. Glucose 6-phosphatase levels increased in the two irradiated muscles and with 7.4x10 4 Bq 45 Ca dose as much as 20-fold and 7-fold elevations are recorded in diaphragm and gastrocnemius, respectively, indicating a radiation-induced stimulation of inhibition of glucose 6-phosphatase channelization for energy generation. The possible role of elevated glucose 6-phosphatase levels in glycogen accumulation on account of radiations in skeletal muscle has been discussed. (author)

Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.

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Wu, Hongmei; Zhang, Quanzhi; Gao, Jingquan; Sun, Caihong; Wang, Jia; Xia, Wei; Cao, Yonggang; Hao, Yanqiu; Wu, Lijie

2018-03-01

Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus. We have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.

A method to attenuate U(VI) mobility in acidic waste plumes using humic acids

Energy Technology Data Exchange (ETDEWEB)

Wan, J.; Dong, W.; Tokunaga, T.K.

2011-02-01

Acidic uranium (U) contaminated plumes have resulted from acid-extraction of plutonium during the Cold War and from U mining and milling operations. A sustainable method for in-situ immobilization of U under acidic conditions is not yet available. Here, we propose to use humic acids (HAs) for in-situ U immobilization in acidic waste plumes. Our laboratory batch experiments show that HA can adsorb onto aquifer sediments rapidly, strongly and practically irreversibly. Adding HA greatly enhanced U adsorption capacity to sediments at pH below 5.0. Our column experiments using historically contaminated sediments from the Savannah River Site under slow flow rates (120 and 12 m/y) show that desorption of U and HA were non-detectable over 100 pore-volumes of leaching with simulated acidic groundwaters. Upon HA-treatment, 99% of the contaminant [U] was immobilized at pH < 4.5, compared to 5% and 58% immobilized in the control columns at pH 3.5 and 4.5, respectively. These results demonstrated that HA-treatment is a promising in-situ remediation method for acidic U waste plumes. As a remediation reagent, HAs are resistant to biodegradation, cost effective, nontoxic, and easily introducible to the subsurface.

Mammary inflammation around parturition appeared to be attenuated by consumption of fish oil rich in n-3 polyunsaturated fatty acids.

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Lin, Sen; Hou, Jia; Xiang, Fang; Zhang, Xiaoling; Che, Lianqiang; Lin, Yan; Xu, Shengyu; Tian, Gang; Zeng, Qiufeng; Yu, Bing; Zhang, Keying; Chen, Daiwen; Wu, De; Fang, Zhengfeng

2013-12-31

Mastitis endangers the health of domestic animals and humans, and may cause problems concerning food safety. It is documented that n-3 polyunsaturated fatty acids (PUFA) play significant roles in attenuating saturated fatty acids (SFA)-induced inflammation. This study was therefore conducted to determine whether mammary inflammation could be affected by consumption of diets rich in n-3 PUFA. Forty-eight rats after mating began to receive diets supplemented with 5% fish oil (FO) or 7% soybean oil (SO). Blood and mammary tissue samples (n = 6) at day 0 and 14 of gestation and day 3 postpartum were collected 9 hours after intramammary infusion of saline or lipopolysaccharide (LPS) to determine free fatty acids (FFA) concentration and FA composition in plasma and inflammation mediators in mammary tissues. At day 14 of gestation and day 3 postpartum, the FO-fed rats had lower plasma concentrations of C18:2n6, C20:4n6, total n-6 PUFA and SFA, and higher plasma concentrations of C20:5n3 and total n-3 PUFA than the SO-fed rats. Plasma C22:6n3 concentration was also higher in the FO-fed than in the SO-fed rats at day 3 postpartum. Compared with the SO-fed rats, the FO-fed rats had lower mammary mRNA abundance of xanthine oxidoreductase (XOR) and protein level of tumor necrosis factor (TNF)-α, but had higher mammary mRNA abundances of interleukin (IL)-10 and peroxisome proliferator-activated receptor (PPAR)-γ at day 14 of gestation. Following LPS infusion at day 3 postpartum, the SO-fed rats had increased plasma concentrations of FFA, C18:1n9, C18:3n3, C18:2n6 and total n-6 PUFA, higher mammary mRNA abundances of IL-1β, TNF-α and XOR but lower mammary mRNA abundance of IL-10 than the FO-fed rats. Mammary inflammation around parturition appeared to be attenuated by consumption of a diet rich in n-3 PUFA, which was associated with up-regulated expression of IL-10 and PPAR-γ.

CaSO4 Scale Formation on Vibrated Piping System in the Presence Citric Acid

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Mangestiyono, W.; Jamari, J.; Muryanto, S.; Bayuseno, A. P.

2018-02-01

Vibration in many industries commonly generated by the operation mechanical equipment such as extruder, mixer, blower, compressor, turbine, generator etc. Vibration propagates into the floor and attacks the pipe around those mechanical equipment. In this paper, the influence of vibration in a pipe on the CaSO4 scale formation was investigated to understand the effect of vibration on the kinetics, mass of scale, crystal phases and crystal polymorph. To generate vibration force, mechanical equipment was prepared consisted of electrical motor, crankshaft, connecting rod and a vibration table at where test pipe section mounted. Deposition rate increased significantly when the vibration affected to the system i.e. 0.5997 and 1.6705 gr/hr for vibration frequency 4.00 and 8.00 Hz. The addition 10.00 ppm of citric acid declined the deposition rate of 8 Hz experiment from 3.4599 gr/hr to 2.2865 gr/hr.

Acidic and uncharged polar residues in the consensus motifs of the yeast Ca2+ transporter Gdt1p are required for calcium transport.

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Colinet, Anne-Sophie; Thines, Louise; Deschamps, Antoine; Flémal, Gaëlle; Demaegd, Didier; Morsomme, Pierre

2017-07-01

The UPF0016 family is a recently identified group of poorly characterized membrane proteins whose function is conserved through evolution and that are defined by the presence of 1 or 2 copies of the E-φ-G-D-[KR]-[TS] consensus motif in their transmembrane domain. We showed that 2 members of this family, the human TMEM165 and the budding yeast Gdt1p, are functionally related and are likely to form a new group of Ca 2+ transporters. Mutations in TMEM165 have been demonstrated to cause a new type of rare human genetic diseases denominated as Congenital Disorders of Glycosylation. Using site-directed mutagenesis, we generated 17 mutations in the yeast Golgi-localized Ca 2+ transporter Gdt1p. Single alanine substitutions were targeted to the highly conserved consensus motifs, 4 acidic residues localized in the central cytosolic loop, and the arginine at position 71. The mutants were screened in a yeast strain devoid of both the endogenous Gdt1p exchanger and Pmr1p, the Ca 2+ -ATPase of the Golgi apparatus. We show here that acidic and polar uncharged residues of the consensus motifs play a crucial role in calcium tolerance and calcium transport activity and are therefore likely to be architectural components of the cation binding site of Gdt1p. Importantly, we confirm the essential role of the E53 residue whose mutation in humans triggers congenital disorders of glycosylation. © 2017 John Wiley & Sons Ltd.

CD36- and GPR120-mediated Ca²⁺ signaling in human taste bud cells mediates differential responses to fatty acids and is altered in obese mice.

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Ozdener, Mehmet Hakan; Subramaniam, Selvakumar; Sundaresan, Sinju; Sery, Omar; Hashimoto, Toshihiro; Asakawa, Yoshinori; Besnard, Philippe; Abumrad, Nada A; Khan, Naim Akhtar

2014-04-01

It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca(2+) signaling in fungiform taste bud cells (TBC). We measured Ca(2+) signaling in human TBC, transfected with small interfering RNAs against messenger RNAs encoding CD36 and GPR120 (or control small interfering RNAs). We also studied Ca(2+) signaling in TBC from CD36(-/-) mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and glucagon-like peptide-1 from human and mice TBC in response to CD36 and GPR120 activation. High concentrations of linoleic acid induced Ca(2+) signaling via CD36 and GPR120 in human and mice TBC, as well as in STC-1 cells, and low concentrations induced Ca(2+) signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid down-regulated CD36 and up-regulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca(2+) and serotonin responses, but increased release of glucagon-like peptide-1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

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Abdel-Moneim, Adel; Yousef, Ahmed I; Abd El-Twab, Sanaa M; Abdel Reheim, Eman S; Ashour, Mohamed B

2017-08-01

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

Chlorogenic acid in a Nicotiana plumbaginifolia cell suspension.

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Gillet; Mesnard; Fliniaux; Monti; Fliniaux

1999-11-01

A phenylpropanoid compound has been characterized in a Nicotiana plumbaginifolia cell suspension. This compound has been isolated and purified by semi-preparative reverse phase-high performance liquid chromatography. Its structure has been identified by NMR spectroscopy as 5-O-caffeoylquinic acid, which is chlorogenic acid (CA). The influence of culture conditions on the accumulation of this metabolite by N. plumbaginifolia cell suspensions has been studied. Darkness strongly inhibits the CA accumulation. Moreover, it has been shown that feeding experiments with caffeic acid had a deleterious effect upon the CA content. This one was not influenced by a supplementation with quinic acid.

Silencing of dehydrin CaDHN1 diminishes tolerance to multiple abiotic stresses in Capsicum annuum L.

Science.gov (United States)

Chen, Ru-gang; Jing, Hua; Guo, Wei-li; Wang, Shu-Bin; Ma, Fang; Pan, Bao-Gui; Gong, Zhen-Hui

2015-12-01

We cloned a dehydrins gene CaDHN1 from pepper and the expression of CaDHN1 was markedly upregulated by cold, salt, osmotic stresses and salicylic acid (SA) treatment. Dehydrins (DHNs) are a subfamily of group 2 late embryogenesis-abundant (LEA) proteins that are thought to play an important role in enhancing abiotic stress tolerance in plants. In this study, a DHN EST (Expressed Sequence Tag) was obtained from 6 to 8 true leaves seedlings of pepper cv P70 (Capsicum annuum L.) by our laboratory. However, the DHN gene in pepper was not well characterized. According to this EST sequence, we isolated a DHN gene, designated as CaDHN1, and investigated the response and expression of this gene under various stresses. Our results indicated that CaDHN1 has the DHN-specific and conserved K- and S- domain and encodes 219 amino acids. Phylogenetic analysis showed that CaDHN1 belonged to the SKn subgroup. Tissue expression profile analysis revealed that CaDH N1 was expressed predominantly in fruits and flowers. The expression of CaDHN1 was markedly upregulated in response to cold, salt, osmotic stresses and salicylic acid (SA) treatment, but no significant change by abscisic acid (ABA) and heavy metals treatment. Loss of function of CaDHN1 using the virus-induced gene silencing (VIGS) technique led to decreased tolerance to cold-, salt- and osmotic-induced stresses. Overall, these results suggest that CaDHN1 plays an important role in regulating the abiotic stress resistance in pepper plants.

Amino acid infusion during anesthesia attenuates the surgery induced decline in IGF-1 and diminishes the "diabetes of injury"

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Eksborg Staffan

2007-01-01

infusion to the volunteers did not affect any of the variables studied. Conclusion Amino acid infusion during surgery attenuates the decrease in IGF-1 and diminishes the "diabetes of injury".

Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

NARCIS (Netherlands)

Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

2013-01-01

Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta

Science.gov (United States)

Ok, Seong-Ho; Byon, Hyo-Jin; Kwon, Seong-Chun; Park, Jungchul; Lee, Youngju; Hwang, Yeran; Baik, Jiseok; Choi, Mun-Jeoung; Sohn, Ju-Tae

2015-01-01

Lipid emulsions are widely used for the treatment of systemic toxicity that arises from local anesthetics. The goal of this in vitro study was to examine the cellular mechanism associated with the lipid emulsion-mediated attenuation of vasodilation induced by a toxic dose of bupivacaine in isolated endothelium-denuded rat aorta. The effects of lipid emulsion on vasodilation induced by bupivacaine, mepivacaine, and verapamil were assessed in isolated aorta precontracted with phenylephrine, the Rho kinase stimulant NaF, and the protein kinase C activator phorbol 12,13-dibutyrate (PDBu). The effects of Rho kinase inhibitor Y-27632 on contraction induced by phenylephrine or NaF were assessed. The effects of bupivacaine on intracellular calcium concentrations ([Ca2+]i) and tension induced by NaF were simultaneously measured. The effects of bupivacaine alone and lipid emulsion plus bupivacaine on myosin phosphatase target subunit 1 (MYPT1) phosphorylation induced by NaF were examined in rat aortic vascular smooth muscle cells. In precontracted aorta, the lipid emulsion attenuated bupivacaine-induced vasodilation but had no effect on mepivacaine-induced vasodilation. Y-27632 attenuated contraction induced by either phenylephrine or NaF. The lipid emulsion attenuated verapamil-induced vasodilation. Compared with phenylephrine-induced precontracted aorta, bupivacaine-induced vasodilation was slightly attenuated in NaF-induced precontracted aorta. The magnitude of the bupivacaine-induced vasodilation was higher than that of a bupivacaine-induced decrease in [Ca2+]i. Bupivacaine attenuated NaF-induced MYPT1 phosphorylation, whereas lipid emulsion pretreatment attenuated the bupivacaine-induced inhibition of MYPT1 phosphorylation induced by NaF. Taken together, these results suggest that lipid emulsions attenuate bupivacaine-induced vasodilation via the attenuation of inhibition of MYPT1 phosphorylation evoked by NaF. PMID:26664257

The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

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Aiken Christopher

2004-06-01

Full Text Available Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug. Conclusions These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.

IP3-dependent intracellular Ca2+ release is required for cAMP-induced c-fos expression in hippocampal neurons

International Nuclear Information System (INIS)

Zhang, Wenting; Tingare, Asmita; Ng, David Chi-Heng; Johnson, Hong W.; Schell, Michael J.; Lord, Rebecca L.; Chawla, Sangeeta

2012-01-01

Highlights: ► cAMP-induced c-fos expression in hippocampal neurons requires a submembraneous Ca 2+ pool. ► The submembraneous Ca 2+ pool derives from intracellular ER stores. ► Expression of IP 3 -metabolizing enzymes inhibits cAMP-induced c-fos expression. ► SRE-mediated and CRE-mediated gene expression is sensitive to IP 3 -metabolizing enzymes. ► Intracellular Ca 2+ release is required for cAMP-induced nuclear translocation of TORC1. -- Abstract: Ca 2+ and cAMP are widely used in concert by neurons to relay signals from the synapse to the nucleus, where synaptic activity modulates gene expression required for synaptic plasticity. Neurons utilize different transcriptional regulators to integrate information encoded in the spatiotemporal dynamics and magnitude of Ca 2+ and cAMP signals, including some that are Ca 2+ -responsive, some that are cAMP-responsive and some that detect coincident Ca 2+ and cAMP signals. Because Ca 2+ and cAMP can influence each other’s amplitude and spatiotemporal characteristics, we investigated how cAMP acts to regulate gene expression when increases in intracellular Ca 2+ are buffered. We show here that cAMP-mobilizing stimuli are unable to induce expression of the immediate early gene c-fos in hippocampal neurons in the presence of the intracellular Ca 2+ buffer BAPTA-AM. Expression of enzymes that attenuate intracellular IP 3 levels also inhibited cAMP-dependent c-fos induction. Synaptic activity induces c-fos transcription through two cis regulatory DNA elements – the CRE and the SRE. We show here that in response to cAMP both CRE-mediated and SRE-mediated induction of a luciferase reporter gene is attenuated by IP 3 metabolizing enzymes. Furthermore, cAMP-induced nuclear translocation of the CREB coactivator TORC1 was inhibited by depletion of intracellular Ca 2+ stores. Our data indicate that Ca 2+ release from IP 3 -sensitive pools is required for cAMP-induced transcription in hippocampal neurons.

Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

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Karina Reyes-Gordillo

2016-01-01

Full Text Available Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA that primarily regulates PGC1α and soy protein (SP that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK. Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress

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Neeharika Nemani

2018-04-01

Full Text Available Summary: Mitochondria shape cytosolic calcium ([Ca2+]c transients and utilize the mitochondrial Ca2+ ([Ca2+]m in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+-induced shape change that is distinct from mitochondrial fission and swelling. [Ca2+]c elevation, but not MCU-mediated Ca2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST. MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca2+-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca2+ sensor that decodes metazoan Ca2+ signals as MiST. : Metazoan Ca2+ signal determines mitochondrial shape transition (MiST and cellular quality control. Nemani et al. find that mitochondria undergo shape changes upon Ca2+ stress. MiST is distinct from matrix Ca2+-induced swelling and mitochondrial dynamics. The conserved Ca2+ sensor Miro1 enables MiST and promotes autophagy/mitophagy. Keywords: mitochondrial shape, MiST, calcium, Miro, EF hand, PTP, MCU, mitophagy, autophagy, mitochondrial dynamics

Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

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Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

2016-10-01

Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

Microscopic theory of ultrasonic attenuation in high-Tc superconductors in normal state

International Nuclear Information System (INIS)

Bishoyi, K.C.; Rout, G.C.; Behera, S.N.

2001-01-01

The mechanism of the ultrasonic attenuation in high temperature superconductors is not yet studied thoroughly both experimentally and theoretically. A microscopic theoretical model is proposed here to study the attenuation in the electron doped and hole doped compounds like L 2-x M x CuO 4 (L=La,Nd; M=Sr,Ca,Ce). The model Hamiltonian contains the staggered magnetic field in the d-electrons of copper, the doped f-electrons term and the hybridisation between d- and f-electrons. The electron-phonon interaction arises due to the volume strain dependence of the hybridisation. The phonon Green's function is calculated by equations of motion of Zubarev technique. The temperature dependence of the ultrasonic attenuation coefficient (α) is calculated from the imaginary part of the phonon self energy and the velocity of sound in the dynamic and long wavelength limit. The dimensionless parameters involved in the calculations are the electron-phonon coupling (g), staggered magnetic field (h) , hybridization (υ), position of the f-level (d), frequency (ω), and temperature (t). The results are discussed. (author)

Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose

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Zhu, Shu Yun; Dong, Ying; Tu, Jie; Zhou, Yue; Zhou, Xing Hua; Xu, Bin

2014-01-01

Background: Silybum marianum has been used as herbal medicine for the treatment of liver disease, liver cirrhosis, and to prevent liver cancer in Europe and Asia since ancient times. Silybum marianum oil (SMO), a by-product of silymarin production, is rich in essential fatty acids, phospholipids, sterols, and vitamin E. However, it has not been very good development and use. Objective: In the present study, we used olive oil as a control to investigate the antioxidant and anti-aging effect of SMO in D-galactose (D-gal)-induced aging mice. Materials and Methods: D-gal was injected intraperitoneally (500 mg/kg body weight daily) for 7 weeks while SMO was simultaneously administered orally. The triglycerides (TRIG) and cholesterol (CHOL) levels were estimated in the serum. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), monoamine oxidase (MAO), malondialdehyde (MDA), caspase-3, and Bcl-2 were determined in the liver and brain. The activities of Na+-K+-adenosine triphosphatase (ATPase), Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity of the liver mitochondrial were estimated. Results: SMO decreased levels of TRIG and CHOL in aging mice. SMO administration elevated the activities of SOD, GSH-Px, and T-AOC, which are suppressed by aging. The levels of MAO and MDA in the liver and brain were reduced by SMO administration in aging mice. Enzyme linked immunosorbent assay showed that SMO significantly decreased the concentration of caspase-3 and improved the activity of Bcl-2 in the liver and brain of aging mice. Furthermore, SMO significantly attenuated the D-gal induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity. Conclusion: These results indicate that SMO effectively attenuated oxidative damage and improved apoptosis related factors as well as liver mitochondrial dysfunction in aging mice. PMID:24914315

Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis.

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Edwards, Jason M; Neeb, Zachary P; Alloosh, Mouhamad A; Long, Xin; Bratz, Ian N; Peller, Cassandra R; Byrd, James P; Kumar, Sanjay; Obukhov, Alexander G; Sturek, Michael

2010-02-01

Stenting attenuates restenosis, but accelerated coronary artery disease (CAD) adjacent to the stent (peri-stent CAD) remains a concern in metabolic syndrome (MetS). Smooth muscle cell proliferation, a major mechanism of CAD, is mediated partly by myoplasmic Ca2+ dysregulation and store-operated Ca2+ entry (SOCE) via canonical transient receptor potential 1 (TRPC1) channels is proposed to play a key role. Exercise is known to prevent Ca2+ dysregulation in CAD. We tested the hypothesis that MetS increases SOCE and peri-stent CAD and exercise attenuates these events. Groups (n = 9 pigs each) were (i) healthy lean Ossabaw swine fed standard chow, (ii) excess calorie atherogenic diet fed (MetS), and (iii) aerobically exercise trained starting after 50 weeks of development of MetS (XMetS). Bare metal stents were placed after 54 weeks on diets, and CAD and SOCE were assessed 4 weeks later. Coronary cells were dispersed proximal to the stent (peri-stent) and from non-stent segments, and fura-2 fluorescence was used to assess SOCE, which was verified by Ni2+ blockade and insensitivity to nifedipine. XMetS pigs had increased physical work capacity and decreased LDL/HDL (P molecular expression of TRPC1, STIM1, and Orai1 in MetS.

Eicosapentaenoic acid inhibits TNF-α-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells

International Nuclear Information System (INIS)

Kim, Hyeon Ho; Lee, Youngae; Eun, Hee Chul; Chung, Jin Ho

2008-01-01

Eicosapentaenoic acid (EPA) is an omega-3 (ω-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-κB activation induced by tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS) in various cells. However, its detailed mode of action is unclear. In this report, we investigated whether EPA inhibits the expression of TNF-α-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-α induced MMP-9 expression by NF-κB-dependent pathway. Pretreatment of EPA inhibited TNF-α-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect IκB-α phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-κB. EPA inhibited TNF-α-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKKα-dependent event. Taken together, we demonstrate that EPA inhibits TNF-α-induced MMP-9 expression through inhibition of p38 and Akt activation

Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling.

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Fernández-Ruiz, Antonio; Oliva, Azahara; Nagy, Gergő A; Maurer, Andrew P; Berényi, Antal; Buzsáki, György

2017-03-08

Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons. The theta-phase preference and excitatory strength of the afferent CA3 and entorhinal inputs effectively timed the principal neuron activity, as well as regulated distinct CA1 interneuron populations in multiple tasks and behavioral states. Feedback potentiation of distal dendritic inhibition by CA1 place cells attenuated the excitatory entorhinal input at place field entry, coupled with feedback depression of proximal dendritic and perisomatic inhibition, allowing the CA3 input to gain control toward the exit. Thus, upstream inputs interact with local mechanisms to determine theta-phase timing of hippocampal neurons to support memory and spatial navigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats.

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Feijuan Kong

Full Text Available Postoperative cognitive dysfunction (POCD is a clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery, especially in geriatric surgical patients. Although it has been documented that isoflurane exposure impaired cognitive function in several aged animal models, there are few clinical interventions and treatments available to prevent this disorder. Minocycline has been well established to exert neuroprotective effects in various experimental animal models and neurodegenerative diseases. Therefore, we hypothesized that pretreatment with minocycline attenuates isoflurane-induced cognitive decline in aged rats. In the present study, twenty-month-old rats were administered minocycline or an equal volume of saline by intraperitoneal injection 12 h before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Two weeks later, spatial learning and memory of the rats were examined using the Morris Water Maze. We found that pretreatment with minocycline mitigated isoflurane-induced cognitive deficits and suppressed the isoflurane-induced excessive release of IL-1β and caspase-3 in the hippocampal CA1 region at 4 h after isoflurane exposure, as well as the number of TUNEL-positive nuclei. In addition, minocycline treatment also prevented the changes of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane. In conclusion, pretreatment with minocycline attenuated isoflurane-induced cognitive impairment in aged rats.

Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

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Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

2014-01-01

γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation.

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Holeček, Milan

2017-09-01

Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles. The article also demonstrates that the favorable effects of BCAA supplementation might be associated with three adverse effects: draining of α-KG from tricarboxylic acid cycle (cataplerosis), increased GLN content and altered glutamatergic neurotransmission in the brain, and activated GLN catabolism to ammonia in the gut and kidneys. Cataplerosis of α-KG can be attenuated by dimethyl-α-ketoglutarate, l-ornithine-l-aspartate, and ornithine salt of α-KG. The pros and cons of GLN elimination from the body using phenylbutyrate (phenylacetate), which may impair liver regeneration and decrease BCAA levels, should be examined. The therapeutic potential of BCAA might be enhanced also by optimizing its supplementation protocol. It is concluded that the search for strategies attenuating adverse and increasing positive effects of the BCAA is needed to include the BCAA among standard medications for patients with cirrhosis of the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

The bile acid composition of crane gallbladder bile

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Serafin, J.A.

1983-01-01

1. The biliary bile acids of the whooping crane (Grus americana) and the Florida sandhill crane (G. canadensis pratensis) have been examined.2. Cholic acid (CA), chenodeoxycholic acid (CDOCA) and lithocholic acid were found in bile from both species of these North American cranes.3. CDOCA and CA were the primary bile acids in both species, together constituting 70% or more of the bile acids by weight.4. The primary bile acids of cranes appear to be the same as those that have been identified in other avian species.

Organic products from Ca14Co3 autoradiolysis: effects of thermal annealing

International Nuclear Information System (INIS)

Albarran S, M.G.; Collins, K.E.; Collins, C.H.

1986-01-01

Autoradiolysis of Ca 14 Co 3 produces several different low molecular mass organic compounds which can be conveniently observed after ion exclusion-partition chromatographic separation of the dissolved sample, provided that the solid was prepared with high specific activity carbon-14 and has been stored for a sufficiently long period. Subsequent thermal annealing changes the distribution of these observed compounds, demonstrating that chemical reactions of the precursor species take place in the solid Ca 14 Co 3 matrix. Specifically, the following products were observed after an autoradiolytic dose of 5 MGy: methanol, formaldehyde, formic acid, oxalic acid, glyoxylic acid, glycolic acid and acetic acid, with-G-values ranging from 5x10 -6 to 2x10 -3 . Isochronal annealing to 500 0 C markedly changes the yields of carbon-14 labelled formic and acetic acids but has lesser effects on the other acidic products. This indicates that several different precursor species are present in the autoradiolyzed solid. (Author) [pt

A novel technology for neutralizing acidity and attenuating toxic chemical species from acid mine drainage using cryptocrystalline magnesite tailings

CSIR Research Space (South Africa)

Masindi, Vhahangwele

2016-04-01

Full Text Available neutralize and attenuate elevated concentrations of chemical species in AMD to within prescribed legal frameworks for water use in agricultural and industrial sectors in South Africa....

Wild type measles virus attenuation independent of type I IFN

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Horvat Branka

2008-02-01

Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing.

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Mroz, Magdalena S; Lajczak, Natalia K; Goggins, Bridie J; Keely, Simon; Keely, Stephen J

2018-03-01

The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T 84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl - channels, whereas inhibition of CFTR activity with either CFTR- inh -172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes

Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α(1)-adrenoceptor stimulation of mouse aorta segments.

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Leloup, Arthur J; Van Hove, Cor E; De Meyer, Guido R Y; Schrijvers, Dorien M; Fransen, Paul

2015-08-05

α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous dynamic control of time-independent basal Ca(2+) influx via L-type voltage-gated Ca(2+) channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca(2+) (0Ca) to measure phasic isometric contractions. They gradually decreased with time in 0Ca, were inhibited with 2-aminoethoxydiphenyl borate, and declined with previous membrane potential hyperpolarization (levcromakalim) or with previous inhibition of LCC (diltiazem). Former basal stimulation of LCC with depolarization (15 mM K(+)) or with BAY K8644 increased the subsequent phasic contractions by phenylephrine in 0Ca. Although exogenous NO (diethylamine NONOate) reduced the phasic contractions by phenylephrine, stimulation of endothelial cells with acetylcholine in 0Ca failed to attenuate these phasic contractions. Finally, inhibition of the basal release of NO with N(Ω)-nitro-L-arginine methyl ester also attenuated the phasic contractions by phenylephrine. Results indicated that α1-adrenoceptor stimulation with phenylephrine causes phasic contractions, which are controlled by basal LCC and endothelial NO synthase activity. Endothelial NO release by acetylcholine was absent in 0Ca. Given the growing interest in the active regulation of arterial compliance, the dependence of contractile SR Ca(2+) store-refilling in basal conditions on the activity of LCC and basal eNOS may contribute to a more thorough understanding of physiological mechanisms leading to arterial stiffness. Copyright © 2015. Published by Elsevier B.V.

The use of Zeolite into the controlling of Lithium concentration in the PWR primary water coolant (I) : the influences of Ca, Mg and Boric Acid concentration into the exchanges capacity of Ammonium Zeolite

International Nuclear Information System (INIS)

Sumijanto; Siti-Amini

1996-01-01

In this first part of research, the influences of calsium, magnesium and boric acid concentrations to the zeolite uptake of lithium in the PWR primary water coolant have been studied. The ammonium form of zeolite was found by modification of the natural zeolite which was originated from Bayah. The results showed that the boric acid concentration in the normal condition of PWR operation absolutely did not affects the lithium uptake. The Li uptake efficiency was influenced by the presence of Ca and Mg ions in order to the presence of cations competition which was dominated by Ca ion

Combined effects of spatially variable flow and mineralogy on the attenuation of acid mine drainage in groundwater

International Nuclear Information System (INIS)

Malmstroem, Maria E.; Berglund, Sten; Jarsjoe, Jerker

2008-01-01

Quantifications of the spreading of acid mine drainage (AMD) in groundwater are needed for risk assessments of mining sites. However, due to subsurface heterogeneity, available field data may prove insufficient for deterministic process descriptions, even at well-characterized sites. Here, the probabilistic LaSAR-PHREEQC model is used to consider multicomponent reactions and transport in heterogeneous (flow and geochemistry) groundwater surrounding a mine waste site, with specific focus on the spreading of Zn. Model results, using field data from a mill tailings impoundment in northern Sweden (including major component geochemistry), indicate that precipitation of smithsonite (ZnCO 3 ) may drastically delay the downstream arrival of Zn, but may also cause a peak concentration once the retained Zn is released. The amount of smithsonite formed is, however, minute and its spatial variation large, such that detection of smithsonite in soil samples may be difficult. Results further show that even a low degree of flow heterogeneity can effectively smooth otherwise distinctive temporal concentration changes attributed to the considered chemical reactions, and thereby mask the attenuation processes. By contrast, the existence of preferential flow paths can cause temporally separated concentration peaks in response to a single chemical reaction chain, even in a geochemically homogeneous domain, making the interpretation of the concentration curves non-trivial. The stochastic modelling results for Zn considering flow and/or mineralogical heterogeneity indicate a less efficient Zn attenuation than predicted by standard, deterministic reactive-transport models. In addition, in all considered probabilistic Zn and SO 4 2- scenarios, the spatial variability in downstream pollutant concentration was high, implying that a relatively large number of point samples are needed to determine field-scale mean concentrations

Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

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Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

2015-09-01

Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

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Rui-Xing Wang

2015-03-01

Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon.

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Ward, Joseph B J; Lajczak, Natalia K; Kelly, Orlaith B; O'Dwyer, Aoife M; Giddam, Ashwini K; Ní Gabhann, Joan; Franco, Placido; Tambuwala, Murtaza M; Jefferies, Caroline A; Keely, Simon; Roda, Aldo; Keely, Stephen J

2017-06-01

Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 312: G550-G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.-Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-γ) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic

Effects of methods of attenuation correction on source parameter determination

Science.gov (United States)

Sonley, Eleanor; Abercrombie, Rachel E.

We quantify the effects of using different approaches to model individual earthquake spectra. Applying different approaches can introduce significant variability in the calculated source parameters, even when applied to the same data. To compare large and small earthquake source parameters, the results of multiple studies need to be combined to extend the magnitude range, but the variability introduced by the different approaches hampers the outcome. When studies are combined, there is large uncertainty and large scatter and some systematic differences have been neglected. We model individual earthquake spectra from repeating earthquakes (M˜2) at Parkfield, CA, recorded by a borehole network. We focus on the effects of trade-offs between attenuation (Q) and corner frequency in spectral fitting and the effect of the model shape at the corner frequency on radiated energy. The trade-off between attenuation and corner frequency can increase radiated energy by up to 400% and seismic moment by up to 100%.

Activity coefficients of CaCl{sub 2} in (serine or proline + water) mixtures at T = 298.15 K

Energy Technology Data Exchange (ETDEWEB)

Ma Jingjing [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); Zhang Xinkuan [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); School of Chemistry and Chemical Engineering, Xinxiang University, Xinxiang, Henan 453003 (China); Zhuo Kelei, E-mail: lchow@mail.ucf.ed [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); Liu Hongxun; Wang Jianji [School of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China)

2010-05-15

Activity coefficients for the (CaCl{sub 2} + amino acid + water) system were determined at a temperature of 298.15 K using ion-selective electrodes. The range of molalities of CaCl{sub 2} is (0.01 to 0.20) mol . kg{sup -1}, and that of amino acids is (0.10 to 0.40) mol . kg{sup -1}. The activity coefficients obtained from the Debye-Hueckel extended equation and the Pitzer equation are in good agreement with each other. Results show that the interactions between CaCl{sub 2} and amino acid are controlled mainly by the electrostatic interactions (attraction). Gibbs free energy interaction parameters (g{sub EA}) and salting constants (k{sub S}) are positive, indicating that these amino acids are salted out by CaCl{sub 2}. These results are discussed based on group additivity model.

TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+.

Science.gov (United States)

Pitt, Samantha J; Funnell, Tim M; Sitsapesan, Mano; Venturi, Elisa; Rietdorf, Katja; Ruas, Margarida; Ganesan, A; Gosain, Rajendra; Churchill, Grant C; Zhu, Michael X; Parrington, John; Galione, Antony; Sitsapesan, Rebecca

2010-11-05

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a molecule capable of initiating the release of intracellular Ca(2+) required for many essential cellular processes. Recent evidence links two-pore channels (TPCs) with NAADP-induced release of Ca(2+) from lysosome-like acidic organelles; however, there has been no direct demonstration that TPCs can act as NAADP-sensitive Ca(2+) release channels. Controversial evidence also proposes ryanodine receptors as the primary target of NAADP. We show that TPC2, the major lysosomal targeted isoform, is a cation channel with selectivity for Ca(2+) that will enable it to act as a Ca(2+) release channel in the cellular environment. NAADP opens TPC2 channels in a concentration-dependent manner, binding to high affinity activation and low affinity inhibition sites. At the core of this process is the luminal environment of the channel. The sensitivity of TPC2 to NAADP is steeply dependent on the luminal [Ca(2+)] allowing extremely low levels of NAADP to open the channel. In parallel, luminal pH controls NAADP affinity for TPC2 by switching from reversible activation of TPC2 at low pH to irreversible activation at neutral pH. Further evidence earmarking TPCs as the likely pathway for NAADP-induced intracellular Ca(2+) release is obtained from the use of Ned-19, the selective blocker of cellular NAADP-induced Ca(2+) release. Ned-19 antagonizes NAADP-activation of TPC2 in a non-competitive manner at 1 μM but potentiates NAADP activation at nanomolar concentrations. This single-channel study provides a long awaited molecular basis for the peculiar mechanistic features of NAADP signaling and a framework for understanding how NAADP can mediate key physiological events.

Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro.

Science.gov (United States)

Ogawa, Motohiko; Shirasago, Yoshitaka; Ando, Shuji; Shimojima, Masayuki; Saijo, Masayuki; Fukasawa, Masayoshi

2018-04-05

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) causes tick-borne hemorrhagic fever in East Asia. The disease is characterized by high morbidity and mortality. Here, we evaluated the effects of caffeic acid (CA), a coffee-related organic acid with antiviral effects, against SFTSV infection. CA dose-dependently inhibited SFTSV infection in permissive human hepatoma Huh7.5.1-8 cells when SFTSV was added into the culture medium with CA. However, quinic acid (QA), another coffee-related organic acid, did not inhibit SFTSV infection. The 50% inhibitory concentration (IC 50 ) of CA against SFTSV was 0.048 mM, whereas its 50% cytotoxic concentration was 7.6 mM. The selectivity index (SI) was 158. Pre-incubation of SFTSV with CA for 4 h resulted in a greater inhibition of SFTSV infection (IC 50  = 0.019 mM; SI = 400). The pre-incubation substantially decreased viral attachment to the cells. CA treatment of the SFTSV-infected cells also inhibited the infection, albeit less effectively. CA activity after cell infection with SFTSV was more pronounced at a low multiplicity of infection (MOI) of 0.01 per cell (IC 50  = 0.18 mM) than at a high MOI of 1 per cell (IC 50  > 1 mM). Thus, CA inhibited virus spread by acting directly on the virus rather than on the infected cells. In conclusion, CA acted on SFTSV and inhibited viral infection and spread, mainly by inhibiting the binding of SFTSV to the cells. We therefore demonstrated CA to be a potential anti-SFTSV drug for preventing and treating SFTS. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

Science.gov (United States)

Kim, Hyun-Bum; Lee, Seok; Hwang, Eun-Sang; Maeng, Sungho; Park, Ji-Ho

2017-10-21

Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

IDH1 deficiency attenuates gluconeogenesis in mouse liver by impairing amino acid utilization.

Science.gov (United States)

Ye, Jing; Gu, Yu; Zhang, Feng; Zhao, Yuanlin; Yuan, Yuan; Hao, Zhenyue; Sheng, Yi; Li, Wanda Y; Wakeham, Andrew; Cairns, Rob A; Mak, Tak W

2017-01-10

Although the enzymatic activity of isocitrate dehydrogenase 1 (IDH1) was defined decades ago, its functions in vivo are not yet fully understood. Cytosolic IDH1 converts isocitrate to α-ketoglutarate (α-KG), a key metabolite regulating nitrogen homeostasis in catabolic pathways. It was thought that IDH1 might enhance lipid biosynthesis in liver or adipose tissue by generating NADPH, but we show here that lipid contents are relatively unchanged in both IDH1-null mouse liver and IDH1-deficient HepG2 cells generated using the CRISPR-Cas9 system. Instead, we found that IDH1 is critical for liver amino acid (AA) utilization. Body weights of IDH1-null mice fed a high-protein diet (HPD) were abnormally low. After prolonged fasting, IDH1-null mice exhibited decreased blood glucose but elevated blood alanine and glycine compared with wild-type (WT) controls. Similarly, in IDH1-deficient HepG2 cells, glucose consumption was increased, but alanine utilization and levels of intracellular α-KG and glutamate were reduced. In IDH1-deficient primary hepatocytes, gluconeogenesis as well as production of ammonia and urea were decreased. In IDH1-deficient whole livers, expression levels of genes involved in AA metabolism were reduced, whereas those involved in gluconeogenesis were up-regulated. Thus, IDH1 is critical for AA utilization in vivo and its deficiency attenuates gluconeogenesis primarily by impairing α-KG-dependent transamination of glucogenic AAs such as alanine.

Korean Red Ginseng Extract Attenuates 3-Nitropropionic Acid-Induced Huntington’s-Like Symptoms

Directory of Open Access Journals (Sweden)

Minhee Jang

2013-01-01

Full Text Available Korean red ginseng (KRG possesses neuroprotective activity. However, the potential neuroprotective value of KRG for the striatal toxicity is largely unknown. We investigated whether KRG extract (KRGE could have a neuroprotective effect in a 3-nitropropionic acid- (3-NP induced (i.p. Huntington’s disease (HD model. KRGE (50, 100, and 250 mg/kg/day, p.o. was administrated 10 days before 3-NP injection (pre-administration, from the same time with 3-NP injection (co-administration, or from the peak point of neurological impairment by 3-NP injection (post-administration. Pre-administration of KRGE produced the greatest neuroprotective effect in this model. Pre-administration of KRGE significantly decreased 3-NP-induced neurological impairment, lethality, lesion area, and neuronal loss in the 3-NP-injected striatum. KRGE attenuated microglial activation and phosphorylation of mitogen-activated protein kinases (MAPKs and nuclear factor-kappa B (NF-κB signal pathway. KRGE also reduced the level of mRNA expression of tumor necrosis factor-alpha, interleukin- (IL- 1β, IL-6, inducible nitric oxide synthase, and OX-42. Interestingly, the intrathecal administration of SB203580 (a p38 inhibitor or PD98059 (an inhibitor of MAPK Kinase, MEK increased the survival rate in the 3-NP-induced HD model. Pre-administration of KRGE may effectively inhibit 3-NP-induced striatal toxicity via the inhibition of the phosphorylation of MAPKs and NF-κB pathways, indicating its therapeutic potential for suppressing Huntington’s-like symptoms.

Microbial communities associated with uranium in-situ recovery mining process are related to acid mine drainage assemblages.

Science.gov (United States)

Coral, Thomas; Descostes, Michaël; De Boissezon, Hélène; Bernier-Latmani, Rizlan; de Alencastro, Luiz Felippe; Rossi, Pierre

2018-07-01

A large fraction (47%) of the world's uranium is mined by a technique called "In Situ Recovery" (ISR). This mining technique involves the injection of a leaching fluid (acidic or alkaline) into a uranium-bearing aquifer and the pumping of the resulting solution through cation exchange columns for the recovery of dissolved uranium. The present study reports the in-depth alterations brought to autochthonous microbial communities during acidic ISR activities. Water samples were collected from a uranium roll-front deposit that is part of an ISR mine in operation (Tortkuduk, Kazakhstan). Water samples were obtained at a depth of ca 500 m below ground level from several zones of the Uyuk aquifer following the natural redox zonation inherited from the roll front deposit, including the native mineralized orebody and both upstream and downstream adjacent locations. Samples were collected equally from both the entrance and the exit of the uranium concentration plant. Next-generation sequencing data showed that the redox gradient shaped the community structures, within the anaerobic, reduced, and oligotrophic habitats of the native aquifer zones. Acid injection induced drastic changes in the structures of these communities, with a large decrease in both cell numbers and diversity. Communities present in the acidified (pH values acid mine drainage, with the dominance of Sulfobacillus sp., Leptospirillum sp. and Acidithiobacillus sp., as well as the archaean Ferroplasma sp. Communities located up- and downstream of the mineralized zone under ISR and affected by acidic fluids were blended with additional facultative anaerobic and acidophilic microorganisms. These mixed biomes may be suitable communities for the natural attenuation of ISR mining-affected subsurface through the reduction of metals and sulfate. Assessing the effect of acidification on the microbial community is critical to evaluating the potential for natural attenuation or active bioremediation strategies

Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice

Directory of Open Access Journals (Sweden)

Pilar Mancera

2017-06-01

Full Text Available Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS and Interferon-gamma (IFN-γ. TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE, 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.

Comparative effects of commercial lime (CaCO 3 ) and ground ...

African Journals Online (AJOL)

Greenhouse study was carried out to investigate the comparative effect of commercial lime (CaCO3) and ground eggshell on the uptake of calcium and dry matter yield of maize in an ultisol of Southeastern Nigeria using maize (variety Oba supper 92) as the test crop. The soil was acidic and deficient in N, O.C., K, Ca and ...

CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

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Čabarkapa, A; Borozan, S; Živković, L; Stojanović, S; Milanović-Čabarkapa, M; Bajić, V; Spremo-Potparević, B

2015-12-05

Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory.

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Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-Lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-07-14

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

Science.gov (United States)

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-01-01

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID:27411738

β-Hydroxy-β-methylbutyrate (HMB)-free acid attenuates circulating TNF-α and TNFR1 expression postresistance exercise.

Science.gov (United States)

Townsend, Jeremy R; Fragala, Maren S; Jajtner, Adam R; Gonzalez, Adam M; Wells, Adam J; Mangine, Gerald T; Robinson, Edward H; McCormack, William P; Beyer, Kyle S; Pruna, Gabriel J; Boone, Carleigh H; Scanlon, Tyler M; Bohner, Jonathan D; Stout, Jeffrey R; Hoffman, Jay R

2013-10-15

The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyrate-free acid (HMB-FA) and cold-water immersion (CWI) on circulating concentrations of TNF-α and monocyte TNF-α receptor 1 (TNFR1) expression. Forty resistance-trained men (22.3 ± 2.4 yr) were randomized into four groups [placebo (PL), HMB-FA, CWI, and HMB-FA-CWI] and performed an acute, intense exercise protocol (four sets of up to 10 repetitions of the squat, dead lift, and split squat). Participants also performed four sets of up to 10 repetitions of the squat at 24 and 48 h following the initial exercise bout. Blood was sampled before exercise (PRE), immediately postexercise (IP), and 30 min, 24 h, and 48 h postexercise (30P, 24P, and 48P, respectively). Circulating TNF-α was assayed, and TNFR1 expression on CD14+ monocytes was measured by flow cytometry. The exercise protocol significantly elevated TNF-α in only PL (P = 0.006) and CWI (P = 0.045) IP. Mean percent changes show that TNF-α significantly increased from PRE to IP for only PL and CWI groups (P < 0.05), whereas the percent change of TNF-α for HMB-FA and HMB-FA-CWI was not significant. TNFR1 expression was elevated in PL (P = 0.023) and CWI (P = 0.02) at 30P compared with PRE, whereas both HMB-FA-treated groups did not increase significantly. In conclusion, HMB-FA attenuated circulating TNF-α IP and TNFR1 expression during recovery compared with PL and CWI. HMB-FA supplementation may attenuate the initial immune response to intense exercise, which may reduce recovery time following intense exercise.

Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

Science.gov (United States)

Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

2018-02-01

Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

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Chan, Jiangping; Guan, Xin; Ni, Yiling; Luo, Lilu; Yang, Liqiang; Zhang, Pengyue; Zhang, Jichuan; Chen, Yanmei

2017-03-15

The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

Microstructural dependence on relevant physical-mechanical properties on SiO2-Na2O-CaO-P2O5 biological glasses.

Science.gov (United States)

Rajendran, V; Begum, A Nishara; Azooz, M A; el Batal, F H

2002-11-01

Bioactive glasses of the system SiO2-Na2O-CaO-P2O5 have been prepared by the normal melting and annealing technique. The elastic moduli, attenuation, Vickers hardness, fracture toughness and fracture surface energy have been obtained using the known method at room temperature. The temperature dependence of elastic moduli and attenuation measurements have been extended over a wide range of temperature from 150 to 500 K. The SiO2 content dependence of velocities, attenuation, elastic moduli, and other parameters show an interesting observation at 45 wt% of SiO2 by exhibiting an anomalous behaviour. A linear relation is developed for Tg, which explores the influence of Na2O on SiO2-Na2O-CaO-P2O5 bioactive glasses. The measured hardness, fracture toughness and fracture surface energy show a linear relation with Young's modulus. It is also interesting to note that the observed results are functions of polymerisation and the number of non-bridging oxygens (NBO) prevailing in the network with change in SiO2 content. The temperature dependence of velocities, attenuation and elastic moduli show the existence of softening in the glass network structure as temperature increases.

The role of Ca(2+) mediated signaling pathways on the effect of taurine against Streptococcus uberis infection.

Science.gov (United States)

Dai, Bin; Zhang, Jinqiu; Liu, Ming; Lu, Jinye; Zhang, Yuanshu; Xu, Yuanyuan; Miao, Jinfeng; Yin, Yulong

2016-08-30

To provide insight into the mechanisms of taurine attenuation of pro-inflammatory response in mouse mammary epithelial cell line (EpH4-Ev, purchased by ATCC, USA) after Streptococcus uberis (S. uberis, 0140J) challenge, we infected MECs with S. uberis (2.5×10(7)cfumL(-1), MOI=10) for 3h and quantified changes in TLR-2 and calcium (Ca(2+)) mediated signaling pathways. The results indicate that S. uberis infection significantly increases the expression of TLR-2, intracellular Ca(2+) levels, PLC-γ1 and PKC-α, the activities of transcription factors NF-κB and NFAT, and related cytokines (TNF-α, IL-1β, IL-6, G-CSF, IL-2, KC, IL-15, FasL, MCP-1, and LIX) in culture supernatants. Taurine administration downregulated all these indices, the activities of NF-κB and NFAT. Cytokine secretions were similar using special PKC inhibitor Go 6983 and NFAT inhibitor VIVIT. Our data indicate that S. uberis infection induces pro-inflammatory response of MECs through a TLR-2 mediated signaling pathway. In addition, taurine can prevent MEC damage by affecting both PLC-γ1-Ca(2+)-PKC-α-NF-κB and PLC-γ1-Ca(2+)-NFATs signaling pathways. This is the first report to demonstrate the mechanisms of taurine attenuated pro-inflammatory response in MECs after S. uberis challenge. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of inhibition effects of some benzoic acid derivatives on sheep heart carbonic anhydrase

Science.gov (United States)

Kiliç, Deryanur; Yildiz, Melike; Şentürk, Murat; Erdoǧan, Orhan; Küfrevioǧlu, Ömer Irfan

2016-04-01

Carbonic anhydrase (CA) is a family of metalloenzymes that requires Zn as a cofactor and catalyze the quick conversion of CO2 to HCO3- and H+. Inhibitors of the carbonic anhydrases (CAs) have medical usage of significant diseases such as glaucoma, epilepsy, gastroduodenal ulcers, acid-base disequilibria and neurological disorders. In the present study, inhibition of CA with some benzoic derivatives (1-6) were investigated. Sheep heart CA (shCA) enzyme was isolated by means of designed affinity chromatography gel (cellulose-benzyl-sulfanylamide) 42.45-fold in a yield of 44 % with 564.65 EU/mg. Purified shCA enzyme was used in vitro studies. In the studies, IC50 values were calculated for 3-aminobenzoic acid (1), 4-aminobenzoic acid (2), 2-hydroxybenzoic acid (3), 2-benzoylbenzoic acid (4), 2,3-dimethoxybenzoic acid (5), and 3,4,5-trimethoxybenzoic acid (6), showing the inhibition effects on the purified enzyme. Such molecules can be used as pioneer for discovery of novel effective CA inhibitors for medicinal chemistry applications.

Bacteria attenuation by iron electrocoagulation governed by interactions between bacterial phosphate groups and Fe(III) precipitates.

Science.gov (United States)

Delaire, Caroline; van Genuchten, Case M; Amrose, Susan E; Gadgil, Ashok J

2016-10-15

Iron electrocoagulation (Fe-EC) is a low-cost process in which Fe(II) generated from an Fe(0) anode reacts with dissolved O2 to form (1) Fe(III) precipitates with an affinity for bacterial cell walls and (2) bactericidal reactive oxidants. Previous work suggests that Fe-EC is a promising treatment option for groundwater containing arsenic and bacterial contamination. However, the mechanisms of bacteria attenuation and the impact of major groundwater ions are not well understood. In this work, using the model indicator Escherichia coli (E. coli), we show that physical removal via enmeshment in EC precipitate flocs is the primary process of bacteria attenuation in the presence of HCO3(-), which significantly inhibits inactivation, possibly due to a reduction in the lifetime of reactive oxidants. We demonstrate that the adhesion of EC precipitates to cell walls, which results in bacteria encapsulation in flocs, is driven primarily by interactions between EC precipitates and phosphate functional groups on bacteria surfaces. In single solute electrolytes, both P (0.4 mM) and Ca/Mg (1-13 mM) inhibited the adhesion of EC precipitates to bacterial cell walls, whereas Si (0.4 mM) and ionic strength (2-200 mM) did not impact E. coli attenuation. Interestingly, P (0.4 mM) did not affect E. coli attenuation in electrolytes containing Ca/Mg, consistent with bivalent cation bridging between bacterial phosphate groups and inorganic P sorbed to EC precipitates. Finally, we found that EC precipitate adhesion is largely independent of cell wall composition, consistent with comparable densities of phosphate functional groups on Gram-positive and Gram-negative cells. Our results are critical to predict the performance of Fe-EC to eliminate bacterial contaminants from waters with diverse chemical compositions. Copyright © 2016 Elsevier Ltd. All rights reserved.

TRPC1, STIM1, and ORAI influence signal-regulated intracellular and endoplasmic reticulum calcium dynamics in human myometrial cells.

Science.gov (United States)

Murtazina, Dilyara A; Chung, Daesuk; Ulloa, Aida; Bryan, Emily; Galan, Henry L; Sanborn, Barbara M

2011-08-01

To explore the relationship between signal-stimulated increases in intracellular calcium ([Ca(2+)](i)) and depletion and refilling of the endoplasmic reticulum (ER) Ca(2+) stores ([Ca(2+)](L)) in human myometrial cells, we measured simultaneous changes in [Ca(2+)](i) and [Ca(2+)](L) using Fura-2 and Mag-fluo-4, respectively, in PHM1-41 immortalized and primary cells derived from pregnant myometrium and in primary cells derived from nonpregnant tissue. Signal- and extracellular Ca(2+)-dependent increases in [Ca(2+)](i) (SRCE) and ER refilling stimulated by oxytocin and cyclopiazonic acid were not inhibited by voltage-operated channel blocker nifedipine or mibefradil, inhibition of Na(+)/Ca(2+) exchange with KB-R7943, or zero extracellular Na(+) in PHM1-41 cells. Gadolinium-inhibited oxytocin- and cyclopiazonic acid-induced SRCE and slowed ER store refilling. TRPC1 mRNA knockdown specifically inhibited oxytocin-stimulated SRCE but had no statistically significant effect on ER store refilling and no effect on either parameter following cyclopiazonic acid treatment. Dominant negative STIMΔERM expression attenuated oxytocin- and thapsigargin-stimulated SRCE. Both STIM1 and ORAI1-ORAI3 mRNA knockdowns significantly attenuated oxytocin- and cyclopiazonic acid-stimulated SRCE. The data also suggest that reduction in STIM1 or ORAI1-ORAI3 mRNA can impede the rate of ER store refilling following removal of SERCA inhibition. These data provide evidence for both distinct and overlapping influences of TRPC1, STIM1, and ORAI1-ORAI3 on SRCE and ER store refilling in human myometrial cells that may contribute to the regulation of myometrial Ca(2+) dynamics. These findings have important implications for understanding the control of myometrial Ca(2+) dynamics in relation to myometrial contractile function.

Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation.

Science.gov (United States)

Li, Chen; Wang, Haiwei; Yuan, Tiangang; Woodman, Andrew; Yang, Decheng; Zhou, Guohui; Cameron, Craig E; Yu, Li

2018-05-01

Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D pol fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3D pol in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV. Copyright © 2018 Elsevier Inc. All rights reserved.

The investigation of minoxidil-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

Science.gov (United States)

Chen, I-Shu; Chou, Chiang-Ting; Liu, Yuan-Yuarn; Yu, Chia-Cheng; Liang, Wei-Zhe; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Chen, Fu-An; Jan, Chung-Ren

2017-02-01

Minoxidil is clinically used to prevent hair loss. However, its effect on Ca 2+ homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca 2+ levels ([Ca 2+ ] i ) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca 2+ ] i rises in a concentration-dependent manner. This Ca 2+ signal was inhibited by 60% by removal of extracellular Ca 2+ . Minoxidil-induced Ca 2+ influx was confirmed by Mn 2+ -induced quench of fura-2 fluorescence. Pre-treatment with the protein kinase C (PKC) inhibitor GF109203X, PKC activator phorbol 12-myristate 13 acetate (PMA), nifedipine and SKF96365 inhibited minoxidil-induced Ca 2+ signal in Ca 2+ containing medium by 60%. Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca 2+ -free medium abolished minoxidil-induced [Ca 2+ ] i rises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca 2+ ] i rises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca 2+ ] i rises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelation of cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent minoxidil's cytotoxicity. Together, in PC3 cells, minoxidil induced [Ca 2+ ] i rises that involved Ca 2+ entry through PKC-regulated store-operated Ca 2+ channels and PLC-dependent Ca 2+ release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca 2+ -independent manner.

Biliary Bile Acids in Primary Biliary Cirrhosis: Effect of Ursodeoxycholic Acid

Science.gov (United States)

Combes, Burton; Carithers, Robert L.; Maddrey, Willis C.; Munoz, Santiago; Garcia-Tsao, Guadalupe; Bonner, Gregory F.; Boyer, James L.; Luketic, Velimir A.; Shiffman, Mitchell L.; Peters, Marion G.; White, Heather; Zetterman, Rowen K.; Risser, Richard; Rossi, Stephen S.; Hofmann, Alan F.

2014-01-01

Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10–12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean ± SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 ± 18.6, 31.5 ± 15.5, 8.0 ± 9.3, 0.3 ± 1.0, and 0.6 ± 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%–64%) than with taurine (36%–48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%–31%) fell (P < .05). Administered UDCA was also conjugated predominantly with glycine (87%). PMID:10347103

Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization

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Ke-Li Tsai

2013-06-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration.

Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice

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Yoo-Ri Chung

2017-01-01

Full Text Available Loss of pericytes, an early hallmark of diabetic retinopathy (DR, results in breakdown of the blood-retinal barrier. Endoplasmic reticulum (ER stress may be involved in this process. The purpose of this study was to examine the effects of ursodeoxycholic acid (UDCA, a known ameliorator of ER stress, on pericyte loss in DR of streptozotocin- (STZ- induced diabetic mice. To assess the extent of DR, the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice were evaluated. Additionally, induction of ER stress and the unfolded protein response (UPR were assessed in diabetic mice and human retinal pericytes exposed to advanced glycation end products (AGE or modified low-density lipoprotein (mLDL. Fluorescein dye leakage during angiography and retinal capillary density were improved in UDCA-treated diabetic mice, compared to the nontreated diabetic group. Among the UPR markers, those involved in the protein kinase-like ER kinase (PERK pathway were increased, while UDCA attenuated UPR in STZ-induced diabetic mice as well as AGE- or mLDL-exposed retinal pericytes in culture. Consequently, vascular integrity was improved and pericyte loss reduced in the retina of STZ-induced diabetic mice. Our findings suggest that UDCA might be effective in protecting against DR.

Attenuation of UV-B exposure-induced inflammation by abalone hypobranchial gland and gill extracts.

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Kuanpradit, Chitraporn; Jaisin, Yamaratee; Jungudomjaroen, Sumon; Akter Mitu, Shahida; Puttikamonkul, Srisombat; Sobhon, Prasert; Cummins, Scott F

2017-05-01

Exposure to solar ultraviolet B (UV-B) is a known causative factor for many skin complications such as wrinkles, black spots, shedding and inflammation. Within the wavelengths 280‑320 nm, UV-B can penetrate to the epidermal level. This investigation aimed to test whether extracts from the tropical abalone [Haliotis asinina (H. asinina)] mucus-secreting tissues, the hypobranchial gland (HBG) and gills, were able to attenuate the inflammatory process, using the human keratinocyte HaCaT cell line. Cytotoxicity of abalone tissue extracts was determined using an AlamarBlue viability assay. Results showed that HaCaT cells could survive when incubated in crude HBG and gill extracts at concentrations between abalone extract from both the HBG and gill (0, 0.1, 2.5, 5 µg/ml). A significant increase in cell viability was observed (P2.5 µg/ml extract showed a significant decrease in intensity for COX‑2, phospho‑p38 and phospho‑SPK/JNK. The present study demonstrated that abalone extracts from the HGB and gill can attenuate inflammatory proteins triggered by UV-B. Hence, the contents of abalone extract, including cellmetabolites and peptides, may provide new agents for skin anti‑inflammation, preventing damage due to UV-B.

Mechanochemical synthesis and intercalation of Ca(II)Fe(III)-layered double hydroxides

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Ferencz, Zs.; Szabados, M.; Varga, G.; Csendes, Z. [Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged H-6720 (Hungary); Materials and Solution Structure Research Group, Institute of Chemistry, University of Szeged, Aradi Vértanúk tere 1, Szeged H-6720 (Hungary); Kukovecz, Á. [Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, Szeged H-6720 (Hungary); MTA-SZTE “Lendület” Porous Nanocomposites Research Group, Rerrich Béla tér 1, Szeged H-6720 (Hungary); Kónya, Z. [Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, Szeged H-6720 (Hungary); MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Rerrich Béla tér 1, Szeged H-6720 (Hungary); Carlson, S. [MAX IV Laboratory, Ole Römers väg 1, Lund SE-223 63 (Sweden); Sipos, P. [Materials and Solution Structure Research Group, Institute of Chemistry, University of Szeged, Aradi Vértanúk tere 1, Szeged H-6720 (Hungary); Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged H-6720 (Hungary); and others

2016-01-15

A mechanochemical method (grinding the components without added water – dry grinding, followed by further grinding in the presence of minute amount of water or NaOH solution – wet grinding) was used in this work for the preparation and intercalation of CaFe-layered double hydroxides (LDHs). Both the pristine LDHs and the amino acid anion (cystinate and tyrosinate) intercalated varieties were prepared by the two-step grinding procedure in a mixer mill. By systematically changing the conditions of the preparation method, a set of parameters could be determined, which led to the formation of close to phase-pure LDH. The optimisation procedure was also applied for the intercalation processes of the amino acid anions. The resulting materials were structurally characterised by a range of methods (X-ray diffractometry, scanning electron microscopy, energy dispersive analysis, thermogravimetry, X-ray absorption and infra-red spectroscopies). It was proven that this simple mechanochemical procedure was able to produce complex organic–inorganic nanocomposites: LDHs intercalated with amino acid anions. - Graphical abstract: Amino acid anion-Ca(II)Fe(III)-LDHs were successfully prepared by a two-step milling procedure. - Highlights: • Synthesis of pristine and amino acid intercalated CaFe-LDHs by two-step milling. • Identifying the optimum synthesis and intercalation parameters. • Characterisation of the samples with a range of instrumental methods.

Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

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Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

2001-01-01

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

Investigation of beta ray attenuation in CaSO4:Dy(Tm)-teflon rods

International Nuclear Information System (INIS)

Szabo, P.P.

1990-12-01

Ultrathin discs were prepared from CaSO 4 :Dy(Tm)-teflon rods by cutting them with a microtom. The effect of cutting was studied experimentally. It was found that the cutting does not affect the TL signal of the discs, so one will be able to irradiate the rod and cut it afterwards which means that this method can be applied in the dosimetry of boundaries or to establish the energy of beta radiation. Depth dose distribution measurements were carried out by irradiating the rods with beta sources. (K.A.) 5 refs.; 6 figs

Cloning and expression analysis of CaPIP1-1 gene in pepper (Capsicum annuum L.).

Science.gov (United States)

Yin, Yan-Xu; Wang, Shu-Bin; Zhang, Huai-Xia; Xiao, Huai-Juan; Jin, Jing-Hao; Ji, Jiao-Jiao; Jing, Hua; Chen, Ru-Gang; Arisha, Mohamed Hamed; Gong, Zhen-Hui

2015-05-25

Plant aquaporins are responsible for water transmembrane transport, which play an important role on abiotic and biotic stresses. A novel plasma membrane intrinsic protein of CaPIP1-1 was isolated from the pepper P70 according to transcriptome databases of Phytophthora capsici inoculation and chilling stress library. CaPIP1-1, which is 1155 bp in length with an open reading frame of 861 bp, encoded 286 amino acids. Three introns, exhibited CT/AC splice junctions, were observed in CaPIP1-1. The numbers and location of introns in CaPIP1-1 were the same as observed in tomato and potato. CaPIP1-1 was abundantly expressed in pepper fruit. Increased transcription levels of CaPIP1-1 were found in the different stresses, including chilling stress, salt stress, mannitol stress, salicylic acid, ABA treatment and Phytophthora capsici infection. The expression of CaPIP1-1 was downregulated by 50 μM HgCl2 and 100 μM fluridone. The pepper plants silenced CaPIP1-1 in cv. Qiemen showed growth inhibition and decreased tolerance to salt and mannitol stresses using detached leaf method. Copyright © 2015 Elsevier B.V. All rights reserved.

Amino acid 489 is encoded by a mutational "hot spot" on the beta 3 integrin chain: the CA/TU human platelet alloantigen system.

Science.gov (United States)

Wang, R; McFarland, J G; Kekomaki, R; Newman, P J

1993-12-01

A new platelet alloantigen, termed CA, has recently been implicated in a case of neonatal alloimmune thrombocytopenia (NATP) in a Filipino family in Canada. Maternal anti-CA serum reacted with glycoprotein (GP) IIIa and maintained its reactivity after removal of high mannose carbohydrate residues from GPIIIa. The monoclonal antibody (MoAb) AP3 partially blocked binding of anti-CA to GPIIIa, suggesting that the CA polymorphism is proximal to the AP3 epitope. Platelet RNA polymerase chain reaction (PCR) was used to amplify the region of GPIIIa cDNA that encodes this region of the protein. DNA sequence analysis showed a GA nucleotide substitution at base 1564 that results in an arginine (Arg) (CGG)glutamine (Gln) (CAG) polymorphism in amino acid (AA) 489. Further analysis of PCR-amplified genomic DNA from 27 normal individuals showed that AA 489 is encoded by a mutational "hot spot" of the GPIIIa gene, as three different codons for the wild-type Arg489 of GPIIIa were also found. The codon usage for Arg489 was found to be: CGG (63%), CGA (37%), and CGC (Definition of these new molecular variants of the beta 3 integrin chain should prove valuable in the diagnosis of NATP in these two geographically disparate populations, and it may also provide useful genetic markers for examining other pathologic variations of the GPIIb-IIIa complex.

Metabolic inhibitors as stimulating factors for citric acid production

International Nuclear Information System (INIS)

Adham, N.Z.; Ahmed, E.M.; Refai, H.A.E.

2008-01-01

The effect of some metabolic inhibitors on citric acid (CA) production by Aspergillus niger in cane molasses medium was investigated. Addition of 0.01-0.1 mM iodoacetic acid and sodium arsenate, 0.05-1.0 mM sodium malonate, 0.01 mM sodium azide, 0.01-0.05 mM sodium fluoride, 0.1-1.0 mM EDTA stimulated CA production (5-49%). Higher concentrations (10 mM) of iodoacetic acid, sodium malonate and 0.5 mM sodium azide caused a complete inhibition of fungal growth, Iodoacetic acid, sodium arsenate and sodium fluoride (0.2 mM) caused a remarkable inhibition of CA production. The implications of those preliminary functions was discussed. (author)

STUDY OF THERMAL AND ACID STABILITY OF BENTONITE CLAY

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Karna Wijaya

2010-06-01

Full Text Available The thermal and acid stability of the bentonite clays (Na- and Ca-bentonite have been tested. The thermal stability testing has been carried out by heating 5 gram of the clays  for five hours at 200, 300 and 500 °C respectively, meanwhile acid stability testing was performed by immersing 5 gram clays into 100 mL sulphuric acid 1M, 2M and 3M for 24 hours. The tested clays, then were characterized by means of X-Ray difractometry and IR-spectroscopy methods. The characterization results showed that upon heating, both Ca- and Na-bentonites indicated same thermal stability. However, upon acid treatment, Na-bentonite was found relatively stabiler and more resistance then Ca-bentonite.   Keywords: bentonite, clay, thermal stability, acid stability.

Rapid determination of free fatty acid content in waste deodorizer distillates using single bounce-attenuated total reflectance-FTIR spectroscopy.

Science.gov (United States)

Naz, Saba; Sherazi, Sayed Tufail Hussain; Talpur, Farah N; Mahesar, Sarfaraz A; Kara, Huseyin

2012-01-01

A simple, rapid, economical, and environmentally friendly analytical method was developed for the quantitative assessment of free fatty acids (FFAs) present in deodorizer distillates and crude oils by single bounce-attenuated total reflectance-FTIR spectroscopy. Partial least squares was applied for the calibration model based on the peak region of the carbonyl group (C=O) from 1726 to 1664 cm(-1) associated with the FFAs. The proposed method totally avoided the use of organic solvents or costly standards and could be applied easily in the oil processing industry. The accuracy of the method was checked by comparison to a conventional standard American Oil Chemists' Society (AOCS) titrimetric procedure, which provided good correlation (R = 0.99980), with an SD of +/- 0.05%. Therefore, the proposed method could be used as an alternate to the AOCS titrimetric method for the quantitative determination of FFAs especially in deodorizer distillates.

Synthetic water soluble di-/tritopic molecular receptors exhibiting Ca2+/Mg2+ exchange.

Science.gov (United States)

Lavie-Cambot, Aurélie; Tron, Arnaud; Ducrot, Aurélien; Castet, Frédéric; Kauffmann, Brice; Beauté, Louis; Allouchi, Hassan; Pozzo, Jean-Luc; Bonnet, Célia S; McClenaghan, Nathan D

2017-05-23

Structural integration of two synthetic water soluble receptors for Ca 2+ and Mg 2+ , namely 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and o-aminophenol-N,N,O-triacetic acid (APTRA), respectively, gave novel di- and tritopic ionophores (1 and 2). As Mg 2+ and Ca 2+ cannot be simultaneously complexed by the receptors, allosteric control of complexation results. Potentiometric measurements established stepwise protonation constants and showed high affinity for Ca 2+ (log K = 6.08 and 8.70 for 1 and 2, respectively) and an excellent selectivity over Mg 2+ (log K = 3.70 and 5.60 for 1 and 2, respectively), which is compatible with magnesium-calcium ion exchange. While ion-exchange of a single Mg 2+ for a single Ca 2+ is possible in both 1 and 2, the simultaneous binding of two Mg 2+ by 2 appears prohibitive for replacement of these two ions by a single Ca 2+ . Ion-binding and exchange was further rationalized by DFT calculations.

Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.

Science.gov (United States)

Kuck, Jamie L; Bastarache, Julie A; Shaver, Ciara M; Fessel, Joshua P; Dikalov, Sergey I; May, James M; Ware, Lorraine B

2018-01-01

Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity. Human umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of 14 C-inulin. Viability was measured by trypan blue exclusion. Intracellular ascorbate was measured by HPLC. CFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability. CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts

International Nuclear Information System (INIS)

Murata, Naohiko; Ito, Satoru; Furuya, Kishio; Takahara, Norihiro; Naruse, Keiji; Aso, Hiromichi; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori

2014-01-01

Highlights: • Uniaxial stretching activates Ca 2+ signaling in human lung fibroblasts. • Stretch-induced intracellular Ca 2+ elevation is mainly via Ca 2+ influx. • Mechanical strain enhances ATP release from fibroblasts. • Stretch-induced Ca 2+ influx is not mediated by released ATP or actin cytoskeleton. - Abstract: One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10–30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca 2+ ] i transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca 2+ ] i . The stretch-induced [Ca 2+ ] i elevation was attenuated in Ca 2+ -free solution. In contrast, the increase of [Ca 2+ ] i by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd 3+ , ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca 2+ ] i elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca 2+ influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP

In vitro degradation and electrochemical corrosion evaluations of microarc oxidized pure Mg, Mg-Ca and Mg-Ca-Zn alloys for biomedical applications.

Science.gov (United States)

Pan, Yaokun; He, Siyu; Wang, Diangang; Huang, Danlan; Zheng, Tingting; Wang, Siqi; Dong, Pan; Chen, Chuanzhong

2015-02-01

Calcium phosphate (CaP) ceramic coatings were fabricated on pure magnesium (Mg) and self-designed Mg-0.6Ca, Mg-0.55Ca-1.74Zn alloys by microarc oxidation (MAO). The coating formation, growth and biomineralization mechanisms were discussed. The coating degradability and bioactivity were evaluated by immersion tests in trishydroxymethyl-aminomethane hydrochloric acid (Tris-HCl) buffer and simulated body fluid (SBF) solutions, respectively. The coatings and corrosion products were characterized by scanning electron microscope (SEM), X-ray diffractometer (XRD), X-ray photoelectron spectrometer (XPS) and fourier transform infrared spectrometer (FT-IR). The electrochemical workstation was used to investigate the electrochemical corrosion behaviors of substrates and coatings. Results showed that Mg-0.55Ca-1.74Zn alloy exhibits the highest mechanical strength and electrochemical corrosion resistance among the three alloys. The MAO-coated Mg-0.55Ca-1.74Zn alloy has the potential to be served as a biodegradable implant. Copyright © 2014 Elsevier B.V. All rights reserved.

The influence of body mass index and gender on coronary arterial attenuation with fixed iodine load per body weight at dual-source CT coronary angiography

International Nuclear Information System (INIS)

Zhu, Xiaomei; Zhu, Yinsu; Xu, Hai; Tang, Lijun; Xu, Yi

2012-01-01

Background. Most of current coronary CT angiography protocols are not adapted to body weight (BW) or cardiac output and no literature about influence of gender on coronary attenuation are reported with administration of a fixed iodine load per BW. Purpose. To determine the influence of body mass index (BMI) and gender on coronary arterial attenuation if contrast material dose is linearly adjusted to a patient's BW at dual-source CT coronary angiography (DSCT-CA). Material and Methods. A total of 207 consecutive patients (mean age 60.6 years) undergoing DSCT-CA were included. Contrast material (370 mg I/mL) dose calculation was randomly categorized into two groups (Group1: 1.10 mL/kg for men and women; Group 2: men 1.10 mL/kg, women 0.99 mL/kg) and flow rate was calculated as dose was divided by scan time plus 8 s. Mean arterial attenuations between men and women were compared with respect to attenuations of ascending aorta (AA) above coronary ostia, left main coronary artery (LM), proximal segments of right coronary artery (RCA), left anterior descending (LAD), and left circumflex artery (LCX) in two groups, respectively. Attenuations of coronary arteries were correlated with BW and BMI with simple linear regression. Results. The mean attenuations of AA, LM, RCA, LAD, and LCX were 407.8 ± 53.6 HU, 412.6 ± 55.4 HU, 411.4 ± 64.3 HU, 399.1 ± 56.7 HU, and 399.1 ± 60.2 HU, respectively, and there were no significant differences between men and women in group 1 (AA, P = 0.571; LM, P = 0.670; RCA, P = 0.737; LAD, P = 0.439, and LCX, P = 0.888). In group 2, the mean attenuations of AA, LM, RCA, LAD, and LCX in men were significantly higher than those in women (AA, P = 0.008; LM, P = 0.025; RCA, P = 0.017; LAD, P = 0.015, and LCX, P = 0.002). Positive linear regression between BW and attenuations of AA (R 2 = 0.047, P = 0.02), LM (R 2 = 0.036, P = 0.04), RCA (R 2 = 0.080, P 2 = 0.078, P 2 = 0.033, P = 0.05) was found in group 1, suggesting that attenuations of coronary

HIGHLY ACTIVE CaO FOR THE TRANSESTERIFICATION TO ...

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1College of Chemistry and Chemical Engineering, Xi'an Shiyou University, Xi'an Shannxi, ... acid methyl esters (FAME) yield of the modified CaO was greatly enhanced ... same properties as diesel, to supply or replace such fossil fuel[1, 2].

Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

Science.gov (United States)

Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta

2006-01-01

Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127

Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

Directory of Open Access Journals (Sweden)

Amorsolo L Suguitan

2006-09-01

Full Text Available Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses.The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

Thermal unfolding of a Ca- and Lanthanide-binding protein

Energy Technology Data Exchange (ETDEWEB)

Fahmy, Karim [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Goettfert, M. [Technische Univ. Dresden (Germany); Knoeppel, J.

2017-06-01

The MIIA (metal ion-induced autocleavage)-domain of the protein Vic001052 from the pathogen Vibrio coralliilyticus, comprises 173 amino acids and exhibits Ca-dependent autoproteolytic activity. It shows homology to nodulation proteins which are secreted by Rhizobiacea into plant host cells where they exert Ca-dependent functions. We have studied the structural and energetic aspects of metal protein interactions of the MIIA domain which appear attractive for engineering metal-binding synthetic peptides. Using a non-cleavable MIIA domain construct, we detected very similar structural changes upon binding to Ca{sup 2+} and Eu{sup 3+}. The thermal denaturation of the Ca-bound state was studied by circular dichroism spectroscopy. The metal-bound folded state unfolds reversibly into an unstructured metal-free state similar to the metal-free state at room temperature.

Formation of CaSO4(aq) and CaSeO4(aq) studied as a function of ionic strength and temperature by CE

International Nuclear Information System (INIS)

Philippini, V.; Aupiais, J.; Moulin, Ch.; Vercouter, Th.

2009-01-01

Ca 2+ complexation by both sulfate and selenate ligands was studied by CE. The species were observed to give a unique retention peak as a result of a fast equilibrium between the free ions and the complexes. The change in the corresponding retention time was interpreted with respect to the equilibrium constant of the complexation reaction. The results confirmed the formation of CaSO 4 (aq) and CaSeO 4 (aq) under our experimental conditions. The formation data were derived from the series of measurements carried out at about 15, 25, 35, 45 and 55 degrees C in 0.1 mol/L NaNO 3 ionic strength solutions, and in 0.5 and 1.0 mol/L NaNO 3 ionic strength solutions at 25 degrees C. Using a constant enthalpy of reaction enabled to fit all the experimental data in a 0.1 mol/L medium, leading to the thermodynamic parameters: Δ r G 0.1M (25 degrees C) = -(7.59±0.23) kJ/mol, Δ r H 0.1M = 5.57±0.80 kJ/mol, and Δ r S 0.1M (25 degrees C) = 44.0±3.0 J mol -1 K -1 for CaSO 4 (aq) and Δ r G 0.1M )(25 degrees C) = - (6.66±0.23) kJ/mol, Δ r H 0.1M = 6.45±0.73 kJ/mol, and Δ r S 0.1M (25 degrees C) = 44.0±3.0 J mol -1 K -1 for CaSeO 4 (aq). Both formation reactions were found to be endothermic and entropy driven. CaSO 4 (aq) appears to be more stable than CaSe O 4(aq) by 0.93 kJ/mol under these experimental conditions, which correlates with the difference of acidity of the anions as expected for interactions between hard acids and hard bases according to the hard and soft acids and bases theory. The effect of the ionic medium on the formation constants was successfully treated using the Specific ion Interaction Theory, leading to significantly different binary coefficients ε Na + ,SO 4 2- (0.15±0.06) mol/kg -1 and ε Na + ,SeO 4 2- -(0.26±0.10)mol/kg -1 . (authors)

Unesterified docosahexaenoic acid is protective in neuroinflammation

Science.gov (United States)

Orr, Sarah K; Palumbo, Sara; Bosetti, Francesca; Mount, Howard T; Kang, Jing X; E, Carol; Greenwood; Ma, David WL; Serhan, Charles N; Bazinet, Richard P

2014-01-01

Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 PUFA modulation in transgenic and wildtype mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry. Further, docosahexaenoic acid protected against lipopolysaccharide-induced neuronal loss. Acute intracerebroventricular infusion of unesterified docosahexaenoic acid or its 12/15-lipoxygenase product and precursor to protectins and resolvins, 17S-hydroperoxy-docosahexaenoic acid, mimics anti-neuroinflammatory aspects of chronically increased unesterified docosahexaenoic acid. LCMS/MS revealed that neuroprotectin D1 and several other docosahexaenoic acid-derived specialized pro-resolving mediators are present in the hippocampus. Acute icv infusion of 17S-hydroperoxydocosahexaenoic acid increases hippocampal neuroprotectin D1 levels concomitant to attenuating neuroinflammation. These results show that unesterified docosahexaenoic acid is protective in a lipopolysaccharide-initiated mouse model of acute neuroinflammation, at least in part, via its conversion to specialized pro-resolving mediators; these docosahexaenoic acid stores may provide novel targets for the prevention and treatment(s) of neurological disorders with a neuroinflammatory component. PMID:23919613

Ca2+ pump and Ca2+/H+ antiporter in plasma membrane vesicles isolated by aqueous two-phase partitioning from corn leaves

International Nuclear Information System (INIS)

Kasai, M.; Muto, S.

1990-01-01

Plasma membrane vesicles, which are mostly right side-out, were isolated from corn leaves by aqueous two-phase partitioning method. Characteristics of Ca2+ transport were investigated after preparing inside-out vesicles by Triton X-100 treatment. 45Ca2+ transport was assayed by membrane filtration technique. Results showed that Ca2+ transport into the plasma membrane vesicles was Mg-ATP dependent. The active Ca2+ transport system had a high affinity for Ca2+(Km(Ca2+) = 0.4 microM) and ATP(Km(ATP) = 3.9 microM), and showed pH optimum at 7.5. ATP-dependent Ca2+ uptake in the plasma membrane vesicles was stimulated in the presence of Cl- or NO3-. Quenching of quinacrine fluorescence showed that these anions also induced H+ transport into the vesicles. The Ca2+ uptake stimulated by Cl- was dependent on the activity of H+ transport into the vesicles. However, carbonylcyanide m-chlorophenylhydrazone (CCCP) and VO4(3-) which is known to inhibit the H+ pump associated with the plasma membrane, canceled almost all of the Cl(-)-stimulated Ca2+ uptake. Furthermore, artificially imposed pH gradient (acid inside) caused Ca2+ uptake into the vesicles. These results suggest that the Cl(-)-stimulated Ca2+ uptake is caused by the efflux of H+ from the vesicles by the operation of Ca2+/H+ antiport system in the plasma membrane. In Cl(-)-free medium, H+ transport into the vesicles scarcely occurred and the addition of CCCP caused only a slight inhibition of the active Ca2+ uptake into the vesicles. These results suggest that two Ca2+ transport systems are operating in the plasma membrane from corn leaves, i.e., one is an ATP-dependent active Ca2+ transport system (Ca2+ pump) and the other is a Ca2+/H+ antiport system. Little difference in characteristics of Ca2+ transport was observed between the plasma membranes isolated from etiolated and green corn leaves

Enhanced Expression of WD Repeat-Containing Protein 35 via CaMKK/AMPK Activation in Bupivacaine-Treated Neuro2a Cells

Science.gov (United States)

Huang, Lei; Kondo, Fumio; Gosho, Masahiko; Feng, Guo-Gang; Harato, Misako; Xia, Zhong-yuan; Ishikawa, Naohisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

We previously reported that bupivacaine induces reactive oxygen species (ROS) generation, p38 mitogen-activated protein kinase (MAPK) activation and nuclear factor-kappa B activation, resulting in an increase in expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. However, the identity of signaling upstream of p38 MAPK pathways to WDR35 expression remains unclear. It has been shown that AMP-activated protein kinase (AMPK) can activate p38 MAPK through diverse mechanisms. In addition, several kinases acting upstream of AMPK have been identified including Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Recent studies reported that AMPK may be involved in bupivacaine-induced cytotoxicity in Schwann cells and in human neuroblastoma SH-SY5Y cells. The present study was undertaken to test whether CaMKK and AMPK are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Our results showed that bupivacaine induced activation of AMPK and p38 MAPK in Neuro2a cells. The AMPK inhibitors, compound C and iodotubercidin, attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. Treatment with the CaMKK inhibitor STO-609 also attenuated the bupivacaine-induced activation of AMPK and p38 MAPK, resulting in an inhibition of the bupivacaine-induced increase in WDR35 expression. These results suggest that bupivacaine activates AMPK and p38 MAPK via CaMKK in Neuro2a cells, and that the CaMKK/AMPK/p38 MAPK pathway is involved in regulating WDR35 expression. PMID:24859235

Ca2+-exchange in layered zirconium orthophosphate, α-ZrP: Chemical study and potential application for zinc corrosion inhibition

Science.gov (United States)

Bouali, Imane; Rocca, Emmanuel; Veys-Renaux, Delphine; Rhouta, Benaissa; Khalil, Aziza; Aït Aghzzaf, Ahmed

2017-11-01

The control of the corrosion phenomenon occurring at the metal interface requires the development of new non-toxic anticorrosion additives. For this purpose, zirconium orthophosphate compounds (Zr(HPO4)2,H2O noted α-ZrP) were synthesized by both hydrothermal and refluxing methods The Ca2+-cationic exchange in the layered structure is kinetically favoured by low crystallinity of α-ZrP synthesized by refluxing process, and leads to the formation of CaZr(PO4)2,4H2O, noted Ca2+-ZrP. The H+/Ca2+ exchange mechanism is mainly triggered by acid-base considerations, and especially the pKa of α-ZrP/Ca2+-ZrP acid-base couple (evaluated to 2.5). Both compounds are acidic compounds by internal exchangeable H+ for α-ZrP and surface protons for Ca2+-ZrP, and can be used as potential inhibitors of zinc corrosion. Electrochemical measurements show that Ca2+-ZrP compounds dispersed in the NaCl electrolyte buffer the pH value over a long time and therefore allow controlling the corrosion rate of zinc.

In situ biosynthesis of bacterial nanocellulose-CaCO3 hybrid bionanocomposite: One-step process.

Science.gov (United States)

Mohammadkazemi, Faranak; Faria, Marisa; Cordeiro, Nereida

2016-08-01

In this work, a simple and green route to the synthesis of the bacterial nanocellulose-calcium carbonate (BNC/CaCO3) hybrid bionanocomposites using one-step in situ biosynthesis was studied. The CaCO3 was incorporated in the bacterial nanocellulose structure during the cellulose biosynthesis by Gluconacetobacter xylinus PTCC 1734 bacteria. Hestrin-Schramm (HS) and Zhou (Z) culture media were used to the hybrid bionanocomposites production and the effect of ethanol addition was investigated. Attenuated total reflection Fourier transform infrared spectroscopy, field emission scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, inverse gas chromatography and thermogravimetric analysis were used to characterize the samples. The experimental results demonstrated that the ethanol and culture medium play an important role in the BNC/CaCO3 hybrid bionanocomposites production, structure and properties. The BNC/CaCO3 biosynthesized in Z culture medium revealed higher O/C ratio and amphoteric surface character, which justify the highest CaCO3 content incorporation. The CaCO3 was incorporated into the cellulosic matrix decreasing the bacterial nanocellulose crystallinity. This work reveals the high potential of in situ biosynthesis of BNC/CaCO3 hybrid bionanocomposites and opens a new way to the high value-added applications of bacterial nanocellulose. Copyright © 2016 Elsevier B.V. All rights reserved.

Protein Kinase Cα and P-Type Ca2+ Channel CaV2.1 in Red Blood Cell Calcium Signalling

Directory of Open Access Journals (Sweden)

Lisa Wagner-Britz

2013-06-01

Full Text Available Background/Aims: Protein kinase Cα (PKCα is activated by an increase in cytosolic Ca2+ in red blood cells (RBCs. Previous work has suggested that PKCα directly stimulates the CaV2.1 channel, whereas other studies revealed that CaV2.1 is insensitive to activation by PKC. The aim of this study was to resolve this discrepancy. Methods: We performed experiments based on a single cell read-out of the intracellular Ca2+ concentration in terms of Fluo-4 fluorescence intensity and phosphatidylserine exposure to the external membrane leaflet. Measurement modalities included flow cytometry and live cell imaging. Results: Treatment of RBCs with phorbol 12-myristate 13-acetate (PMA led to two distinct populations of cells with an increase in intracellular Ca2+: a weak-responding and a strong-responding population. The EC50 of PMA for the number of cells with Ca2+ elevation was 2.7±1.2 µM; for phosphatidylserine exposure to the external membrane surface, it was 2.8±0.5 µM; and for RBC haemolysis, it was 2.9±0.5 µM. Using pharmacological manipulation with the CaV2.1 inhibitor ω-agatoxin TK and the broad protein kinase C inhibitor Gö6983, we are able to show that there are two independent PMA-activated Ca2+ entry processes: the first is independent of CaV2.1 and directly PKCα-activated, while the second is associated with a likely indirect activation of CaV2.1. Further studies using lysophosphatidic acid (LPA as a stimulation agent have provided additional evidence that PKCα and CaV2.1 are not directly interconnected in a signalling chain. Conclusion: Although we provide evidence for a lack of interaction between PKCα and CaV2.1 in RBCs, further studies are required to decipher the signalling relationship between LPA, PKCα and CaV2.1.

Measurement of conjugated linoleic acid (CLA) in CLA-rich soy oil by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR).

Science.gov (United States)

Kadamne, Jeta V; Jain, Vishal P; Saleh, Mohammed; Proctor, Andrew

2009-11-25

Conjugated linoleic acid (CLA) isomers in oils are currently measured as fatty acid methyl esters by a gas chromatography-flame ionization detector (GC-FID) technique, which requires approximately 2 h to complete the analysis. Hence, we aim to develop a method to rapidly determine CLA isomers in CLA-rich soy oil. Soy oil with 0.38-25.11% total CLA was obtained by photo-isomerization of 96 soy oil samples for 24 h. A sample was withdrawn at 30 min intervals with repeated processing using a second batch of oil. Six replicates of GC-FID fatty acid analysis were conducted for each oil sample. The oil samples were scanned using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the spectrum was collected. Calibration models were developed using partial least-squares (PLS-1) regression using Unscrambler software. Models were validated using a full cross-validation technique and tested using samples that were not included in the calibration sample set. Measured and predicted total CLA, trans,trans CLA isomers, total mono trans CLA isomers, trans-10,cis-12 CLA, trans-9,cis-11 CLA and cis-10,trans-12 CLA, and cis-9,trans-11 CLA had cross-validated coefficients of determinations (R2v) of 0.97, 0.98, 0.97, 0.98, 0.97, and 0.99 and corresponding root-mean-square error of validation (RMSEV) of 1.14, 0.69, 0.27, 0.07, 0.14, and 0.07% CLA, respectively. The ATR-FTIR technique is a rapid and less expensive method for determining CLA isomers in linoleic acid photo-isomerized soy oil than GC-FID.

Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity

DEFF Research Database (Denmark)

Bjelke, Jais R; Olsen, Ole H; Fodje, Michel

2008-01-01

between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity. Moreover, mutation of the Lys(161)-interactive residue Asp(217) or Asp(219) to Ala reduced the amidolytic...... activity by 40-50%, whereas the K161A mutation resulted in 80% reduction. Hence one of these Asp residues in the Ca(2+)-binding loop appears to suffice for some residual interaction with Lys(161), whereas the more severe effect upon replacement of Lys(161) is due to abrogation of the interaction with the N......-terminal tail. However, Ca(2+) attenuation of the repulsion between Asp(212) and Glu(296) keeps the activity above that of apoFVIIa. Altogether, our data suggest that repulsion involving Asp(212) in the Ca(2+)-binding loop suppresses FVIIa activity and that optimal activity requires a favorable interaction...

Endogenous n-3 polyunsaturated fatty acids attenuate T cell-mediated hepatitis via autophagy activation

Directory of Open Access Journals (Sweden)

Yanli Li

2016-09-01

Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFAs exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A was administered intravenously to wild-type (WT and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase (ALT activity, and inhibited production of pro-inflammatory cytokines (e.g. TNF-α, IL-6, IL-17A and IFN-γ. In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism, and could be exploited as a new therapeutic approach for autoimmune hepatitis.

Control algorithms for dynamic attenuators

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

2014-06-15

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators

International Nuclear Information System (INIS)

Hsieh, Scott S.; Pelc, Norbert J.

2014-01-01

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators.

Science.gov (United States)

Hsieh, Scott S; Pelc, Norbert J

2014-06-01

The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

LENUS (Irish Health Repository)

Robb, W B

2010-03-01

The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine\\'s effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy.

CaSO{sub 4}:Dy microphosphor for thermal neutron dosimetry

Energy Technology Data Exchange (ETDEWEB)

Bhadane, Mahesh S. [Microtron Accelerator Laboratory, Department of Physics, Savitribai Phule Pune University, Pune 411007 (India); Mandlik, Nandkumar [Department of Physics, Fergusson College, Savitribai Phule Pune University, Pune 411007 (India); Patil, B.J. [Department of Physics, Abasaheb Garware College, Pune 411004 (India); Dahiwale, S.S.; Sature, K.R.; Bhoraskar, V.N. [Microtron Accelerator Laboratory, Department of Physics, Savitribai Phule Pune University, Pune 411007 (India); Dhole, S.D., E-mail: sanjay@physics.unipune.ac.in [Microtron Accelerator Laboratory, Department of Physics, Savitribai Phule Pune University, Pune 411007 (India)

2016-02-15

Dysprosium-doped calcium sulphate (CaSO{sub 4}:Dy) microphosphor was synthesized by acid re-crystallization method and its thermoluminescence (TL) properties irradiated with thermal neutrons was studied. Structural and morphological characteristics have been studied using X-ray diffraction and SEM which mainly exhibits a orthorhombic structure with particle size of 200 to 250 µm. Moreover, thermal neutron dosimetric characteristics of the microphosphor such as thermoluminescence glow curve, TL dose–response have been studied. This microphosphor powder represents a TL glow peak (T{sub max}) centered at around 240 °C. The TL response of CaSO{sub 4}:Dy microphosphor as a function of thermal neutron fluence is observed to be very linear upto the fluence of 52×10{sup 11} n/cm{sup 2} and further saturates. In addition, TL glow curves were deconvoluted by computerized glow curve deconvolution (CGCD) method and corresponding trapping parameters have been determined. It has been found that for every deconvoluted peak there is change in the order of kinetics. Overall, the experimental results show that the CaSO{sub 4}:Dy microphosphor can have potential to be an effective thermal neutron dosimetry. - Highlights: • Acid-recrystallization method is used to prepare CaSO{sub 4}:Dy microphosphor • CaSO{sub 4}:Dy phosphor irradiated thermal neutrons for dosimetric application. • TL response curve showed to be a perfect linear. • Trapping parameters has been calculated using CGCD curve fitting.

Ultrasonic Investigations on Polonides of Ba, Ca, and Pb

Science.gov (United States)

Singh, Devraj; Bhalla, Vyoma; Bala, Jyoti; Wadhwa, Shikha

2017-10-01

The temperature-dependent mechanical and ultrasonic properties of barium, calcium, and lead polonides (BaPo, CaPo, and PbPo) were investigated in the temperature range 100-300 K. The second- and third-order elastic constants (SOECs and TOECs) were computed using Coulomb and Born-Mayer potential and these in turn have been used to estimate other secondary elastic properties such as strength, anisotropy, microhardness, etc. The theoretical approach followed the prediction that BaPo, CaPo, and PbPo are brittle in nature. PbPo is found to be the hardest amongst the chosen compounds. Further the SOECs and TOECs are applied to determine ultrasonic velocities, Debye temperature, and acoustic coupling constants along , , and orientations at room temperature. Additionally thermal conductivity has been computed using Morelli and Slack's approach along different crystallographic directions at room temperature. Finally ultrasonic attenuation due to phonon-phonon interaction and thermoelastic relaxation mechanisms has been computed for BaPo, CaPo, and PbPo. The behaviour of these compounds is similar to that of semi-metals with thermal relaxation time of the order 10-11 s. The present computation study is reasonably in agreement with the available theoretical data for the similar type of materials.

Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

Directory of Open Access Journals (Sweden)

Francisco J Ortega

Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

Removal of uranium and gross radioactivity from coal bottom ash by CaCl{sub 2} roasting followed by HNO{sub 3} leaching

Energy Technology Data Exchange (ETDEWEB)

Lei, Xuefei; Qi, Guangxia; Sun, Yinglong; Xu, Hui; Wang, Yi, E-mail: yi_wang@tsinghua.edu.cn

2014-07-15

Highlight: • Roasting the ash with CaCl{sub 2} enhanced the removal of uranium and gross radioactivity. • 87.3% of the total uranium was removed via the optimized roast-leach process. • Nearly 90% of gross α and β radioactivity was removed via the roast-leach process. • Molten CaCl{sub 2} promoted the incorporation of Ca and Al into Si-O matrices in ash. • Radionuclides were removed by the acid decomposition of newly formed silicates. - Abstract: A roast-leach method using CaCl{sub 2} and HNO{sub 3} to remove uranium and gross radioactivity in coal bottom ash was investigated. Heat treatment of the ash with 100% CaCl{sub 2} (900 °C, 2 h) significantly enhanced uranium leachability (>95%) compared with direct acid-leaching (22.6–25.5%). The removal efficiency of uranium and gross radioactivity increased steeply with increasing CaCl{sub 2} content, from 10% to 50%, and a HNO{sub 3} leaching time from 5 min to 1 h, but remained nearly constant or decreased slightly with increasing CaCl{sub 2} dosage >50% or acid-leaching time >1 h. The majority of the uranium (87.3%), gross α (92.9%) and gross β (84.9%) were removed under the optimized roast-leach conditions (50% CaCl{sub 2}, 1 M HNO{sub 3} leaching for 1 h). The mineralogical characteristics of roasted clinker indicated that molten CaCl{sub 2} promoted the incorporation of Ca into silica and silicates and resulted in its progressive susceptibility to acid attack. Uranium and other radionuclides, most likely present in the form of silicates or in association with miscellaneous silicates in the highest density fraction (>2.5 g mL{sup −1}), were probably leached out as the result of the acid decomposition of newly formed “gelatinizing silicates”.

Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter isolated from ambient air by attenuating oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Park, Hyelim [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University, Seoul (Korea, Republic of); Park, Sanghoon; Jeon, Hyunju [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Song, Byeong-Wook [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University, Seoul (Korea, Republic of); Kim, Jin-Bae [Division of Cardiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Kim, Chang-Soo [The Department of Preventive Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Pak, Hui-Nam [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Hwang, Ki-Chul [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University, Seoul (Korea, Republic of); Lee, Moon-Hyoung [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Ji Hyung, E-mail: jhchung@yuhs.ac [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Joung, Boyoung, E-mail: cby6908@yuhs.ac [The Division of Cardiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University, Seoul (Korea, Republic of)

2013-01-15

Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) is activated by particulate matter (PM) isolated from ambient air and linked to prolonged repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin (CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT-protein transduction domain (TAT-CryAB). ECGs were measured before and after tracheal exposure of diesel exhaust particles (DEP) and each intervention in adult Sprague–Dawley rats. After endotracheal exposure of DEP (200 μg/mL for 30 minutes, n = 11), QT intervals were prolonged from 115 ± 14 ms to 144 ± 20 ms (p = 0.03), and premature ventricular contractions were observed more frequently (0% vs. 44%) than control (n = 5) and TAT-Cry (n = 5). However, DEP-induced arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n = 5). In optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP infusion of 12.5 μg/mL (n = 12) increased apicobasal action potential duration (APD) differences from 2 ± 6 ms to 36 ± 15 ms (p < 0.001), APD restitution slope from 0.26 ± 0.07 to 1.19 ± 0.11 (p < 0.001) and ventricular tachycardia (VT) from 0% to 75% (p < 0.001). DEP infusion easily induced spatially discordant alternans. However, the effects of DEP were prevented by TAT-CryAB (1 mg/kg, n = 9). In rat myocytes, while DEP increased reactive oxygen species (ROS) generation and phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a small heat shock protein, might prevent the arrhythmogenic effects of PM by attenuating ROS generation and CaMKII activation. -- Highlights: ► Particulate matter (PM) increases arrhythmia. ► PM induced arrhythmias are related with oxidative stress and CaMKII activation. ► Alpha B-crystallin (CryAB) could attenuate the arrhythmogenic effect of PM. ► CryAB decreases oxidative stress and CaMKII activation

Photon attenuation by intensifying screens

International Nuclear Information System (INIS)

Holje, G.

1983-01-01

The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

Clusterin silencing sensitizes pancreatic cancer MIA-PaCa-2 cells to gmcitabine via regulation of NF-kB/Bcl-2 signaling.

Science.gov (United States)

Xu, Miao; Chen, Xiumei; Han, Yanling; Ma, Chunqing; Ma, Lin; Li, Shirong

2015-01-01

Clusterin (CLU) is known as a multifunctional protein involved in a variety of physiological processes including lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis. Our recent study has demonstrated that knockdown of clusterin sensitizes pancreatic cancer cell lines to gmcitabine treatment. However the details of this survival mechanism remain undefined. Of the various downstream targets of CLU, we examined activation of the NF-kB transcription factor and subsequent transcriptional regulation of BCL-2 gene in pancreatic cancer cell MIA-PaCa-2. The MIA-PaCa-2 cells were transfected with an antisense oligonucleotide (ASO) against clusterin, which led to a decreased protein level of the antiapoptotic gene BCL-2. Furthermore, inhibition of CLU decreased the function of NF-kB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway increased the apoptotic effect of gmcitabine chemotherapy. Re-activated NF-kB resulted in attenuation of ASO-induced effects, followed by the bcl-2 upregulation, and bcl-2 re-inhibition resulted in attenuation of Re-activated NF-kB -induced effects. Animals injected with ASO CLU in MIA-PaCa-2 cells combined with gmcitabine treatment had fewer tumors than gmcitabine or ASO CLU alone. These findings suggest that knockdown of CLU sensitized MIA-PaCa-2 cells to gmcitabine chemotherapy through modulating NF-Kb/bcl-2 pathway.

Evidence that radio-sensitive cells are central to skin-phase protective immunity in CBA/Ca mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni as well as in naive mice protected with vaccine serum

International Nuclear Information System (INIS)

Delgado, V.S.; McLaren, D.J.

1990-01-01

Naive CBA/Ca mice and CBA/ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were subjected to 550 rad of whole body (gamma) irradiation and then challenged 3 days later with normal cercariae. The perfusion recovery data showed that this procedure reduced the primary worm burden in naive mice by 22% and the challence worm burden in vaccinated mice by 82%. Irradiation also ablated the peripheral blood leucocytes of both mouse groups by 90-100% at the time of challenge. Histological data revealed that such treatment caused a dramatic change in number, size and leucocyte composition of cutaneous inflammatory skin reactions that characterize challenged vacccinated mice and are known to entrap invading larvae; cutaneous eosinophils were preferentially abolished by this treatment. Polyvaccine mouse serum that conferred protection passively upon naive recipient mice, failed to protect naive/irradiated mice when administered by the same protocol. Distraction of macrophages by treatment of mice with silica did not affect the establishment of a primary worm burden and reduced the protection exhibited by vaccinated mice by only 16%. These data indicade that radio-sensitive cells are important to both innate and specific acquired resistance in this mouse model and that macrophages contribute only marginally to the expression of vaccine immunity. (author)

Induction of Ca2+-dependent cyclosporin A-insensitive nonspecific permeability of the inner membrane of liver mitochondria and cytochrome c release by α,ω-hexadecanedioic acid in media of varying ionic strength.

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Dubinin, M V; Vedernikov, A A; Khoroshavina, E I; Samartsev, V N

2014-06-01

In liver mitochondria loaded with Ca2+ or Sr(2+), α,ω-hexadecanedioic acid (HDA) can induce nonspecific permeability of the inner membrane (mitochondrial pore) by the mechanism insensitive to cyclosporin A (CsA). In this work we studied the effect of ionic strength of the incubation medium on the kinetics of the processes that accompany Ca2+-dependent induction of the mitochondrial pore by fatty acid: organelle swelling, Ca2+ release from the matrix, changes in transmembrane potential (Δψ) and rate of oxygen consumption, and the release of cytochrome c from the intermembrane space. Two basic incubation media were used: sucrose medium and isotonic ionic medium containing KCl without sucrose. We found that 200 μM Ca2+ and 20 μM HDA in the presence of CsA effectively induce high-amplitude swelling of mitochondria both in the case of sucrose and in the ionic incubation medium. In the presence of CsA, mitochondria can rapidly absorb Ca2+ and retain it in the matrix for a while without reducing Δψ. Upon incubation in the ionic medium, mitochondria retain most of the added Ca2+ in the matrix for a short time without reducing the Δψ. In both cases the addition of HDA to the mitochondria 2 min after the introduction of Ca2+ leads to the rapid release of these ions from the matrix and total drop in Δψ. The mitochondrial swelling induced by Ca2+ and HDA in non-ionic medium is accompanied by almost maximal stimulation of respiration. Under the same conditions, but during incubation of mitochondria in the ionic medium, it is necessary to add cytochrome c for significant stimulation of respiration. The mitochondrial swelling induced by Ca2+ and HDA leads to the release of cytochrome c in a larger amount in the case of ionic medium than for the sucrose medium. We conclude that high ionic strength of the incubation medium determines the massive release of cytochrome c from mitochondria and liberates it from the respiratory chain, which leads to blockade of electron

Tracer attenuation in groundwater

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Cvetkovic, Vladimir

2011-12-01

The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats

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Liu, Zhongyang; Xi, Ronggang; Zhang, Zhiran; Li, Wangping; Liu, Yan; Jin, Faguang; Wang, Xiaobo

2014-01-01

4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. PMID:25050781

In situ synthesis carbonated hydroxyapatite layers on enamel slices with acidic amino acids by a novel two-step method.

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Wu, Xiaoguang; Zhao, Xu; Li, Yi; Yang, Tao; Yan, Xiujuan; Wang, Ke

2015-09-01

In situ fabrication of carbonated hydroxyapatite (CHA) remineralization layer on an enamel slice was completed in a novel, biomimetic two-step method. First, a CaCO3 layer was synthesized on the surface of demineralized enamel using an acidic amino acid (aspartic acid or glutamate acid) as a soft template. Second, at the same concentration of the acidic amino acid, rod-like carbonated hydroxyapatite was produced with the CaCO3 layer as a sacrificial template and a reactant. The morphology, crystallinity and other physicochemical properties of the crystals were characterized using field emission scanning electron microscopy (FESEM), Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy-dispersive X-ray analysis (EDAX), respectively. Acidic amino acid could promote the uniform deposition of hydroxyapatite with rod-like crystals via absorption of phosphate and carbonate ions from the reaction solution. Moreover, compared with hydroxyapatite crystals coated on the enamel when synthesized by a one-step method, the CaCO3 coating that was synthesized in the first step acted as an active bridge layer and sacrificial template. It played a vital role in orienting the artificial coating layer through the template effect. The results show that the rod-like carbonated hydroxyapatite crystals grow into bundles, which are similar in size and appearance to prisms in human enamel, when using the two-step method with either aspartic acid or acidic glutamate (20.00 mmol/L). Copyright © 2015 Elsevier B.V. All rights reserved.

Cocaine- and amphetamine-regulated transcript peptide in the nucleus accumbens shell inhibits cocaine-induced locomotor sensitization to transient over-expression of α-Ca2+ /calmodulin-dependent protein kinase II.

Science.gov (United States)

Xiong, Lixia; Meng, Qing; Sun, Xi; Lu, Xiangtong; Fu, Qiang; Peng, Qinghua; Yang, Jianhua; Oh, Ki-Wan; Hu, Zhenzhen

2018-01-04

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine-induced locomotor activity is related to a reduction in cocaine-enhanced phosphorylated Ca 2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca 2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus-transfected CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca 2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-over-expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine-induced locomotor sensitization. © 2018 International Society for Neurochemistry.

Influence of density and mean atomic number on CT attenuation corrected PET: Phantom studies

International Nuclear Information System (INIS)

Maintas, D.; Houzard, C.; Galy, G.; Maintas, C.; Itti, R.; Cachin, F.; Mognetti, Th.; Slosman

2007-01-01

Aim: the aim of this work is to study the influence of medium density on the CT or external source attenuation corrected images, by simulation on a phantom, with various positron emission tomographs. Material and method: a series of experiments on a cylindrical phantom filled with water marked with [18 F]-FDG, containing six vials filled per pair with mediums of different densities or solutions of KI, CaCl 2 and saccharose with various densities, was carried out under comparable conditions on three different tomographs. In only one of the vials of each pair, an identical radioactivity of [18 F]-FDG was added, three to five fold the surrounding activity. The reconstructions and attenuation corrections suggested by the manufacturers, were carried out under the usual conditions of each site. The activity of each structure was estimated by the methods of profiles and regions of interest, on the non attenuation corrected images (N.A.C.), the images corrected by CT (C.T.A.C.), and/or external source (G.P.A.C.). Results: with all three tomographs, the activities estimated on the N.A.C. images present an inverse correlation to the medium density (important absorption by dense material). On C.T.A.C. images, we observed with only two of the three tomographs, an overestimation of the activity in the 'radioactive' vials, depending on the medium mean Z number and density (over correction), and a artifactual 'activity' in the denser 'cold' vial (incorrect attenuation correction. The dense saccharose solutions, with non elevated Z number, do not affect the CT attenuation correction. (authors)

Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

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Takeda, Atsushi; Kanno, Shingo; Sakurada, Naomi; Ando, Masaki; Oku, Naoto

2008-10-01

The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. (c) 2008 Wiley-Liss, Inc.

In situ biosynthesis of bacterial nanocellulose-CaCO3 hybrid bionanocomposite: One-step process

International Nuclear Information System (INIS)

Mohammadkazemi, Faranak; Faria, Marisa; Cordeiro, Nereida

2016-01-01

In this work, a simple and green route to the synthesis of the bacterial nanocellulose-calcium carbonate (BNC/CaCO 3 ) hybrid bionanocomposites using one-step in situ biosynthesis was studied. The CaCO 3 was incorporated in the bacterial nanocellulose structure during the cellulose biosynthesis by Gluconacetobacter xylinus PTCC 1734 bacteria. Hestrin-Schramm (HS) and Zhou (Z) culture media were used to the hybrid bionanocomposites production and the effect of ethanol addition was investigated. Attenuated total reflection Fourier transform infrared spectroscopy, field emission scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, inverse gas chromatography and thermogravimetric analysis were used to characterize the samples. The experimental results demonstrated that the ethanol and culture medium play an important role in the BNC/CaCO 3 hybrid bionanocomposites production, structure and properties. The BNC/CaCO 3 biosynthesized in Z culture medium revealed higher O/C ratio and amphoteric surface character, which justify the highest CaCO 3 content incorporation. The CaCO 3 was incorporated into the cellulosic matrix decreasing the bacterial nanocellulose crystallinity. This work reveals the high potential of in situ biosynthesis of BNC/CaCO 3 hybrid bionanocomposites and opens a new way to the high value-added applications of bacterial nanocellulose. - Graphical Abstract: Display Omitted - Highlights: • BNC/CaCO 3 hybrid bionanocomposites were produced using in situ biosynthesis process. • Ethanol and culture medium play an important role in the production and properties. • Z-BNC/CaCO 3 bionanocomposites revealed higher O/C ratio and amphoteric surface character. • CaCO 3 incorporated into the BNC decreased crystallinity.

134Cs uptake by four plant species and Cs-K relations in the soil-plant system as affected by Ca(OH)2 application to an acid soil

International Nuclear Information System (INIS)

Massas, I.; Skarlou, V.; Haidouti, C.; Giannakopoulou, F.

2010-01-01

Three rates of Ca(OH) 2 were applied to an acid soil and the 134 Cs uptake by radish, cucumber, soybean and sunflower plants was studied. The 134 Cs concentration in all plant species was reduced from 1.6-fold in the sunflower seeds to 6-fold in the soybean vegetative parts at the higher Ca(OH) 2 rate. Potassium (K) concentration in plants was also reduced, but less effectively. The significantly decreased 134 Cs-K soil to plant distribution factors (D.F.) clearly suggest a stronger effect of soil liming on 134 Cs than on K plant uptake. This observation was discussed in terms of ionic interactions in the soil matrix and within the plants. The results also indicated that the increased Ca 2+ concentration in the exchange phase and in the soil solution along with the improved root activity, due to the soil liming, enhanced the immobilization of 134 Cs in the soil matrix and consequently lowered the 134 Cs availability for plant uptake.

Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.

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Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi

2015-04-28

Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice.

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Kong, Qin; Zhang, Haojun; Zhao, Tingting; Zhang, Weiku; Yan, Meihua; Dong, Xi; Li, Ping

2016-12-01

Tangshen formula (TSF), a well-prescribed traditional Chinese formula, has been used in the treatment of diabetic nephropathy. However, whether TSF ameliorates dyslipidemia and liver injury associated with diabetes remains unclear. In this study, we examined the effects of TSF on lipid profiles and hepatic steatosis in db/db mice. For this purpose, 8‑week-old db/db mice were treated with TSF or saline for 12 weeks via gavage and db/m mice were used as controls. Body weight and blood glucose levels were monitored weekly and bi-weekly, respectively. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology, immunohistochemistry and molecular examination. The results revealed that TSF markedly reduced body weight, liver index [liver/body weight (LW/BW)] and improved lipid profiles, hepatic function and steatosis in db/db mice. TSF induced the phosphoralation of AMP-activated protein kinase and inhibited the activity of sterol regulatory element-binding protein 1 together with the inhibition of the expression of genes involved in de novo lipogenesis (DNL) and gluconeogenesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl CoA desaturase 1 (SCD1), glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1). Additionally, the silent mating type information regulation 2 homolog 1 (Sirt1)/peroxisome proliferator-activated receptor α (PPARα)/malonyl-CoA decarboxylase (MLYCD) cascade was potently activated by TSF in the liver and skeletal muscle of db/db mice, which led to enhanced fatty acid oxidation. These findings demonstrated that TSF attenuated hepatic fat accumulation and steatosis in db/db mice by inhibiting lipogenesis and augmenting fatty acid oxidation.

Terahertz time-domain attenuated total reflection spectroscopy applied to the rapid discrimination of the botanical origin of honeys

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Liu, Wen; Zhang, Yuying; Yang, Si; Han, Donghai

2018-05-01

A new technique to identify the floral resources of honeys is demanded. Terahertz time-domain attenuated total reflection spectroscopy combined with chemometrics methods was applied to discriminate different categorizes (Medlar honey, Vitex honey, and Acacia honey). Principal component analysis (PCA), cluster analysis (CA) and partial least squares-discriminant analysis (PLS-DA) have been used to find information of the botanical origins of honeys. Spectral range also was discussed to increase the precision of PLS-DA model. The accuracy of 88.46% for validation set was obtained, using PLS-DA model in 0.5-1.5 THz. This work indicated terahertz time-domain attenuated total reflection spectroscopy was an available approach to evaluate the quality of honey rapidly.

Central l-proline attenuates stress-induced dopamine and serotonin metabolism in the chick forebrain.

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Hamasu, Kousuke; Shigemi, Kazutaka; Kabuki, Yusuke; Tomonaga, Shozo; Denbow, D Michael; Furuse, Mitsuhiro

2009-08-21

Using microdialysis, we investigated the effect of l-proline on monoamine release in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) of freely moving and restricted chicks. A 30 min handling-stress resulted in a significant increase in extracellular homovallinic acid (HVA), a dopamine metabolite, and 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in the MNH. l-Proline, perfused through the microdialysis probe into the MNH during the stressed condition, significantly attenuated the average dialysate concentration of HVA produced by handling-stress. Handling-stress resulted in a significant increase in 5-HIAA levels in the control group, which were attenuated by profusion with l-proline. l-Proline did not significantly modify basal concentrations of HVA or 5-HIAA in the MNH during control conditions. These results show that perfusion of l-proline modified the turnover/metabolism of dopamine and serotonin in the MNH caused by handling-stress.

Characteristics of transfer of europium ions from phosphoric acid solution into the CaSO4·O.5H2O solid phase

International Nuclear Information System (INIS)

Berdonosova, D.G.; Burlakova, E.V.; Yasenkova, M.A.; Ivanov, L.N.; Melikhov, I.V.

1989-01-01

The mechanism of formation of the precipitated CaSO 4 ·0.5H 2 O phase was studied in detail; the precipitation was performed at 80 degree, equimolar solutions of Ca(H 2 PO 4 ) 2 and H 2 SO 4 in phosphoric acid of 38% concentration being used. The availability of detailed information on the mechanism of formation of CaSO 4 ·0.5H 2 O precipitates determined the choice of conditions of study of capture of rare earths. In particular, H 3 PO 4 of 38% P 2 O 5 concentration was used as the medium of formation of the calcium sulfate precipitate. Europium was chosen as the rare earth. Its behavior in the liquid and solid phases was studied by radiometric and luminescence methods. The radionuclide 152 Eu is convenient as a radioactive tracer while luminescence of europium is structure-sensitive; therefore, europium is often used in physicochemical investigations as a luminescent probe. It follows from the data that most of the europium captured by the precipitate during coagulation of the ultramicrocrystals is retained firmly by the solid phase. Therefore, in order to diminish capture of europium (and other rare earths) by the precipitate coagulation of the latter should be prevented

Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

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Laville Martine

2011-07-01

Full Text Available Abstract Background Accumulating data suggest a novel role for bile acids (BAs in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans. Findings Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D, and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects. Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA, chenodeoxycholic acid (CDCA and deoxycholic acid (DCA concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001, CA (β = 0.03, p = 0.09 and DCA concentrations (β = 0.07, p Conclusions Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

Preemptive hemodynamic intervention restricting the administration of fluids attenuates lung edema progression in oleic acid-induced lung injury.

Science.gov (United States)

Gil Cano, A; Gracia Romero, M; Monge García, M I; Guijo González, P; Ruiz Campos, J

2017-04-01

A study is made of the influence of preemptive hemodynamic intervention restricting fluid administration upon the development of oleic acid-induced lung injury. A randomized in vivo study in rabbits was carried out. University research laboratory. Sixteen anesthetized, mechanically ventilated rabbits. Hemodynamic measurements obtained by transesophageal Doppler signal. Respiratory mechanics computed by a least square fitting method. Lung edema assessed by the ratio of wet weight to dry weight of the right lung. Histological examination of the left lung. Animals were randomly assigned to either the early protective lung strategy (EPLS) (n=8) or the early protective hemodynamic strategy (EPHS) (n=8). In both groups, lung injury was induced by the intravenous infusion of oleic acid (OA) (0.133mlkg -1 h -1 for 2h). At the same time, the EPLS group received 15mlkg -1 h -1 of Ringer lactate solution, while the EPHS group received 30mlkg -1 h -1 . Measurements were obtained at baseline and 1 and 2h after starting OA infusion. After 2h, the cardiac index decreased in the EPLS group (p<0.05), whereas in the EPHS group it remained unchanged. Lung compliance decreased significantly only in the EPHS group (p<0.05). Lung edema was greater in the EPHS group (p<0.05). Histological damage proved similar in both groups (p=0.4). In this experimental model of early lung injury, lung edema progression was attenuated by preemptively restricting the administration of fluids. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Interactions between hydrated cement paste and organic acids: Thermodynamic data and speciation modeling

Energy Technology Data Exchange (ETDEWEB)

De Windt, Laurent, E-mail: laurent.dewindt@mines-paristech.fr [MINES ParisTech, PSL Research University, Centre de Géosciences, 35 Rue St-Honoré, 77305 Fontainebleau Cedex (France); Bertron, Alexandra; Larreur-Cayol, Steeves; Escadeillas, Gilles [University of Toulouse, UPS/INSA/LMDC, 135 Av. de Rangueil, 31077 Toulouse Cedex 04 (France)

2015-03-15

Interactions of short-chain organic acids with hydrated cement phases affect structure durability in the agro-food and nuclear waste industries but can also be used to modify cement properties. Most previous studies have been experimental, performed at fixed concentrations and pH, without quantitatively discriminating among polyacidity effects, or complexation and salt precipitation processes. This paper addresses such issues by thermodynamic equilibrium calculations for acetic, citric, oxalic, succinic acids and a simplified hydrated CEM-I. The thermodynamic constants collected from the literature allow the speciation to be modeled over a wide range of pH and concentrations. Citric and oxalic had a stronger chelating effect than acetic acid, while succinic acid was intermediate. Similarly, Ca-citrate and Ca-oxalate salts were more insoluble than Ca-acetate and Ca-succinate salts. Regarding aluminium complexation, hydroxyls, sulfates, and acid competition was highlighted. The exploration of acid mixtures showed the preponderant effect of oxalate and citrate over acetate and succinate.

Elevation dependent sensitivity of northern hardwoods to Ca addition at Hubbard Brook Experimental Forest, NH USA

Science.gov (United States)

Rakesh Minocha; Stephanie Long; Palaniswamy Thangavel; Subhash C. Minocha; Christopher Eagar; Charles T. Driscoll

2010-01-01

Acidic deposition has caused a depletion of calcium (Ca) in the northeastern forest soils. Wollastonite (Ca silicate) was added to watershed 1 (WS1) at the Hubbard Brook Experimental Forest (HBEF) in 1999 to evaluate its effects on various functions of the HBEF ecosystem. The effects of Ca addition on foliar soluble (extractable in 5% HClO4) ions...

Biological attenuation of arsenic and iron in a continuous flow bioreactor treating acid mine drainage (AMD).

Science.gov (United States)

Fernandez-Rojo, L; Héry, M; Le Pape, P; Braungardt, C; Desoeuvre, A; Torres, E; Tardy, V; Resongles, E; Laroche, E; Delpoux, S; Joulian, C; Battaglia-Brunet, F; Boisson, J; Grapin, G; Morin, G; Casiot, C

2017-10-15

Passive water treatments based on biological attenuation can be effective for arsenic-rich acid mine drainage (AMD). However, the key factors driving the biological processes involved in this attenuation are not well-known. Here, the efficiency of arsenic (As) removal was investigated in a bench-scale continuous flow channel bioreactor treating As-rich AMD (∼30-40 mg L -1 ). In this bioreactor, As removal proceeds via the formation of biogenic precipitates consisting of iron- and arsenic-rich mineral phases encrusting a microbial biofilm. Ferrous iron (Fe(II)) oxidation and iron (Fe) and arsenic removal rates were monitored at two different water heights (4 and 25 mm) and with/without forced aeration. A maximum of 80% As removal was achieved within 500 min at the lowest water height. This operating condition promoted intense Fe(II) microbial oxidation and subsequent precipitation of As-bearing schwertmannite and amorphous ferric arsenate. Higher water height slowed down Fe(II) oxidation, Fe precipitation and As removal, in relation with limited oxygen transfer through the water column. The lower oxygen transfer at higher water height could be partly counteracted by aeration. The presence of an iridescent floating film that developed at the water surface was found to limit oxygen transfer to the water column and delayed Fe(II) oxidation, but did not affect As removal. The bacterial community structure in the biogenic precipitates in the bottom of the bioreactor differed from that of the inlet water and was influenced to some extent by water height and aeration. Although potential for microbial mediated As oxidation was revealed by the detection of aioA genes, removal of Fe and As was mainly attributable to microbial Fe oxidation activity. Increasing the proportion of dissolved As(V) in the inlet water improved As removal and favoured the formation of amorphous ferric arsenate over As-sorbed schwertmannite. This study proved the ability of this bioreactor

Carbonic anhydrase 5 regulates acid-base homeostasis in zebrafish.

Directory of Open Access Journals (Sweden)

Ruben Postel

Full Text Available The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5 mutation, collapse of fins (cof, which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.

Injectable hydrogels derived from phosphorylated alginic acid calcium complexes

Energy Technology Data Exchange (ETDEWEB)

Kim, Han-Sem; Song, Minsoo, E-mail: minsoosong00@gmail.com; Lee, Eun-Jung; Shin, Ueon Sang, E-mail: usshin12@dankook.ac.kr

2015-06-01

Phosphorylation of sodium alginate salt (NaAlg) was carried out using H{sub 3}PO{sub 4}/P{sub 2}O{sub 5}/Et{sub 3}PO{sub 4} followed by acid–base reaction with Ca(OAc){sub 2} to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for {sup 1}H, and {sup 31}P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2 w/v%) with NaAlg solution (2 w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO{sub 4} or CaCl{sub 2} were added externally. The gelation was completed within about 3–40 min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤ 6.7 kPa for compressive strength at break and about 8.4 kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100–800 μm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering. - Highlights: • Preparation of water-soluble alginic acid complexes with calcium phosphate • Self-assembly of the phosphorylated alginic acid calcium complexes with sodium alginate • Preparation of injectable hydrogels with diverse gelation times within about 3–40 min.

Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

Science.gov (United States)

Cheng, Yuanyuan; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

2015-01-01

Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

Combined effect of Bacillus coagulans GBI-30, 6086 and HMB supplementation on muscle integrity and cytokine response during intense military training.

Science.gov (United States)

Gepner, Yftach; Hoffman, Jay R; Shemesh, Elad; Stout, Jeffrey R; Church, David D; Varanoske, Alyssa N; Zelicha, Hila; Shelef, Ilan; Chen, Yacov; Frankel, Hagai; Ostfeld, Ishay

2017-07-01

The purpose of this study was to compare the coadministration of the probiotic Bacillus coagulans GBI-30, 6086 (BC30) with β-hydroxy-β-methylbutyrate (HMB) calcium (CaHMB) to CaHMB alone on inflammatory response and muscle integrity during 40 days of intense military training. Soldiers were randomly assigned to one of two groups: CaHMB with BC30 (CaHMBBC30; n = 9) or CaHMB with placebo (CaHMBPL, n = 9). A third group of participants served as a control (CTL; n = 8). During the first 28 days soldiers were garrisoned on base and participated in the same training tasks. During the final 2 wk soldiers navigated 25-30 km per night in difficult terrain carrying ~35 kg of equipment. All assessments (blood draws and diffusion tensor imaging to assess muscle integrity) were conducted before and ~12 h after final supplement consumption. Analysis of covariance was used to analyze all blood and muscle measures. Significant attenuations were noted in IL-1β, IL-2, IL-6, CX3CL1, and TNF-α for both CaHMBBC30 and CaHMBPL compared with CTL. Plasma IL-10 concentrations were significantly attenuated for CaHMBBC30 compared with CTL only. A significant decrease in apparent diffusion coefficients was also observed for CaHMBBC30 compared with CaHMBPL. Results provide further evidence that HMB supplementation may attenuate the inflammatory response to intense training and that the combination of the probiotic BC30 with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training. NEW & NOTEWORTHY β-Hydroxy-β-methylbutyrate (HMB) in its free acid form was reported to attenuate inflammation and maintain muscle integrity during military training. However, this formulation was difficult to maintain in the field. In this investigation, soldiers ingested HMB calcium (CaHMB) with Bacillus coagulans (BC30) or CaHMB alone during 40 days of training. Results indicated that CaHMB attenuated the inflammatory response and that BC30 combined with

Recovery of Acrylic Acid Using Calcium Peroxide Nanoparticles: Synthesis, Characterisation, Batch Study, Equilibrium, and Kinetics

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B. S. De

2018-03-01

Full Text Available Recovery of acrylic acid from aqueous solution using low-cost CaO2 nanoparticles was investigated. CaO2 nanoparticles were synthesized by co-precipitation technique and characterised using XRD and FTIR. A mechanism was proposed for adsorption of acrylic acid onto CaO2 nanoparticles based on FTIR analysis. Acrylic acid recovery is highly dependent on contact time, CaO2 nanoparticle dosage, initial acrylic concentration, and temperature. Langmuir, Freundlich, Dubinin-Radushkevich, Tempkin, Hill, Redlich-Peterson, Sips and Toth isotherms were used and well represented by Redlich-Peterson isotherm (R2 = 0.9998 as compared to other isotherms. Kinetic studies revealed pseudo-second-order kinetics (k2 = 1.962·10–4 g mg–1 min–1 for adsorption of acrylic acid onto CaO2 nanoparticles. CaO2 nanoparticles exhibited high acrylic acid recovery over varied concentration ranges. The acrylic acid can be regenerated by desorption from the surface of adsorbent and utilised for numerous applications. The presented results may be useful for the design of adsorption system using nanoparticles, which can be extended to other systems.

Stanniocalcin 2 Regulates Non-capacitative Ca2+ Entry and Aggregation in Mouse Platelets

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Esther López

2018-03-01

Full Text Available Stanniocalcin 2 (STC2 is a fish protein that controls body Ca2+ and phosphate metabolism. STC2 has also been described in mammals, and as platelet function highly depends on both extracellular and intracellular Ca2+, we have explored its expression and function in these cells. STC2−/− mice exhibit shorter tail bleeding time than WT mice. Platelets from STC2-deficient mice showed enhanced aggregation, as well as enhanced Ca2+ mobilization in response to the physiological agonist thrombin (Thr and the diacylglycerol analog, OAG, a selective activator of the non-capacitative Ca2+ entry channels. Interestingly, platelets from STC2−/− mice exhibit attenuated interaction between STIM1 and Orai1 in response to Thr, thus suggesting that STC2 is required for Thr-evoked STIM1-Orai1 interaction and the subsequent store-operated Ca2+ entry (SOCE. We have further assessed possible changes in the expression of the most relevant channels involved in non-capacitative Ca2+ entry in platelets. Then, protein expression of Orai3, TRPC3 and TRPC6 were evaluated by Western blotting, and the results revealed that while the expression of Orai3 was enhanced in the STC2-deficient mice, others like TRPC3 and TRPC6 remains almost unaltered. Summarizing, our results provide for the first time evidence for a role of STC2 in platelet physiology through the regulation of agonist-induced Ca2+ entry, which might be mediated by the regulation of Orai3 channel expression.

Ca{sup 2+} influx and ATP release mediated by mechanical stretch in human lung fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Murata, Naohiko [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ito, Satoru, E-mail: itori@med.nagoya-u.ac.jp [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Furuya, Kishio [Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Takahara, Norihiro [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Naruse, Keiji [Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Okayama 700-8558 (Japan); Aso, Hiromichi; Kondo, Masashi [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Sokabe, Masahiro [Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Hasegawa, Yoshinori [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan)

2014-10-10

Highlights: • Uniaxial stretching activates Ca{sup 2+} signaling in human lung fibroblasts. • Stretch-induced intracellular Ca{sup 2+} elevation is mainly via Ca{sup 2+} influx. • Mechanical strain enhances ATP release from fibroblasts. • Stretch-induced Ca{sup 2+} influx is not mediated by released ATP or actin cytoskeleton. - Abstract: One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10–30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca{sup 2+}]{sub i} transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca{sup 2+}]{sub i}. The stretch-induced [Ca{sup 2+}]{sub i} elevation was attenuated in Ca{sup 2+}-free solution. In contrast, the increase of [Ca{sup 2+}]{sub i} by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd{sup 3+}, ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca{sup 2+}]{sub i} elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca{sup 2+} influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP.

Micronutrients (Ca, Fe, K, Na, Se, Zn) assessment and fatty acids profile in fish most consumed by Cubatao community, Sao Paulo, Brazil

International Nuclear Information System (INIS)

Curcho, Michel R.S.M.; Farias, Luciana A.; Fonseca, Barbara C.; Nascimento, Soraia M.; Favaro, Deborah I.T.; Kuniyoshi, Leonardo S.; Braga, Elisabete S.; Baggio, Sueli R.

2009-01-01

Fish are a healthy source of protein, providing omega-3 (n-3) the fatty acids that reduce cholesterol levels, and reduce the incidence of heart disease and stroke. The purpose of the present study was to assess the concentration of some micronutrients and also fatty acids profile in muscles of the most consumed fish species from Cubatao coastal region. Cubatao carnivorous fish species analyzed were: Micropogonias furnieri (Corvina), Macrodon ancylodon (Pescada) and Menticirrhus americanus (Perna-de-Moca), and planktivorous species Sardinella braziliensis (Sardinha) and Mugil liza (Tainha). Micronutrients (Ca, Fe, K, Na, Se, Zn) in fish muscle were determined by means of instrumental neutron activation analysis (INAA). Fatty acids profiles in these muscle fish samples were performed by gas chromatography. Total saturated fatty acids ranged from 23.0% in M. ancylodon to 50.0% in M. liza. Total polyunsaturated fatty acid contents varied from 10.9% in M. liza 38.4% in S. braziliensis. These fish species presented different proportions of polyunsaturated fatty acids of the n-3 family and of the n-6 family. Regarding the n-6 family, M. furnieri showed the highest values (13.3%) and M. ancylodon, the lowest ones (4.1%). On the other hand, for the n-3 family, S. braziliensis presented the highest value (31.8%) and M. liza the lowest one (5.7%). Regarding micronutrients content, great concentration variations between individual of the same species and between different species were observed. From the nutritional point of view S. braziliensis is the best choice showing highest content of fatty acid n-3 family and micronutrient concentrations. (author)

Micronutrients (Ca, Fe, K, Na, Se, Zn) assessment and fatty acids profile in fish most consumed by Cubatao community, Sao Paulo, Brazil

Energy Technology Data Exchange (ETDEWEB)

Curcho, Michel R.S.M.; Farias, Luciana A.; Fonseca, Barbara C.; Nascimento, Soraia M.; Favaro, Deborah I.T., E-mail: mrcurcho@ipen.b, E-mail: defavaro@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Kuniyoshi, Leonardo S.; Braga, Elisabete S., E-mail: edsbraga@usp.b [Universidade de Sao Paulo (USP), SP (Brazil). Inst. Oceanografico. Lab. de Nutrientes, Micronutrientes e Tracos nos Oceanos (LABNUT); Baggio, Sueli R., E-mail: sueli@ital.sp.gov.b [Instituto de Tecnologia de Alimentos (ITAL), Campinas, SP (Brazil). Centro de Ciencia e Qualidade de Alimentos

2009-07-01

Fish are a healthy source of protein, providing omega-3 (n-3) the fatty acids that reduce cholesterol levels, and reduce the incidence of heart disease and stroke. The purpose of the present study was to assess the concentration of some micronutrients and also fatty acids profile in muscles of the most consumed fish species from Cubatao coastal region. Cubatao carnivorous fish species analyzed were: Micropogonias furnieri (Corvina), Macrodon ancylodon (Pescada) and Menticirrhus americanus (Perna-de-Moca), and planktivorous species Sardinella braziliensis (Sardinha) and Mugil liza (Tainha). Micronutrients (Ca, Fe, K, Na, Se, Zn) in fish muscle were determined by means of instrumental neutron activation analysis (INAA). Fatty acids profiles in these muscle fish samples were performed by gas chromatography. Total saturated fatty acids ranged from 23.0% in M. ancylodon to 50.0% in M. liza. Total polyunsaturated fatty acid contents varied from 10.9% in M. liza 38.4% in S. braziliensis. These fish species presented different proportions of polyunsaturated fatty acids of the n-3 family and of the n-6 family. Regarding the n-6 family, M. furnieri showed the highest values (13.3%) and M. ancylodon, the lowest ones (4.1%). On the other hand, for the n-3 family, S. braziliensis presented the highest value (31.8%) and M. liza the lowest one (5.7%). Regarding micronutrients content, great concentration variations between individual of the same species and between different species were observed. From the nutritional point of view S. braziliensis is the best choice showing highest content of fatty acid n-3 family and micronutrient concentrations. (author)

Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia.

Science.gov (United States)

Blair, Hannah A; Dhillon, Sohita

2014-10-01

Omega-3 carboxylic acids (Epanova) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥ 500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.

12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

Energy Technology Data Exchange (ETDEWEB)

Taki-Nakano, Nozomi [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Kotera, Jun [Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Ohta, Hiroyuki, E-mail: ohta.h.ab@m.titech.ac.jp [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan)

2016-05-13

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

International Nuclear Information System (INIS)

Taki-Nakano, Nozomi; Kotera, Jun; Ohta, Hiroyuki

2016-01-01

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

Hierarchical CaCO3 chromatography: a stationary phase based on biominerals.

Science.gov (United States)

Sato, Kosuke; Oaki, Yuya; Takahashi, Daisuke; Toshima, Kazunobu; Imai, Hiroaki

2015-03-23

In biomineralization, acidic macromolecules play important roles for the growth control of crystals through a specific interaction. Inspired by this interaction, we report on an application of the hierarchical structures in CaCO3 biominerals to a stationary phase of chromatography. The separation and purification of acidic small organic molecules are achieved by thin-layer chromatography and flash chromatography using the powder of biominerals as the stationary phase. The unit nanocrystals and their oriented assembly, the hierarchical structure, are suitable for the adsorption site of the target organic molecules and the flow path of the elution solvents, respectively. The separation mode is ascribed to the specific adsorption of the acidic molecules on the crystal face and the coordination of the functional groups to the calcium ions. The results imply that a new family of stationary phase of chromatography can be developed by the fine tuning of hierarchical structures in CaCO3 materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

Science.gov (United States)

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Sequential separation of cs, ca and ba for 90sr assessment

International Nuclear Information System (INIS)

Dianu, M.; Bucur, C.

2015-01-01

A two-steps chemical treatment technique for strontium assessment from aqueous samples is described in this paper. The method was applied to simulated samples containing stable elements of Ni, Cs, Ca, Ba, Mn, Fe, Co and Eu. The transition elements (Ni, Mn, Fe, Co, Eu) were precipitated as hydroxides, followed by alkaline-earth metals separation (Ca, Ba) as carbonates. Finally, the Sr was purified by extraction chromatography using Triskem International Sr resin. The strength of Sr sorption in nitric acid increases with increasing acid concentration, and the optimal bonding strength is achieved in 8 M HNO3. The combination of successive precipitations with extraction chromatography for complete removal of other interferences from Sr matrix leads to good recovery and decontamination factor values. (authors)

Late calcium EDTA rescues hippocampal CA1 neurons from global ischemia-induced death.

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Calderone, Agata; Jover, Teresa; Mashiko, Toshihiro; Noh, Kyung-min; Tanaka, Hidenobu; Bennett, Michael V L; Zukin, R Suzanne

2004-11-03

Transient global ischemia induces a delayed rise in intracellular Zn2+, which may be mediated via glutamate receptor 2 (GluR2)-lacking AMPA receptors (AMPARs), and selective, delayed death of hippocampal CA1 neurons. The molecular mechanisms underlying Zn2+ toxicity in vivo are not well delineated. Here we show the striking finding that intraventricular injection of the high-affinity Zn2+ chelator calcium EDTA (CaEDTA) at 30 min before ischemia (early CaEDTA) or at 48-60 hr (late CaEDTA), but not 3-6 hr, after ischemia, afforded robust protection of CA1 neurons in approximately 50% (late CaEDTA) to 75% (early CaEDTA) of animals. We also show that Zn2+ acts via temporally distinct mechanisms to promote neuronal death. Early CaEDTA attenuated ischemia-induced GluR2 mRNA and protein downregulation (and, by inference, formation of Zn2+-permeable AMPARs), the delayed rise in Zn2+, and neuronal death. These findings suggest that Zn2+ acts at step(s) upstream from GluR2 gene downregulation and implicate Zn2+ in transcriptional regulation and/or GluR2 mRNA stability. Early CaEDTA also blocked mitochondrial release of cytochrome c and Smac/DIABLO (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein-binding protein with low pI), caspase-3 activity (but not procaspase-3 cleavage), p75NTR induction, and DNA fragmentation. These findings indicate that CaEDTA preserves the functional integrity of the mitochondrial outer membrane and arrests the caspase death cascade. Late injection of CaEDTA at a time when GluR2 is downregulated and caspase is activated inhibited the delayed rise in Zn2+, p75NTR induction, DNA fragmentation, and cell death. The finding of neuroprotection by late CaEDTA administration has striking implications for intervention in the delayed neuronal death associated with global ischemia.

Association mapping of main tomato fruit sugars and organic acids

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Jiantao Zhao

2016-08-01

Full Text Available Association mapping has been widely used to map the significant associated loci responsible for natural variation in complex traits and are valuable for crop improvement. Sugars and organic acids are the most important metabolites in tomato fruits. We used a collection of 174 tomato accessions composed of S. lycopersicum (123 accessions and S. lycopersicum var cerasiforme (51 accessions to detect significantly associated loci controlling the variation of main sugars and organic acids. The accessions were genotyped with 182 SSRs spreading over the tomato genome. Association mapping was conducted on the main sugars and organic acids detected by gas chromatography-mass spectrometer (GC-MS over two years using the mixed linear model (MLM. We detected a total of 58 significantly associated loci (P<0.001 for the 17 sugars and organic acids, including fructose, glucose, sucrose, citric acid, malic acid. These results not only co-localized with several reported QTLs, including fru9.1/PV, suc9.1/PV, ca2.1/HS, ca3.1/PV, ca4.1/PV and ca8.1/PV, but also provided a list of candidate significantly associated loci to be functionally validated. These significantly associated loci could be used for deciphering the genetic architecture of tomato fruit sugars and organic acids and for tomato quality breeding.

Attenuation of hypoxic current by intracellular applications of ATP regenerating agents in hippocampal CA1 neurons of rat brain slices.

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Chung, I; Zhang, Y; Eubanks, J H; Zhang, L

1998-10-01

Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell recording technique. Hypoxic episodes were induced by perfusing slices with an artificial cerebrospinal fluid aerated with 5% CO2/95% N2 rather than 5% CO2/95% O2, for about 3 min. The hypoxic current was consistently and reproducibly induced in CA1 neurons dialysed with an ATP-free patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at -78 +/- 2.5 mV, with a linear I-V relation in the range of -100 to -40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution, including MgATP alone, MgATP + phosphocreatine + creatine kinase, or MgATP + creatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with those observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP + creatine was the most effective at decreasing the hypoxic outward currents. We suggest that the hypoxic hyperpolarization is closely related to energy metabolism in individual CA1 neurons, and that the energy supply provided by phosphocreatine metabolism may play a critical role during transient metabolic stress.

Characterization of the differences in the cyclopiazonic acid binding mode to mammalian and P. Falciparum Ca2+ pumps: a computational study.

KAUST Repository

Di Marino, Daniele

2015-03-01

Despite the investments in malaria research, an effective vaccine has not yet been developed and the causative parasites are becoming increasingly resistant to most of the available drugs. PfATP6, the sarco/endoplasmic reticulum Ca2+ pump (SERCA) of P. falciparum, has been recently genetically validated as a potential antimalarial target and cyclopiazonic acid (CPA) has been found to be a potent inhibitor of SERCAs in several organisms, including P. falciparum. In position 263, PfATP6 displays a leucine residue, whilst the corresponding position in the mammalian SERCA is occupied by a glutamic acid. The PfATP6 L263E mutation has been studied in relation to the artemisinin inhibitory effect on P. falciparum and recent studies have provided evidence that the parasite with this mutation is more susceptible to CPA. Here, we characterized, for the first time, the interaction of CPA with PfATP6 and its mammalian counterpart to understand similarities and differences in the mode of binding of the inhibitor to the two Ca2+ pumps. We found that, even though CPA does not directly interact with the residue in position 263, the presence of a hydrophobic residue in this position in PfATP6 rather than a negatively charged one, as in the mammalian SERCA, entails a conformational arrangement of the binding pocket which, in turn, determines a relaxation of CPA leading to a different binding mode of the compound. Our findings highlight differences between the plasmodial and human SERCA CPA-binding pockets that may be exploited to design CPA derivatives more selective toward PfATP6.

Characterization of the differences in the cyclopiazonic acid binding mode to mammalian and P. Falciparum Ca2+ pumps: a computational study.

KAUST Repository

Di Marino, Daniele; D'Annessa, Ilda; Coletta, Andrea; Via, Allegra; Tramontano, Anna

2015-01-01

Despite the investments in malaria research, an effective vaccine has not yet been developed and the causative parasites are becoming increasingly resistant to most of the available drugs. PfATP6, the sarco/endoplasmic reticulum Ca2+ pump (SERCA) of P. falciparum, has been recently genetically validated as a potential antimalarial target and cyclopiazonic acid (CPA) has been found to be a potent inhibitor of SERCAs in several organisms, including P. falciparum. In position 263, PfATP6 displays a leucine residue, whilst the corresponding position in the mammalian SERCA is occupied by a glutamic acid. The PfATP6 L263E mutation has been studied in relation to the artemisinin inhibitory effect on P. falciparum and recent studies have provided evidence that the parasite with this mutation is more susceptible to CPA. Here, we characterized, for the first time, the interaction of CPA with PfATP6 and its mammalian counterpart to understand similarities and differences in the mode of binding of the inhibitor to the two Ca2+ pumps. We found that, even though CPA does not directly interact with the residue in position 263, the presence of a hydrophobic residue in this position in PfATP6 rather than a negatively charged one, as in the mammalian SERCA, entails a conformational arrangement of the binding pocket which, in turn, determines a relaxation of CPA leading to a different binding mode of the compound. Our findings highlight differences between the plasmodial and human SERCA CPA-binding pockets that may be exploited to design CPA derivatives more selective toward PfATP6.

Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

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Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

2014-12-01

Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

Tranexamic Acid Attenuates The Loss of Lung Barrier Function in a Rat Model of Polytrauma And Hemorrhage With Resuscitation.

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Wu, Xiaowu; Dubick, Michael A; Schwacha, Martin G; Cap, Andrew P; Darlington, Daniel N

2017-04-01

Severe trauma, hemorrhage, and resuscitation can lead to a trauma-related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage, and resuscitation. Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle, and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10 mg/kg in 0.2 mL). Polytrauma, hemorrhage, and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase, and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.

The Mixture of Salvianolic Acids from Salvia miltiorrhiza and Total Flavonoids from Anemarrhena asphodeloides Attenuate Sulfur Mustard-Induced Injury

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Jianzhong Li

2015-10-01

Full Text Available Sulfur mustard (SM is a vesicating chemical warfare agent used in numerous military conflicts and remains a potential chemical threat to the present day. Exposure to SM causes the depletion of cellular antioxidant thiols, mainly glutathione (GSH, which may lead to a series of SM-associated toxic responses. MSTF is the mixture of salvianolic acids (SA of Salvia miltiorrhiza and total flavonoids (TFA of Anemarrhena asphodeloides. SA is the main water-soluble phenolic compound in Salvia miltiorrhiza. TFA mainly includes mangiferin, isomangiferin and neomangiferin. SA and TFA possess diverse activities, including antioxidant and anti-inflammation activities. In this study, we mainly investigated the therapeutic effects of MSTF on SM toxicity in Sprague Dawley rats. Treatment with MSTF 1 h after subcutaneous injection with 3.5 mg/kg (equivalent to 0.7 LD50 SM significantly increased the survival levels of rats and attenuated the SM-induced morphological changes in the testis, small intestine and liver tissues. Treatment with MSTF at doses of 60 and 120 mg/kg caused a significant (p < 0.05 reversal in SM-induced GSH depletion. Gene expression profiles revealed that treatment with MSTF had a dramatic effect on gene expression changes caused by SM. Treatment with MSTF prevented SM-induced differential expression of 93.8% (973 genes of 1037 genes. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 36 pathways, such as the MAPK signaling pathway, pathways in cancer, antigen processing and presentation. These data suggest that MSTF attenuates SM-induced injury by increasing GSH and targeting multiple pathways, including the MAPK signaling pathway, as well as antigen processing and presentation. These results suggest that MSTF has the potential to be used as a potential therapeutic agent against SM injuries.

Effects of 45Ca on murine skeletal muscle. 3

International Nuclear Information System (INIS)

Malhotra, R.K.; Asotra, K.; Katoch, S.S.; Krishan, K.

1983-01-01

Swiss albino mice were injected intraperitoneally with 3.7x10 4 Bq and 7.4x10 4 Bq 45 Ca/g body weight. Mice of both dose groups were autopsied on days 1, 3, 5, 7, 14 and 28 and activities of alanine aminotransferase and aspartate aminotransferase bioassayed in diaphragm and gastrocnemius in 45 Ca-treated and normal mice. Alanine aminotransferase activity in the two muscles increased in response to 45 Ca administration suggesting a stepped up utilization of alanine in glucose generation. Aspartate aminotransferase levels, on the other hand, diminished in both the 45 Ca-treated muscles and are maintained at low values throughout the 28 day period of study. The results suggest an innate ability of skeletal muscle to selectively utilize either of the two glucogenic amino acids during radiation stress. The data are discussed in light of previous findings on glycogen accumulation in irradiated skeletal muscle. (author)

Sulfated caffeic acid dehydropolymer attenuates elastase and cigarette smoke extract-induced emphysema in rats: sustained activity and a need of pulmonary delivery.

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Saluja, Bhawana; Li, Hua; Desai, Umesh R; Voelkel, Norbert F; Sakagami, Masahiro

2014-08-01

Although emphysema destroys alveolar structures progressively and causes death eventually, no drug has been discovered to prevent, intervene, and/or resolve this life-threatening disease. We recently reported that sulfated caffeic acid dehydropolymer CDSO3 is a novel potent triple-action inhibitor of elastolysis, oxidation, and inflammation in vitro, and therefore, a potential anti-emphysema agent. However, the in vivo therapeutic potency, duration and mode of actions, and effective route remain to be demonstrated. Emphysema was induced in rats with human sputum elastase (HSE) combined with cigarette smoke extract (CSE). CDSO3 at 5, 30, or 100 μg/kg was dosed to the lung or injected subcutaneously at 2, 6, or 24 h before or 1 or 24 h or 1 week after the HSE/CSE instillation. At 1 h or 48 h or on day 21-22 or day 28, lungs were examined for airway-to-blood injurious barrier damage; their elastolytic, oxidative, and inflammatory activities; lung luminal leukocytes infiltration; functional treadmill exercise endurance; and/or morphological airspace enlargement. CDSO3, when dosed to the lung at 30 or 100 μg/kg, but not via systemic subcutaneous injection, significantly (43-93 %) attenuated HSE/CSE-induced (1) barrier damage measured by luminal hemorrhage and protein leak; (2) elastolytic, oxidative, and inflammatory activities measured with elastase, reduced glutathione, and TNFα levels, respectively; (3) luminal neutrophil infiltration and tissue myeloperoxidase activity; (4) functional impairment of exercise endurance; and (5) airspace enlargement, in both preventive and interventional dosing protocols. Notably, the effects were shown to last for 24 h at the greater 100-μg/kg dose, and the 1-week-delayed administration was also capable of attenuating the development of emphysema. CDSO3 is a novel, potent, long-acting, nonpeptidic macromolecule that inhibits HSE/CSE-induced elastolysis, oxidation, and inflammation in the lung and thereby attenuates the development

In situ biosynthesis of bacterial nanocellulose-CaCO{sub 3} hybrid bionanocomposite: One-step process

Energy Technology Data Exchange (ETDEWEB)

Mohammadkazemi, Faranak, E-mail: f_mkazemi@sbu.ac.ir [Department of Cellulose and Paper Technology, Faculty of New Technologies Engineering, Shahid Beheshti University, Science and Research Campus, Zirab, Savadkooh, Mazandaran (Iran, Islamic Republic of); Faria, Marisa; Cordeiro, Nereida [Faculty of Exact Science and Engineering, University of Madeira, Funchal (Portugal)

2016-08-01

In this work, a simple and green route to the synthesis of the bacterial nanocellulose-calcium carbonate (BNC/CaCO{sub 3}) hybrid bionanocomposites using one-step in situ biosynthesis was studied. The CaCO{sub 3} was incorporated in the bacterial nanocellulose structure during the cellulose biosynthesis by Gluconacetobacter xylinus PTCC 1734 bacteria. Hestrin-Schramm (HS) and Zhou (Z) culture media were used to the hybrid bionanocomposites production and the effect of ethanol addition was investigated. Attenuated total reflection Fourier transform infrared spectroscopy, field emission scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, inverse gas chromatography and thermogravimetric analysis were used to characterize the samples. The experimental results demonstrated that the ethanol and culture medium play an important role in the BNC/CaCO{sub 3} hybrid bionanocomposites production, structure and properties. The BNC/CaCO{sub 3} biosynthesized in Z culture medium revealed higher O/C ratio and amphoteric surface character, which justify the highest CaCO{sub 3} content incorporation. The CaCO{sub 3} was incorporated into the cellulosic matrix decreasing the bacterial nanocellulose crystallinity. This work reveals the high potential of in situ biosynthesis of BNC/CaCO{sub 3} hybrid bionanocomposites and opens a new way to the high value-added applications of bacterial nanocellulose. - Graphical Abstract: Display Omitted - Highlights: • BNC/CaCO{sub 3} hybrid bionanocomposites were produced using in situ biosynthesis process. • Ethanol and culture medium play an important role in the production and properties. • Z-BNC/CaCO{sub 3} bionanocomposites revealed higher O/C ratio and amphoteric surface character. • CaCO{sub 3} incorporated into the BNC decreased crystallinity.

Ultrasonic investigations on polonides of Ba, Ca, and Pb

Energy Technology Data Exchange (ETDEWEB)

Singh, Devraj; Bhalla, Vyoma [Amity School of Engineering and Technology, New Delhi (India). Dept. of Applied Physics; Bala, Jyoti [Amity School of Engineering and Technology, New Delhi (India). Dept. of Applied Physics; Guru Gobind Singh Indraprastha Univ., New Delhi (India). USICT; Wadhwa, Shikha [Amity Univ., Noida (India). Amity Inst. of Nanotechnology

2017-07-01

The temperature-dependent mechanical and ultrasonic properties of barium, calcium, and lead polonides (BaPo, CaPo, and PbPo) were investigated in the temperature range 100-300 K. The second- and third-order elastic constants (SOECs and TOECs) were computed using Coulomb and Born-Mayer potential and these in turn have been used to estimate other secondary elastic properties such as strength, anisotropy, microhardness, etc. The theoretical approach followed the prediction that BaPo, CaPo, and PbPo are brittle in nature. PbPo is found to be the hardest amongst the chosen compounds. Further the SOECs and TOECs are applied to determine ultrasonic velocities, Debye temperature, and acoustic coupling constants along left angle 100 right angle, left angle 110 right angle, and left angle 111 right angle orientations at room temperature. Additionally thermal conductivity has been computed using Morelli and Slack's approach along different crystallographic directions at room temperature. Finally ultrasonic attenuation due to phonon-phonon interaction and thermoelastic relaxation mechanisms has been computed for BaPo, CaPo, and PbPo. The behaviour of these compounds is similar to that of semi-metals with thermal relaxation time of the order 10{sup -11} s. The present computation study is reasonably in agreement with the available theoretical data for the similar type of materials.

The Modulatory Effect of Ellagic Acid and Rosmarinic Acid on Ultraviolet-B-Induced Cytokine/Chemokine Gene Expression in Skin Keratinocyte (HaCaT Cells

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Serena Lembo

2014-01-01

Full Text Available Ultraviolet radiation (UV induces an increase in multiple cutaneous inflammatory mediators. Ellagic acid (EA and rosmarinic acid (RA are natural anti-inflammatory and immunomodulatory compounds found in many plants, fruits, and nuts. We assessed the ability of EA and RA to modulate IL-1β, IL-6, IL-8, IL-10, MCP-1, and TNF-α gene expression in HaCaT cells after UVB irradiation. Cells were treated with UVB (100 mJ/cm2 and simultaneously with EA (5 μM in 0.1% DMSO or RA (2.7 μM in 0.5% DMSO. Moreover, these substances were added to the UVB-irradiated cells 1 h or 6 h before harvesting, depending on the established UVB-induced cytokine expression peak. Cytokine gene expression was examined using quantitative real time polymerase chain reaction. RA produced a significant reduction in UVB-induced expression of IL-6, IL-8, MCP-1, and TNF-α when applied at the same time as irradiation. EA showed milder effects compared with RA, except for TNF-α. Both substances decreased IL-6 expression, also when applied 5 h after irradiation, and always produced a significant increase in UVB-induced IL-10 expression. Our findings suggest that EA and RA are able to prevent and/or limit the UVB-induced inflammatory cascade, through a reduction in proinflammatory mediators and the enhancement of IL-10, with its protective function.

Peripheral δ-opioid receptors attenuate the exercise pressor reflex.

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Leal, Anna K; Yamauchi, Katsuya; Kim, Joyce; Ruiz-Velasco, Victor; Kaufman, Marc P

2013-10-15

In rats with ligated femoral arteries, the exercise pressor reflex is exaggerated, an effect that is attenuated by stimulation of peripheral μ-opioid receptors on group IV metabosensitive afferents. In contrast, δ-opioid receptors are expressed mostly on group III mechanosensitive afferents, a finding that prompted us to determine whether stimulation of these opioid receptors could also attenuate the exaggerated exercise pressor reflex in "ligated" rats. We found femoral arterial injection of [D-Pen2,D-Pen5]enkephalin (DPDPE; 1.0 μg), a δ-opioid agonist, significantly attenuated the pressor and cardioaccelerator components of the exercise pressor reflex evoked by hindlimb muscle contraction in both rats with ligated and patent femoral arteries. DPDPE significantly decreased the pressor responses to muscle mechanoreflex activation, evoked by tendon stretch, in ligated rats only. DPDPE (1.0 μg) had no effect in either group on the pressor and cardioaccelerator responses to capsaicin (0.2 μg), which primarily stimulates group IV afferents. DPDPE (1.0 μg) had no effect on the pressor and cardioaccelerator responses to lactic acid (24 mM), which stimulates group III and IV afferents, in rats with patent femoral arteries but significantly decreased the pressor response in ligated rats. Western blots revealed the amount of protein comprising the δ-opioid receptor was greater in dorsal root ganglia innervating hindlimbs with ligated femoral arteries than in dorsal root ganglia innervating hindlimbs with patent femoral arteries. Our findings support the hypothesis that stimulation of δ-opioid receptors on group III afferents attenuated the exercise pressor reflex.

Comparison of the antioxidant effects of carnosic acid and synthetic antioxidants on tara seed oil.

Science.gov (United States)

Li, Zhan-Jun; Yang, Feng-Jian; Yang, Lei; Zu, Yuan-Gang

2018-04-04

In the present study, tara seed oil was obtained by supercritical fluid extraction and used to investigate the antioxidant strength of carnosic acid (CA) compared with conventional synthetic antioxidants. The antioxidants were added to the tara seed oil at 0.2 mg of antioxidant per gram of oil. The samples were then submitted to at 60 °C 15 days for an accelerated oxidation process, with samples taken regularly for analysis. After oxidation, the samples were analyzed to determine the peroxide value, thiobarbituric acid reactive substances, conjugated diene content, and free fatty acid content. CA was investigated at three purity levels (CA20, CA60, CA99), and compared with three synthetic antioxidants (butylatedhydroxyanisole, butylatedhydroxytoluene, and tert-butylhydroquinone). The oxidation indicators showed that CA was a strong antioxidant compared to the synthetic antioxidants. The antioxidant activities decreased in the order: tert-butylhydroquinone > CA99 > CA60 > CA20 > butylatedhydroxyanisole > butylatedhydroxytoluene. These results show that CA could be used to replace synthetic antioxidants in oil products, and should be safer for human consumption and the environment.

Longitudinal acoustic properties of poly(lactic acid) and poly(lactic-co-glycolic acid)

International Nuclear Information System (INIS)

Parker, N G; Povey, M J W; Mather, M L; Morgan, S P

2010-01-01

Acoustics offers rich possibilities for characterizing and monitoring the biopolymer structures being employed in the field of biomedical engineering. Here we explore the rudimentary acoustic properties of two common biodegradable polymers: poly(lactic acid) and poly(lactic-co-glycolic acid). A pulse-echo technique is developed to reveal the bulk speed of sound, acoustic impedance and acoustic attenuation of small samples of the polymer across a pertinent temperature range of 0-70 0 C. The glass transition appears markedly as both a discontinuity in the first derivative of the speed of sound and a sharp increase in the acoustic attenuation. We further extend our analysis to consider the role of ethanol, whose presence is observed to dramatically modify the acoustic properties and reduce the glass transition temperature of the polymers. Our results highlight the sensitivity of acoustic properties to a range of bulk properties, including visco-elasticity, molecular weight, co-polymer ratio, crystallinity and the presence of plasticizers.

Periodic DFT study of acidic trace atmospheric gas molecule adsorption on Ca- and Fe-doped MgO(001) surface basic sites.

Science.gov (United States)

Baltrusaitis, Jonas; Hatch, Courtney; Orlando, Roberto

2012-08-02

The electronic properties of undoped and Ca- or Fe-doped MgO(001) surfaces, as well as their propensity toward atmospheric acidic gas (CO2, SO2, and NO2) uptake was investigated with an emphasis on gas adsorption on the basic MgO oxygen surface sites, O(surf), using periodic density functional theory (DFT) calculations. Adsorption energy calculations show that MgO doping will provide stronger interactions of the adsorbate with the O(surf) sites than the undoped MgO for a given adsorbate molecule. Charge transfer from the iron atom in Fe-doped MgO(001) to NO2 was shown to increase the binding interaction between adsorbate by an order of magnitude, when compared to that of undoped and Ca-doped MgO(001) surfaces. Secondary binding interactions of adsorbate oxygen atoms were observed with surface magnesium sites at distances close to those of the Mg-O bond within the crystal. These interactions may serve as a preliminary step for adsorption and facilitate further adsorbate transformations into other binding configurations. Impacts on global atmospheric chemistry are discussed as these adsorption phenomena can affect atmospheric gas budgets via altered partitioning and retention on mineral aerosol surfaces.

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

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Xubo Chen

2017-08-01

Full Text Available Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKβ and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKβ and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD, declined. These effects were also achieved by activating CaMKKβ/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKβ and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKβ and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease. Keywords: Aging, Hydrogen sulfide, ROS, Mitochondria, PI3K/AKT, CaMKKβ/AMPK

Inhibition of Ca2+-activated Cl− channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea

Science.gov (United States)

Namkung, Wan; Thiagarajah, Jay R.; Phuan, Puay-Wah; Verkman, A. S.

2010-01-01

TMEM16A was found recently to be a calcium-activated Cl− channel (CaCC). CaCCs perform important functions in cell physiology, including regulation of epithelial secretion, cardiac and neuronal excitability, and smooth muscle contraction. CaCC modulators are of potential utility for treatment of hypertension, diarrhea, and cystic fibrosis. Screening of drug and natural product collections identified tannic acid as an inhibitor of TMEM16A, with IC50 ∼ 6 μM and ∼100% inhibition at higher concentrations. Tannic acid inhibited CaCCs in multiple cell types but did not affect CFTR Cl− channels. Structure-activity analysis indicated the requirement of gallic or digallic acid substituents on a macromolecular scaffold (gallotannins), as are present in green tea and red wine. Other polyphenolic components of teas and wines, including epicatechin, catechin, and malvidin-3-glucoside, poorly inhibited CaCCs. Remarkably, a 1000-fold dilution of red wine and 100-fold dilution of green tea inhibited CaCCs by >50%. Tannic acid, red wine, and green tea inhibited arterial smooth muscle contraction and intestinal Cl− secretion. Gallotannins are thus potent CaCC inhibitors whose biological activity provides a potential molecular basis for the cardioprotective and antisecretory benefits of red wine and green tea.—Namkung, W., Thiagarajah, J. R., Phuan, P.-W., Verkman, A. S. Inhibition of Ca2+-activated Cl− channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. PMID:20581223

Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.