The Helicobacter pylori Ferric Uptake Regulator (Fur) is Essential for Growth Under Sodium Chloride Stress

PubMed Central

Gancz, Hanan; Merrell, D. Scott

2011-01-01

Epidemiological data and animal models indicate that Helicobacter pylori and dietary NaCl have a synergistic ill effect on gastric maladies. Here we show that the Ferric Uptake Regulator (Fur), which is a crucial regulatory factor required for H. pylori colonization, is essential for growth in the presence of high NaCl concentrations. Moreover, we demonstrate that the transcriptional response induced by sodium chloride stress exhibits similarities to that seen under iron depletion. PMID:21538253

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle

PubMed Central

Yim, Peter D.; Gallos, George; Perez-zoghbi, Jose F.; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W.

2014-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K+ channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. PMID:24662476

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Aqueous chloride stress corrosion cracking of titanium: A comparison with environmental hydrogen embrittlement

NASA Technical Reports Server (NTRS)

Nelson, H. G.

1973-01-01

The physical characteristics of stress corrosion cracking of titanium in an aqueous chloride environment are compared with those of embrittlement of titanium by a gaseous hydrogen environment in an effort to help contribute to the understanding of the possible role of hydrogen in the complex stress corrosion cracking process. Based on previous studies, the two forms of embrittlement are shown to be similar at low hydrogen pressures (100 N/sqm) but dissimilar at higher hydrogen pressures. In an effort to quantify this comparison, tests were conducted in an aqueous chloride solution using the same material and test techniques as had previously been employed in a gaseous hydrogen environment. The results of these tests strongly support models based on hydrogen as the embrittling species in an aqueous chloride environment. Further, it is shown that if hydrogen is the causal species, the effective hydrogen fugacity at the surface of titanium exposed to an aqueous chloride environment is equivalent to a molecular hydrogen pressure of approximately 10 N/sqm.

Temperature-induced lipocalin (TIL) is translocated under salt stress and protects chloroplasts from ion toxicity.

PubMed

Abo-Ogiala, Atef; Carsjens, Caroline; Diekmann, Heike; Fayyaz, Payam; Herrfurth, Cornelia; Feussner, Ivo; Polle, Andrea

2014-02-15

Temperature-induced lipocalins (TIL) have been invoked in the defense from heat, cold and oxidative stress. Here we document a function of TIL for basal protection from salinity stress. Heterologous expression of TIL from the salt resistant poplar Populus euphratica did not rescue growth but prevented chlorophyll b destruction in salt-exposed Arabidopsis thaliana. The protein was localized to the plasma membrane but was re-translocated to the symplast under salt stress. The A. thaliana knock out and knock down lines Attil1-1 and Attil1-2 showed stronger stress symptoms and stronger chlorophyll b degradation than the wildtype (WT) under excess salinity. They accumulated more chloride and sodium in chloroplasts than the WT. Chloroplast chloride accumulation was found even in the absence of salt stress. Since lipocalins are known to bind regulatory fatty acids of channel proteins as well as iron, we suggest that the salt-induced trafficking of TIL may be required for protection of chloroplasts by affecting ion homeostasis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Aqueous chloride stress corrosion cracking of titanium - A comparison with environmental hydrogen embrittlement

NASA Technical Reports Server (NTRS)

Nelson, H. G.

1974-01-01

The physical characteristics of stress corrosion cracking of titanium in an aqueous chloride environment are compared with those of embrittlement of titanium by a gaseous hydrogen environment in an effort to help contribute to the understanding of the possible role of hydrogen in the complex stress corrosion cracking process. Based on previous studies, the two forms of embrittlement are shown to be similar at low hydrogen pressures (100 N/sq m) but dissimilar at higher hydrogen pressures. In an effort to quantify this comparison, tests were conducted in an aqueous chloride solution using the same material and test techniques as had previously been employed in a gaseous hydrogen environment. The results of these tests strongly support models based on hydrogen as the embrittling species in an aqueous chloride environment.

Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

PubMed

Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

1995-08-01

Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yanlong; Department of Medicine, University of Louisville, Louisville, KY; Wang, Chunhong

2012-10-15

Fibroblast growth factor-21 (FGF21) is a potential metabolic regulator with multiple beneficial effects on metabolic diseases. FGF21 is mainly expressed in the liver, but is also found in other tissues including the intestine, which expresses β-klotho abundantly. The intestine is a unique organ that operates in a physiologically hypoxic environment, and is responsible for the fat absorption processes including triglyceride breakdown, re-synthesis and absorption into the portal circulation. In the present study, we investigated the effects of hypoxia and the chemical hypoxia inducer, cobalt chloride (CoCl{sub 2}), on FGF21 expression in Caco-2 cells and the consequence of fat accumulation. Physicalmore » hypoxia (1% oxygen) and CoCl{sub 2} treatment decreased both FGF21 mRNA and secreted protein levels. Gene silence and inhibition of hypoxia-inducible factor-α (HIFα) did not affect the reduction of FGF21 mRNA and protein levels by hypoxia. However, CoCl{sub 2} administration caused a significant increase in oxidative stress. The addition of n-acetylcysteine (NAC) suppressed CoCl{sub 2}-induced reactive oxygen species (ROS) formation and completely negated CoCl{sub 2}-induced FGF21 loss. mRNA stability analysis demonstrated that the CoCl{sub 2} administration caused a remarkable reduction in FGF21 mRNA stability. Furthermore, CoCl{sub 2} increased intracellular triglyceride (TG) accumulation, along with a reduction in mRNA levels of lipid lipase, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), and an increase of sterol regulatory element-binding protein-1c (SREBP1c) and stearoyl-coenzyme A (SCD1). Addition of both NAC and recombinant FGF21 significantly attenuated the CoCl{sub 2}-induced TG accumulation. In conclusion, the decrease of FGF21 in Caco-2 cells by chemical hypoxia is independent of HIFα, but dependent on an oxidative stress-mediated mechanism. The regulation of FGF21 by hypoxia may contribute to intestinal lipid metabolism and

Lead induced stress corrosion cracking of Alloy 690 in high temperature water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, K.K.; Lim, J.K.; Moriya, Shinichi

1995-12-31

Recent investigations of cracked steam generator tubes at nuclear power plants concluded that lead significantly contributed to cracking the Alloy 600 materials. In order to investigate the stress corrosion cracking (SCC) behavior of Alloy 690, slow strain rate tests (SSRT) and anodic polarization measurements were performed. The SSRTs were conducted in a lead-chloride solution (PbCl{sub 2}) and in a chloride but lead free solution (NaCl) at pH of 3 and 4.5 at 288 C. The anodic polarization measurements were carried out at 30 C using the same solutions as in SSRT. The SSRT results showed that Alloy 690 was susceptiblemore » to SCC in both solutions. In the lead chloride solution, cracking had slight dependence on lead concentration and pH. Cracking tend to increase with a higher lead concentration and a lower pH and was mainly intergranular and was to be a few tens to hundreds micrometers in length. In the chloride only solution, cracking was similar to the lead induced SCC. The results of anodic polarization measurement and electron probe micro analysis (EPMA) helped to understand lead induced SCC. Lead was a stronger active corrosive element but had a minor affect on cracking susceptibility of the alloy. While, chloride was quite different from lead effect to SCC. A possible mechanism of lead induced SCC of Alloy 690 was also discussed based on the test results.« less

Synergistic Effect of Quercetin and α-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats.

PubMed

Al-Otaibi, Sooad Saud; Arafah, Maha Mohamad; Sharma, Bechan; Alhomida, Abdullah Salih; Siddiqi, Nikhat Jamal

2018-01-01

. Quercetin and α -lipoic acid complemented each other in protecting the rat brain against oxidative stress induced by aluminium chloride.

Synergistic Effect of Quercetin and α-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats

PubMed Central

Al-Otaibi, Sooad Saud

2018-01-01

normalization of most of the parameters. Conclusions Quercetin and α-lipoic acid complemented each other in protecting the rat brain against oxidative stress induced by aluminium chloride. PMID:29861723

Stress Corrosion Cracking of an Austenitic Stainless Steel in Nitrite-Containing Chloride Solutions

PubMed Central

Singh Raman, R. K.; Siew, Wai Hoong

2014-01-01

This article describes the susceptibility of 316L stainless steel to stress corrosion cracking (SCC) in a nitrite-containing chloride solution. Slow strain rate testing (SSRT) in 30 wt. % MgCl2 solution established SCC susceptibility, as evidenced by post-SSRT fractography. Addition of nitrite to the chloride solution, which is reported to have inhibitive influence on corrosion of stainless steels, was found to increase SCC susceptibility. The susceptibility was also found to increase with nitrite concentration. This behaviour is explained on the basis of the passivation and pitting characteristics of 316L steel in chloride solution. PMID:28788276

Hepatoprotective effect of manganese chloride against CCl4-induced liver injury in rats.

PubMed

Eidi, Akram; Mortazavi, Pejman; Behzadi, Khodabakhsh; Rohani, Ali Haeri; Safi, Shahabeddin

2013-11-01

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl4)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl4-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl4 increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl4 intoxication alone. Thus, the histopathological studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl4-induced oxidative liver damage.

Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions.

PubMed

Rabin, B M; Hunt, W A

1983-04-01

A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.

Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

NASA Technical Reports Server (NTRS)

Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

2002-01-01

Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

Dacomitinib-induced diarrhea: Targeting chloride secretion with crofelemer.

PubMed

Van Sebille, Ysabella Z A; Gibson, Rachel J; Wardill, Hannah R; Ball, Imogen A; Keefe, Dorothy M K; Bowen, Joanne M

2018-01-15

Dacomitinib, an irreversible small-molecule pan-ErbB TKI, has a high incidence of diarrhea, which has been suggested to be due to chloride secretory mechanisms. Based on this hypothesis, crofelemer, an antisecretory agent may be an effective intervention. T84 monolayers were treated with 1 µM dacomitinib and 10 µM crofelemer, and mounted into Ussing chambers for electrogenic ion analysis. Crofelemer attenuated increases in chloride secretion in cells treated with dacomitinib. Albino Wistar rats (n = 48) were treated with 7.5 mg/kg dacomitinib and/or 25 mg/kg crofelemer via oral gavage for 21 days. Crofelemer significantly worsened dacomitinib-induced diarrhea (p = 0.0003), and did not attenuate weight loss (p < 0.0001). Sections of the ileum and colon were mounted into Ussing chambers, and secretory processes analyzed. This indicated that crofelemer lost its anti-secretory action in the presence of dacomitinib in this model. Mass spectrometry revealed that crofelemer did not change serum concentration of dacomitinib. Serum FITC dextran levels indicated that crofelemer was unable to attenuate dacomitinib-induced barrier dysfunction. Tight junction proteins were visualized with immunofluorescence. Qualitative analysis showed dacomitinib induced proteolysis of ZO-1 and occludin, and internalization of claudin-1, which was not attenuated by crofelemer. Detailed histopathological analysis showed that crofelemer was unable to attenuate dacomitinib-induced ileal damage. Crofelemer worsened dacomitinib-induced diarrhea, suggesting that antisecretory drug therapy may be ineffective in this setting. © 2017 UICC.

Surface buffing and its effect on chloride induced SCC of 304L austenitic stainless steel

NASA Astrophysics Data System (ADS)

kumar, Pandu Sunil; Ghosh Acharyya, Swati; Ramana Rao, S. V.; Kapoor, Komal

2018-02-01

The study focuses on the impact of buffing operation on the stress corrosion cracking (SCC) susceptibility of 304L austenitic stainless steel (SS). The SCC susceptibility of the buffed surfaces were determined by testing in boiling magnesium chloride (MgCl2) environment as per ASTM G 36. Test was conducted for 3hr, 9hr and 72hr to study the SCC susceptibility. Buffed surfaces were resistant to SCC even after 72hr of exposure to boiling MgCl2. The surface and cross section of the samples were examined for both before and after exposure to boiling MgCl2 and was characterized using optical microscopy. The study revealed that buffing operation induces compressive residual stresses on the surface, which helps in protecting the surface from SCC.

Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and oxidative stress induced by mercuric chloride in male rats: A protective approach.

PubMed

Joshi, Deepmala; Srivastav, Sunil Kumar; Belemkar, Sateesh; Dixit, Vaibhav A

2017-07-01

Mercury toxicity is an emerging problem in the world as its concentration is rising continuously due to increased industrial, medicinal and domestic uses. Exposure to mercury represents a serious challenge to humans and other living biomes. The aim of the present study was to assess the protective effect of natural products as Zingiber officinale extract and its active compound (6-gingerol) against mercuric chloride-induced hepatorenal toxicity and oxidative stress in male rats. Male Sprague-Dawley rats (150±10g, n=6 per group) were administered HgCl 2 (12μmol/kg, ip; once only) the treatment of Zingiber officinale Rosc. extract (ZO: 125mg/kg, po) and 6-gingerol (GG: 50mg/kg, po) for three days after 24h of HgCl 2 administration. Acute HgCl 2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol, urea, creatinine, uric acid and blood urea nitrogen contents with a concomitant decline in protein and albumin concentration in serum. In addition, a significant rise in lipid peroxidation level with concomitant decrease in reduced glutathione content and the antioxidant enzymes activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase after acute HgCl 2 exposure. Results of the present investigation clearly showed that both treatments as Zingiber officinale extract and 6-gingerol provide protection against acute mercuric chloride-intoxication by preventing oxidative degradation of a biological membrane from metal mediated free radical attacks. Biochemical data were well supported by histopathological findings. In conclusion, natural products may be an ideal choice against oxidative damage induced by mercury poisoning. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Ginkgo biloba extract alleviates oxidative stress and some neurotransmitters changes induced by aluminum chloride in rats.

PubMed

Mohamed, Naglaa El-Shahat; Abd El-Moneim, Ahmed E

2017-03-01

In the present study, twenty four adult male albino rats were classified into four groups. The control group received normal diet and water; the second group was treated daily with oral dose of Ginkgo biloba (200 mg/kg body weight [b.wt]) for 3 mo; the third group was treated daily with oral dose of aluminum chloride (10 mg/kg b.wt) for 3 mo; and the fourth group was treated with both Ginkgo biloba and aluminum chloride (200 and 10 mg/kg b.wt, respectively) using a stomach tube for 3 mo. The results showed that administration of AlCl 3 to rats induced significant increase (P < 0.05) in thiobarbituric acid reactive substance and decrease (P < 0.05) in glutathione, catalase, and superoxide dismutase in brain and testis homogenates. The data also showed significant decrease (P < 0.05) in noradrenaline, dopamine, and serotonin (5-HT) levels in brain tissue. The rats administered AlCl 3 showed significant decrease (P < 0.05) in serum zinc (Zn) and copper (Cu), significant increase (P < 0.05) in serum iron (Fe), and non-significant decrease in magnesium (Mg). Furthermore, significant increase (P < 0.05) in serum alkaline phosphatase and acid phosphatase and significant decrease (P < 0.05) in testosterone were recorded. The histologic examination showed some degenerative changes in both brain and testis tissues while significant improvement in biochemical and histologic changes were observed in the aluminum chloride plus Ginkgo biloba group. It could be concluded that the protective effect of Ginkgo biloba may be attributed to its antioxidant properties. Copyright © 2017 Elsevier Inc. All rights reserved.

Tributyltin-induced endoplasmic reticulum stress and its Ca{sup 2+}-mediated mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isomura, Midori; Kotake, Yaichiro, E-mail: yaichiro@hiroshima-u.ac.jp; Masuda, Kyoichi

2013-10-01

Organotin compounds, especially tributyltin chloride (TBT), have been widely used in antifouling paints for marine vessels, but exhibit various toxicities in mammals. The endoplasmic reticulum (ER) is a multifunctional organelle that controls post-translational modification and intracellular Ca{sup 2+} signaling. When the capacity of the quality control system of ER is exceeded under stress including ER Ca{sup 2+} homeostasis disruption, ER functions are impaired and unfolded proteins are accumulated in ER lumen, which is called ER stress. Here, we examined whether TBT causes ER stress in human neuroblastoma SH-SY5Y cells. We found that 700 nM TBT induced ER stress markers suchmore » as CHOP, GRP78, spliced XBP1 mRNA and phosphorylated eIF2α. TBT also decreased the cell viability both concentration- and time-dependently. Dibutyltin and monobutyltin did not induce ER stress markers. We hypothesized that TBT induces ER stress via Ca{sup 2+} depletion, and to test this idea, we examined the effect of TBT on intracellular Ca{sup 2+} concentration using fura-2 AM, a Ca{sup 2+} fluorescent probe. TBT increased intracellular Ca{sup 2+} concentration in a TBT-concentration-dependent manner, and Ca{sup 2+} increase in 700 nM TBT was mainly blocked by 50 μM dantrolene, a ryanodine receptor antagonist (about 70% inhibition). Dantrolene also partially but significantly inhibited TBT-induced GRP78 expression and cell death. These results suggest that TBT increases intracellular Ca{sup 2+} concentration by releasing Ca{sup 2+} from ER, thereby causing ER stress. - Highlights: • We established that tributyltin induces endoplasmic reticulum (ER) stress. • Tributyltin induces ER stress markers in a concentration-dependent manner. • Tributyltin increases Ca{sup 2+} release from ER, thereby causing ER stress. • Dibutyltin and monobutyltin did not increase GRP78 or intracellular Ca{sup 2+}.« less

Tributyltin-induced endoplasmic reticulum stress and its Ca(2+)-mediated mechanism.

PubMed

Isomura, Midori; Kotake, Yaichiro; Masuda, Kyoichi; Miyara, Masatsugu; Okuda, Katsuhiro; Samizo, Shigeyoshi; Sanoh, Seigo; Hosoi, Toru; Ozawa, Koichiro; Ohta, Shigeru

2013-10-01

Organotin compounds, especially tributyltin chloride (TBT), have been widely used in antifouling paints for marine vessels, but exhibit various toxicities in mammals. The endoplasmic reticulum (ER) is a multifunctional organelle that controls post-translational modification and intracellular Ca(2+) signaling. When the capacity of the quality control system of ER is exceeded under stress including ER Ca(2+) homeostasis disruption, ER functions are impaired and unfolded proteins are accumulated in ER lumen, which is called ER stress. Here, we examined whether TBT causes ER stress in human neuroblastoma SH-SY5Y cells. We found that 700nM TBT induced ER stress markers such as CHOP, GRP78, spliced XBP1 mRNA and phosphorylated eIF2α. TBT also decreased the cell viability both concentration- and time-dependently. Dibutyltin and monobutyltin did not induce ER stress markers. We hypothesized that TBT induces ER stress via Ca(2+) depletion, and to test this idea, we examined the effect of TBT on intracellular Ca(2+) concentration using fura-2 AM, a Ca(2+) fluorescent probe. TBT increased intracellular Ca(2+) concentration in a TBT-concentration-dependent manner, and Ca(2+) increase in 700nM TBT was mainly blocked by 50μM dantrolene, a ryanodine receptor antagonist (about 70% inhibition). Dantrolene also partially but significantly inhibited TBT-induced GRP78 expression and cell death. These results suggest that TBT increases intracellular Ca(2+) concentration by releasing Ca(2+) from ER, thereby causing ER stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Summary of available data for estimating chloride-induced SCC crack growth rates for 304/316 stainless steel.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryan, Charles R.; Enos, David

The majority of existing dry storage systems used for spent nuclear fuel (SNF) consist of a welded 304 stainless steel container placed within a passively-ventilated concrete or steel overpack. More recently fielded systems are constructed with dual certified 304/304L and in some cases, 316 or 316L. In service, atmospheric salts, a portion of which will be chloride bearing, will be deposited on the surface of these containers. Initially, the stainless steel canister surface temperatures will be high (exceeding the boiling point of water in many cases) due to decay heat from the SNF. As the SNF cools over time, themore » container surface will also cool, and deposited salts will deliquesce to form potentially corrosive chloride-rich brines. Because austenitic stainless steels are prone to chloride-induced stress corrosion cracking (CISCC), the concern has been raised that SCC may significantly impact long-term canister performance. While the susceptibility of austenitic stainless steels to CISCC in the general sense is well known, the behavior of SCC cracks (i.e., initiation and propagation behavior) under the aforementioned atmospheric conditions is poorly understood.« less

Consequences of tributyltin chloride induced stress in Leydig cells: an ex-vivo approach.

PubMed

Mitra, Sumonto; Srivastava, Ankit; Khanna, Smita; Khandelwal, Shashi

2014-03-01

Tributyltin (TBT), a member of the organotin family, is a known endocrine disruptor. It persists long in the environment and is widely used in various industrial applications. This study was planned to understand its toxic influence on Leydig cells isolated from 28 day old wistar rats. In-vitro exposure to TBT-Chloride (TBTC) (300-3000 nM) reduced cell viability (DNA fragmentation, nuclear condensation and MTT assay) and affected testosterone production. TBTC induced both apoptotic and necrotic cell death (AnnexinV/PI binding assay). Involvement of calcium (Ca(2+)), redox imbalance (ROS, GSH and TBARS) and mitochondria in TBTC toxicity was evaluated by using Ca(2+) inhibitors (BAPTA-AM, EGTA, Ruthenium Red), free radical scavengers (NAC, C-Phycocyanin) and mitochondrial permeability transition pore inhibitor (Cyclosporine A). Protein expression analysis of phosphorylated MAPKinases (ERK1/2, JNK1/2, & p38), steroidogenic proteins (3β-HSD, StAR & TSPO) and apoptotic proteins (Bax, Bcl2) illustrates the cytotoxic and anti-steroidogenic activity of TBTC. Copyright © 2014 Elsevier B.V. All rights reserved.

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

PubMed

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

PubMed

Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Modified chloride diffusion model for concrete under the coupling effect of mechanical load and chloride salt environment

NASA Astrophysics Data System (ADS)

Lei, Mingfeng; Lin, Dayong; Liu, Jianwen; Shi, Chenghua; Ma, Jianjun; Yang, Weichao; Yu, Xiaoniu

2018-03-01

For the purpose of investigating lining concrete durability, this study derives a modified chloride diffusion model for concrete based on the odd continuation of boundary conditions and Fourier transform. In order to achieve this, the linear stress distribution on a sectional structure is considered, detailed procedures and methods are presented for model verification and parametric analysis. Simulation results show that the chloride diffusion model can reflect the effects of linear stress distribution of the sectional structure on the chloride diffusivity with reliable accuracy. Along with the natural environmental characteristics of practical engineering structures, reference value ranges of model parameters are provided. Furthermore, a chloride diffusion model is extended for the consideration of multi-factor coupling of linear stress distribution, chloride concentration and diffusion time. Comparison between model simulation and typical current research results shows that the presented model can produce better considerations with a greater universality.

SCC of 2304 Duplex Stainless Steel—Microstructure, Residual Stress and Surface Grinding Effects

PubMed Central

Zhou, Nian; Peng, Ru Lin; Schönning, Mikael; Pettersson, Rachel

2017-01-01

The influence of surface grinding and microstructure on chloride induced stress corrosion cracking (SCC) behavior of 2304 duplex stainless steel has been investigated. Grinding operations were performed both parallel and perpendicular to the rolling direction of the material. SCC tests were conducted in boiling magnesium chloride according to ASTM G36; specimens were exposed both without external loading and with varied levels of four-point bend loading. Residual stresses were measured on selected specimens before and after exposure using the X-ray diffraction technique. In addition, in-situ surface stress measurements subjected to four-point bend loading were performed to evaluate the deviation between the actual applied loading and the calculated values according to ASTM G39. Micro-cracks, initiated by grinding induced surface tensile residual stresses, were observed for all the ground specimens but not on the as-delivered surfaces. Loading transverse to the rolling direction of the material increased the susceptibility to chloride induced SCC. Grinding induced tensile residual stresses and micro-notches in the as-ground surface topography were also detrimental. PMID:28772582

SCC of 2304 Duplex Stainless Steel-Microstructure, Residual Stress and Surface Grinding Effects.

PubMed

Zhou, Nian; Peng, Ru Lin; Schönning, Mikael; Pettersson, Rachel

2017-02-23

The influence of surface grinding and microstructure on chloride induced stress corrosion cracking (SCC) behavior of 2304 duplex stainless steel has been investigated. Grinding operations were performed both parallel and perpendicular to the rolling direction of the material. SCC tests were conducted in boiling magnesium chloride according to ASTM G36; specimens were exposed both without external loading and with varied levels of four-point bend loading. Residual stresses were measured on selected specimens before and after exposure using the X-ray diffraction technique. In addition, in-situ surface stress measurements subjected to four-point bend loading were performed to evaluate the deviation between the actual applied loading and the calculated values according to ASTM G39. Micro-cracks, initiated by grinding induced surface tensile residual stresses, were observed for all the ground specimens but not on the as-delivered surfaces. Loading transverse to the rolling direction of the material increased the susceptibility to chloride induced SCC. Grinding induced tensile residual stresses and micro-notches in the as-ground surface topography were also detrimental.

Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

PubMed

Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hasan, Hesham F

2016-09-01

Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells

PubMed Central

Kitajima, Shojiro; Lee, Kian Leong; Hikasa, Hiroki; Sun, Wendi; Huang, Ruby Yun-Ju; Yang, Henry; Matsunaga, Shinji; Yamaguchi, Takehiro; Araki, Marito; Kato, Hiroyuki

2017-01-01

Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in a biphasic ammonia stress management in the cancer stem-like cells where GS facilitates cell proliferation and HIF-1α contributes to the metabolic remodeling in energy fuel usage resulting in attenuated proliferation but conversely promoting cell survival. PMID:29383096

Understanding the Risk of Chloride Induced Stress Corrosion Cracking of Interim Storage Containers for the Dry Storage of Spent Nuclear Fuel: Evolution of Brine Chemistry on the Container Surface.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enos, David; Bryan, Charles R.

Although the susceptibility of austenitic stainless steels to chloride-induced stress corrosion cracking is well known, uncertainties exist in terms of the environmental conditions that exist on the surface of the storage containers. While a diversity of salts is present in atmospheric aerosols, many of these are not stable when placed onto a heated surface. Given that the surface temperature of any container storing spent nuclear fuel will be well above ambient, it is likely that salts deposited on its surface may decompose or degas. To characterize this effect, relevant single and multi-salt mixtures are being evaluated as a function ofmore » temperature and relative humidity to establish the rates of degassing, as well as the likely final salt and brine chemistries that will remain on the canister surface.« less

On conductivity changes in shocked potassium chloride

NASA Astrophysics Data System (ADS)

Bourne, N. K.; Townsend, D.; Braithwaite, M.

2005-06-01

A previous work has reported that shock loading of ionic crystals produces an induced polarization and changes in electrical conductivity. However, previous measurements recorded an integrated electrical signal comprising the induced electrical field and that due to current flow. For this reason a differential system was designed to separate these effects that was adapted from that used in the investigation of the conductivity of hydrogen under shock. The measurement removes voltages produced in the shock-induced electrical field, allowing determination of those resulting from resistance changes. Although the mechanical response of potassium chloride to shock has been studied extensively, the electrical response is less studied. Here, experiments are reported in which it is shocked to various stresses in order to observe conductivity changes. The range of stresses induced includes several mechanical thresholds, including the elastic-plastic transition, the B1:B2 phase transformation, and the overdriving of the shock faster than the elastic wave. The behavior observed when single crystal and targets pressed from granular material (to close to full density) are shocked around each of these thresholds is presented. The effects of loading to a particular stress in a single step or in multiple steps are discussed.

Chloride: from Nutrient to Toxicant.

PubMed

Geilfus, Christoph-Martin

2018-05-01

In salinized soils in which chloride (Cl-) is the dominant salt anion, growth of plants that tolerate only low concentrations of salt (glycophytes) is disturbed by Cl- toxicity. Chlorotic discolorations precede necrotic lesions, causing yield reductions. Little is known about the effects of Cl- toxicity on these dysfunctions. A lack of understanding exists regarding (i) the molecular and physiological mechanisms that lead to Cl--induced damage and (ii) the adaptive aspects of induced tolerance to Cl- salinity. Here, mechanistic explanations for the Cl--induced stress responses are proposed and novel ideas and strategies by which glycophytic plants avoid the excessive accumulation of Cl- are reviewed. New experiments are suggested to test the proposed hypotheses. Cl- salinity constrains global food security and thus we urgently need more research into the causes and consequences of Cl- salinity.

CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.

PubMed

Tang, Tiantian; Lang, Xueting; Xu, Congfei; Wang, Xiaqiong; Gong, Tao; Yang, Yanqing; Cui, Jun; Bai, Li; Wang, Jun; Jiang, Wei; Zhou, Rongbin

2017-08-04

The NLRP3 inflammasome can sense different pathogens or danger signals, and has been reported to be involved in the development of many human diseases. Potassium efflux and mitochondrial damage are both reported to mediate NLRP3 inflammasome activation, but the underlying, orchestrating signaling events are still unclear. Here we show that chloride intracellular channels (CLIC) act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation. NLRP3 agonists induce potassium efflux, which causes mitochondrial damage and ROS production. Mitochondrial ROS then induces the translocation of CLICs to the plasma membrane for the induction of chloride efflux to promote NEK7-NLRP3 interaction, inflammasome assembly, caspase-1 activation, and IL-1β secretion. Thus, our results identify CLICs-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation.The NLRP3 inflammasome is key to the regulation of innate immunity against pathogens or stress, but the underlying signaling regulation is still unclear. Here the authors show that chloride intracellular channels (CLIC) interface between mitochondria stress and inflammasome activation to modulate inflammatory responses.

Ursodeoxycholic acid protects cardiomyocytes against cobalt chloride induced hypoxia by regulating transcriptional mediator of cells stress hypoxia inducible factor 1α and p53 protein.

PubMed

Mohamed, Anis Syamimi; Hanafi, Noorul Izzati; Sheikh Abdul Kadir, Siti Hamimah; Md Noor, Julina; Abdul Hamid Hasani, Narimah; Ab Rahim, Sharaniza; Siran, Rosfaiizah

2017-10-01

In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca 2+ ] i ), and sphingosine-1-phosphate (S1P)-receptor via Gα i -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca 2+ ] i , and S1P-Gα i -coupled-receptor. Cardiomyocytes were isolated from newborn rats (0-2 days), and hypoxia was induced by using cobalt chloride (CoCl 2 ). Cardiomyocytes were treated with UDCA and cotreated with either FTY720 (S1P-receptor agonist) or pertussis toxin (PTX; Gα i inhibitor). Cells were subjected for proliferation assay, beating frequency, QuantiGene Plex assay, western blot, immunofluorescence, and calcium imaging. Our findings showed that UDCA counteracted the effects of CoCl 2 on cell viability, beating frequency, HIF-1α, and p53 protein expression. We found that these cardioprotection effects of UDCA were similar to FTY720, S1P agonist. Furthermore, we observed that UDCA protects CMs against CoCl 2 -induced [Ca 2+ ] i dynamic alteration. Pharmacological inhibition of the Gα i -sensitive receptor did not abolish the cardioprotection of UDCA against CoCl 2 detrimental effects, except for cell viability and [Ca 2+ ] i . Pertussis toxin is partially effective in inhibiting UDCA protection against CoCl 2 effects on CM cell viability. Interestingly, PTX fully inhibits UDCA cardioprotection on CoCl 2 -induced [Ca 2+ ] i dynamic changes. We conclude that UDCA cardioprotection against CoCl 2 -induced hypoxia is similar to FTY720, and its actions are not fully mediated by the Gα i -coupled protein sensitive pathways. Ursodeoxycholic acid is the most hydrophilic bile

Genoprotective effect of hyaluronic acid against benzalkonium chloride-induced DNA damage in human corneal epithelial cells

PubMed Central

Wu, Han; Zhang, Huina; Wang, Changjun; Wu, Yihua; Xie, Jiajun; Jin, Xiuming; Yang, Jun

2011-01-01

Purpose The aim of this study was to investigate hyaluronic acid (HA) protection on cultured human corneal epithelial cells (HCEs) against benzalkonium chloride (BAC)-induced DNA damage and intracellular reactive oxygen species (ROS) increase. Methods Cells were incubated with different concentrations of BAC with or without the presence of 0.2% HA for 30 min. DNA damage to HCEs was examined by alkaline comet assay and by immunofluorescence microscopic detection of the phosphorylated form of histone variant H2AX (γH2AX) foci. ROS production was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cell apoptosis was determined with annexin V staining by flow cytometry. Results HA significantly reduced BAC-induced DNA damage as indicated by the tail length (TL) and tail moment (TM) of alkaline comet assay and by γH2AX foci formation, respectively. Moreover, HA significantly decreased BAC-induced ROS increase and cell apoptosis. However, exposure to HA alone did not produce any significant change in DNA damage, ROS generation, or cell apoptosis. Conclusions BAC could induce DNA damage and cell apoptosis in HCEs, probably through increasing oxidative stress. Furthermore, HA was an effective protective agent that had antioxidant properties and could decrease DNA damage and cell apoptosis induced by BAC. PMID:22219631

Inhibition of nitrite-induced toxicity in channel catfish by calcium chloride and sodium chloride

USGS Publications Warehouse

Tommasso J.R., Wright; Simco, B.A.; Davis, K.B.

1980-01-01

Environmental chloride has been shown to inhibit methemoglobin formation in fish, thereby offering a protective effect against nitrite toxicity. Channel catfish (Ictalurus punctatus) were simultaneously exposed to various environmental nitrite and chloride levels (as either CaCl2 or NaCl) in dechlorinated tap water (40 mg/L total hardness, 47 mg/L alkalinity, 4 mg/L chloride, pH = 6.9-7.1, and temperature 21-24°C). Methemoglobin levels in fish simultaneously exposed to 2.5 mg/L nitrite and up to 30 mg/L chloride as either CaCl2 or NaCl were similar but significantly lower than in unprotected fish. Exposure to 10 mg/L nitrite and 60 mg/L chloride resulted in methemoglobin levels similar to those of the controls; most unprotected fish died. Fish exposed to 10 mg/L nitrite had significantly lower methemoglobin levels when protected with 15.0 mg/L chloride as CaCl2 than with NaCl. Fish exposed to nitrite in the presence of 60 mg/L chloride (as either CaCl2 or NaCl) had similar 24-h LC50 values that were significantly elevated above those obtained in the absence of chloride. Calcium had little effect on tolerance to nitrite toxicity in channel catfish in contrast to its large effect reported in steelhead trout (Salmo gairdneri).

The physiological determinants of drug-induced lysosomal stress resistance

PubMed Central

Woldemichael, Tehetina; Rosania, Gus R.

2017-01-01

Many weakly basic, lipophilic drugs accumulate in lysosomes and exert complex, pleiotropic effects on organelle structure and function. Thus, modeling how perturbations of lysosomal physiology affect the maintenance of lysosomal ion homeostasis is necessary to elucidate the key factors which determine the toxicological effects of lysosomotropic agents, in a cell-type dependent manner. Accordingly, a physiologically-based mathematical modeling and simulation approach was used to explore the dynamic, multi-parameter phenomenon of lysosomal stress. With this approach, parameters that are either directly involved in lysosomal ion transportation or lysosomal morphology were transiently altered to investigate their downstream effects on lysosomal physiology reflected by the changes they induce in lysosomal pH, chloride, and membrane potential. In addition, combinations of parameters were simultaneously altered to assess which parameter was most critical for recovery of normal lysosomal physiology. Lastly, to explore the relationship between organelle morphology and induced stress, we investigated the effects of parameters controlling organelle geometry on the restoration of normal lysosomal physiology following a transient perturbation. Collectively, our results indicate a key, interdependent role of V-ATPase number and membrane proton permeability in lysosomal stress tolerance. This suggests that the cell-type dependent regulation of V-ATPase subunit expression and turnover, together with the proton permeability properties of the lysosomal membrane, is critical to understand the differential sensitivity or resistance of different cell types to the toxic effects of lysosomotropic drugs. PMID:29117253

Effect of baclofen on morphine-induced conditioned place preference, extinction, and stress-induced reinstatement in chronically stressed mice.

PubMed

Meng, Shanshan; Quan, Wuxing; Qi, Xu; Su, Zhiqiang; Yang, Shanshan

2014-01-01

A stress-induced increase in excitability can result from a reduction in inhibitory neurotransmission. Modulation of gamma-aminobutyric acid (GABA)ergic transmission is an effective treatment for drug seeking and relapse. This study investigated whether baclofen, a GABA(B) receptor agonist, had an impact on morphine-induced conditioned place preference (CPP), extinction, and stress-induced relapse in chronically stressed mice. Chronic stress was induced by restraining mice for 2 h for seven consecutive days. We first investigated whether chronic stress influenced morphine-induced CPP, extinction, and stress-induced relapse in the stressed mice. Next, we investigated whether three different doses of baclofen influenced chronic stress as measured by the expression of morphine-induced CPP. We chose the most effective dose for subsequent extinction and reinstatement experiments. Reinstatement of morphine-induced CPP was induced by a 6-min forced swim stress. Locomotor activity was also measured for each test. Chronic stress facilitated the expression of morphine-induced CPP and prolonged extinction time. Forced swim stress primed the reinstatement of morphine-induced CPP in mice. Baclofen treatment affected the impact of chronic stress on different phases of morphine-induced CPP. Our results showed that baclofen antagonized the effects of chronic stress on morphine-induced CPP. These findings suggest the potential clinical utility of GABA(B) receptor-positive modulators as an anti-addiction agent in people suffering from chronic stress.

Aqueous sodium chloride induced intergranular corrosion of Al-Li-Cu alloys

NASA Technical Reports Server (NTRS)

Pizzo, P. P.; Daeschner, D. L.

1986-01-01

Two methods have been explored to assess the susceptibility of Al-Li-Cu alloys to intergranular corrosion in aqueous sodium chloride solution. They are: (1) constant extension rate testing with and without alternate-immersion preexposure and (2) metallographic examination after exposure to a NaCl-H2O2 corrosive solution per Mil-H-6088F. Intergranular corrosion was found to occur in both powder and ingot metallurgy alloys of similar composition, using both methods. Underaging rendered the alloys most susceptible. The results correlate to stress-corrosion data generated in conventional time-to-failure and crack growth-rate tests. Alternate-immersion preexposure may be a reliable means to assess stress corrosion susceptibility of Al-Li-Cu alloys.

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

NASA Astrophysics Data System (ADS)

Busschaert, Nathalie; Park, Seong-Hyun; Baek, Kyung-Hwa; Choi, Yoon Pyo; Park, Jinhong; Howe, Ethan N. W.; Hiscock, Jennifer R.; Karagiannidis, Louise E.; Marques, Igor; Félix, Vítor; Namkung, Wan; Sessler, Jonathan L.; Gale, Philip A.; Shin, Injae

2017-07-01

Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Cobalt chloride induces metaphase when topically applied to larvae and pupae of the stingless bee Melipona scutellaris (Hymenoptera, Apidae, Meliponini).

PubMed

Ueira-Vieira, C; Tavares, R R; Morelli, S; Pereira, B B; Silva, R P; Torres-Mariano, A R; Kerr, W E; Bonetti, A M

2013-06-20

In order to optimize preparations of bee metaphases, we tested cobalt chloride, which has been used as a metaphase inducer in other organisms, such as hamsters and fish. Four microliters of 65 mM cobalt chloride aqueous solution was topically applied to larval and pupal stages of the stingless bee Melipona scutellaris. The cerebral ganglion was removed after treatment and prepared for cytogenetic analysis. Identically manipulated untreated individuals were used as controls. The number of metaphases was increased 3-fold in treated individuals compared to controls. The micronucleus test showed no mutagenic effects of cobalt chloride on M. scutellaris cells. We concluded that cobalt chloride is a metaphase-inducing agent in M. scutellaris, thus being useful for cytogenetic analyses.

Pycnogenol (PYC) induces apoptosis in human fibrosarcoma (HFS) cells under metal-mediated oxidative stress.

PubMed

Park, Yeon Sun; Kim, Young Gon

2011-01-01

Pycnogenol (PYC), polyphenolic compounds with antioxidant activity, acted as a prooxidant. PYC caused oxidative stress in human fibrosarcoma cells (HFS) when administered following pretreatment with iron chloride. The generated reactive oxygen species (ROS) caused the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA and resulted in more apoptosis in HFS cells than in the human fibroblastoma (HFB) cells. DNA damage and cellular viability at different PYC concentrations were closely consistent with cell growth, high performance liquid chromatography (HPLC), Enzyme Linked Immunosorbent Assay (ELISA) and assays of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase. Although the presence of PYC induced total SOD and catalase activities under oxidative stress in dose dependent fashion, more apoptotic cells were induced in HFS cells with increased [8-OHdG] than in HFB cells. The results suggest that PYC selectively induced cell death in HFS cells. This further confirmed that PYC-induced apoptosis is mediated primarily through the activation of caspase-3 apoptotic marker in HFS cells but not in HFB cells. We conclude that PYC would behave as either antioxidant or prooxidant dependant upon the cellular types.

Hepatoprotective and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice.

PubMed

Karuppanan, Muthupillai; Krishnan, Manigandan; Padarthi, Pavankumar; Namasivayam, Elangovan

2014-01-01

To explore the antioxidant and hepatoprotective effect of ethanolic Mangifera indica (EMI) and methanolic Mangifera indica (MMI) leaf extracts in mercuric chloride (HgCl 2 ) induced toxicity in Swiss albino mice. Toxicity in mice was induced with HgCl 2 (5.0 mg/kg, i.p.), followed by oral intervention with EMI and MMI extracts (25 mg and 50 mg/kg. body wt.) for 30 days. The extent of liver damage was assessed from the extents of histopathological, morphological, antioxidant and liver enzymes. Mercuric chloride-induced mice showed an increased cellular damage whereas leaf extracts of EMI and MMI-treated mice showed recovery of damaged hepatocytes. Mercuric chloride intoxicated mice exhibited a significant (p < 0.05) elevation in the liver enzymes (Aspartate amino transferase and Alanine amino transferase) and gradual decline in the cellular radical scavenging enzyme levels (Catalase, Glutathione-s-transferase and Glutathione peroxidase. The combined treatment with EMI and MMI leaf extracts significantly (p < 0.05) reversed these parameters. However, the effects of MMI leaf extract (50 mg/kg) were superior to those of EMI- treated mice possibly due to its potent radical scavenging property. These results suggest that oral supplementation of Mangifera indica extract remarkably reduces hepatotoxicity in mice possibly through its antioxidant potentials. How to cite this article: Karuppanan M, Krishnan M, Padarthi P, Namasivayam E. Hepatoprotec-tive and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice. Euroasian J Hepato-Gastroenterol 2014;4(1):18-24.

Acquisition of lithium chloride- and radiation-induced taste aversions in hypophysectomized rats.

PubMed

Rabin, B M; Hunt, W A; Lee, J

1983-03-01

The effects of hypophysectomy on the acquisition of conditioned taste aversions following injection of lithium chloride and following exposure to ionizing radiation were studied using a two-bottle preference test. Hypophysectomy did not disrupt the acquisition of a taste aversion following either treatment. The results are interpreted as: (a) suggesting that pituitary/adrenal hormones do not mediate the acquisition of a conditioned taste aversion following injections of lithium chloride or following exposure to ionizing radiation in a two-bottle preference test, and (b) consistent with other research suggesting that the involvement of pituitary/adrenal hormones in taste aversion learning may be related to the conflict induced by using a one-bottle test and not to the learning itself.

Sodium chloride stress induced morphological and ultrastructural changes in Aspergillus repens.

PubMed

Kelavkar, U; Rao, K S; Ghhatpar, H S

1993-06-01

Halotolerant fungus, A. repens, showed a considerable difference in its growth rate, morphology, ultrastructural and molecular composition under NaCl stress as compared to control i.e. non-stressed condition. Light microscopic observations revealed significant differences in their mycelial thickness, their branching and septa. Transmission electron microscopic observations of both the conditions depicted significant differences in the qualitative and quantitative changes in mitochondria. Frequent pinocytotic vesiculation (vacuoles) of plasma membrane was observed in fungus under stress but no such vesiculation in control. The multivesiculate structures observed under stress with their origin from the cell membranes and subsequent release into vacuoles have not been reported in fungi under normal physiological conditions. The observations on pinocytosis are discussed in relation to ion compartmentation and salt tolerance in A. repens.

Hepatoprotective and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice

PubMed Central

Karuppanan, Muthupillai; Krishnan, Manigandan; Padarthi, Pavankumar

2014-01-01

ABSTRACT Background To explore the antioxidant and hepatoprotective effect of ethanolic Mangifera indica (EMI) and methanolic Mangifera indica (MMI) leaf extracts in mercuric chloride (HgCl2) induced toxicity in Swiss albino mice. Materials and methods Toxicity in mice was induced with HgCl2 (5.0 mg/kg, i.p.), followed by oral intervention with EMI and MMI extracts (25 mg and 50 mg/kg. body wt.) for 30 days. Results and discussion The extent of liver damage was assessed from the extents of histopathological, morphological, antioxidant and liver enzymes. Mercuric chloride-induced mice showed an increased cellular damage whereas leaf extracts of EMI and MMI-treated mice showed recovery of damaged hepatocytes. Mercuric chloride intoxicated mice exhibited a significant (p < 0.05) elevation in the liver enzymes (Aspartate amino transferase and Alanine amino transferase) and gradual decline in the cellular radical scavenging enzyme levels (Catalase, Glutathione-s-transferase and Glutathione peroxidase. The combined treatment with EMI and MMI leaf extracts significantly (p < 0.05) reversed these parameters. However, the effects of MMI leaf extract (50 mg/kg) were superior to those of EMI- treated mice possibly due to its potent radical scavenging property. These results suggest that oral supplementation of Mangifera indica extract remarkably reduces hepatotoxicity in mice possibly through its antioxidant potentials. How to cite this article: Karuppanan M, Krishnan M, Padarthi P, Namasivayam E. Hepatoprotec-tive and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice. Euroasian J Hepato-Gastroenterol 2014;4(1):18-24. PMID:29264314

Does stress induce bowel dysfunction?

PubMed

Chang, Yu-Ming; El-Zaatari, Mohamad; Kao, John Y

2014-08-01

Psychological stress is known to induce somatic symptoms. Classically, many gut physiological responses to stress are mediated by the hypothalamus-pituitary-adrenal axis. There is, however, a growing body of evidence of stress-induced corticotrophin-releasing factor (CRF) release causing bowel dysfunction through multiple pathways, either through the HPA axis, the autonomic nervous systems, or directly on the bowel itself. In addition, recent findings of CRF influencing the composition of gut microbiota lend support for the use of probiotics, antibiotics, and other microbiota-altering agents as potential therapeutic measures in stress-induced bowel dysfunction.

Protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl2)-induced hepatotoxicity in rats.

PubMed

Elkhadragy, Manal F; Abdel Moneim, Ahmed E

2017-06-01

This study investigated the protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl 2 )-induced hepatotoxicity in rats. CdCl 2 was intraperitoneally injected at a dose of 6.5 mg/kg of body weight for 5 d with or without methanol extract of Fragaria ananassa (250 mg/kg). The hepatic cadmium concentration, lipid peroxidation, nitric oxide, glutathione (GSH) content, and antioxidant enzyme activities, including superoxide dismutase, catalase (CAT), GSH peroxidase, and GSH reductase, were estimated. CdCl 2 injection induced a significant elevation in cadmium concentration, lipid peroxidation, and nitric oxide and caused a significant depletion in GSH content compared to controls, along with a remarkable decrease in antioxidant enzymes. Oxidative stress induction and cadmium accumulation in the liver were successfully ameliorated by F. ananassa (strawberry) pre-administration. In addition, the pre-administration of strawberry decreased the elevated gene expression of the pro-apoptotic Bax gene as well as the protein expression of caspases-3 in the liver of CdCl 2 -injected rats. In addition, the reduced gene expression of anti-apoptotic Bcl-2 was increased. Our results show an increase in the expression of tumor necrosis factor α in the liver of rats treated with cadmium. In sum, our results suggested that F. ananassa successfully prevented deleterious effects on liver function by reinforcing the antioxidant defense system, inhibiting oxidative stress and reducing apoptosis.

In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).

PubMed

Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

2012-12-01

Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.

O-Hexadecyl-Dextran Entrapped Berberine Nanoparticles Abrogate High Glucose Stress Induced Apoptosis in Primary Rat Hepatocytes

PubMed Central

Tripathi, Madhulika; Bhatnagar, Priyanka; Kakkar, Poonam; Gupta, Kailash Chand

2014-01-01

Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs) were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR) treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM), showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼3.5 fold during co-treatment, prevented GSH depletion by ∼1.6 fold, reduced NO formation by ∼5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/−3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death. PMID:24586539

Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram.

PubMed

Parker, R B; Perry, G Y; Horan, L G; Flowers, N C

1999-12-01

Cocaine abuse is associated with a number of cardiovascular complications that include arrhythmias and sudden cardiac death. Although the mechanism(s) remain unclear, cocaine-induced block of sodium channels resulting in slowed cardiac conduction is thought to play an important role. Several reports suggest that the effects of cocaine effects on cardiac sodium channels can be reversed by administration of sodium bicarbonate. Whether the beneficial effects of sodium bicarbonate are due to sodium ions or an increase in blood pH is unknown. Therefore the purpose of this study was to compare the effects of sodium loading alone (by using sodium chloride) versus sodium loading with an associated increase in arterial pH (by using sodium bicarbonate) on reversing cocaine-induced effects on the electrocardiogram (ECG) in a canine model. Seventeen anesthetized dogs received three i.v. injections of cocaine, 5 mg/kg, with each dose separated by 15 min. Two minutes after the third cocaine dose, each dog was randomly assigned to receive 2 mEq/kg i.v. sodium bicarbonate (1 mEq/ml) or 2 mEq/kg i.v. sodium chloride (1 mEq/ml). ECG, electrophysiologic, and hemodynamic data were recorded at baseline, after each cocaine injection, and after administration of sodium bicarbonate or sodium chloride. In both groups of animals, the first cocaine injection significantly (p < 0.05) prolonged the PR, QTc, AH, and HV intervals, and QRS duration compared with baseline. All intervals continued to lengthen in a dose-dependent manner after the second and third cocaine doses. Sodium bicarbonate significantly (p < 0.05) reduced cocaine-induced prolongation of PR [(147 +/- 5-130 +/- 5 ms), AH (81 +/- 6 - 72 +/- 6 ms), and HV intervals (55 +/- 2 - 39 +/- 1 ms). and QRS duration (96 +/- 6 - 66 +/- 4 ms), peak effect after third cocaine dose versus after sodium bicarbonate, respectively]. Sodium chloride had no effect on reversing cocaine-induced effects on the ECG. Cocaine produces dose

Effect of temperature gradient on the optical quality of mercurous chloride crystals

NASA Technical Reports Server (NTRS)

Singh, N. B.; Davies, D. K.; Gottlieb, M.; Henningsen, T.; Mazelsky, R.

1989-01-01

Single crystals of mercurous chloride were grown at temperature gradients of 8, 11 and 17 K/cm by the physical vapor transport method. The optical quality of these crystals was evaluated by measuring bulk scattering and inhomogeneity of refractive index by birefringence interferometry. It was observed that a high temperature gradient at the solid-vapor interface induced thermal stresses and crystals showed higher scattering and irregular fringes.

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xin; Xu, Mei; Frank, Jacqueline A.

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stemmore » cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

PubMed

Tatsuta, M; Iishi, H; Baba, M; Yano, H; Uehara, H; Nakaizumi, A

1999-01-29

The effects of prolonged administration of genistein, a tyrosine-kinase inhibitor, on sodium-chloride-enhanced induction of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic indices and vessel counts in the gastric mucosa and gastric cancers, were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were fed chow pellets containing 10% sodium chloride and were given s.c. injections of genistein at dosages of 15 mg/kg or 30 mg/kg body weight every other day. In week 52, the incidence of gastric cancers was significantly greater in rats fed sodium chloride than in untreated control rats. Prolonged administration of genistein at a dosage of 30 mg/kg, but not 15 mg/kg, body weight significantly reduced the incidence of gastric cancers, which was increased by oral treatment with sodium chloride. Genistein at the higher dose significantly decreased the labeling index and vessel counts of the antral mucosa and the gastric cancers (which were increased by treatment with sodium chloride) and significantly increased the apoptotic index of the antral mucosa and the cancers (which was lowered by the treatment with sodium chloride). These findings suggest that genistein attenuates gastric carcinogenesis promoted by sodium chloride, by inducing increased apoptosis and lower cell proliferation and angiogenesis of antral mucosa and gastric cancers.

Improvement of Mercuric Chloride-Induced Testis Injuries and Sperm Quality Deteriorations by Spirulina platensis in Rats

PubMed Central

El-Desoky, Gaber E.; Bashandy, Samir A.; Alhazza, Ibrahim M.; Al-Othman, Zeid A.; Aboul-Soud, Mourad A. M.; Yusuf, Kareem

2013-01-01

The present study was undertaken to investigate the protective effect of the filamentous cyanobacterium Spirulina platensis (S. platensis) on mercury (II) chloride (HgCl2)-induced oxidative damages and histopathological alterations in the testis of Wistar albino rats. The animals were divided into four equal groups, i ) control, ii ) HgCl2, iii ) S. platensis and iv ) combination of HgCl2+S. platensis. Oxidative stress, induced by a single dose of HgCl2 (5 mg/kg, bw; subcutaneously, s.c.), substantially decreased (P<0.01) the activity level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT and glutathione peroxidase, GPx), oxidative stress makers (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde, MDA), and testicular mercury levels. Moreover, HgCl2 administration resulted in a significant (P<0.01) increase in the number of sperms with abnormal morphology and decrease in epididymal sperm count, motility, plasma testosterone level and testicular cholesterol. Furthermore, HgCl2 exposure induced histopathological changes to the testis including morphological alterations of the seminiferous tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral pretreatment of animals with Spirulina (300 mg/kg, bw) lowered the extent of the observed HgCl2-mediated toxicity, whereby significantly reducing the resulting lipid peroxidation products, mercury accumulation in the testis, histopathological changes of the testes and spermatozoal abnormalities. In parallel, the pretreatment with Spirulina also completely reverted the observed Hg-Cl2-induced inhibition in enzymatic activities of antioxidant biomarkers (SOD, CAT and GPx) back to control levels. The pretreatment of rats with S. platensis significantly recovered the observed HgCl2-mediated decrease in the weight of accessory sex organs. Taken together, our findings clearly highlight the role of S. platensis as a protective modulator of

Improvement of mercuric chloride-induced testis injuries and sperm quality deteriorations by Spirulina platensis in rats.

PubMed

El-Desoky, Gaber E; Bashandy, Samir A; Alhazza, Ibrahim M; Al-Othman, Zeid A; Aboul-Soud, Mourad A M; Yusuf, Kareem

2013-01-01

The present study was undertaken to investigate the protective effect of the filamentous cyanobacterium Spirulina platensis (S. platensis) on mercury (II) chloride (HgCl(2))-induced oxidative damages and histopathological alterations in the testis of Wistar albino rats. The animals were divided into four equal groups, i) control, ii) HgCl(2), iii) S. platensis and iv) combination of HgCl(2)+S. platensis. Oxidative stress, induced by a single dose of HgCl(2) (5 mg/kg, bw; subcutaneously, s.c.), substantially decreased (P<0.01) the activity level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT and glutathione peroxidase, GPx), oxidative stress makers (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde, MDA), and testicular mercury levels. Moreover, HgCl(2) administration resulted in a significant (P<0.01) increase in the number of sperms with abnormal morphology and decrease in epididymal sperm count, motility, plasma testosterone level and testicular cholesterol. Furthermore, HgCl(2) exposure induced histopathological changes to the testis including morphological alterations of the seminiferous tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral pretreatment of animals with Spirulina (300 mg/kg, bw) lowered the extent of the observed HgCl(2)-mediated toxicity, whereby significantly reducing the resulting lipid peroxidation products, mercury accumulation in the testis, histopathological changes of the testes and spermatozoal abnormalities. In parallel, the pretreatment with Spirulina also completely reverted the observed Hg-Cl(2)-induced inhibition in enzymatic activities of antioxidant biomarkers (SOD, CAT and GPx) back to control levels. The pretreatment of rats with S. platensis significantly recovered the observed HgCl(2)-mediated decrease in the weight of accessory sex organs. Taken together, our findings clearly highlight the role of S. platensis as a protective

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

PubMed Central

Shor, Erika; Fox, Catherine A.; Broach, James R.

2013-01-01

Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors. PMID:23935537

Effects of diadenosine tetraphosphate on FGF9-induced chloride flux changes in achondroplastic chondrocytes.

PubMed

Huete, Fernando; Guzman-Aranguez, Ana; Ortín, Javier; Hoyle, Charles H V; Pintor, Jesús

2011-06-01

Achondroplasia, the most common type of dwarfism, is characterized by a mutation in the fibroblast growth factor receptor 3 (FGFR3). Achondroplasia is an orphan pathology with no pharmacological treatment so far. However, the possibility of using the dinucleotide diadenosine tetraphosphate (Ap(4)A) with therapeutic purposes in achondroplasia has been previously suggested. The pathogenesis involves the constitutive activation of FGFR3, resulting in altered biochemical and physiological processes in chondrocytes. Some of these altered processes can be influenced by changes in cell volume and ionic currents. In this study, the action of mutant FGFR3 on chondrocyte size and chloride flux in achondroplastic chondrocytes was investigated as well as the effect of the Ap(4)A on these processes triggered by mutant FGFR3. Stimulation with the fibroblast growth factor 9 (FGF9), the preferred ligand for FGFR3, induced an enlarged achondroplastic chondrocyte size and an increase in the intracellular chloride concentration, suggesting the blockade of chloride efflux. Treatment with the Ap(4)A reversed the morphological changes triggered by FGF9 and restored the chloride efflux. These data provide further evidence for the therapeutic potential of this dinucleotide in achondroplasia treatment.

Ergothioneine prevents endothelial dysfunction induced by mercury chloride.

PubMed

Gökçe, Göksel; Arun, Mehmet Zuhuri; Ertuna, Elif

2018-06-01

Exposure to mercury has detrimental effects on the cardiovascular system, particularly the vascular endothelium. The present study aimed to investigate the effects of ergothioneine (EGT) on endothelial dysfunction induced by low-dose mercury chloride (HgCl 2 ). Agonist-induced contractions and relaxations were evaluated in isolated aortic rings from 3-month-old male Wistar rats treated by intra-muscular injection to caudal hind leg muscle with HgCl 2 (first dose, 4.6 µg/kg; subsequent doses, 0.07 µg/kg/day for 15 days) and optionally with EGT (2 µg/kg for 30 days). Reactive oxygen species (ROS) in aortic rings were measured by means of lucigenin- and luminol-enhanced chemiluminescence. The protein level of endothelial nitric oxide synthase was evaluated by ELISA. Blood glutathione (GSH) and catalase levels, lipid peroxidation and total nitrite were measured spectrophotometrically. The results indicated that low-dose HgCl 2 administration impaired acetylcholine (ACh)-induced relaxation and potentiated phenylephrine- and serotonin-induced contractions in rat aortas. In addition, HgCl 2 significantly increased the levels of ROS in the aortic tissue. EGT prevented the loss of ACh-induced relaxations and the increase in contractile responses. These effects were accompanied by a significant decrease in ROS levels. EGT also improved the ratio of reduced GSH to oxidized GSH and catalase levels with a concomitant decrease in lipid peroxidation. In conclusion, to the best of our knowledge, the present study was the first to report that EGT prevents endothelial dysfunction induced by low-dose HgCl 2 administration. EGT may serve as a therapeutic tool to reduce mercury-associated cardiovascular complications via improving the antioxidant status.

In Vitro and in Vivo Experimental Studies on Trabecular Meshwork Degeneration Induced by Benzalkonium Chloride (An American Ophthalmological Society Thesis)

PubMed Central

Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

2012-01-01

Purpose: Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Methods: Trabecular specimens were examined using immunohistology and reverse transcriptase–polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Results: Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. Conclusion: BAK enhances all characteristics of TM degeneration typical of glaucoma—trabecular apoptosis, oxidative stress, induction of inflammatory chemokines—and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the

Fluid shear stress enhances the cell volume decrease of osteoblast cells by increasing the expression of the ClC-3 chloride channel

PubMed Central

LIU, LI; CAI, SIYI; QIU, GUIXING; LIN, JIN

2016-01-01

ClC-3 is a volume-sensitive chloride channel that is responsible for cell volume adjustment and regulatory cell volume decrease (RVD). In order to evaluate the effects of fluid shear stress (FSS) stimulation on the osteoblast ClC-3 chloride channel, MC3T3-E1 cells were stimulated by FSS in the experimental group. Fluorescence quantitative polymerase chain reaction was used to detect changes in ClC-3 mRNA expression, the chloride ion fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) was used to detect the chloride channel activity, and whole-cell patch clamping was used to monitor the changes in the volume-sensitive chloride current activated by a hypotonic environment following mechanical stimulation. The results show that the expression of the osteoblast chloride channel ClC-3 was significantly higher in the FSS group compared with the control group. MQAE fluorescence intensity was significantly reduced in the FSS group compared to the control group, suggesting that mechanical stimulation increased chloride channel activity and increased the efflux of intracellular chloride ions. Image analysis of osteoblast volume changes showed that osteoblast RVD was enhanced by mechanical stimulation. Whole-cell patch clamping showed that the osteoblast volume-sensitive chloride current was larger in the stimulated group compared to the control group, suggesting that elevated ClC-3 chloride channel expression results in an increased volume-sensitive chloride current. In conclusion, FSS stimulation enhances the RVD of osteoblast cell by increasing the expression of the ClC-3 and enhancing the chloride channel activity. PMID:27073622

Sodium chloride and hypertension.

PubMed

Huang, Y W

1997-09-01

The hypothesis that sodium chloride deficiency, and not its overuse, is prime cause of hypertension and arteriosclerosis is presented. In the author's home town--a farflung part of northern China--hypertension is a rare disease and arteriosclerosis is a virtually unknown condition. The average intake of sodium chloride for these people is > 30 g/day compared with the typical sodium chloride intake of 10-12 g per day in the USA. When the 10-12 g salt ingested is mixed with the average daily water intake (2100 ml), 0.47% to 0.57% saline mixture is produced, which is hypotonic to extracellular fluid in salt content. Thus sodium conservation becomes necessary. All the hormones and ions involved in sodium conservation are inducers of hypertension; these include aldosterone, angiotensin 11, glucocorticoids, catecholamine, and vasopression. Plus, potassium waste, induced under the influence of aldosterone excess, participates in the development of hypertension.

Apocynin prevented inflammation and oxidative stress in carbon tetra chloride induced hepatic dysfunction in rats.

PubMed

Rahman, Md Mizanur; Muse, Awale Yousuf; Khan, D M Isha Olive; Ahmed, Ismaile Hussein; Subhan, Nusrat; Reza, Hasan Mahmud; Alam, Md Ashraful; Nahar, Lutfun; Sarker, Satyajit Dey

2017-08-01

Liver fibrosis is a leading pathway to cirrhosis and a global clinical issue. Oxidative stress mediated tissue damage is one of the prime causes of hepatic dysfunction and fibrosis. Apocynin is one of many strong antioxidants. To evaluate the effect of apocynin in the CCl 4 administered hepatic dysfunction in rats. Female Long Evans rats were administered with CCl 4 orally (1mL/kg) twice a week for 2 weeks and were treated with apocynin (100mg/kg). Both plasma and liver tissues were analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase activities. Oxidative stress parameters were also measured by determining malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), advanced protein oxidation product (APOP). In addition, antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase activities in plasma and liver tissues were analyzed. Moreover, inflammation and tissue fibrosis were confirmed by histological staining of liver tissue sections. Apocynin significantly reduced serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. It also exhibited a considerable reduction of the oxidative stress markers (MDA, MPO, NO, and APOP level) which was elevated due to CCl 4 administration in rats. Apocynin treatment also restored the catalase and superoxide dismutase activity in CCl 4 treated rats. Histological analysis of liver sections revealed that apocynin prevented inflammatory cells infiltration and fibrosis in CCl 4 administered rats. These results suggest that apocynin protects liver damage induced by CCl 4 by inhibiting lipid peroxidation and stimulating the cellular antioxidant system. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Corrosion Product Film-Induced Stress Facilitates Stress Corrosion Cracking

PubMed Central

Wang, Wenwen; Zhang, Zhiliang; Ren, Xuechong; Guan, Yongjun; Su, Yanjing

2015-01-01

Finite element analyses were conducted to clarify the role of corrosion product films (CPFs) in stress corrosion cracking (SCC). Flat and U-shaped edge-notched specimens were investigated in terms of the CPF-induced stress in the metallic substrate and the stress in the CPF. For a U-shaped edge-notched specimen, the stress field in front of the notch tip is affected by the Young’s modulus of the CPF and the CPF thickness and notch geometry. The CPF-induced tensile stress in the metallic substrate is superimposed on the applied load to increase the crack tip strain and facilitate localized plasticity deformation. In addition, the stress in the CPF surface contributes to the rupture of the CPFs. The results provide physical insights into the role of CPFs in SCC. PMID:26066367

Relations of enzymes inAspergillus repens grown under sodium chloride stress.

PubMed

Kelavkar, U P; Chhatpar, H S

1993-09-01

Aspergillus repens, a salt-pan isolate, was halotolerant. When grown for 72 h (log phase) and 144 h (beginning of stationary phase) in a medium containing 2M sodium chloride, the activities of invertase, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH), and glutamate dehydrogenase (GDH) were found to have increased. Control cultures grown in a medium devoid of 2M NaCl failed to show such changes. The activities of MDH, G6PDH, and GDH increased with rising concentrations of Na(+) (as NaCl) when added up to 100MM in vitro. At higher concentrations they decreased. Changes in kinetic constants, Km and Vmax of these enzymes, as well as their de novo synthesis, were found to be some of the responses to NaCl stress-mediated changes.

The Surgically Induced Stress Response

PubMed Central

Finnerty, Celeste C.; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A.; Herndon, David N.

2013-01-01

The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes which induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Although the stress response to acute trauma evolved to improve chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

Effect of sodium chloride and cadmium on the growth, oxidative stress and antioxidant enzyme activities of Zygosaccharomyces rouxii

NASA Astrophysics Data System (ADS)

Li, Chunsheng; Xu, Ying; Jiang, Wei; Lv, Xin; Dong, Xiaoyan

2014-06-01

Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium (Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride (NaCl) and Cd are poorly understood. This study investigated the effects of NaCl and Cd on the growth, oxidative stress and antioxidant enzyme activities of Z. rouxii after stress treatment for 24 h. Results showed that NaCl or Cd alone negatively affected the growth of Z. rouxii, but the growth-inhibiting effect of Cd on Z. rouxii was reduced in the presence of NaCl. Flow cytometry assay showed that under Cd stress, NaCl significantly reduced the production of reactive oxygen species (ROS) and cell death of Z. rouxii compared with those in the absence of NaCl. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) of Z. rouxii were significantly enhanced by 2%-6% NaCl, which likely contributed to the high salt tolerance of Z. rouxii. The POD activity was inhibited by 20 mg L-1 Cd while the SOD and CAT activities were enhanced by 8 mg L-1 Cd and inhibited by 20 mg L-1 or 50 mg L-1 Cd. The inhibitory effect of high-level Cd on the antioxidant enzyme activities of Z. rouxii was counteracted by the combined use of NaCl, especially at 6%. This probably accounted for the decrease in Cd-induced ROS production and cell death of Z. rouxii after incubation with NaCl and Cd. Our work provided physiological clues as to the use of Z. rouxii as a biosorbent for Cd removal from seawater and liquid highly salty food.

Anisotropy induced in a silver chloride emulsion by two successive beams of white light perpendicularly polarized

NASA Astrophysics Data System (ADS)

Attia, Mondher; Debrus, Solange; Henriot, M. P.; May, Marie

1983-04-01

This paper is a study of the anisotropy induced in a silver chloride photographic emulsion by two successive beams of white light, linearly polarized at right angle. After the first exposure, the colloidal medium contains silver ellipsoids e generated by the photolysis of silver chloride and silver ellipsoids e b resulting of the partial destruction of some of the previous ones by long wavelengths. This medium is then illuminated by the second beam linearly polarized at right angle of the first beam. Short wavelengths induced silver ellipsoids e' identical to the ellopsoids e but rotated through π/2 with respect to them. As in the first exposure, some of them are partly broken up and transformed into ellipsoids e' b identical to ellipsoids e b but the direction of their major axis. Moreover, the long wavelengths of second exposure transform some of the particles e and e b generated during the first exposure, into smaller ellipsoids e eb and e bb. Finally, the colloidal medium resulting of these two exposures, contains silver chloride and six sorts of silver particles. By calculating the indices of the medium, we show that the wavelengths characterizing the zero birefringence and zero dichroism of the emulsion are dependent on the energies recorded during each of the exposures.

Development of remote sensing techniques for assessment of salinity induced plant stresses

NASA Astrophysics Data System (ADS)

Stong, Matthew Harold

Salinity has been shown to reduce vegetative growth, crop quality, and yield in agricultural crops. Remote sensing is capable of providing data about large areas. This project was designed to induce salinity stress in a crop, pak choi, and thereafter monitor the response of the crop as expressed by its spectral reflectances. The project was conducted in the National Taiwan University Phytotron, and spectral data was collected using a GER 2600. Yield and soil salinity (ECe) were also measured. After three seasons of data were collected, wavelengths sensitive to salinity were selected. These wavelengths, which are within the spectral response of biochemicals produced by plants as a response to soil salinity, were used to create two indices, the Salinity Stress Index (SSI) and the Normalized Salinity Stress Index (NSSI). After creating the indices tests were conducted to determine the efficacy of these indices in detecting salinity and drought stresses as compared to existing indices (SRVI and NDVI). This project induced salinity and drought stress in a crop, pak choi, and thereafter monitored the response of the crop as expressed by its spectral reflectances. The SSI and NSSI correlated well to both ECe and marketable yield. Additionally the SSI and NSSI were found to provide statistical differences between salinity stressed treatments and the control treatment. Drought stress was not detected well by any of the indices reviewed although the SSI and NSSI indices tended to increase with drought stress and decrease with salinity stress. As a final test, specific ion toxicities of sodium and chloride were tested against the developed indices (SSI and NSSI) and existing indices (NDVI, SRVI, and NDWI). There were no differences in SSI and NSSI responses to specific ion concentration in the high salinity treatments. These results indicated that the SSI and NSSI are not sensitive to the specific ion concentration in irrigation water. However, the SSI and NSSI were higher

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

PubMed

Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia

2017-04-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Carcinogenicity of benzyl chloride, benzal chloride, benzotrichloride and benzoyl chloride in mice by skin application.

PubMed

Fukuda, K; Matsushita, H; Sakabe, H; Takemoto, K

1981-10-01

The carcinogenicity of benzyl chloride (BYC), benzal chloride (BAC), benzotrichloride (BTC) and benzoyl chloride (BOC), which were suspected as causative agents of lung cancer and maxillary malignant lymphoma of workers employed in factories producing BOC, was examined by skin applications in female ICR mice. After rather high dose exposure, BTC exhibited leukemogenic and pulmonary tumorigenic activities as well as potent dermal carcinogenic activity. After administration of the chemicals at the dose of 2.3 microliter/animal, twice a week for 50 weeks, BTC induced 68% incidence of skin cancers and 58% incidence of pulmonary tumors (including 10% of lung carcinomas) within 399 days. Incidence of skin cancers was 58% for BAC, 15% for BYC and 10% for BOC within 560 days. Considering the extent of possible exposure of the workers to these chemicals in the working environment and the carcinogenic potency of the chemicals tested, it can be concluded that BTC was very probably responsible for causing the cancers seen int he workers employed in manufacturing BOC.

Exposure to Vinyl Chloride and Its Influence on Western Diet-Induced Cardiac Remodeling.

PubMed

Liang, Yaqin; Lang, Anna L; Zhang, Jian; Chen, Jing; Wang, Kai; Chen, Liya; Beier, Juliane I; Qian, Yan; Cai, Lu

2018-06-18

Obesity, usually caused by high fat diets (HFD), is a major public health issue worldwide, causing obesity associated cardiomyopathy. Moreover, the environmental toxicant vinyl chloride (VC) can exacerbate HFD-induced fatty liver disease. However, whether VC serves to enhance obesity-associated cardiomyopathy remains unclear. This study aims to investigate the interaction of western diet (WD) containing relatively low fat (42%) with VC on cardiac remodeling and its underling mechanisms. Adult male C57BL/6J mice were exposed to WD coinhalation of low-dose VC (<1 ppm/d) for 12 weeks. Results showed that WD feeding for 12 weeks caused slight cardiac systolic dysfunction without significant hypertrophy or fibrosis, even with VC. Nevertheless, WD upregulated NF-κB function and expression of IL-1β and PAI-1, while VC showed no significant impact on these effects. In contrast, WD together with VC significantly increased the expression of CHOP and TGF-β1, key markers for endoplasmic reticulum stress and profibrotic cytokine, respectively. In summary, exposure to low-dose of environmental toxicant VC while a WD is consumed for a relatively short time does not have significant impact on cardiac remodeling except for a mild systolic dysfunction of the heart.

Barium chloride induces redox status unbalance, upregulates cytokine genes expression and confers hepatotoxicity in rats-alleviation by pomegranate peel.

PubMed

Elwej, Awatef; Grojja, Yousri; Ghorbel, Imen; Boudawara, Ons; Jarraya, Raoudha; Boudawara, Tahia; Zeghal, Najiba

2016-04-01

The present study was performed to establish the therapeutic efficacy of pomegranate peel against barium chloride induced liver injury. Adult rats were divided into four groups of six animals each: group I, serving as controls, received distilled water; group II received by their drinking water 67 ppm of BaCl2; group III received both 67 ppm of BaCl2 by the same way than group II and 5 % of pomegranate peel (PP) via diet; group IV received 5 % of PP. Analysis by HPLC/MS of PP showed its rich composition in flavonoids such as gallic acid, castalin, hyperin, quercitrin, syringic acid, and quercetin. The protective effects of pomegranate peel against hepatotoxicity induced by barium chloride were assessed using biochemical parameters and histological studies. Exposure of rats to barium caused oxidative stress in the liver as evidenced by an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOHs), H2O2 and advanced oxidation protein product (AOPP) levels, and lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities, a decrease in catalase (CAT) and glutathione peroxidase (GPx) activities, glutathion (GSH), non-protein thiol (NPSH), vitamin C levels, and Mn-SOD gene expression. Liver total MT levels, MT-1, and MT-2 and pro-inflammatory cytokine genes expression like TNF-α, IL-1β and IL-6 were increased. Pomegranate peel, supplemented in the diet of barium-treated rats, showed an improvement of all the parameters indicated above.The present work provided ethnopharmacological relevance of pomegranate peel against the toxic effects of barium, suggesting its beneficial role as a potential antioxidant.

Transient alkalinization of the leaf apoplast stiffens the cell wall during onset of chloride salinity in corn leaves.

PubMed

Geilfus, Christoph-Martin; Tenhaken, Raimund; Carpentier, Sebastien Christian

2017-11-17

During chloride salinity, the pH of the leaf apoplast (pH apo ) transiently alkalizes. There is an ongoing debate about the physiological relevance of these stress-induced pH apo changes. Using proteomic analyses of expanding leaves of corn ( Zea mays L.), we show that this transition in pH apo conveys functionality by (i) adjusting protein abundances and (ii) affecting the rheological properties of the cell wall. pH apo was monitored in planta via microscopy-based ratio imaging, and the leaf-proteomic response to the transient leaf apoplastic alkalinization was analyzed via ultra-high performance liquid chromatography-MS. This analysis identified 1459 proteins, of which 44 exhibited increased abundance specifically through the chloride-induced transient rise in pH apo These elevated protein abundances did not directly arise from high tissue concentrations of Cl - or Na + but were due to changes in the pH apo Most of these proteins functioned in growth-relevant processes and in the synthesis of cell wall-building components such as arabinose. Measurements with a linear-variable differential transducer revealed that the transient alkalinization rigidified ( i.e. stiffened) the cell wall during the onset of chloride salinity. A decrease in t -coumaric and t -ferulic acids indicates that the wall stiffening arises from cross-linkage to cell wall polymers. We conclude that the pH of the apoplast represents a dynamic factor that is mechanistically coupled to cellular responses to chloride stress. By hardening the wall, the increased pH abrogates wall loosening required for cell expansion and growth. We conclude that the transient alkalinization of the leaf apoplast is related to salinity-induced growth reduction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Surface Chloride Levels in Colorado Structural Concrete

DOT National Transportation Integrated Search

2018-01-01

This project focused on the chloride-induced corrosion of reinforcing steel in structural concrete. The primary goal of this project is to analyze the surface chloride concentration level of the concrete bridge decks throughout Colorado. The study in...

[Stress-induced cellular adaptive mutagenesis].

PubMed

Zhu, Linjiang; Li, Qi

2014-04-01

The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

Physical Exercise Counteracts Stress-induced Upregulation of Melanin-concentrating Hormone in the Brain and Stress-induced Persisting Anxiety-like Behaviors.

PubMed

Kim, Tae-Kyung; Han, Pyung-Lim

2016-08-01

Chronic stress induces anxiety disorders, whereas physical exercise is believed to help people with clinical anxiety. In the present study, we investigated the mechanisms underlying stress-induced anxiety and its counteraction by exercise using an established animal model of anxiety. Mice treated with restraint for 2 h daily for 14 days exhibited anxiety-like behaviors, including social and nonsocial behavioral symptoms, and these behavioral impairments lasted for more than 12 weeks after the stress treatment was removed. Despite these lasting behavioral changes, wheel-running exercise treatment for 1 h daily from post-stress days 1 - 21 counteracted anxiety-like behaviors, and these anxiolytic effects of exercise persisted for more than 2 months, suggesting that anxiolytic effects of exercise stably induced. Repeated restraint treatment up-regulated the expression of the neuropeptide, melanin-concentrating hormone (MCH), in the lateral hypothalamus, hippocampus, and basolateral amygdala, the brain regions important for emotional behaviors. In an in vitro study, treatment of HT22 hippocampal cells with glucocorticoid increased MCH expression, suggesting that MCH upregulation can be initially triggered by the stress hormone, corticosterone. In contrast, post-stress treatment with wheel-running exercise reduced the stress-induced increase in MCH expression to control levels in the lateral hypothalamus, hippocampus and basolateral amygdala. Administration of an MCH receptor antagonist (SNAP94847) to stress-treated mice was therapeutic against stress-induced anxiety-like behaviors. These results suggest that repeated stress produces long-lasting anxiety-like behaviors and upregulates MCH in the brain, while exercise counteracts stress-induced MCH expression and persisting anxiety-like behaviors.

High salt intake enhances swim stress-induced PVN vasopressin cell activation and active stress coping.

PubMed

Mitchell, N C; Gilman, T L; Daws, L C; Toney, G M

2018-07-01

Stress contributes to many psychiatric disorders; however, responsivity to stressors can vary depending on previous or current stress exposure. Relatively innocuous heterotypic (differing in type) stressors can summate to result in exaggerated neuronal and behavioral responses. Here we investigated the ability of prior high dietary sodium chloride (salt) intake, a dehydrating osmotic stressor, to enhance neuronal and behavioral responses of mice to an acute psychogenic swim stress (SS). Further, we evaluated the contribution of the osmo-regulatory stress-related neuropeptide arginine vasopressin (VP) in the hypothalamic paraventricular nucleus (PVN), one of only a few brain regions that synthesize VP. The purpose of this study was to determine the impact of high dietary salt intake on responsivity to heterotypic stress and the potential contribution of VPergic-mediated neuronal activity on high salt-induced stress modulation, thereby providing insight into how dietary (homeostatic) and environmental (psychogenic) stressors might interact to facilitate psychiatric disorder vulnerability. Salt loading (SL) with 4% saline for 7 days was used to dehydrate and osmotically stress mice prior to exposure to an acute SS. Fluid intake and hematological measurements were taken to quantify osmotic dehydration, and serum corticosterone levels were measured to index stress axis activation. Immunohistochemistry (IHC) was used to stain for the immediate early gene product c-Fos to quantify effects of SL on SS-induced activation of neurons in the PVN and extended amygdala - brain regions that are synaptically connected and implicated in responding to osmotic stress and in modulation of SS behavior, respectively. Lastly, the role of VPergic PVN neurons and VP type 1 receptor (V1R) activity in the amygdala in mediating effects of SL on SS behavior was evaluated by quantifying c-Fos activation of VPergic PVN neurons and, in functional experiments, by nano-injecting the V1R selective

Ion Transport and Precipitation Kinetics as Key Aspects of Stress Generation on Pore Walls Induced by Salt Crystallization

NASA Astrophysics Data System (ADS)

Naillon, A.; Joseph, P.; Prat, M.

2018-01-01

The stress generation on pore walls due to the growth of a sodium chloride crystal in a confined aqueous solution is studied from evaporation experiments in microfluidic channels in conjunction with numerical computations of crystal growth. The study indicates that the stress buildup on the pore walls is a highly transient process taking place over a very short period of time (in less than 1 s in our experiments). The analysis makes clear that what matters for the stress generation is not the maximum supersaturation at the onset of the crystal growth but the supersaturation at the interface between the solution and the crystal when the latter is about to be confined between the pore walls. The stress generation is summarized in a simple stress diagram involving the pore aspect ratio and the Damkhöler number characterizing the competition between the precipitation reaction kinetics and the ion transport towards the growing crystal. This opens up the route for a better understanding of the damage of porous materials induced by salt crystallization, an important issue in Earth sciences, reservoir engineering, and civil engineering.

Lycium barbarum Polysaccharides Protect against Trimethyltin Chloride-Induced Apoptosis via Sonic Hedgehog and PI3K/Akt Signaling Pathways in Mouse Neuro-2a Cells.

PubMed

Zhao, Wanyun; Pan, Xiaoqi; Li, Tao; Zhang, Changchun; Shi, Nian

2016-01-01

Trimethyltin chloride (TMT) is a classic neurotoxicant that can cause severe neurodegenerative diseases. Some signaling pathways involving cell death play pivotal roles in the central nervous system. In this study, the role of Sonic Hedgehog (Shh) and PI3K/Akt pathways in TMT-induced apoptosis and protective effect of Lycium barbarum polysaccharides (LBP) on mouse neuro-2a (N2a) cells were investigated. Results showed that TMT treatment significantly enhanced apoptosis, upregulated proapoptotic Bax, downregulated antiapoptotic Bcl-2 expression, and increased caspase-3 activity in a dose-dependent manner in N2a cells. TMT induced oxidative stress in cells, performing reactive oxygen species (ROS) and malondialdehyde (MDA) excessive generation, and superoxide dismutase (SOD) activity reduction. TMT significantly decreased phosphorylated glycogen synthase kinase-3β (GSK-3β) and inhibited Shh and PI3K/Akt pathways. However, the addition of LBP upregulated GSK-3β phosphorylation, activated Shh and PI3K/Akt pathways, and eventually reduced apoptosis and oxidative stress caused by TMT. The interaction between Shh and PI3K/Akt pathways was clarified by specific PI3K inhibitor LY294002 or Shh inhibitor GDC-0449. Moreover, LY294002 and GDC-0449 pretreatment both induced phosphorylated GSK-3β downregulation and significantly promoted apoptosis induced by TMT. These results suggest that LBP could reduce TMT-induced N2a cells apoptosis by regulating GSK-3β phosphorylation, Shh, and PI3K/Akt signaling pathways.

Lycium barbarum Polysaccharides Protect against Trimethyltin Chloride-Induced Apoptosis via Sonic Hedgehog and PI3K/Akt Signaling Pathways in Mouse Neuro-2a Cells

PubMed Central

Zhao, Wanyun; Pan, Xiaoqi; Li, Tao; Zhang, Changchun; Shi, Nian

2016-01-01

Trimethyltin chloride (TMT) is a classic neurotoxicant that can cause severe neurodegenerative diseases. Some signaling pathways involving cell death play pivotal roles in the central nervous system. In this study, the role of Sonic Hedgehog (Shh) and PI3K/Akt pathways in TMT-induced apoptosis and protective effect of Lycium barbarum polysaccharides (LBP) on mouse neuro-2a (N2a) cells were investigated. Results showed that TMT treatment significantly enhanced apoptosis, upregulated proapoptotic Bax, downregulated antiapoptotic Bcl-2 expression, and increased caspase-3 activity in a dose-dependent manner in N2a cells. TMT induced oxidative stress in cells, performing reactive oxygen species (ROS) and malondialdehyde (MDA) excessive generation, and superoxide dismutase (SOD) activity reduction. TMT significantly decreased phosphorylated glycogen synthase kinase-3β (GSK-3β) and inhibited Shh and PI3K/Akt pathways. However, the addition of LBP upregulated GSK-3β phosphorylation, activated Shh and PI3K/Akt pathways, and eventually reduced apoptosis and oxidative stress caused by TMT. The interaction between Shh and PI3K/Akt pathways was clarified by specific PI3K inhibitor LY294002 or Shh inhibitor GDC-0449. Moreover, LY294002 and GDC-0449 pretreatment both induced phosphorylated GSK-3β downregulation and significantly promoted apoptosis induced by TMT. These results suggest that LBP could reduce TMT-induced N2a cells apoptosis by regulating GSK-3β phosphorylation, Shh, and PI3K/Akt signaling pathways. PMID:27143997

Comparison of effects of isotonic sodium chloride with diltiazem in prevention of contrast-induced nephropathy.

PubMed

Beyazal, Hatice; Caliskan, Zuhal; Utaç, Cengiz

2014-04-01

Contrast-induced nephropathy (CIN) significantly increases the morbidity and mortality of patients. The aim of this study is to investigate and compare the protective effects of isotonic sodium chloride with sodium bicarbonate infusion and isotonic sodium chloride infusion with diltiazem, a calcium channel blocker, in preventing CIN. Our study included patients who were administered 30-60 mL of iodinated contrast agent for percutaneous coronary angiography (PCAG), all with creatinine values between 1.1 and 3.1 mg/dL. Patients were divided into three groups and each group had 20 patients. The first group of patients was administered isotonic sodium chloride; the second group was administered a solution that of 5% dextrose and sodium bicarbonate, while the third group was administered isotonic sodium chloride before and after the contrast injection. The third group received an additional injection of diltiazem the day before and first 2 days after the contrast injection. All of the patients' plasma blood urea nitrogen (BUN) and creatinine levels were measured on the second and seventh day after the administration of intravenous contrast material. The basal creatinine levels were similar for all three groups (p > 0.05). Among a total of 60 patients included in the study, 16 patients developed acute renal failure (ARF) on the second day after contrast material was injected (26.6%). The number of patients who developed ARF on the second day after the injection in the first group was five (25%), in the second group was six (30%) and the third group was five (25%) (p > 0.05). There was no significant difference between isotonic sodium chloride, sodium bicarbonate and isotonic sodium chloride with diltiazem application in prevention of CIN.

Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy

PubMed Central

Nordquist, Lina; Friederich-Persson, Malou; Fasching, Angelica; Liss, Per; Shoji, Kumi; Nangaku, Masaomi; Hansell, Peter

2015-01-01

Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs. We elucidated the involvement of oxidative stress by studying the effects of acute administration of the superoxide dismutase mimetic tempol. Compared with controls, diabetic rats displayed tissue hypoxia throughout the kidney, glomerular hyperfiltration, increased oxygen consumption, increased total mitochondrial leak respiration, and decreased tubular sodium transport efficiency. Diabetic kidneys showed proteinuria and tubulointerstitial damage. Cobalt chloride activated HIFs, prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, and kidney function, and reduced proteinuria and tubulointerstitial damage. The beneficial effects of tempol were less pronounced after activation of HIFs, indicating improved oxidative stress status. In conclusion, activation of HIFs prevents diabetes-induced alteration in kidney oxygen metabolism by normalizing glomerular filtration, which reduces tubular electrolyte load, preventing mitochondrial leak respiration and improving tubular transport efficiency. These improvements could be related to reduced oxidative stress and account for the reduced proteinuria and tubulointerstitial damage. Thus, pharmacologic activation of the HIF system may prevent development of diabetic nephropathy. PMID:25183809

Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice.

PubMed

Tabrizian, Kaveh; Yazdani, Abdolmajid; Baheri, Behnam; Payandemehr, Borna; Sanati, Mehdi; Hashemzaei, Mahmoud; Miri, Abdolhossein; Zandkarimi, Majid; Belaran, Maryam; Fanoudi, Sahar; Sharifzadeh, Mohammad

2016-01-01

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

[Sodium chloride 0.9%: nephrotoxic crystalloid?].

PubMed

Dombre, Vincent; De Seigneux, Sophie; Schiffer, Eduardo

2016-02-03

Sodium chloride 0.9%, often incorrectly called physiological saline, contains higher concentration of chloride compared to plasma. It is known that the administration of sodium chloride 0.9% can cause hyperchloremic metabolic acidosis in a reproducible manner. The elevated chloride concentration in 0.9% NaCl solution can also adversely affect renal perfusion. This effect is thought to be induced by hyperchloremia that causes renal artery vasoconstriction. For these reasons, the use of 0.9% NaCl solution is raising attention and some would advocate the use of a more "physiological" solution, such as balanced solutions that contain a level of chloride closer to that of plasma. Few prospective, randomized, controlled trials are available today and most were done in a perioperative setting. Some studies suggest that the chloride excess in 0.9% NaCl solution could have clinical consequences; however, this remains to be established by quality randomized controlled trials.

Gravity-induced stresses in stratified rock masses

USGS Publications Warehouse

Amadei, B.; Swolfs, H.S.; Savage, W.Z.

1988-01-01

This paper presents closed-form solutions for the stress field induced by gravity in anisotropic and stratified rock masses. These rocks are assumed to be laterally restrained. The rock mass consists of finite mechanical units, each unit being modeled as a homogeneous, transversely isotropic or isotropic linearly elastic material. The following results are found. The nature of the gravity induced stress field in a stratified rock mass depends on the elastic properties of each rock unit and how these properties vary with depth. It is thermodynamically admissible for the induced horizontal stress component in a given stratified rock mass to exceed the vertical stress component in certain units and to be smaller in other units; this is not possible for the classical unstratified isotropic solution. Examples are presented to explore the nature of the gravity induced stress field in stratified rock masses. It is found that a decrease in rock mass anisotropy and a stiffening of rock masses with depth can generate stress distributions comparable to empirical hyperbolic distributions previously proposed in the literature. ?? 1988 Springer-Verlag.

Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression.

PubMed

Zhou, Rui; Lu, Yi; Han, Yong; Li, Xia; Lou, Huifang; Zhu, Liya; Zhen, Xuechu; Duan, Shumin

2015-12-03

Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective effects of Curcuma longa against neurobehavioral and neurochemical damage caused by cerium chloride in mice.

PubMed

Kadri, Yamina; Nciri, Riadh; Brahmi, Noura; Saidi, Saber; Harrath, Abdel Halim; Alwasel, Saleh; Aldahmash, Waleed; El Feki, Abdelfatteh; Allagui, Mohamed Salah

2018-05-07

Cerium chloride (CeCl 3 ) is considered an environmental pollutant and a potent neurotoxic agent. Medicinal plants have many bioactive compounds that provide protection against damage caused by such pollutants. Curcuma longa is a bioactive compound-rich plant with very important antioxidant properties. To study the preventive and healing effects of Curcuma longa on cerium-damaged mouse brains, we intraperitoneally injected cerium chloride (CeCl 3 , 20 mg/kg BW) along with Curcuma longa extract, administrated by gavage (100 mg/kg BW), into mice for 60 days. We then examined mouse behavior, brain tissue damage, and brain oxidative stress parameters. Our results revealed a significant modification in the behavior of the CeCl 3 -treated mice. In addition, CeCl 3 induced a significant increment in lipid peroxidation, carbonyl protein (PCO), and advanced oxidation protein product levels, as well as a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Acetylcholinesterase (AChE) activity remarkably increased in the brain of CeCl 3 -treated mice. Histopathological observations confirmed these results. Curcuma longa attenuated CeCl 3 -induced oxidative stress and increased the activities of antioxidant enzymes. It also decreased AChE activity in the CeCl 3 -damaged mouse brain that was confirmed by histopathology. In conclusion, this study suggests that Curcuma longa has a neuroprotective effect against CeCl 3 -induced damage in the brain.

Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

PubMed

Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

2015-01-01

We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats.

PubMed

Yılmaz, Seval; Kaya, Emre; Comakli, Selim

2017-09-01

Aflatoxins are toxic metabolites produced by Aspergillus flavus and Aspergillus parasiticus and are classified as group I carcinogens by the International Agency for Research on Cancer (IARC). The purpose of this study was to investigate the possible preventive role of vitamin E (Vit E) on aflatoxin (AF) induced toxicity by using biochemical and histopathological approaches. Wistar-Albino rats were divided into 4 groups as follows: control group, Vit E group (Vit E was administered), AFB1 group (a single dose of AFB1 was administered), AF + Vit E group (AF and Vit E were administered). The effects of Vit E on AFB1 induced tissue toxicity were evaluated by using malondialdehyde (MDA), reduced glutathione (GSH) levels, antioxidant enzyme activities, and histopathological examination in tissues. AF caused the oxidative stress by the increased MDA level and the reduced GSH level, glutathioneS-transferase (GST), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glucose-6-phosphate dehydrogenase (G6PD) activities in tissues. Plasma aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities, creatinine, and urea concentrations significantly increased; whereas, chloride, phosphorus, and magnesium concentrations were insignificantly affected. Plasma glucose, protein and sodium concentrations significantly decreased. Administration of AF caused hepatotoxicity, cardiotoxicity, and nephrotoxicity. As far as histopathological changes are concerned, a statistically significant difference was found in AFB1 group compared to the control group. Vit E considerably reduced plasma AST, ALT, ALP, LDH activities, and urea concentration and ameliorated the deleterious effects of AF on oxidative stress markers and pathological changes. This data indicated that the natural antioxidant Vit E might have a protective effect against AF-induced toxicity and oxidative stress.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

PubMed Central

Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

2016-01-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus–pituitary–adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. PMID:26668010

Molecular mechanism of emotional stress-induced and catecholamine-induced heart attack.

PubMed

Ueyama, Takashi; Senba, Emiko; Kasamatsu, Ken; Hano, Takuzo; Yamamoto, Katsuhiro; Nishio, Ichiro; Tsuruo, Yoshihiro; Yoshida, Ken-ichi

2003-01-01

Emotional or physical stress triggers 'tako-tsubo' cardiomyopathy or 'transient left ventricular apical ballooning', but the pathogenesis is unclear. In response to the immobilization stress of rats, a useful model of emotional stress, rapid activation of p44/p42 mitogen-activated protein kinase was observed in the heart, followed by a transient upregulation of immediate early genes in the smooth muscle cells of coronary arteries, the endothelial cells and the myocardium. Heat shock protein 70 was induced in the aortic and coronary arterial smooth muscle cells and in the myocardium. Natriuretic peptide genes were also upregulated in the myocardium. Sequential gene expression can be considered as an adaptive response to emotional stress. Blocking of both alpha-adrenoceptors and beta-adrenoceptors eliminated the upregulation of immediate early genes induced by stress, while alpha-agonists and beta-agonists upregulated immediate early genes in the perfused heart. Activation of alpha-adrenoceptors and beta-adrenoceptors is the primary trigger of emotional stress-induced molecular changes in the heart.

Role of CFTR in oxidative stress and suicidal death of renal cells during cisplatin-induced nephrotoxicity

PubMed Central

Rubera, I; Duranton, C; Melis, N; Cougnon, M; Mograbi, B; Tauc, M

2013-01-01

The clinical use of the antineoplastic drug cisplatin is limited by its deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to renal cell death and irreversible kidney dysfunction. Oxidative stress could be modified by the cystic fibrosis transmembrane conductance regulator protein (CFTR), a Cl− channel not only involved in chloride secretion but as well in glutathione (GSH) transport. Thus, we tested whether the inhibition of CFTR could protect against cisplatin-induced nephrotoxicity. Using a renal proximal cell line, we show that the specific inhibitor of CFTR, CFTRinh-172, prevents cisplatin-induced cell death and apoptosis by modulating the intracellular reactive oxygen species balance and the intracellular GSH concentration. This CFTRinh-172-mediated protective effect occurs without affecting cellular cisplatin uptake or the formation of platinum-DNA adducts. The protective effect of CFTRinh-172 in cisplatin-induced nephrotoxicity was also investigated in a rat model. Five days after receiving a single cisplatin injection (5 mg/kg), rats exhibited renal failure, as evidenced by the alteration of biochemical and functional parameters. Pretreatment of rats with CFTRinh-172 (1 mg/kg) prior to cisplatin injection significantly prevented these deleterious cisplatin-induced nephrotoxic effects. Finally, we demonstrate that CFTRinh-172 does not impair cisplatin-induced cell death in the cisplatin-sensitive A549 cancer cell line. In conclusion, the use of a specific inhibitor of CFTR may represent a novel therapeutic approach in the prevention of nephrotoxic side effects during cisplatin treatment without affecting its antitumor efficacy. PMID:24091660

Electrochemical chloride extraction : influence of concrete surface on treatment.

DOT National Transportation Integrated Search

2002-10-01

One bridge restoration technique available for reducing corrosion-induced concrete deterioration, which removes : chloride ions while simultaneously realkalizing the concrete adjacent to the steel, is electrochemical chloride extraction : (ECE). Stud...

Electrochemical Chloride Extraction : Influence of Concrete Surface on Treatment

DOT National Transportation Integrated Search

2002-09-01

One bridge restoration technique available for reducing corrosion-induced concrete deterioration, which removes chloride ions while simultaneously realkalizing the concrete adjacent to the steel, is electrochemical chloride extraction (ECE). Studies ...

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

PubMed

Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

2016-04-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malatynska, E.; Knapp, R.J.; Ikeda, M.

1988-01-01

Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated /sup 36/Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced bymore » them.« less

Effect of the Type of Surface Treatment and Cement on the Chloride Induced Corrosion of Galvanized Reinforcements

NASA Astrophysics Data System (ADS)

Tittarelli, Francesca; Mobili, Alessandra; Vicerè, Anna Maria; Roventi, Gabriella; Bellezze, Tiziano

2017-10-01

The effect of a new passivation treatment, obtained by immersion of the galvanized reinforcements in a trivalent chromium salts based solution, on the chlorides induced corrosion has been investigated. To investigate also the effect of cement alkalinity on corrosion behaviour of reinforcements, concretes manufactured with three different European cements were compared. The obtained results show that the alternative treatment based on hexavalent chromium-free baths forms effective protection layers on the galvanized rebar surfaces. The higher corrosion rates of zinc coating in concrete manufactured with Portland cement compared to those recorded for bars in concrete manufactured with pozzolanic cement depends strongly on the higher chloride content at the steel concrete interface.

Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response

PubMed Central

Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B.; De Giovanni, Laura N.; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E.; Spear, Linda P.; Pautassi, Ricardo Marcos

2016-01-01

Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. PMID:26830848

Case report of occupational asthma induced by polyvinyl chloride and nickel.

PubMed

Song, Ga-Won; Ban, Ga-Young; Nam, Young-Hee; Park, Hae-Sim; Ye, Young-Min

2013-10-01

Polyvinyl chloride (PVC) is a widely used chemical for production of plastics. However occupational asthma (OA) caused by PVC has been reported only rarely. We report a 34-yr-old male wallpaper factory worker with OA due to PVC and nickel (Ni) whose job was mixing PVC with plasticizers. He visited the emergency room due to an asthma attack with moderate airflow obstruction and markedly increased sputum eosinophil numbers. A methacholine challenge test was positive (PC20 2.5 mg/mL). Bronchoprovocation tests with both PVC and Ni showed early and late asthmatic responses, respectively. Moreover, the fractional concentration of exhaled nitric oxide (FeNO) was increased after challenge with PVC. To our knowledge, this is the first case of OA in Korea induced by exposure to both PVC and Ni. We suggest that eosinophilic inflammation may be involved in the pathogenesis of PVC-induced OA and that FeNO monitoring can be used for its diagnosis.

Case Report of Occupational Asthma Induced by Polyvinyl Chloride and Nickel

PubMed Central

Song, Ga-Won; Ban, Ga-Young; Nam, Young-Hee; Park, Hae-Sim

2013-01-01

Polyvinyl chloride (PVC) is a widely used chemical for production of plastics. However occupational asthma (OA) caused by PVC has been reported only rarely. We report a 34-yr-old male wallpaper factory worker with OA due to PVC and nickel (Ni) whose job was mixing PVC with plasticizers. He visited the emergency room due to an asthma attack with moderate airflow obstruction and markedly increased sputum eosinophil numbers. A methacholine challenge test was positive (PC20 2.5 mg/mL). Bronchoprovocation tests with both PVC and Ni showed early and late asthmatic responses, respectively. Moreover, the fractional concentration of exhaled nitric oxide (FeNO) was increased after challenge with PVC. To our knowledge, this is the first case of OA in Korea induced by exposure to both PVC and Ni. We suggest that eosinophilic inflammation may be involved in the pathogenesis of PVC-induced OA and that FeNO monitoring can be used for its diagnosis. PMID:24133363

Stress antagonizes morphine-induced analgesia in rats

NASA Technical Reports Server (NTRS)

Vernikos, J.; Shannon, L.; Heybach, J. P.

1981-01-01

Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported.

Stress and salicylic acid induce the expression of PnFT2 in the regulation of the stress-induced flowering of Pharbitis nil.

PubMed

Yamada, Mizuki; Takeno, Kiyotoshi

2014-02-15

Poor nutrition and low temperature stress treatments induced flowering in the Japanese morning glory Pharbitis nil (synonym Ipomoea nil) cv. Violet. The expression of PnFT2, one of two homologs of the floral pathway integrator gene FLOWERING LOCUS T (FT), was induced by stress, whereas the expression of both PnFT1 and PnFT2 was induced by a short-day treatment. There was no positive correlation between the flowering response and the homolog expression of another floral pathway integrator gene SUPPRESSOR OF OVEREXPRESSION OF CO1 and genes upstream of PnFT, such as CONSTANS. In another cultivar, Tendan, flowering and PnFT2 expression were not induced by poor nutrition stress. Aminooxyacetic acid (AOA), a phenylalanine ammonia-lyase inhibitor, inhibited the flowering and PnFT2 expression induced by poor nutrition stress in Violet. Salicylic acid (SA) eliminated the inhibitory effects of AOA. SA enhanced PnFT2 expression under the poor nutrition stress but not under non-stress conditions. These results suggest that SA induces PnFT2 expression, which in turn induces flowering; SA on its own, however, may not be sufficient for induction. Copyright © 2013 Elsevier GmbH. All rights reserved.

Inhalation exposure to methylene chloride does not induce systemic immunotoxicity in rats.

PubMed

Warbrick, E V; Kilgour, J D; Dearman, R J; Kimber, I; Dugard, P H

2003-07-11

Methylene chloride (dichloromethane) is used in a variety of industrial applications. To date, there has been no formal assessment of immunotoxicity attributed to methylene chloride. Studies were undertaken to examine whether methylene chloride has any potential to influence the integrity of immune function. For this purpose, Sprague-Dawley rats of both genders were exposed by inhalation to a single high dose (5000 ppm) of methylene chloride for 6 h/d, 5 d/wk for 28 d. This was considered the relevant route of administration, as not only is inhalation a primary route for human exposure to methylene chloride, but, also, the chemical is absorbed rapidly via the lungs. Under these conditions of exposure, methylene chloride failed to influence absolute or relative thymus weights in either gender and produced a significant reduction in relative, but not absolute, spleen weight in female rats only. Immunocompetence was measured as a function of the ability of treated animals to mount immunoglobulin M (IgM) antibody responses to sheep red blood cells (SRBC) as determined by enzyme-linked immunosorbent assay (ELISA). Exposure to methylene chloride did not affect antibody production. Evidence indicates that under these conditions of exposure, methylene chloride did not compromise immune function.

Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels.

PubMed

Ma, Lianshun; Yang, Yaping; Yin, Zizhang; Liu, Mei; Wang, Liwei; Chen, Lixin; Zhu, Linyan; Yang, Haifeng

2017-06-01

Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry. The results indicated that emodin inhibited the CNE-2Z cell growth more significantly than NP69-SV40T cells and induced cell cycle arrest and apoptosis in CNE-2Z cells but not in NP69-SV40T cells. Chloride channel blocker 5-nitro-2-(3-phenylprop ylamino)-benzoate (NPPB) or tamoxifen both can prevent the apoptosis of CNE-2Z cells induced by emodin. Optical microscope and atomic force microscope (AFM) demonstrated that emodin can induce apoptotic volume decrease (AVD) and ultrastructure changes in CNE-2Z cell and inhibited by chloride channel blocker. These data could be a further evidence of chloride channel for preventing CNE-2Z cells from apoptosis induced by emodin. Whole cell patch clamp study also demonstrated that emodin can activate chloride channel in CNE-2Z cells but not in NP69-SV40T cells. Furthermore, the activated chloride currents can also be inhibited by chloride channel blockers indicating that chloride channel may be the potential target molecular of emodin exerting its anti-tumor efficiency in CNE-2Z cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Gravity-induced stresses in finite slopes

USGS Publications Warehouse

Savage, W.Z.

1994-01-01

An exact solution for gravity-induced stresses in finite elastic slopes is presented. This solution, which is applied for gravity-induced stresses in 15, 30, 45 and 90?? finite slopes, has application in pit-slope design, compares favorably with published finite element results for this problem and satisfies the conditions that shear and normal stresses vanish on the ground surface. The solution predicts that horizontal stresses are compressive along the top of the slopes (zero in the case of the 90?? slope) and tensile away from the bottom of the slopes, effects which are caused by downward movement and near-surface horizontal extension in front of the slope in response to gravity loading caused by the additional material associated with the finite slope. ?? 1994.

Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.

PubMed

Frank, Matthew G; Watkins, Linda R; Maier, Steven F

2011-06-01

Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

NASA Technical Reports Server (NTRS)

Bhattacharya, Sharmila; Hosamani, Ravikumar

2015-01-01

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Determination of chloride in brazilian crude oils by ion chromatography after extraction induced by emulsion breaking.

PubMed

Robaina, Nicolle F; Feiteira, Fernanda N; Cassella, Alessandra R; Cassella, Ricardo J

2016-08-05

The present paper reports on the development of a novel extraction induced by emulsion breaking (EIEB) method for the determination of chloride in crude oils. The proposed method was based on the formation and breaking of oil-in-water emulsions with the samples and the consequential transference of the highly water-soluble chloride to the aqueous phase during emulsion breaking, which was achieved by centrifugation. The determination of chloride in the extracts was performed by ion chromatography (IC) with conductivity detection. Several parameters (oil phase:aqueous phase ratio, crude oil:mineral oil ratio, shaking time and type and concentration of surfactant) that could affect the performance of the method were evaluated. Total extraction of chloride from samples could be achieved when 1.0g of oil phase (0.5g of sample+0.5g of mineral oil) was emulsified in 5mL of a 2.5% (m/v) solution of Triton X-114. The obtained emulsion was shaken for 60min and broken by centrifugation for 5min at 5000rpm. The separated aqueous phase was collected, filtered and diluted before analysis by IC. Under these conditions, the limit of detection was 0.5μgg(-1) NaCl and the limit of quantification was 1.6μgg(-1) NaCl. We applied the method to the determination of chloride in six Brazilian crude oils and the results did not differ statistically from those obtained by the ASTM D6470 method when the paired Student-t-test, at 95% confidence level, was applied. Copyright © 2016 Elsevier B.V. All rights reserved.

The apoptotic effect of Zoledronic acid on the nasopharyngeal carcinoma cells via ROS mediated chloride channel activation.

PubMed

Wang, Liang; Gao, Hong; Yang, Xiaoya; Liang, Xiechou; Tan, Qiuchan; Chen, Zhanru; Zhao, Chan; Gu, Zhuoyu; Yu, Meisheng; Zheng, Yanfang; Huang, Yanqing; Zhu, Linyan; Jacob, Tim J C; Wang, Liwei; Chen, Lixin

2018-06-08

Zoledronic acid (ZA), a third-generation bisphosphonate, has been applied for treatment of bone metastases caused by malignant tumors. Recent studies have found its anti-cancer effects on various tumor cells. One of the mechanisms of anti-cancer effects of ZA is induction of apoptosis. However, the mechanisms of ZA-induced apoptosis in tumor cells have not been clarified clearly. In this study, we investigated the roles of chloride channels in ZA-induced apoptosis in nasopharyngeal carcinoma CNE-2Z cells. Apoptosis and chloride current were induced by ZA and suppressed by chloride channel blockers. After the knockdown of ClC-3 expression by ClC-3 siRNA, ZA-induced chloride current and apoptosis were significantly suppressed, indicating that the chloride channel participated in ZA-induced apoptosis may be ClC-3. When reactive oxygen species (ROS) generation was inhibited by the antioxidant N-acetyl-L-cysteine (L-NAC), ZA-induced apoptosis and chloride current were blocked accordingly, suggesting that ZA induces apoptosis through promoting ROS production and subsequently activating chloride channel. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effects of induced stress on seismic forward modelling and inversion

NASA Astrophysics Data System (ADS)

Tromp, Jeroen; Trampert, Jeannot

2018-05-01

We demonstrate how effects of induced stress may be incorporated in seismic modelling and inversion. Our approach is motivated by the accommodation of pre-stress in global seismology. Induced stress modifies both the equation of motion and the constitutive relationship. The theory predicts that induced pressure linearly affects the unstressed isotropic moduli with a slope determined by their adiabatic pressure derivatives. The induced deviatoric stress produces anisotropic compressional and shear wave speeds; the latter result in shear wave splitting. For forward modelling purposes, we determine the weak form of the equation of motion under induced stress. In the context of the inverse problem, we determine induced stress sensitivity kernels, which may be used for adjoint tomography. The theory is illustrated by considering 2-D propagation of SH waves and related Fréchet derivatives based on a spectral-element method.

Central mechanisms of stress-induced headache.

PubMed

Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

2010-03-01

Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

Inhibitory effect of DIDS, NPPB, and phloretin on intracellular chloride channels.

PubMed

Malekova, Lubica; Tomaskova, Jana; Novakova, Marie; Stefanik, Peter; Kopacek, Juraj; Lakatos, Boris; Pastorekova, Silvia; Krizanova, Olga; Breier, Albert; Ondrias, Karol

2007-11-01

We studied the effects of the chloride channel blockers, 5-nitro-2-(phenylpropylamino)-benzoate (NPPB), dihydro-4,4' diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), and phloretin on H2O2-induced primary culture cardiomyocyte apoptosis and activity of intracellular chloride channels obtained from rat heart mitochondrial and lysosomal vesicles. The chloride channel blockers (100 micromol/l) inhibited the H2O2-induced cardiomyocytes apoptosis. We characterized the effect of the blockers on single channel properties of the chloride channels derived from the mitochondrial and lysosomal vesicles incorporated into a bilayer lipid membrane. The single chloride channel currents were measured in 250:50 mmol/l KCl cis/trans solutions. NPPB, DIDS, and phloretin inhibited the chloride channels by decreasing the channel open probability in a concentration-dependent manner with EC50 values of 42, 7, and 20 micromol/l, respectively. NPPB and phloretin inhibited the channel's conductance and open dwell time, indicating that they could affect the chloride selective filter, pore permeability, and gating mechanism of the chloride channels. DIDS and NPPB inhibited the channels from the other side than bongkrekic acid and carboxyatractyloside. The results may contribute to understand a possible involvement of intracellular chloride channels in apoptosis and cardioprotection.

Ghrelin mediates stress-induced food-reward behavior in mice

PubMed Central

Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M.; Lutter, Michael; Zigman, Jeffrey M.

2011-01-01

The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense “comfort foods.” Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin’s orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating. PMID:21701068

Ghrelin mediates stress-induced food-reward behavior in mice.

PubMed

Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M; Lutter, Michael; Zigman, Jeffrey M

2011-07-01

The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

Impact of mechanical stress induced in silica vacuum windows on laser-induced damage.

PubMed

Gingreau, Clémence; Lanternier, Thomas; Lamaignère, Laurent; Donval, Thierry; Courchinoux, Roger; Leymarie, Christophe; Néauport, Jérôme

2018-04-15

At the interface between vacuum and air, optical windows must keep their optical properties, despite being subjected to mechanical stress. In this Letter, we investigate the impact of such stress on the laser-induced damage of fused silica windows at the wavelength of 351 nm in the nanosecond regime. Different stress values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect of the stress on the laser-induced damage was evidenced.

Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

PubMed

Tatsuta, M; Iishi, H; Baba, M; Hirasawa, R; Yano, H; Sakai, N; Nakaizumi, A

1999-02-01

The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) alpha in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-alpha immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

Stress induced obesity: lessons from rodent models of stress

PubMed Central

Patterson, Zachary R.; Abizaid, Alfonso

2013-01-01

Stress was once defined as the non-specific result of the body to any demand or challenge to homeostasis. A more current view of stress is the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA) axis. When an organism encounters a stressor (social, physical, etc.), these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and lose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the

The effects of varenicline on stress-induced and cue-induced craving for cigarettes.

PubMed

Ray, Lara A; Lunny, Katy; Bujarski, Spencer; Moallem, Nathasha; Krull, Jennifer L; Miotto, Karen

2013-07-01

Varenicline is a partial agonist of the α4β2 nicotinic acetylcholine receptor approved by the FDA for the treatment of nicotine dependence. While the clinical efficacy of varenicline for smoking cessation is well-supported, its biobehavioral mechanisms of action remain poorly understood. This randomized, crossover, placebo-controlled, human laboratory study combines guided imagery stress exposure with in vivo presentation of cigarette cues to test the effects of varenicline on stress-induced and cue-induced craving for cigarettes. A total of 40 (13 females) daily smokers (≥10 cigarettes per day) completed a guided imagery exposure (stress and neutral) followed by the presentation of cigarette cues at the target dose of varenicline (1mg twice per day) and on matched placebo. Multilevel regression models revealed a significant main effect of varenicline (p<.01) such that it reduced cigarette craving across the experimental paradigm, compared to placebo. There was also a significant medication×stress×trial interaction indicating that varenicline attenuated cue induced craving following neutral imagery but not when cues were preceded by stress induction (i.e., stress+cues). These results elucidate the biobehavioral effects of varenicline for nicotine dependence and suggest that varenicline-induced amelioration of cigarette craving is unique to tonic craving and cue-induced craving following neutral imagery but does not extend to the combination of stress plus cues. Copyright © 2013. Published by Elsevier Ireland Ltd.

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

PubMed Central

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

2017-01-01

Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

PubMed Central

Mantsch, John R; Baker, David A; Funk, Douglas; Lê, Anh D; Shaham, Yavin

2016-01-01

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse. PMID:25976297

Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene.

PubMed

Bagchi, D; Bagchi, M; Stohs, S J

2001-06-01

Chromium (VI) is a widely used industrial chemical, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome, and wood treatment. On the contrary, chromium (III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been demonstrated to exhibit a significant number of health benefits in rodents and humans. However, the cause for the hexavalent chromium to induce cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that chromium (VI) induces an oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following chromium (VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. In this paper, we have demonstrated concentration- and time-dependent effects of sodium dichromate (chromium (VI) or Cr (VI)) on enhanced production of superoxide anion and hydroxyl radicals, changes in intracellular oxidized states as determined by laser scanning confocal microscopy, DNA fragmentation and apoptotic cell death (by flow cytometry) in human peripheral blood mononuclear cells. These results were compared with the concentration-dependent effects of chromium (VI) on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Chromium (VI)-induced enhanced production of ROS, as well as oxidative tissue and DNA damage were observed in these cells. More pronounced effect was observed on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Furthermore, we have assessed the effect of a

Alleviation of mortality induced by salicylate and stress.

PubMed

Jastreboff, P J; Brennan, J F

1994-05-15

Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2 x 2 x 4 factorial design, rats were assigned to groups defined by: A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution; B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements; C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group.

FMRFamide signaling promotes stress-induced sleep in Drosophila

PubMed Central

Lenz, Olivia; Xiong, Jianmei; Nelson, Matthew D.; Raizen, David M.; Williams, Julie A.

2015-01-01

Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress. PMID:25668617

FMRFamide signaling promotes stress-induced sleep in Drosophila.

PubMed

Lenz, Olivia; Xiong, Jianmei; Nelson, Matthew D; Raizen, David M; Williams, Julie A

2015-07-01

Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress. Copyright © 2015 Elsevier Inc. All rights reserved.

A9C sensitive Cl− - accumulation in A. thaliana root cells during salt stress is controlled by internal and external calcium

PubMed Central

Saleh, Livia; Plieth, Christoph

2013-01-01

The involvement of chloride in salt stress symptoms and salt tolerance mechanisms in plants has been less investigated in the past. Therefore, we studied the salt-induced chloride influx in Arabidopsis expressing the GFP-based anion indicator Clomeleon. High salt concentrations induce two phases of chloride influx. The fast kinetic phase is likely caused by membrane depolarization, and is assumed to be mediated by channels. This is followed by a slower "saturation" phase, where chloride is accumulated in the cytoplasm. Both phases of chloride uptake are dependent on the presence of external calcium. In general: with high [Ca2+] less chloride is accumulated in the cytoplasm. Surprisingly, also the internal calcium availability has an impact on chloride transport. A complete block of the second phase of chloride influx is achieved by the anion channel blocker A9C and trivalent cations (La3+, Gd3+, and Al3+). Other channel blockers and diuretics were found to inhibit the process partially. The results suggest that several transporter species are involved here, including electroneutral cation-chloride-cotransporters, and a part of chloride possibly enters the cells through cation channels after salt application. PMID:23603974

Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tetz, Lauren M., E-mail: ltetz@umich.edu; Cheng, Adrienne A.; Korte, Cassandra S.

Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and thenmore » measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a

Sodium Chloride Crystal-Induced SERS Platform for Controlled Highly Sensitive Detection of Illicit Drugs.

PubMed

Yu, Borong; Li, Pan; Zhou, Binbin; Tang, Xianghu; Li, Shaofei; Yang, Liangbao

2018-04-03

A sodium chloride crystal-driven spontaneous 'hot spot' structure was demonstrated as a SERS-active platform, to get reproducible SERS signals, and eliminate the need for mapping large areas, in comparison with solution phase testing. During the process of solvent evaporation, the crystals produced induced silver aggregates to assemble around themselves. The micro-scale crystals can also act as a template to obtain an optical position, such that the assembled hot area is conveniently located during SERS measurements. More importantly, the chloride ions added in colloids can also replace the citrate and on the surface of the silver sol, and further decrease the background interference. High quality SERS spectra from heroin, methamphetamine (MAMP), and cocaine have been obtained on the crystal-driven hot spot structure with high sensitivity and credible reproducibility. This approach can not only bring the nanoparticles to form plasmonic hot spots in a controlled way, and thus provide high sensitivity, but also potentially be explored as an active substrate for label-free detection of other illicit drugs or additives. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lithium Chloride can Induce Differentiation of Human Immortalized RenVm Cells into Dopaminergic Neurons.

PubMed

Soleimani, Mitra; Ghasemi, Nazem

2017-01-01

Stem cell-based therapy is a novel strategy for the treatment of neurodegenerative diseases. The transplantation of fully differentiated cells instead of stem cells in order to decrease serious adverse complications of stem cell therapy is a new idea. In this study, the effect of lithium chloride on dopaminergic differentiation of human immortalized RenVm cells was investigated in order to access a population of fully differentiated cells for transplantation in Parkinson disease. The immortalized RenVm cells were induced to dopaminergic differentiation using a neurobasal medium supplemented with N2 and different concentrations (1, 3, 6 mM ) of Lithium Chloride (LiCl) for 4, 8 and 12 days. The efficiency of dopaminergic differentiation was evaluated using immunocytochemistry and western blot techniques for tyrosine hydroxylase and β-catenin marker expression. Our results indicated that LiCl can promote dopaminergic differentiation of RenVm cells in a dose-dependent manner. It can be concluded that LiCl is able to facilitate dopaminergic differentiation of cultured cells by affecting Wnt-frizzled signaling pathway.

Salubrious effects of oxytocin on social stress-induced deficits

PubMed Central

Smith, Adam S.; Wang, Zuoxin

2012-01-01

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

Thermodynamic analysis on the role of hydrogen in anodic stress corrosion cracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, L.; Mao, X.

1995-11-01

A synergistic effect of hydrogen and stress on a corrosion rate was analyzed with thermodynamics. The results showed that an interaction of stress and hydrogen could increase the corrosion rate remarkably. Stress corrosion cracking (SCC) of austenitic stainless steel (ASS) was investigated in boiling chloride solution to confirm the analysis. Hydrogen could be introduced into the specimen concentrated at the crack tip during SCC in boiling LiCl solution (143 C). The concentrating factor is about 3 which is consistent with calculated results according to stress induced diffusion.

78 FR 2195 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-10

... of silver chloride-induced stress corrosion cracking of the HP compressor stages 1 to 6 rotor disc...: Silver chloride-induced stress corrosion cracking was identified during overhaul of a BR700-715 engine... a report of silver chloride-induced stress corrosion cracking of the high-pressure (HP) compressor...

Horizontal stresses induced by vertical processes in planetary lithospheres

NASA Technical Reports Server (NTRS)

Banerdt, W. B.

1993-01-01

Understanding the state of stress in the elastic lithosphere is of fundamental importance for planetary geophysics, as it is the link between the observed geologic structures on the surface and the processes which form and modify these structures. As such, it can provide valuable constraints for the difficult problem of determining interior structure and processes. On the Earth, most large scale, organized deformation can be related to lateral tectonics associated with plate dynamics; however, the tectonics on many extraterrestrial bodies (such as the Moon, Mars, and most of the outer-planet satellites) appears to be primarily vertical in nature, and the horizontal stresses induced by vertical motions and loads are expected to dominate the deformation of their lithospheres. The largest stress contributions from vertical loading come from the flexure of the lithosphere, which induces both bending moments and membrane stresses. We are concerned here only with nonflexural changes in the state of stress induced by processes such as sedimentary and volcanic deposition, erosional denudation, and changes in the thermal gradient that induce uplift or subsidence. This analysis is important both for evaluating stresses for specific regions in which the vertical stress history can be estimated, as well as for applying the proper loading conditions to global stress models. It is also of interest for providing a reference state of stress for interpreting stress measurements in the crust of the Earth.

Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress.

PubMed

Spencer, Jennifer; Phister, Trevor G; Smart, Katherine A; Greetham, Darren

2014-03-17

Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress.

Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress

PubMed Central

2014-01-01

Background Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. Results Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. Conclusions Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress. PMID:24636079

Tannic acid and chromic chloride-induced binding of protein to red cells: a preliminary study of possible binding sites and reaction mechanisms.

PubMed

Hunt, A F; Reed, M I

1990-07-01

The binding mechanisms and binding sites involved in the tannic acid and chromic chloride-induced binding of protein to red cells were investigated using the binding of IgA paraprotein to red cells as model systems. Inhibition studies of these model systems using amino acid homopolymers and compounds (common as red cell membrane constituents) suggest that the mechanisms involved are similar to those proposed for the conversion of hide or skin collagen to leather, as in commercial tanning. These studies also suggest that tannic acid-induced binding of IgA paraprotein to red cells involves the amino acid residues of L-arginine, L-lysine, L-histidine, and L-proline analogous to tanning with phenolic plant extracts. The amino acid residues of L-aspartate, L-glutamate and L-asparagine are involved in a similar manner in chronic chloride-induced binding of protein to red cells.

Effects of vitamin E on mercuric chloride-induced renal interstitial fibrosis in rats and the antioxidative mechanism.

PubMed

Tao, Yan-yan; Wang, Qing-lan; Yuan, Ji-li; Shen, Li; Liu, Cheng-hai

2011-02-01

To observe the effects of vitamin E (Vit E) on mercuric chloride (HgCl2)-induced renal interstitial fibrosis (RIF) in rats and discuss its antioxidative mechanism. A total of 32 Sprague-Dawley rats were randomly assigned to three groups: normal group, model group and Vit E group. RIF was induced by oral administration of HgCl(2) at a dose of 8 mg/kg body weight once a day for 9 weeks. Rats in Vit E group were administered with Vit E capsule at 100 mg/kg body weight, and rats in normal and model groups were treated with normal saline. At the end of the 9th week, rats were sacrificed and renal hydroxyproline (Hyp)'s trichrome and periodic acid-silver methenamine (PASM) staining. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and contents of glutathione (GSH) and malondialdehyde (MDA) in kidney tissue were tested with commercial kits. The expressions of nuclear factor-κB (NF-κB), inhibitor-κB (IκB), phospho-IκB (p-IκB) and tumor necrosis factor-α (TNF-α) were determined by Western blot. The expression of α-smooth muscle actin (α-SMA) was assayed by Western blot and immunofluorescent staining. Renal Hyp content, HE, Masson's trichrome and PASM staining results and α-SMA expression confirmed development of HgCl2-induced RIF in rats. Oxidative stress markers GSH, GSH-Px and MDA confirmed oxidative stress in RIF rats. Compared with model rats, rats in Vit E group had lower kidney Hyp content (P<0.01). GSH and MDA contents decreased significantly in Vit E group compared with model group (P<0.01). The expressions of NF-κB and IκB had no significant difference among all groups (P>0.05). In Vit E group, the expressions of p-IκB and TNF-α decreased significantly compared with model group (P<0.01). The expression of α-SMA in Vit E group was also decreased significantly compared with model group (P<0.01). Vit E has a protective effect on experimental RIF induced by HgCl(2) in rats and it is related to inhibition of lipid

Chloride channel blockade relaxes airway smooth muscle and potentiates relaxation by β-agonists

PubMed Central

Yim, Peter; Rinderspacher, Alison; Fu, Xiao Wen; Zhang, Yi; Landry, Donald W.; Emala, Charles W.

2014-01-01

Severe bronchospasm refractory to β-agonists continues to cause significant morbidity and mortality in asthmatic patients. We questioned whether chloride channels/transporters are novel targets for the relaxation of airway smooth muscle (ASM). We have screened a library of compounds, derivatives of anthranilic and indanyloxyacetic acid, that were originally developed to antagonize chloride channels in the kidney. We hypothesized that members of this library would be novel calcium-activated chloride channel blockers for the airway. The initial screen of this compound library identified 4 of 20 compounds that relaxed a tetraethylammonium chloride-induced contraction in guinea pig tracheal rings. The two most effective compounds, compounds 1 and 13, were further studied for their potential to either prevent the initiation of or relax the maintenance phase of an acetylcholine (ACh)-induced contraction or to potentiate β-agonist-mediated relaxation. Both relaxed an established ACh-induced contraction in human and guinea pig ex vivo ASM. In contrast, the prevention of an ACh-induced contraction required copretreatment with the sodium-potassium-chloride cotransporter blocker bumetanide. The combination of compound 13 and bumetanide also potentiated relaxation by the β-agonist isoproterenol in guinea pig tracheal rings. Compounds 1 and 13 hyperpolarized the plasma cell membrane of human ASM cells and blocked spontaneous transient inward currents, a measure of chloride currents in these cells. These functional and electrophysiological data suggest that modulating ASM chloride flux is a novel therapeutic target in asthma and other bronchoconstrictive diseases. PMID:24879056

Effect of Applied Stress and Temperature on Residual Stresses Induced by Peening Surface Treatments in Alloy 600

NASA Astrophysics Data System (ADS)

Telang, A.; Gnäupel-Herold, T.; Gill, A.; Vasudevan, V. K.

2018-04-01

In this study, the effects of applied tensile stress and temperature on laser shock peening (LSP) and cavitation shotless peening (CSP)-induced compressive residual stresses were investigated using neutron and x-ray diffraction. Residual stresses on the surface, measured in situ, were lower than the applied stress in LSP- and CSP-treated Alloy 600 samples (2 mm thick). The residual stress averaged over the volume was similar to the applied stress. Compressive residual stresses on the surface and balancing tensile stresses in the interior relax differently due to hardening induced by LSP. Ex situ residual stress measurements, using XRD, show that residual stresses relaxed as the applied stress exceeded the yield strength of the LSP- and CSP-treated Alloy 600. Compressive residual stresses induced by CSP and LSP decreased by 15-25% in magnitude, respectively, on exposure to 250-450 °C for more than 500 h with 10-11% of relaxation occurring in the first few hours. Further, 80% of the compressive residual stresses induced by LSP and CSP treatments in Alloy 600 were retained even after long-term aging at 350 °C for 2400 h.

Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response.

PubMed

House, S D; Guidon, P T; Perdrizet, G A; Rewinski, M; Kyriakos, R; Bockman, R S; Mistry, T; Gallagher, R A; Hightower, L E

2001-04-01

Heat and a variety of other stressors cause mammalian cells and tissues to acquire cytoprotection. This transient state of altered cellular physiology is nonproliferative and antiapoptotic. In this study, male Wistar rats were stress conditioned with either stannous chloride or gallium nitrate, which have immunosuppressive effects in vivo and in vitro, or heat shock, the most intensively studied inducer of cytoprotection. The early stages of inflammation in response to topical suffusion of mesentery tissue with formyl-methionyl-leucyl-phenylalanine (FMLP) were monitored using intravital microscopy. Microvascular hemodynamics (venular diameter, red blood cell velocity [Vrbc], white blood cell [WBC] flux, and leukocyte-endothelial adhesion [LEA]) were used as indicators of inflammation, and tissue levels of inducible Hsp70, determined using immunoblot assays, provided a marker of cytoprotection. None of the experimental treatments blocked decreases in WBC flux during FMLP suffusion, an indicator of increased low-affinity interactions between leukocytes and vascular endothelium known as rolling adhesion. During FMLP suffusion LEA, an indicator of firm attachment between leukocytes and vascular endothelial cells increased in placebo and gallium nitrate-treated animals but not in heat- and stannous chloride-treated animals, an anti-inflammatory effect. Hsp70 was not detected in aortic tissue from placebo and gallium nitrate-treated animals, indicating that Hsp70-dependent cytoprotection was not present. In contrast, Hsp70 was detected in aortic tissues from heat- and stannous chloride-treated animals, indicating that these tissues were in a cytoprotected state that was also an anti-inflammatory state.

Social factors modulate restraint stress induced hyperthermia in mice.

PubMed

Watanabe, Shigeru

2015-10-22

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacological Effect of Berberine Chloride in Propyl Thiouracil Induced Thyroidal Dysfunction - A Time Bound Study in Female Rats.

PubMed

Maurya, Harikesh; Dhiman, Sheena; Dua, Kamal; Gupta, Gaurav

2016-01-01

The present study is aimed at bringing out the information on the effect of berberine chloride in hyper and hypo thyroidal model with two dose levels. The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms. Sixty female wistar rats weighing between 150-250 gm were divided in to 10 groups. The animals were grouped in to solvent control; hypothyroid; hyperthyroid; prophylactic with two different doses of berberine chloride (50 and 100 mg/kg); treatment groups similar to that of the prophylactic and therapeutic group. To substantiate the dose dependent effect of berberine chloride in 6-n-propyL-2-thiouracil (PTU) induced hypothyroidism, lipid profile, thyroid profile, enzymes profiles and blood profiles, in addition to histopathological studies were also carried out. There was no any significant difference in the lipid profile among solvent control, treatment and prophylactic groups. However, there was a significant difference (***p<0.001) in serum triglycerides, LDL and VLDL of hypothyroid group when compound to that of the rest. As far as thyroid profile is concerned, T3 level of berberine chloride (50 mg/kg) treated groups (prophylactic+ treatment) showed a significant rise compared to hypothyroid group. TSH level in prophylactic groups was far higher than the rest of the groups (3.002±0.0192, 1.051±0.0008 against the solvent control, 0.308±0.008). SGOT, SGPT levels were significantly higher with the therapeutic group than that of the normal and hypo-thyroidal group. Blood profile of berberine chloride (100 mg/kg) treated therapeutic group was comparable to that of the solvent control than all other groups. The probable mechanism underlying may be that inactivation of type I 5.-iodothyronine deiodinase (5.DI) enzyme by NF-kB pathway. From the findings of the current study it can be concluded that berberine chloride possesses both thyroid

Metallurgical effects on chloride ion corrosion threshold of steel in concrete.

DOT National Transportation Integrated Search

2001-11-30

The chloride-induced corrosion of reinforcing steel bars (rebar) in concrete seriously limits durability of reinforcing concrete structures. This investigation examines key issues in pitting corrosion and chloride corrosion threshold of rebar in alka...

Stress state in turbopump bearing induced by shrink fitting

NASA Technical Reports Server (NTRS)

Sims, P.; Zee, R.

1991-01-01

The stress generated by shrink fitting in bearing-like geometries is studied. The feasibility of using strain gages to determine the strain induced by shrink fitting process is demonstrated. Results from a ring with a uniform cross section reveal the validity of simple stress mechanics calculations for determining the stress state induced in this geometry by shrink fitting.

Role of chloride ions in the promotion of auxin-induced growth of maize coleoptile segments.

PubMed

Burdach, Zbigniew; Kurtyka, Renata; Siemieniuk, Agnieszka; Karcz, Waldemar

2014-10-01

The mechanism of auxin action on ion transport in growing cells has not been determined in detail. In particular, little is known about the role of chloride in the auxin-induced growth of coleoptile cells. Moreover, the data that do exist in the literature are controversial. This study describes experiments that were carried out with maize (Zea mays) coleoptile segments, this being a classical model system for studies of plant cell elongation growth. Growth kinetics or growth and pH changes were recorded in maize coleoptiles using two independent measuring systems. The growth rate of the segments was measured simultaneously with medium pH changes. Membrane potential changes in parenchymal cells of the segments were also determined for chosen variants. The question of whether anion transport is involved in auxin-induced growth of maize coleoptile segments was primarily studied using anion channel blockers [anthracene-9-carboxylic acid (A-9-C) and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS)]. In addition, experiments in which KCl was replaced by KNO3 were also performed. Both anion channel blockers, added at 0·1 mm, diminished indole-3-acetic acid (IAA)-induced elongation growth by ~30 %. Medium pH changes measured simultaneously with growth indicated that while DIDS stopped IAA-induced proton extrusion, A-9-C diminished it by only 50 %. Addition of A-9-C to medium containing 1 mm KCl did not affect the characteristic kinetics of IAA-induced membrane potential changes, while in the presence of 10 mm KCl the channel blocker stopped IAA-induced membrane hyperpolarization. Replacement of KCl with KNO3 significantly decreased IAA-induced growth and inhibited proton extrusion. In contrast to the KCl concentration, the concentration of KNO3 did not affect the growth-stimulatory effect of IAA. For comparison, the effects of the cation channel blocker tetraethylammonium chloride (TEA-Cl) on IAA-induced growth and proton extrusion were also determined. TEA

Clonidine blocks stress-induced craving in cocaine users.

PubMed

Jobes, Michelle L; Ghitza, Udi E; Epstein, David H; Phillips, Karran A; Heishman, Stephen J; Preston, Kenzie L

2011-11-01

Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

PubMed

Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood–Brain Barrier Damage

PubMed Central

Qie, Xiaojuan; Wen, Di; Guo, Hongyan; Xu, Guanjie; Liu, Shuai; Shen, Qianchao; Liu, Yi; Zhang, Wenfang; Cong, Bin; Ma, Chunling

2017-01-01

Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood–brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers. METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP. The ER stress inhibitors significantly blocked the upregulation of CHOP. Knockdown of CHOP protected bEnd.3 cells from METH-induced cytotoxicity. Furthermore, METH elevated the production of reactive oxygen species (ROS) and induced the dysfunction of mitochondrial characterized by a Bcl2/Bax ratio decrease, mitochondrial membrane potential collapse, and cytochrome c. ER stress release was partially reversed by ROS inhibition, and cytochrome c release was partially blocked by knockdown of CHOP. Finally, PBA significantly attenuated METH-induced sodium fluorescein (NaFluo) and Evans Blue leakage, as well as tight junction protein loss, in C57BL/6J mice. These data suggest that BBB endothelial cell damage was caused by METH-induced endoplasmic reticulum stress, which further induced mitochondrial dysfunction, and that PBA was an effective treatment for METH-induced BBB disruption. PMID:28959203

Geranylgeranylacetone prevents stress-induced decline of leptin secretion in mice.

PubMed

Itai, Miki; Kuwano, Yuki; Nishikawa, Tatsuya; Rokutan, Kazuhito; Kensei, Nishida

2018-01-01

Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

PubMed Central

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

PubMed

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

Study of inducer load and stress, volume 2

NASA Technical Reports Server (NTRS)

1972-01-01

A program of analysis, design, fabrication and testing has been conducted to develop computer programs for predicting rocket engine turbopump inducer hydrodynamic loading, stress magnitude and distribution, and vibration characteristics. Methods of predicting blade loading, stress, and vibration characteristics were selected from a literature search and used as a basis for the computer programs. An inducer, representative of typical rocket engine inducers, was designed, fabricated, and tested with special instrumentation selected to provide measurements of blade surface pressures and stresses. Data from the tests were compared with predicted values and the computer programs were revised as required to improve correlation. For Volume 1 see N71-20403. For Volume 2 see N71-20404.

Unraveling earthquake stresses: Insights from dynamically triggered and induced earthquakes

NASA Astrophysics Data System (ADS)

Velasco, A. A.; Alfaro-Diaz, R. A.

2017-12-01

Induced seismicity, earthquakes caused by anthropogenic activity, has more than doubled in the last several years resulting from practices related to oil and gas production. Furthermore, large earthquakes have been shown to promote the triggering of other events within two fault lengths (static triggering), due to static stresses caused by physical movement along the fault, and also remotely from the passage of seismic waves (dynamic triggering). Thus, in order to understand the mechanisms for earthquake failure, we investigate regions where natural, induced, and dynamically triggered events occur, and specifically target Oklahoma. We first analyze data from EarthScope's USArray Transportable Array (TA) and local seismic networks implementing an optimized (STA/LTA) detector in order to develop local detection and earthquake catalogs. After we identify triggered events through statistical analysis, and perform a stress analysis to gain insight on the stress-states leading to triggered earthquake failure. We use our observations to determine the role of different transient stresses in contributing to natural and induced seismicity by comparing these stresses to regional stress orientation. We also delineate critically stressed regions of triggered seismicity that may indicate areas susceptible to earthquake hazards associated with sustained fluid injection in provinces of induced seismicity. Anthropogenic injection and extraction activity can alter the stress state and fluid flow within production basins. By analyzing the stress release of these ancient faults caused by dynamic stresses, we may be able to determine if fluids are solely responsible for increased seismic activity in induced regions.

Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response.

PubMed

Kim, Sou Hyun; Oh, Dal-Seok; Oh, Ji Youn; Son, Tae Gen; Yuk, Dong Yeon; Jung, Young-Suk

2016-04-01

Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has been reported to prevent liver injuries induced by various chemicals or toxins. Our recent study suggested that silymarin induces hepatic synthesis of glutathione by increasing cysteine availability, which may consequently contribute to increased antioxidant capacity of the liver. In the present study, we investigated the effects of silymarin on acute liver injury induced by restraint stress. Silymarin (100 mg/kg) was orally administered to BALB/c mice every 12 h (3 times in total). After the last dose, mice were subjected to restraint stress for 6 h, and serum levels of aspartate and alanine aminotransferases, and hepatic levels of lipid peroxidation were determined. Hepatic levels of sulfur-containing metabolites such as methionine, S-adenosylmethionine, cysteine, and glutathione were also measured. The level of pro-inflammatory mediators in both liver and serum was determined. To study the mechanism of the effects of silymarin, we assessed Jun N-terminal kinase (JNK) activation and apoptotic signaling. Restraint stress induced severe oxidative stress and increased mRNA levels of pro-inflammatory mediators; both effects of restraint stress were significantly inhibited by silymarin. Moreover, administration of silymarin significantly prevented acute liver injury induced by restraint stress by blocking JNK activation and subsequently apoptotic signaling. In conclusion, these results suggest that the inhibition of restraint stress-induced liver injury by silymarin is due at least in part to its anti-oxidant activity and its ability to suppress the inflammatory response.

Endoplasmic reticulum stress preconditioning attenuates methylmercury-induced cellular damage by inducing favorable stress responses

PubMed Central

Usuki, Fusako; Fujimura, Masatake; Yamashita, Akio

2013-01-01

We demonstrate that methylmercury (MeHg)-susceptible cells preconditioned with an inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase, thapsigargin, showed resistance to MeHg cytotoxicity through favorable stress responses, which included phosphorylation of eukaryotic initiation factor 2 alpha (Eif2α), accumulation of activating transcription factor 4 (Atf4), upregulation of stress-related proteins, and activation of extracellular signal regulated kinase pathway. In addition, ER stress preconditioning induced suppression of nonsense-mediated mRNA decay (NMD) mainly through the phospho-Eif2α-mediated general suppression of translation initiation and possible combined effects of decreased several NMD components expression. Atf4 accumulation was not mediated by NMD inhibition but translation inhibition of its upstream open reading frame (uORF) and translation facilitation of its protein-coding ORF by the phospho-Eif2α. These results suggested that ER stress plays an important role in MeHg cytotoxicity and that the modulation of ER stress has therapeutic potential to attenuate MeHg cytotoxicity, the underlying mechanism being the induction of integrated stress responses. PMID:23907635

Time-dependent effects of rapamycin on consolidation of predator stress-induced hyperarousal.

PubMed

Fifield, Kathleen; Hebert, Mark; Williams, Kimberly; Linehan, Victoria; Whiteman, Jesse D; Mac Callum, Phillip; Blundell, Jacqueline

2015-06-01

Previous studies have indicated that rapamycin, a potent inhibitor of the mammalian target of rapamycin (mTOR) pathway, blocks consolidation of shock-induced associative fear memories. Moreover, rapamycin's block of associative fear memories is time-dependent. It is unknown, however, if rapamycin blocks consolidation of predator stress-induced non-associative fear memories. Furthermore, the temporal pattern of mTOR activation following predator stress is unknown. Thus, the goal of the current studies was to determine if rapamycin blocks consolidation of predator stress-induced fear memories and if so, whether rapamycin's effect is time-dependent. Male rats were injected systemically with rapamycin at various time points following predator stress. Predator stress involves an acute, unprotected exposure of a rat to a cat, which causes long-lasting non-associative fear memories manifested as generalized hyperarousal and increased anxiety-like behaviour. We show that rapamycin injected immediately after predator stress blocked consolidation of stress-induced startle. However, rapamycin injected 9, 24 or 48h post predator stress potentiated stress-induced startle. Consistent with shock-induced associative fear memories, we show that mTOR signalling is essential for consolidation of predator stress-induced hyperarousal. However, unlike shock-induced fear memories, a second, persistent, late phase mTOR-dependent process following predator stress actually dampens startle. Consistent with previous findings, our data support the potential role for rapamycin in treatment of stress related disorders such as posttraumatic stress disorder. However, our data suggest timing of rapamycin administration is critical. Copyright © 2015 Elsevier B.V. All rights reserved.

Features of residual stresses in duplex stainless steel butt welds

NASA Astrophysics Data System (ADS)

Um, Tae-Hwan; Lee, Chin-Hyung; Chang, Kyong-Ho; Nguyen Van Do, Vuong

2018-04-01

Duplex stainless steel finds increasing use as an alternative to austenitic stainless steel, particularly where chloride or sulphide stress corrosion cracking is of primary concern, due to the excellent combination of strength and corrosion resistance. During welding, duplex stainless steel does not create the same magnitude or distribution of weld-induced residual stresses as those in welded austenitic stainless steel due to the different physical and mechanical properties between them. In this work, an experimental study on the residual stresses in butt-welded duplex stainless steel is performed utilizing the layering technique to investigate the characteristics of residual stresses in the weldment. Three-dimensional thermos-mechanical-metallurgical finite element analysis is also performed to confirm the residual stress measurements.

No evidence for attenuated stress-induced extrastriatal dopamine signaling in psychotic disorder

PubMed Central

Hernaus, D; Collip, D; Kasanova, Z; Winz, O; Heinzel, A; van Amelsvoort, T; Shali, S M; Booij, J; Rong, Y; Piel, M; Pruessner, J; Mottaghy, F M; Myin-Germeys, I

2015-01-01

Stress is an important risk factor in the etiology of psychotic disorder. Preclinical work has shown that stress primarily increases dopamine (DA) transmission in the frontal cortex. Given that DA-mediated hypofrontality is hypothesized to be a cardinal feature of psychotic disorder, stress-related extrastriatal DA release may be altered in psychotic disorder. Here we quantified for the first time stress-induced extrastriatal DA release and the spatial extent of extrastriatal DA release in individuals with non-affective psychotic disorder (NAPD). Twelve healthy volunteers (HV) and 12 matched drug-free NAPD patients underwent a single infusion [18F]fallypride positron emission tomography scan during which they completed the control and stress condition of the Montreal Imaging Stress Task. HV and NAPD did not differ in stress-induced [18F]fallypride displacement and the spatial extent of stress-induced [18F]fallypride displacement in medial prefrontal cortex (mPFC) and temporal cortex (TC). In the whole sample, the spatial extent of stress-induced radioligand displacement in right ventro-mPFC, but not dorso-mPFC or TC, was positively associated with task-induced subjective stress. Psychotic symptoms during the scan or negative, positive and general subscales of the Positive and Negative Syndrome Scale were not associated with stress-induced [18F]fallypride displacement nor the spatial extent of stress-induced [18F]fallypride displacement in NAPD. Our results do not offer evidence for altered stress-induced extrastriatal DA signaling in NAPD, nor altered functional relevance. The implications of these findings for the role of the DA system in NAPD and stress processing are discussed. PMID:25871972

Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christen, Verena; Capelle, Martinus; Fent, Karl, E-mail: karl.fent@fhnw.ch

2013-10-15

Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL andmore » Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.« less

Quantitative estimation of carbonation and chloride penetration in reinforced concrete by laser-induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Eto, Shuzo; Matsuo, Toyofumi; Matsumura, Takuro; Fujii, Takashi; Tanaka, Masayoshi Y.

2014-11-01

The penetration profile of chlorine in a reinforced concrete (RC) specimen was determined by laser-induced breakdown spectroscopy (LIBS). The concrete core was prepared from RC beams with cracking damage induced by bending load and salt water spraying. LIBS was performed using a specimen that was obtained by splitting the concrete core, and the line scan of laser pulses gave the two-dimensional emission intensity profiles of 100 × 80 mm2 within one hour. The two-dimensional profile of the emission intensity suggests that the presence of the crack had less effect on the emission intensity when the measurement interval was larger than the crack width. The chlorine emission spectrum was measured without using the buffer gas, which is usually used for chlorine measurement, by collinear double-pulse LIBS. The apparent diffusion coefficient, which is one of the most important parameters for chloride penetration in concrete, was estimated using the depth profile of chlorine emission intensity and Fick's law. The carbonation depth was estimated on the basis of the relationship between carbon and calcium emission intensities. When the carbon emission intensity was statistically higher than the calcium emission intensity at the measurement point, we determined that the point was carbonated. The estimation results were consistent with the spraying test results using phenolphthalein solution. These results suggest that the quantitative estimation by LIBS of carbonation depth and chloride penetration can be performed simultaneously.

PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

PubMed Central

Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

2014-01-01

Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

Remote detection of stress corrosion cracking: Surface composition and crack detection

NASA Astrophysics Data System (ADS)

Lissenden, Cliff J.; Jovanovic, Igor; Motta, Arthur T.; Xiao, Xuan; Le Berre, Samuel; Fobar, David; Cho, Hwanjeong; Choi, Sungho

2018-04-01

Chloride induced stress corrosion cracking (SCC) of austenitic stainless steel is a potential issue in long term dry storage of spent nuclear fuel canisters. In order for SCC to occur there must be a corrosive environment, a susceptible material, and a driving force. Because it is likely that the material in the heat affected zone (HAZ) of welded stainless steel structures has been sensitized as a result of chromium depletion at the grain boundaries and a thermal residual stress driving force is likely present if solution annealing is not performed, two issues are critical. Is the environment corrosive, i.e., are chlorides present in solution on the surface? And then, are there cracks that could propagate? Remote detection of chlorides on the surface can be accomplished by laser induced breakdown spectroscopy (LIBS), while cracks can be detected by shear horizontal guided waves generated by electromagnetic acoustic transducers (EMATs). Both are noncontact methods that are amenable to robotic delivery systems and harsh environments. The sensitivity to chlorine on stainless steel of a LIBS system that employs optical fiber for pulse delivery is demonstrated. Likewise, the ability of the EMAT system to detect cracks of a prescribed size and orientation is shown. These results show the potential for remote detection of Cl and cracks in dry storage spent fuel canisters.

Hydrogen-peroxide-induced oxidative stress responses in Desulfovibrio vulgaris Hildenborough

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, A.; He, Z.; Redding-Johanson, A.M.

2010-07-01

To understand how sulphate-reducing bacteria respond to oxidative stresses, the responses of Desulfovibrio vulgaris Hildenborough to H{sub 2}O{sub 2}-induced stresses were investigated with transcriptomic, proteomic and genetic approaches. H{sub 2}O{sub 2} and induced chemical species (e.g. polysulfide, ROS) and redox potential shift increased the expressions of the genes involved in detoxification, thioredoxin-dependent reduction system, protein and DNA repair, and decreased those involved in sulfate reduction, lactate oxidation and protein synthesis. A gene coexpression network analysis revealed complicated network interactions among differentially expressed genes, and suggested possible importance of several hypothetical genes in H{sub 2}O{sub 2} stress. Also, most of themore » genes in PerR and Fur regulons were highly induced, and the abundance of a Fur regulon protein increased. Mutant analysis suggested that PerR and Fur are functionally overlapped in response to stresses induced by H{sub 2}O{sub 2} and reaction products, and the upregulation of thioredoxin-dependent reduction genes was independent of PerR or Fur. It appears that induction of those stress response genes could contribute to the increased resistance of deletion mutants to H{sub 2}O{sub 2}-induced stresses. In addition, a conceptual cellular model of D. vulgaris responses to H{sub 2}O{sub 2} stress was constructed to illustrate that this bacterium may employ a complicated molecular mechanism to defend against the H{sub 2}O{sub 2}-induced stresses.« less

Antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of Laportea ovalifolia (Urticaceae), measured in rats with alloxan-induced diabetes.

PubMed

Momo, C E N; Oben, J E; Tazoo, D; Dongo, E

2006-01-01

A decoction of the leaves of Laportea ovalifolia is widely used in Cameroon for the treatment of several illnesses, including diabetes mellitus. The antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of the aerial parts of L. ovalifolia have now been investigated, in normal rats and rats with diabetes induced by the intraperitoneal injection of alloxan (at 150 mg/kg bodyweight). In the diabetic rats, 2 weeks of daily, intragastric treatment with the L. ovalifolia extract not only produced a significant reduction in the fasting serum glucose concentrations but also lowered the serum concentrations of total cholesterol, triglycerides, and low-density-lipoprotein cholesterol, lowered the ratio of total cholesterol to high-density-lipoprotein (HDL) cholesterol, and increased the serum concentration of HDL cholesterol. At least in rats with alloxan-induced diabetes, the methanol/methylene-chloride extract of L. ovalifolia therefore appears to possess antidiabetic and hypolipidaemic properties.

Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.

PubMed

Rock, Erin M; Boulet, Nathalie; Limebeer, Cheryl L; Mechoulam, Raphael; Parker, Linda A

2016-09-05

We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB2) receptor. We investigated the effect of the selective CB2 agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB2 receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB2 receptor agonist to reduce nausea in animal models, indicating that targeting the CB2 receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting. Copyright © 2016 Elsevier B.V. All rights reserved.

Trial application of electrochemical chloride extraction on concrete bridge components in Virginia.

DOT National Transportation Integrated Search

2000-01-01

Electrochemical chloride extraction is a new technique for mitigating chloride-induced corrosion of the reinforcing bars in concrete bridges. To demonstrate the feasibility of applying this technique on full-sized concrete bridge members and to ident...

Immobilization stress-induced anorexia is mediated independent of MyD88.

PubMed

Hosoi, Toru; Yamawaki, Yosuke; Kimura, Hitomi; Ozawa, Koichiro

2016-09-07

MyD88 is an adaptor protein for the toll-like receptor, which is involved in regulating innate immune function. Lipopolysaccharide-induced activation of toll-like receptor 4 signaling induces hypothalamic signal transducer and activator of transcription 3 (STAT3) phosphorylation and anorexia through MyD88. In the present study, we investigated the possible role of MyD88 in psychological stress-induced anorexia. We found that immobilization stress inhibited food intake in both wild-type mice and MyD88-deficient mice. Immobilization stress slightly increased STAT3 phosphorylation in the hypothalamus, but it was weaker than the lipopolysaccharide-induced increase in STAT3 phosphorylation. These observations suggest that the mechanisms involved in psychological stress-induced anorexia may be regulated differently from those involved in anorexia that is induced by infection.

Chloride ions induce order-disorder transition at water-oxide interfaces

NASA Astrophysics Data System (ADS)

Deshmukh, Sanket; Kamath, Ganesh; Ramanathan, Shriram; Sankaranarayanan, Subramanian K. R. S.

2013-12-01

Water can form quasi-two-dimensional ordered layers near a solid interface. The solvation dynamics and ionic transport phenomena through this ordered water structure is of direct relevance to a variety of problems in interface science. Molecular dynamics simulations are used to study the impact of local fluctuation of the chloride ion density in the vicinity of an oxide surface on the structure and dynamics of water layers. We demonstrate that local increase in chloride ions beyond a threshold concentration near the water-MgO (100) interface introduces an order-disorder transition of this two-dimensional layered network into bulklike water, leading to increased diffusional characteristics and reduced hydrogen bonding lifetimes. We find that the extent of this order-disorder transition can be tuned by modifying the defect chemistry and nature of the underlying substrate. The kinetic fluidity resulting from order-disorder transition at high chloride ion concentration has significance for a broad range of phenomena, ranging from freezing point depression of brine to onset of aqueous corrosion.

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

PubMed Central

Zode, Gulab S.; Sharma, Arti B.; Lin, Xiaolei; Searby, Charles C.; Bugge, Kevin; Kim, Gun Hee; Clark, Abbot F.; Sheffield, Val C.

2014-01-01

Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma. PMID:24691439

Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

NASA Astrophysics Data System (ADS)

Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

2004-03-01

Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

PubMed

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.

PubMed

Datta, Sandipan; Baudouin, Christophe; Brignole-Baudouin, Francoise; Denoyer, Alexandre; Cortopassi, Gino A

2017-04-01

Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells

PubMed Central

Datta, Sandipan; Baudouin, Christophe; Brignole-Baudouin, Francoise; Denoyer, Alexandre; Cortopassi, Gino A.

2017-01-01

Purpose Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as “dry eye” and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Method Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Results Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107–667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Conclusions Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients. PMID:28444329

Bioleaching in brackish waters--effect of chloride ions on the acidophile population and proteomes of model species.

PubMed

Zammit, Carla M; Mangold, Stefanie; Jonna, Venkateswara rao; Mutch, Lesley A; Watling, Helen R; Dopson, Mark; Watkin, Elizabeth L J

2012-01-01

High concentrations of chloride ions inhibit the growth of acidophilic microorganisms used in biomining, a problem particularly relevant to Western Australian and Chilean biomining operations. Despite this, little is known about the mechanisms acidophiles adopt in order to tolerate high chloride ion concentrations. This study aimed to investigate the impact of increasing concentrations of chloride ions on the population dynamics of a mixed culture during pyrite bioleaching and apply proteomics to elucidate how two species from this mixed culture alter their proteomes under chloride stress. A mixture consisting of well-known biomining microorganisms and an enrichment culture obtained from an acidic saline drain were tested for their ability to bioleach pyrite in the presence of 0, 3.5, 7, and 20 g L(-1) NaCl. Microorganisms from the enrichment culture were found to out-compete the known biomining microorganisms, independent of the chloride ion concentration. The proteomes of the Gram-positive acidophile Acidimicrobium ferrooxidans and the Gram-negative acidophile Acidithiobacillus caldus grown in the presence or absence of chloride ions were investigated. Analysis of differential expression showed that acidophilic microorganisms adopted several changes in their proteomes in the presence of chloride ions, suggesting the following strategies to combat the NaCl stress: adaptation of the cell membrane, the accumulation of amino acids possibly as a form of osmoprotectant, and the expression of a YceI family protein involved in acid and osmotic-related stress.

Temporal pore pressure induced stress changes during injection and depletion

NASA Astrophysics Data System (ADS)

Müller, Birgit; Heidbach, Oliver; Schilling, Frank; Fuchs, Karl; Röckel, Thomas

2016-04-01

Induced seismicity is observed during injection of fluids in oil, gas or geothermal wells as a rather immediate response close to the injection wells due to the often high-rate pressurization. It was recognized even earlier in connection with more moderate rate injection of fluid waste on a longer time frame but higher induced event magnitudes. Today, injection-related induced seismicity significantly increased the number of events with M>3 in the Mid U.S. However, induced seismicity is also observed during production of fluids and gas, even years after the onset of production. E.g. in the Groningen gas field production was required to be reduced due to the increase in felt and damaging seismicity after more than 50 years of exploitation of that field. Thus, injection and production induced seismicity can cause severe impact in terms of hazard but also on economic measures. In order to understand the different onset times of induced seismicity we built a generic model to quantify the role of poro-elasticity processes with special emphasis on the factors time, regional crustal stress conditions and fault parameters for three case studies (injection into a low permeable crystalline rock, hydrothermal circulation and production of fluids). With this approach we consider the spatial and temporal variation of reservoir stress paths, the "early" injection-related induced events during stimulation and the "late" production induced ones. Furthermore, in dependence of the undisturbed in situ stress field conditions the stress tensor can change significantly due to injection and long-term production with changes of the tectonic stress regime in which previously not critically stressed faults could turn to be optimally oriented for fault reactivation.

Cellular and molecular basis for stress-induced depression.

PubMed

Seo, J-S; Wei, J; Qin, L; Kim, Y; Yan, Z; Greengard, P

2017-10-01

Chronic stress has a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2 + ) glutamatergic neurons. Viral expression of p11 in D2 + PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2 + neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2 + PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses.

ERdj5 sensitizes neuroblastoma cells to endoplasmic reticulum stress-induced apoptosis.

PubMed

Thomas, Christophoros G; Spyrou, Giannis

2009-03-06

Down-regulation of the unfolded protein response (UPR) can be therapeutically valuable in cancer treatment, and endoplasmic reticulum (ER)-resident chaperone proteins may thus be targets for developing novel chemotherapeutic strategies. ERdj5 is a novel ER chaperone that regulates the ER-associated degradation of misfolded proteins through its associations with EDEM and the ER stress sensor BiP. To investigate whether ERdj5 can regulate ER stress signaling pathways, we exposed neuroblastoma cells overexpressing ERdj5 to ER stress inducers. ERdj5 promoted apoptosis in tunicamycin, thapsigargin, and bortezomib-treated cells. To provide further evidence that ERdj5 induces ER stress-regulated apoptosis, we targeted Bcl-2 to ER of ERdj5-overexpressing cells. Targeting the Bcl-2 to ER prevented the apoptosis induced by ER stress inducers but not by non-ER stress apoptotic stimuli, suggesting induction of ER stress-regulated apoptosis by ERdj5. ERdj5 enhanced apoptosis by abolishing the ER stress-induced phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) and the subsequent translational repression. ERdj5 was found to inhibit the eIF2alpha phosphorylation under ER stress through inactivating the pancreatic endoplasmic reticulum kinase. The compromised integrated stress response observed in ERdj5-overexpressing ER-stressed cells due to repressed eIF2alpha phosphorylation correlated with impaired neuroblastoma cell resistance under ER stress. These results demonstrate that ERdj5 decreases neuroblastoma cell survival by down-regulating the UPR, raising the possibility that this protein could be a target for anti-tumor approaches.

Alkali activated slag mortars provide high resistance to chloride-induced corrosion of steel

NASA Astrophysics Data System (ADS)

Criado, Maria; Provis, John L.

2018-06-01

The pore solutions of alkali-activated slag cements and Portland-based cements are very different in terms of their chemical and redox characteristics, particularly due to the high alkalinity and high sulfide content of alkali-activated slag cement. Therefore, differences in corrosion mechanisms of steel elements embedded in these cements could be expected, with important implications for the durability of reinforced concrete elements. This study assesses the corrosion behaviour of steel embedded in alkali-activated blast furnace slag (BFS) mortars exposed to alkaline solution, alkaline chloride-rich solution, water, and standard laboratory conditions, using electrochemical techniques. White Portland cement (WPC) mortars and blended cement mortars (white Portland cement and blast furnace slag) were also tested for comparative purposes. The steel elements embedded in immersed alkali-activated slag mortars presented very negative redox potentials and high apparent corrosion current values; the presence of sulfide reduced the redox potential, and the oxidation of the reduced sulfur-containing species within the cement itself gave an electrochemical signal that classical electrochemical tests for reinforced concrete durability would interpret as being due to steel corrosion processes. However, the actual observed resistance to chloride-induced corrosion was very high, as measured by extraction and characterisation of the steel at the end of a 9-month exposure period, whereas the steel embedded in white Portland cement mortars was significantly damaged under the same conditions.

Effects of low dietary cation-anion difference induced by ruminal ammonium chloride infusion on performance, serum, and urine metabolites of lactating dairy cows.

PubMed

Wang, Kun; Nan, Xuemei; Zhao, Puyi; Liu, Wei; Drackley, James K; Liu, Shijie; Zhang, Kaizhan; Bu, Dengpan

2018-05-01

The objective of the present study was to determine ammonium chloride tolerance of lactating dairy cows, by examining effects of negative dietary cation anion difference (DCAD) induced by ruminal ammonium chloride infusion on performance, serum and urine minerals, serum metabolites and enzymes of lactating dairy cows. Four primiparous lactating Chinese Holstein cows fitted with ruminal cannulas were infused with increasing amounts (0, 150, 300, or 450 g/d) of ammonium chloride in a crossover design. The DCAD of the base diet was 279 mEq/kg dry matter (DM) using the DCAD formula (Na + K - Cl - S)/kg of DM. Ammonium chloride infusion added the equivalent of 0, 128, 330, and 536 mEq/kg DM of Cl in treatments. According to the different dry matter intakes (DMI), the resulting actual DCAD of the four treatments was 279, 151, -51, and -257 mEq/kg DM, respectively. DMI decreased linearly as DCAD decreased. Yields of milk, 4% fat-corrected milk, energy-corrected milk, milk fat, and milk protein decreased linearly as DCAD decreased. Concentrations of milk protein and milk urea nitrogen increased linearly with decreasing DCAD. Concentration of Cl- in serum increased linearly and concentration of PO43- in serum increased quadratically as DCAD decreased. Urine pH decreased linearly and calculated urine volume increased linearly with decreasing DCAD. Linear increases in daily urinary excretion of Cl - , Ca 2+ , PO 4 3- , urea N, and ammonium were observed as DCAD decreased. Activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase in serum and urea N concentration in serum increased linearly as DCAD decreased. In conclusion, negative DCAD induced by ruminal ammonium chloride infusion resulted in a metabolic acidosis, had a negative influence on performance, and increased serum enzymes indicating potential liver and kidney damage in lactating dairy cows. Daily ammonium chloride intake by lactating dairy cows should not exceed 300 g, and 150

Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

PubMed

Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

2014-10-08

Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

Reversibly bound chloride in the atrial natriuretic peptide receptor hormone-binding domain: possible allosteric regulation and a conserved structural motif for the chloride-binding site.

PubMed

Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S

2010-03-01

The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.

Reversibly Bound Chloride in the Atrial Natriuretic Peptide Receptor Hormone Binding Domain: Possible Allosteric Regulation and a Conserved Structural Motif for the Chloride-binding Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, H.; Qiu, Y; Philo, J

2010-01-01

The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. Amore » new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.« less

Reversibly bound chloride in the atrial natriuretic peptide receptor hormone-binding domain: Possible allosteric regulation and a conserved structural motif for the chloride-binding site

PubMed Central

Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S

2010-01-01

The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(−)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(−) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(−) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis. PMID:20066666

Pathophysiology of Post Transplant Hypertension in Kidney Transplant: Focus on Calcineurin Inhibitors Induced Oxidative Stress and Renal Sodium Retention and Implications with RhoA/Rho Kinase Pathway.

PubMed

Calò, Lorenzo A; Ravarotto, Verdiana; Simioni, Francesca; Naso, Elena; Marchini, Francesco; Bonfante, Luciana; Furian, Lucrezia; Rigotti, Paolo

2017-01-01

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the

Detection of colloidal silver chloride near solubility limit

NASA Astrophysics Data System (ADS)

Putri, K. Y.; Adawiah, R.

2018-03-01

Detection of nanoparticles in solution has been made possible by several means; one of them is laser-induced breakdown detection (LIBD). LIBD is able to distinguish colloids of various sizes and concentrations. This technique has been used in several solubility studies. In this study, the formation of colloids in a mixed system of silver nitrate and sodium chloride was observed by acoustic LIBD. Silver chloride has low solubility limit, therefore LIBD measurement is appropriate. Silver and chloride solutions with equal concentrations, set at below and above the solubility of silver chloride as the expected solid product, were mixed and the resulting colloids were observed. The result of LIBD measurement showed that larger particles were present as more silver and chloride introduced. However, once the concentrations exceeded the solubility limit of silver chloride, the detected particle size seemed to be decreasing, hence suggested the occurrence of coprecipitation process. This phenomenon indicated that the ability of LIBD to detect even small changes in colloid amounts might be a useful tool in study on formation and stability of colloids, i.e. to confirm whether nanoparticles synthesis has been successfully performed and whether the system is stable or not.

Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

PubMed Central

Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

2016-01-01

Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

Stress-induced reversible and irreversible ferroelectric domain switching

NASA Astrophysics Data System (ADS)

Chen, Zibin; Huang, Qianwei; Wang, Feifei; Ringer, Simon P.; Luo, Haosu; Liao, Xiaozhou

2018-04-01

Ferroelectric materials have been extensively explored for applications in electronic devices because of their ferroelectric/ferroelastic domain switching behaviour under electric bias or mechanical stress. Recent findings on applying mechanical loading to manipulate reversible logical signals in non-volatile ferroelectric memory devices make ferroelectric materials more attractive to scientists and engineers. However, the dynamical microscopic structural behaviour of ferroelectric domains under stress is not well understood, which limits the applications of ferroelectric/ferroelastic switching in memory devices. Here, the kinetics of reversible and irreversible ferroelectric domain switching induced by mechanical stress in relaxor-based ferroelectrics was explored. In-situ transmission electron microscopy investigation revealed that 90° ferroelastic and 180° ferroelectric domain switching can be induced by low and high mechanical stresses. The nucleation and growth of nanoscale domains overwhelm the defect-induced pinning effect on the stable micro-domain walls. This study provides deep insights for exploring the mechanical kinetics for ferroelectric/ferroelastic domains and a clear pathway to overcome the domain pinning effect of defects in ferroelectrics.

Swelling-induced chloride current in glioblastoma proliferation, migration, and invasion.

PubMed

Wong, Raymond; Chen, Wenliang; Zhong, Xiao; Rutka, James T; Feng, Zhong-Ping; Sun, Hong-Shuo

2018-01-01

Glioblastoma (GBM) remains as the most common and aggressive brain tumor. The survival of GBM has been linked to the aberrant activation of swelling-induced chloride current I Cl,swell . In this study, we investigated the effects of I Cl,swell on cell viability, proliferation, and migration in the human GBM cell lines, U251 and U87, using a combination of patch clamp electrophysiology, MTT, colony formation, wound healing assays and Western immunoblotting. First, we showed that the specific inhibitor of I Cl,swell , DCPIB, potently reduced the I Cl,swell in U87 cells. Next, in both U87 and U251 cells, we found that DCPIB reduced GBM viability, proliferation, colony formation, migration, and invasion. In addition, our Western immunoblot assay showed that DCPIB-treated U251 cells had a reduction in JAK2, STAT3, and Akt phosphorylation, thus, suggesting that DCPIB potentially suppresses GBM functions through inhibition of the JAK2/STAT3 and PI3K/Akt signaling pathways. Therefore, the I Cl,swell may be a potential drug target for GBM. © 2017 Wiley Periodicals, Inc.

Oxidative stress-induced autophagy: Role in pulmonary toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu

2014-03-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injurymore » associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.« less

Potential role of punicalagin against oxidative stress induced testicular damage.

PubMed

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

Potential role of punicalagin against oxidative stress induced testicular damage

PubMed Central

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

46 CFR 151.50-34 - Vinyl chloride (vinyl chloride monomer).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Vinyl chloride (vinyl chloride monomer). 151.50-34... chloride (vinyl chloride monomer). (a) Copper, aluminum, magnesium, mercury, silver, and their alloys shall... equipment that may come in contact with vinyl chloride liquid or vapor. (b) Valves, flanges, and pipe...

Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats.

PubMed

Yee, Nicole; Plassmann, Kerstin; Fuchs, Eberhard

2011-09-01

Clinical studies have implicated adolescence as an important and vulnerable period during which traumatic experiences can predispose individuals to anxiety and mood disorders. As such, a stress model in juvenile rats (age 27-29 d) was previously developed to investigate the long-term effects of stress exposure during adolescence on behavior and physiology. This paradigm involves exposing rats to different stressors on consecutive days over a 3-day period. Here, we studied the effects of juvenile stress on long-term core body temperature regulation and acute stress-induced hyperthermia (SIH) responses using telemetry. We found no differences between control and juvenile stress rats in anxiety-related behavior on the elevated plus maze, which we attribute to stress associated with surgical implantation of telemetry devices. This highlights the severe impact of surgical stress on the results of subsequent behavioral measurements. Nonetheless, juvenile stress disrupted the circadian rhythmicity of body temperature and decreased circadian amplitude. It also induced chronic hypothermia during the dark phase of the day, when rats are most active. When subjected to acute social defeat stress as adults, juvenile stress had no impact on the SIH response relative to controls. However, 24 h later, juvenile stress rats displayed an elevated SIH response in anticipation of social defeat when re-exposed to the social defeat environment. Taken together, our findings indicate that juvenile stress can induce long-term alterations in body temperature regulation and heighten the increase in temperature associated with anticipation of social defeat. The outcomes of behavioral measurements in these experiments, however, are severely affected by surgical stress. Copyright © 2011 Elsevier Inc. All rights reserved.

Phase Stability and Stress-Induced Transformations in Beta Titanium Alloys

NASA Astrophysics Data System (ADS)

Kolli, R. Prakash; Joost, William J.; Ankem, Sreeramamurthy

2015-06-01

In this article, we provide a brief review of the recent developments related to the relationship between phase stability and stress-induced transformations in metastable body-centered-cubic β-phase titanium alloys. Stress-induced transformations occur during tensile, compressive, and creep loading and influence the mechanical response. These transformations are not fully understood and increased understanding of these mechanisms will permit future development of improved alloys for aerospace, biomedical, and energy applications. In the first part of this article, we review phase stability and discuss a few recent developments. In the second section, we discuss the current status of understanding stress-induced transformations and several areas that require further study. We also provide our perspective on the direction of future research efforts. Additionally, we address the occurrence of the hcp ω-phase and the orthorhombic α″-martensite phase stress-induced transformations.

Permeability of Concrete with Recycled Concrete Aggregate and Pozzolanic Materials under Stress

PubMed Central

Wang, Hailong; Sun, Xiaoyan; Wang, Junjie; Monteiro, Paulo J.M.

2016-01-01

The research reported herein studied the permeability of concrete containing recycled-concrete aggregate (RA), superfine phosphorous slag (PHS), and ground granulated blast-furnace slag (GGBS) with and without stress. Test results showed that the chloride diffusion coefficient of RA concrete (RAC) without external loads decreased with time, and the permeability of RAC is much lower than that of the reference concrete due to the on-going hydration and the pozzolanic reaction provided by the PHS and GGBS additives in the RAC mixture. The permeability of chloride under flexural load is much more sensitive than that under compressive load due to the differences in porosity and cracking pattern. At low compressive stress levels, the permeability of chloride decreased by the closing of pores and microcracks within RAC specimens. However, in a relatively short time the chloride diffusion coefficient and the chloride content increased rapidly with the increase of compressive stress when it exceeded a threshold stress level of approximate 35% of the ultimate compressive strength. Under flexural stress, the chloride transport capability increased with the increase of stress level and time. At high compressive and flexural stress levels, creep had a significant effect on the permeability of chloride in the RAC specimens due to the damage from the nucleation and propagation of microcracks over time. It is apparent that mortar cracking has more of a significant effect on the chloride transport in concrete than cracking in the interfacial transition zone (ITZ). PMID:28773376

Permeability of Concrete with Recycled Concrete Aggregate and Pozzolanic Materials under Stress.

PubMed

Wang, Hailong; Sun, Xiaoyan; Wang, Junjie; Monteiro, Paulo J M

2016-03-30

The research reported herein studied the permeability of concrete containing recycled-concrete aggregate (RA), superfine phosphorous slag (PHS), and ground granulated blast-furnace slag (GGBS) with and without stress. Test results showed that the chloride diffusion coefficient of RA concrete (RAC) without external loads decreased with time, and the permeability of RAC is much lower than that of the reference concrete due to the on-going hydration and the pozzolanic reaction provided by the PHS and GGBS additives in the RAC mixture. The permeability of chloride under flexural load is much more sensitive than that under compressive load due to the differences in porosity and cracking pattern. At low compressive stress levels, the permeability of chloride decreased by the closing of pores and microcracks within RAC specimens. However, in a relatively short time the chloride diffusion coefficient and the chloride content increased rapidly with the increase of compressive stress when it exceeded a threshold stress level of approximate 35% of the ultimate compressive strength. Under flexural stress, the chloride transport capability increased with the increase of stress level and time. At high compressive and flexural stress levels, creep had a significant effect on the permeability of chloride in the RAC specimens due to the damage from the nucleation and propagation of microcracks over time. It is apparent that mortar cracking has more of a significant effect on the chloride transport in concrete than cracking in the interfacial transition zone (ITZ).

Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate

PubMed Central

Pieme, Constant Anatole; Ngoupayo, Joseph; Khou-Kouz Nkoulou, Claude Herve; Moukette Moukette, Bruno; Njinkio Nono, Borgia Legrand; Ama Moor, Vicky Jocelyne; Ze Minkande, Jacqueline; Yonkeu Ngogang, Jeanne

2014-01-01

The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities. PMID:26785075

Inactivation of kupffer cells by gadolinium chloride protects murine liver from radiation-induced apoptosis.

PubMed

Du, Shi-Suo; Qiang, Min; Zeng, Zhao-Chong; Ke, Ai-Wu; Ji, Yuan; Zhang, Zheng-Yu; Zeng, Hai-Ying; Liu, Zhongshan

2010-03-15

To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis. A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining. The expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3. Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage. Copyright 2010 Elsevier Inc. All rights reserved.

Oxidative stress in MeHg-induced neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farina, Marcelo, E-mail: farina@ccb.ufsc.br; Aschner, Michael; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN

2011-11-15

Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have beenmore » reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the

Stress-induced cardiomyopathy caused by heat stroke.

PubMed

Chen, Wei-Ta; Lin, Cheng-Hsin; Hsieh, Ming-Hsiung; Huang, Chun-Yao; Yeh, Jong-Shiuan

2012-07-01

Heat stroke is defined by central nervous system abnormalities and failure of proper maintenance of thermoregulation as a result of high core body temperature ensuing from exposure to high environmental temperatures or strenuous exercise. Common complications include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in cardiac enzyme increase and ST-segment changes on the ECG. Such findings might behave as diagnostic pitfalls by mimicking the presentation of coronary artery occlusive myocardial infarction. A previous case report described a patient with heat stroke and ST-segment elevation, in which the definite cause of the ST-segment elevation was unclear; however, acute myocardial infarction caused by coronary artery disease was ruled out according to the clinical signs, serial ECG changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because of the lack of coronary angiography. We herein report a case of heat stroke presenting with ST-segment elevation and cardiogenic shock. Coronary angiography was performed and coronary artery occlusive myocardial infarction was ruled out because of the presence of patent coronary arteries. Left ventriculography showed midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then determined to be the appropriate diagnosis. Heat stroke causes increase of serum catecholamine levels, in which oversecretion and abnormal responses to catecholamines are a possible cause of stress-induced cardiomyopathy. Catecholamines may therefore be the key in linking heat stroke and stress-induced cardiomyopathy. Copyright © 2011. Published by Mosby, Inc.

Charge transfer induced by MoO3 at boron subphthalocyanine chloride/α-sexithiophene heterojunction interface

NASA Astrophysics Data System (ADS)

Foggiatto, Alexandre L.; Sakurai, Takeaki

2018-03-01

The energy-level alignment of boron subphthalocyanine chloride (SubPc)/α-sexithiophene (6T) grown on MoO3 was investigated using ultraviolet and X-ray photoelectron spectroscopy (UPS and XPS). We demonstrated that the p-doping effect generated by the MoO3 layer can induce charge transfer at the organic-organic heterojunction interface. After the deposition of 6T on MoO3, the fermi level becomes pinned close to the 6T highest occupied molecular orbital (HOMO) level and when SubPc is deposited, owing to its tail states, charge transfer occurs in order to achieve thermodynamic equilibrium. We also demonstrated that the charge transfer can be reduced by annealing the film. We suggested that the reduction of the misalignment on the film induces a reduction in the density of gap states, which controls the charge transfer.

Granular parakeratosis induced by benzalkonium chloride exposure from laundry rinse aids.

PubMed

Robinson, Aaron J; Foster, Rachael S; Halbert, Anne R; King, Emma; Orchard, David

2017-08-01

Benzalkonium chloride is a quaternary ammonium cationic detergent present in a number of household products, which can act as a major skin irritant. We present the case of six children who developed granular parakeratosis after exposure to benzalkonium chloride in laundry rinse aids, presenting as a brightly erythematous, tender but minimally pruritic, intertriginous eruption followed by superficial desquamation. The eruptions resolved over 3-4 weeks after cessation of exposure. © 2016 The Australasian College of Dermatologists.

Gender differences in neural correlates of stress-induced anxiety.

PubMed

Seo, Dongju; Ahluwalia, Aneesha; Potenza, Marc N; Sinha, Rajita

2017-01-02

Although gender differences have been identified as a crucial factor for understanding stress-related anxiety and associated clinical disorders, the neural mechanisms underlying these differences remain unclear. To explore gender differences in the neural correlates of stress-induced anxiety, the current study used functional magnetic resonance imaging to examine brain responses in 96 healthy men and women with commensurable levels of trait anxiety as they engaged in a personalized guided imagery paradigm to provoke stress and neutral-relaxing experiences. During the task, a significant gender main effect emerged, with men displaying greater responses in the caudate, cingulate gyrus, midbrain, thalamus, and cerebellum. In contrast, women showed greater responses in the posterior insula, temporal gyrus, and occipital lobe. Additionally, a significant anxiety ratings × gender interaction from whole-brain regression analyses was observed in the dorsomedial prefrontal cortex, left inferior parietal lobe, left temporal gyrus, occipital gyrus, and cerebellum (P < 0.05, whole-brain family-wise error corrected), with positive associations between activity in these regions and stress-induced anxiety in women, but negative associations in men, indicating that men and women differentially use neural resources when experiencing stress-induced anxiety. The findings suggest that in response to stress, there is a greater use of the medial prefrontal-parietal cortices in experiencing subjective anxiety in women, while decreased use of this circuit was associated with increased subjective anxiety states in men. The current study has implications for understanding gender-specific differences in stress-induced anxiety and vulnerability to stress-related clinical disorders, and for developing more effective treatment strategies tailored to each gender. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Environmental stress induces trinucleotide repeat mutagenesis in human cells

PubMed Central

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.

2015-01-01

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

Heat-Stress and Light-Stress Induce Different Cellular Pathologies in the Symbiotic Dinoflagellate during Coral Bleaching

PubMed Central

Downs, C. A.; McDougall, Kathleen E.; Woodley, Cheryl M.; Fauth, John E.; Richmond, Robert H.; Kushmaro, Ariel; Gibb, Stuart W.; Loya, Yossi; Ostrander, Gary K.; Kramarsky-Winter, Esti

2013-01-01

Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m−2 s−1 PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching. PMID:24324575

Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

PubMed

Downs, C A; McDougall, Kathleen E; Woodley, Cheryl M; Fauth, John E; Richmond, Robert H; Kushmaro, Ariel; Gibb, Stuart W; Loya, Yossi; Ostrander, Gary K; Kramarsky-Winter, Esti

2013-01-01

Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

Stress-induced reliance on habitual behavior is moderated by cortisol reactivity.

PubMed

Smeets, T; van Ruitenbeek, P; Hartogsveld, B; Quaedflieg, Conny W E M

2018-05-25

Instrumental learning, i.e., learning that specific behaviors lead to desired outcomes, occurs through goal-directed and habit memory systems. Exposure to acute stress has been shown to result in less goal-directed control, thus rendering behavior more habitual. The aim of the current studies was to replicate and extend findings on stress-induced prompting of habitual responding and specifically focused on the role of stress-induced cortisol reactivity. Study 1 used an established outcome devaluation paradigm to assess goal-directed and habitual control. Study 2 utilized a modified version of this paradigm that was intended to establish stronger habitual responding through more extensive reward training and applying a relevant behavioral devaluation procedure (i.e., eating to satiety). Both studies failed to replicate that stress overall, i.e., independent of cortisol reactivity, shifted behavior from goal-directed to habitual control. However, both studies found that relative to stress-exposed cortisol non-responders and no-stress controls, participants displaying stress-induced cortisol reactivity displayed prominent habitual responding. These findings highlight the importance of stress-induced cortisol reactivity in facilitating habits. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.

PubMed

Palomer, Xavier; Capdevila-Busquets, Eva; Botteri, Gaia; Salvadó, Laia; Barroso, Emma; Davidson, Mercy M; Michalik, Liliane; Wahli, Walter; Vázquez-Carrera, Manuel

2014-06-01

Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells. Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers. Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neuroendocrine and oxidoreductive mechanisms of stress-induced cardiovascular diseases.

PubMed

Pajović, S B; Radojcić, M B; Kanazir, D T

2008-01-01

The review concerns a number of basic molecular pathways that play a crucial role in perception, transmission, and modulation of the stress signals, and mediate the adaptation of the vital processes in the cardiovascular system (CVS). These highly complex systems for intracellular transfer of information include stress hormones and their receptors, stress-activated phosphoprotein kinases, stress-activated heat shock proteins, and antioxidant enzymes maintaining oxidoreductive homeostasis of the CVS. Failure to compensate for the deleterious effects of stress may result in the development of different pathophysiological states of the CVS, such as ischemia, hypertension, atherosclerosis and infarction. Stress-induced dysbalance in each of the CVS molecular signaling systems and their contribution to the CVS malfunctioning is reviewed. The general picture of the molecular mechanisms of the stress-induced pathophysiology in the CVS pointed out the importance of stress duration and intensity as etiological factors, and suggested that future studies should be complemented by the careful insights into the individual factors of susceptibility to stress, prophylactic effects of 'healthy' life styles and beneficial action of antioxidant-rich nutrition.

Silicon decreases chloride transport in rice (Oryza sativa L.) in saline conditions.

PubMed

Shi, Yu; Wang, Yichao; Flowers, Timothy J; Gong, Haijun

2013-06-15

Silicon can alleviate salt damage to plants, although the mechanism(s) still remains to be elucidated. In this paper, we report the effect of silicon on chloride transport in rice (Oryza sativa L.) seedlings in saline conditions. In the absence of salinity, silicon enhanced the growth of shoots, but not roots in three cultivars (cv. GR4, IR36, and CSR10). Salinity reduced the growth of both shoots and roots in all three genotypes. In saline conditions, addition of silicon to the culture solution again improved the growth of shoots, but not of roots. Under these saline conditions, the concentrations of chloride in the shoot were markedly decreased by adding silicon and the ratio of K(+)/Cl(-) was significantly increased, while the concentration of chloride in the roots was unchanged. The decrease in chloride concentration in the shoot was correlated with the decrease in transpirational bypass flow in rice, as shown by the transport of the apoplastic tracer trisodium-8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS). Addition of silicon increased the net photosynthetic rate, stomata conductance, and transpiration of salt-stressed plants in cv. IR36, indicating that the reduction of chloride (and sodium) uptake by silicon was not through a reduction in transpiration rate. Silicon addition also increased the instantaneous water use efficiency of salt-stressed plants, while it did not change the relative growth rate of shoots. The results suggest that silicon addition decreased transpirational bypass flow in the roots, and therefore decreased the transport of chloride to the shoot. Copyright © 2013 Elsevier GmbH. All rights reserved.

Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

PubMed

Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

2016-11-15

Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

On the function and fate of chloride ions in amyloidogenic self-assembly of insulin in an acidic environment: salt-induced condensation of fibrils.

PubMed

Babenko, Viktoria; Surmacz-Chwedoruk, Weronika; Dzwolak, Wojciech

2015-02-24

Formation of amyloid fibrils is often facilitated in the presence of specific charge-compensating ions. Dissolved sodium chloride is known to accelerate insulin fibrillation at low pH that has been attributed to the shielding of electrostatic repulsion between positively charged insulin molecules by chloride ions. However, the subsequent fate of Cl(-) anions; that is, possible entrapment within elongating fibrils or escape into the bulk solvent, remains unclear. Here, we show that, while the presence of NaCl at the onset of insulin aggregation induces structural variants of amyloid with distinct fingerprint infrared features, a delayed addition of salt to fibrils that have been already formed in its absence and under quiescent conditions triggers a "condensation effect": amyloid superstructures with strong chiroptical properties are formed. Chloride ions appear to stabilize these superstructures in a manner similar to stabilization of DNA condensates by polyvalent cations. The concentration of residual chloride ions trapped within bovine insulin fibrils grown in 0.1 M NaCl, at pD 1.9, and rinsed extensively with water afterward is less than 1 anion per 16 insulin monomers (as estimated using ion chromatography) implying absence of defined solvent-sequestered nesting sites for chloride counterions. Our results have been discussed in the context of mechanisms of insulin aggregation.

CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT WITH SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

2-Chlorohexadecanoic acid induces ER stress and mitochondrial dysfunction in brain microvascular endothelial cells.

PubMed

Bernhart, Eva; Kogelnik, Nora; Prasch, Jürgen; Gottschalk, Benjamin; Goeritzer, Madeleine; Depaoli, Maria Rosa; Reicher, Helga; Nusshold, Christoph; Plastira, Ioanna; Hammer, Astrid; Fauler, Günter; Malli, Roland; Graier, Wolfgang F; Malle, Ernst; Sattler, Wolfgang

2018-05-01

Peripheral leukocytes induce blood-brain barrier (BBB) dysfunction through the release of cytotoxic mediators. These include hypochlorous acid (HOCl) that is formed via the myeloperoxidase-H 2 O 2 -chloride system of activated phagocytes. HOCl targets the endogenous pool of ether phospholipids (plasmalogens) generating chlorinated inflammatory mediators like e.g. 2-chlorohexadecanal and its conversion product 2-chlorohexadecanoic acid (2-ClHA). In the cerebrovasculature these compounds inflict damage to brain microvascular endothelial cells (BMVEC) that form the morphological basis of the BBB. To follow subcellular trafficking of 2-ClHA we synthesized a 'clickable' alkyne derivative (2-ClHyA) that phenocopied the biological activity of the parent compound. Confocal and superresolution structured illumination microscopy revealed accumulation of 2-ClHyA in the endoplasmic reticulum (ER) and mitochondria of human BMVEC (hCMEC/D3 cell line). 2-ClHA and its alkyne analogue interfered with protein palmitoylation, induced ER-stress markers, reduced the ER ATP content, and activated transcription and secretion of interleukin (IL)-6 as well as IL-8. 2-ClHA disrupted the mitochondrial membrane potential and induced procaspase-3 and PARP cleavage. The protein kinase R-like ER kinase (PERK) inhibitor GSK2606414 suppressed 2-ClHA-mediated activating transcription factor 4 synthesis and IL-6/8 secretion, but showed no effect on endothelial barrier dysfunction and cleavage of procaspase-3. Our data indicate that 2-ClHA induces potent lipotoxic responses in brain endothelial cells and could have implications in inflammation-induced BBB dysfunction. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chloride channels in stroke

PubMed Central

Zhang, Ya-ping; Zhang, Hao; Duan, Dayue Darrel

2013-01-01

Vascular remodeling of cerebral arterioles, including proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs), is the major cause of changes in the cross-sectional area and diameter of the arteries and sudden interruption of blood flow or hemorrhage in the brain, ie, stroke. Accumulating evidence strongly supports an important role for chloride (Cl−) channels in vascular remodeling and stroke. At least three Cl− channel genes are expressed in VSMCs: 1) the TMEM16A (or Ano1), which may encode the calcium-activated Cl− channels (CACCs); 2) the CLC-3 Cl− channel and Cl−/H+ antiporter, which is closely related to the volume-regulated Cl− channels (VRCCs); and 3) the cystic fibrosis transmembrane conductance regulator (CFTR), which encodes the PKA- and PKC-activated Cl− channels. Activation of the CACCs by agonist-induced increase in intracellular Ca2+ causes membrane depolarization, vasoconstriction, and inhibition of VSMC proliferation. Activation of VRCCs by cell volume increase or membrane stretch promotes the production of reactive oxygen species, induces proliferation and inhibits apoptosis of VSMCs. Activation of CFTR inhibits oxidative stress and may prevent the development of hypertension. In addition, Cl− current mediated by gamma-aminobutyric acid (GABA) receptor has also been implicated a role in ischemic neuron death. This review focuses on the functional roles of Cl− channels in the development of stroke and provides a perspective on the future directions for research and the potential to develop Cl− channels as new targets for the prevention and treatment of stroke. PMID:23103617

Interaction of chloride and bicarbonate transport across the basolateral membrane of rabbit proximal straight tubule. Evidence for sodium coupled chloride/bicarbonate exchange.

PubMed Central

Sasaki, S; Yoshiyama, N

1988-01-01

The existence of chloride/bicarbonate exchange across the basolateral membrane and its physiologic significance were examined in rabbit proximal tubules. S2 segments of the proximal straight tubule were perfused in vitro and changes in intracellular pH (pHi) and chloride activity (aCli) were monitored by double-barreled microelectrodes. Total peritubular chloride replacement with gluconate increased pHi by 0.8, and this change was inhibited by a pretreatment with an anion transport inhibitor, SITS. Peritubular bicarbonate reduction increased aCli, and most of this increase was lost when ambient sodium was totally removed. The reduction rates of pHi induced by a peritubular bicarbonate reduction or sodium removal were attenuated by 20% by withdrawal of ambient chloride. SITS application to the bath in the control condition quickly increased pHi, but did not change aCli. However, the aCli slightly decreased in response to SITS when the basolateral bicarbonate efflux was increased by reducing peritubular bicarbonate concentration. It is concluded that sodium coupled chloride/bicarbonate exchange is present in parallel with sodium-bicarbonate cotransport in the basolateral membrane of the rabbit proximal tubule, and it contributes to the basolateral bicarbonate and chloride transport. PMID:2450891

Thermally induced stresses and deformations in angle-ply composite tubes

NASA Technical Reports Server (NTRS)

Hyer, M. W.; Rousseau, Carl Q.

1987-01-01

Cure-induced uniform temperature change effects on the stresses, axial expansion, and thermally-induced twist of four specific angle-ply tube designs are discussed with a view to the tubes' use as major space structure components. The stresses and deformations in the tubes are studied as a function of the four designs, the off-axis angle, and the single-material and hybrid reinforcing-material construction used. It is found that tube design has a minor influence on the stresses, axial stiffness, and axial thermal expansion characteristics, which are more directly a function of off-axis angle and material selection; tube design is, however, the primary influence in the definition of thermally-induced twist and torsional stiffness characteristics. None of the designs is free of thermally induced twist.

CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT OF CENTER WITH TOP OF SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

Model for Stress-induced Protein Degradation in Lemna minor1

PubMed Central

Cooke, Robert J.; Roberts, Keith; Davies, David D.

1980-01-01

Transfer of Lemna minor fronds to adverse or stress conditions produces a large increase in the rate of protein degradation. Cycloheximide partially inhibits stress-induced protein degradation and also partially inhibits the protein degradation which occurs in the absence of stress. The increased protein degradation does not appear to be due to an increase in activity of soluble proteolytic enzymes. Biochemical evidence indicates that stress, perhaps acting via hormones, affects the permeability of certain membranes, particularly the tonoplast. A general model for stress-induced protein degradation is presented in which changes in membrane properties allow vacuolar proteolytic enzymes increased access to cytoplasmic proteins. PMID:16661588

Emotional Intelligence, Personality, and Task-Induced Stress

ERIC Educational Resources Information Center

Matthews, Gerald; Emo, Amanda K.; Funke, Gregory; Zeidner, Moshe; Roberts, Richard D.; Costa, Paul T.; Schulze, Ralf

2006-01-01

Emotional intelligence (EI) may predict stress responses and coping strategies in a variety of applied settings. This study compares EI and the personality factors of the Five Factor Model (FFM) as predictors of task-induced stress responses. Participants (N = 200) were randomly assigned to 1 of 4 task conditions, 3 of which were designed to be…

R&D 100, 2016: Stress-Induced Fabrication

ScienceCinema

Fan, Hongyou; Brennan, Tom; Wise, Jack; Liu, Sheng; Hickman, Randy

2018-06-13

Stress-induced fabrication (SIF) uses compressive mechanical stress to create new nanomaterials with lower production costs and enhanced materials performance compared to traditional fabrication routes. Simple, innovative, and with more degrees of freedom than current chemical synthesis methods, SIF uses physical force instead of chemistry applied to form new nanomaterials with precisely controlled structure and tunable properties.

R&D 100, 2016: Stress-Induced Fabrication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Hongyou; Brennan, Tom; Wise, Jack

Stress-induced fabrication (SIF) uses compressive mechanical stress to create new nanomaterials with lower production costs and enhanced materials performance compared to traditional fabrication routes. Simple, innovative, and with more degrees of freedom than current chemical synthesis methods, SIF uses physical force instead of chemistry applied to form new nanomaterials with precisely controlled structure and tunable properties.

[Effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells].

PubMed

Wang, Bao-an; Li, Ming; Mu, Yi-ming; Lu, Zhao-hui; Li, Jiang-yuan

2006-06-01

To investigate the effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells. The rat Leydig cells (LC-540) were incubated with 0 to 80 nmol/L TBT and TPT for 24 to approximately 96 h, and then the cell viability was determined by MTT. DNA fragmentation ladder formation of cell apoptosis was examined by agarose electrophoresis. Effects of chelator of intracellular Ca2+ (BAPTA) and the inhibitors of PKA, PKC and TPK on cell apoptosis induced by TBT were observed. Effects of TBT on testosterone production in primary cultured rat Leydig cells treated with or without hCG were detected. TBT and TPT suppressed Leydig cell survival in a time- and dose-dependent manner. The suppressive effects of TBT and TPT on the cell survival was caused by apoptosis which was determined by DNA ladder formation. The apoptotic effect of TBT was possibly mediated by the rise in intracellular Ca2+ because it could be blocked by BAPTA, the chelator of intracellular Ca2+; PKA, PKC and TPK inhibitors did not prevent the apoptotic effects induced by TBT. TBT markedly suppressed testosterone production of primary cultured rat Leydig cells with or without hCG stimulation. TBT and TPT induced apoptosis in rat testicular Leydig cells possibly through increasing intracellular Ca2+. TBT reduced the testosterone production of rat Leydig cells.

Heat stress protects against mechanical ventilation-induced diaphragmatic atrophy.

PubMed

Ichinoseki-Sekine, Noriko; Yoshihara, Toshinori; Kakigi, Ryo; Sugiura, Takao; Powers, Scott K; Naito, Hisashi

2014-09-01

Mechanical ventilation (MV) is a life-saving intervention in patients who are incapable of maintaining adequate pulmonary gas exchange due to respiratory failure or other disorders. However, prolonged MV is associated with the development of respiratory muscle weakness. We hypothesized that a single exposure to whole body heat stress would increase diaphragm expression of heat shock protein 72 (HSP72) and that this treatment would protect against MV-induced diaphragmatic atrophy. Adult male Wistar rats (n = 38) were randomly assigned to one of four groups: an acutely anesthetized control group (CON) with no MV; 12-h controlled MV group (CMV); 1-h whole body heat stress (HS); or 1-h whole body heat stress 24 h prior to 12-h controlled MV (HSMV). Compared with CON animals, diaphragmatic HSP72 expression increased significantly in the HS and HSMV groups (P < 0.05). Prolonged MV resulted in significant atrophy of type I, type IIa, and type IIx fibers in the costal diaphragm (P < 0.05). Whole body heat stress attenuated this effect. In contrast, heat stress did not protect against MV-induced diaphragm contractile dysfunction. The mechanisms responsible for this heat stress-induced protection remain unclear but may be linked to increased expression of HSP72 in the diaphragm. Copyright © 2014 the American Physiological Society.

Strength and texture of sodium chloride to 56 GPa

NASA Astrophysics Data System (ADS)

Mi, Z.; Shieh, S. R.; Kavner, A.; Kiefer, B.; Wenk, H.-R.; Duffy, T. S.

2018-04-01

The strength and texture of sodium chloride in the B1 (rocksalt) and B2 (cesium chloride) phases were investigated in a diamond anvil cell using synchrotron X-ray diffraction in a radial geometry to 56 GPa. The measured differential stresses within the Reuss limit are in the range of 0.2 GPa for the B1 phase at pressure of 24 GPa and 1.6 GPa for the B2 phase at pressure of 56 GPa. A strength weakening is observed near the B1-B2 phase transition at about 30 GPa. The low strength of NaCl in the B1 phase confirms that it is an effective pressure-transmitting medium for high-pressure experiments to ˜30 GPa. The B2 phase can be also used as a pressure-transmitting medium although it exhibits a steeper increase in strength with pressure than the B1 phase. Deformation induces weak lattice preferred orientation in NaCl, showing a (100) texture in the B1 phase and a (110) texture in the B2 phase. The observed textures were evaluated by viscoplastic self-consistent model and our results suggest {110}⟨ 1 1 ¯ 0 ⟩ as the slip system for the B1 phase and {112} ⟨1 1 ¯ 0 ⟩ for the B2 phase.

Prevention effect of rare ginsenosides against stress-hormone induced MTOC amplification

PubMed Central

Lee, Jee-Hyun; Cheong, Kyu Jin; Jung, Youn-Sang; Woo, Tae-Gyun; Yoon, Min-Ho; Oh, Ah-Young; Kang, So-Mi; Lee, Chunghui; Sun, Hokeun; Hwang, Jihwan; Song, Gyu-Yong; Park, Bum-Joon

2016-01-01

Stress has been suggested as one of important cause of human cancer without molecular biological evidence. Thus, we test the effect of stress-related hormones on cell viability and mitotic fidelity. Similarly to estrogen, stress hormone cortisol and its relative cortisone increase microtubule organizing center (MTOC) number through elevated expression of γ-tubulin and provide the Taxol resistance to human cancer cell lines. However, these effects are achieved by glucocorticoid hormone receptor (GR) but not by estrogen receptor (ER). Since ginsenosides possess steroid-like structure, we hypothesized that it would block the stress or estrogen-induced MTOC amplification and Taxol resistance. Among tested chemicals, rare ginsenoside, CSH1 (Rg6) shows obvious effect on inhibition of MTOC amplification, γ-tubulin induction and Taxol resistance. Comparing to Fulvestant (FST), ER-α specific inhibitor, this chemical can block the cortisol/cortisone-induced MTOC deregulation as well as ER-α signaling. Our results suggest that stress hormone induced tumorigenesis would be achieved by MTOC amplification, and CSH1 would be useful for prevention of stress-hormone or steroid hormone-induced chromosomal instability. PMID:27147573

Changes in translation rate modulate stress-induced damage of diverse proteins

PubMed Central

Kim, Heejung

2013-01-01

Proteostasis is the maintenance of the proper function of cellular proteins. Hypertonic stress disrupts proteostasis and causes rapid and widespread protein aggregation and misfolding in the nematode Caenorhabditis elegans. Optimal survival in hypertonic environments requires degradation of damaged proteins. Inhibition of protein synthesis occurs in response to diverse environmental stressors and may function in part to minimize stress-induced protein damage. We recently tested this idea directly and demonstrated that translation inhibition by acute exposure to cycloheximide suppresses hypertonicity-induced aggregation of polyglutamine::YFP (Q35::YFP) in body wall muscle cells. In this article, we further characterized the relationship between protein synthesis and hypertonic stress-induced protein damage. We demonstrate that inhibition of translation reduces hypertonic stress-induced formation and growth of Q35::YFP, Q44::YFP, and α-synuclein aggregates; misfolding of paramyosin and ras GTPase; and aggregation of multiple endogenous proteins expressed in diverse cell types. Activation of general control nonderepressible-2 (GCN-2) kinase signaling during hypertonic stress inhibits protein synthesis via phosphorylation of eukaryotic initiation factor-2α (eIF-2α). Inhibition of GCN-2 activation prevents the reduction in translation rate and greatly exacerbates the formation and growth of Q35::YFP aggregates and the aggregation of endogenous proteins. The current studies together with our previous work provide the first direct demonstration that hypertonic stress-induced reduction in protein synthesis minimizes protein aggregation and misfolding. Reduction in translation rate also serves as a signal that activates osmoprotective gene expression. The cellular proteostasis network thus plays a critical role in minimizing hypertonic stress-induced protein damage, in degrading stress-damaged proteins, and in cellular osmosensing and signaling. PMID:24153430

Gravity-induced stresses near a vertical cliff

USGS Publications Warehouse

Savage, W.Z.

1993-01-01

The exact solution for gravity-induced stresses beneath a vertical cliff presented here has application to the design of cut slopes in rock, compares favorably with published photoelastic and finite-element results for this problem, and satisfies the condition that shear and normal stresses vanish on the ground surface, except at the bottom corner where stress concentrations exist. The solution predicts that horizontal stresses are tensile away from the bottom of the cliff-effects caused by movement below the cliff in response to the gravity loading of the cliff. Also, it is shown that along the top of the cliff normal stresses reduce to those predicted for laterally constrained flat-lying topography. ?? 1993.

46 CFR 151.50-34 - Vinyl chloride (vinyl chloride monomer).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Vinyl chloride (vinyl chloride monomer). 151.50-34 Section 151.50-34 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS... chloride (vinyl chloride monomer). (a) Copper, aluminum, magnesium, mercury, silver, and their alloys shall...

Comparative analysis reveals genomic features of stress-induced transcriptional readthrough

PubMed Central

Vilborg, Anna; Sabath, Niv; Wiesel, Yuval; Nathans, Jenny; Levy-Adam, Flonia; Yario, Therese A.; Steitz, Joan A.; Shalgi, Reut

2017-01-01

Transcription is a highly regulated process, and stress-induced changes in gene transcription have been shown to play a major role in stress responses and adaptation. Genome-wide studies reveal prevalent transcription beyond known protein-coding gene loci, generating a variety of RNA classes, most of unknown function. One such class, termed downstream of gene-containing transcripts (DoGs), was reported to result from transcriptional readthrough upon osmotic stress in human cells. However, how widespread the readthrough phenomenon is, and what its causes and consequences are, remain elusive. Here we present a genome-wide mapping of transcriptional readthrough, using nuclear RNA-Seq, comparing heat shock, osmotic stress, and oxidative stress in NIH 3T3 mouse fibroblast cells. We observe massive induction of transcriptional readthrough, both in levels and length, under all stress conditions, with significant, yet not complete, overlap of readthrough-induced loci between different conditions. Importantly, our analyses suggest that stress-induced transcriptional readthrough is not a random failure process, but is rather differentially induced across different conditions. We explore potential regulators and find a role for HSF1 in the induction of a subset of heat shock-induced readthrough transcripts. Analysis of public datasets detected increases in polymerase II occupancy in DoG regions after heat shock, supporting our findings. Interestingly, DoGs tend to be produced in the vicinity of neighboring genes, leading to a marked increase in their antisense-generating potential. Finally, we examine genomic features of readthrough transcription and observe a unique chromatin signature typical of DoG-producing regions, suggesting that readthrough transcription is associated with the maintenance of an open chromatin state. PMID:28928151

The APP intracellular domain (AICD) potentiates ER stress-induced apoptosis.

PubMed

Kögel, Donat; Concannon, Caoimhín G; Müller, Thorsten; König, Hildegard; Bonner, Caroline; Poeschel, Simone; Chang, Steffi; Egensperger, Rupert; Prehn, Jochen H M

2012-09-01

Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated with an increased sensitivity to apoptosis induced by the 2 endoplasmic reticulum (ER) stressors thapsigargin and tunicamycin, but not by staurosporine (STS). Basal and ER stress-induced expression of Bip/Grp78 and C/EBP-homologous protein/GADD153 were not altered by AICD implying that AICD potentiated cell death downstream or independent of the conserved unfolded protein response (UPR). Interestingly, quantitative polymerase chain reaction analysis and reporter gene assays revealed that AICD significantly downregulated messenger RNA levels of the Alzheimer's disease susceptibility gene ApoJ/clusterin, indicating transcriptional repression. Knockdown of ApoJ/clusterin mimicked the effect of AICD on ER stress-induced apoptosis, but had no discernible effect on staurosporine-induced cell death. Our data suggest that altered levels of AICD may abolish the prosurvival function of ApoJ/clusterin and increase the susceptibility of neurons to ER stress-mediated cell death, a pathway that may contribute to the pathogenesis of Alzheimer's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Zinc stress induces copper depletion in Acinetobacter baumannii.

PubMed

Hassan, Karl A; Pederick, Victoria G; Elbourne, Liam D H; Paulsen, Ian T; Paton, James C; McDevitt, Christopher A; Eijkelkamp, Bart A

2017-03-11

The first row transition metal ions zinc and copper are essential to the survival of many organisms, although in excess these ions are associated with significant toxicity. Here, we examined the impact of zinc and copper stress on Acinetobacter baumannii, a common opportunistic pathogen. We show that extracellular zinc stress induces a copper-specific depletion phenotype in A. baumannii ATCC 17978. Supplementation with copper not only fails to rescue this phenotype, but further exacerbates the copper depletion. Extensive analysis of the A. baumannii ATCC 17978 genome identified 13 putative zinc/copper resistance efflux pumps. Transcriptional analyses show that four of these transporters are responsive to zinc stress, five to copper stress and seven to the combination of zinc and copper stress, thereby revealing a likely foundation for the zinc-induced copper starvation in A. baumannii. In addition, we show that zinc and copper play crucial roles in management of oxidative stress and the membrane composition of A. baumannii. Further, we reveal that zinc and copper play distinct roles in macrophage-mediated killing of this pathogen. Collectively, this study supports the targeting of metal ion homeostatic mechanisms as an effective antimicrobial strategy against multi-drug resistant bacterial pathogens.

Repeated folding stress-induced morphological changes in the dermal equivalent.

PubMed

Arai, Koji Y; Sugimoto, Mami; Ito, Kanako; Ogura, Yuki; Akutsu, Nobuko; Amano, Satoshi; Adachi, Eijiro; Nishiyama, Toshio

2014-11-01

Repeated mechanical stresses applied to the same region of the skin are thought to induce morphological changes known as wrinkle. However, the underlying mechanisms are not fully understood. To study the mechanisms, we examined effects of repeated mechanical stress on the dermal equivalent. We developed a novel device to apply repeated folding stress to the dermal equivalent. After applying the mechanical stress, morphological changes of the dermal equivalent and expression of several genes related to extracellular matrix turn over and cell contraction were examined. The repeated folding stress induced a noticeable decrease in the width of the dermal equivalent. The mechanical stress altered orientations of collagen fibrils. Hydroxyproline contents, dry weights and cell viability of the dermal equivalents were not affected by the mechanical stress. On the other hand, Rho-associated coiled-coil-containing kinase (ROCK) specific inhibitor Y27632 completely suppressed the decrease in the width of the dermal equivalent. The present results revealed that either degradation of collagen or changes in the number of cells were not responsible for the decrease in the width of the dermal equivalent and indicate that the repeated mechanical stress induces unidirectional contraction in the dermal equivalent through the RhoA-ROCK signaling pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Prediabetes as a riskmarker for stress-induced hyperglycemia in critically ill adults].

PubMed

García-Gallegos, Diego Jesús; Luis-López, Eliseo

2017-01-01

It is not known if patients with prediabetes, a subgroup of non-diabetic patients that usually present hyperinsulinemia, have higher risk to present stress-induced hyperglycemia. The objective was to determine if prediabetes is a risk marker to present stress-induced hyperglycemia. Analytic, observational, prospective cohort study of non-diabetic critically ill patients of a third level hospital. We determined plasmatic glucose and glycated hemoglobin (HbA1c) at admission to diagnose stress-induced hyperglycemia (glucose ≥ 140 mg/dL) and prediabetes (HbA1c between 5.7 and 6.4%), respectively. We examined the proportion of non-prediabetic and prediabetic patients that developed stress hyperglycemia with contingence tables and Fisher's exact test for nominal scales. Of 73 patients studied, we found a proportion of stress-induced hyperglycemia in 6.6% in those without prediabetes and 61.1% in those with prediabetes. The Fisher's exact test value was 22.46 (p < 0.05). Prediabetes is a risk marker for stress-induced hyperglycemia in critically ill adults.

Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

PubMed

Alvarez, Pedro; Green, Paul G; Levine, Jon D

2018-06-01

Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Association between changes in heart rate variability during the anticipation of a stressful situation and the stress-induced cortisol response.

PubMed

Pulopulos, Matias M; Vanderhasselt, Marie-Anne; De Raedt, Rudi

2018-08-01

Vagal activity - reflecting the activation of stress regulatory mechanisms and prefrontal cortex activation - is thought to play an inhibitory role in the regulation of the hypothalamus-pituitary-adrenal axis. However, most studies investigating the association between stress-induced changes in heart rate variability (HRV, an index of cardiac vagal tone) and cortisol have shown a non-significant relationship. It has been proposed that physiological changes observed during anticipation of a stressor allow individuals to make behavioral, cognitive, and physiological adjustments that are necessary to deal with the upcoming actual stressor. In this study, in a large sample of 171 healthy adults (96 men and 75 women; mean age = 29.98, SD = 11.07), we investigated whether the cortisol response to a laboratory-based stress task was related to anticipation-induced or stress task-induced changes in HRV. As expected, regression analyses showed that a larger decrease in HRV during the anticipation of a stress task was related to higher stress task-induced cortisol increase, but not cortisol recovery. In line with prior research, the stress task-induced change in HRV was not significantly related to cortisol increase or recovery. Our results show for the first time that anticipatory HRV (reflecting differences in stress regulation and prefrontal activity before the encounter with the stressor) is important to understand the stress-induced cortisol increase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mercuric chloride induces autoantibodies against U3 small nuclear ribonucleoprotein in susceptible mice.

PubMed Central

Reuter, R; Tessars, G; Vohr, H W; Gleichmann, E; Lührmann, R

1989-01-01

Autoantibodies to nucleolar components are a common serological feature of patients suffering from scleroderma, a collagen vascular autoimmune disease. While animal models, which spontaneously develop abundant anti-nucleolar antibodies, have not yet been described, high titers of such antibodies may be induced by treating susceptible strains of mice with mercuric chloride. We have identified the nucleolar autoantigen against which the HgCl2-induced IgG autoantibodies from mice of strain B10.S are directed. It is a protein with an apparent molecular mass of 36 kDa and a pI value of approximately 8.6, which is associated with the nucleolar small nuclear RNA U3, and by these criteria must be identical with a polypeptide called fibrillarin. It is striking that scleroderma patients spontaneously produce autoantibodies against the same U3 ribonucleoprotein (RNP). The HgCl2-induced murine and the scleroderma-specific human anti-U3 RNP autoantibodies were indistinguishable in their reactivities toward fibrillarin. They further resemble each other insofar as both recognize epitopes on the 36-kDa protein, which have been highly conserved throughout evolution. Our results provide a basis to investigate at the molecular level whether similar immunoregulatory dysfunctions may lead to the preferential anti-U3 RNP autoantibody production in the animal model and in scleroderma patients. Images PMID:2521387

Cell death induced by endoplasmic reticulum stress.

PubMed

Iurlaro, Raffaella; Muñoz-Pinedo, Cristina

2016-07-01

The endoplasmic reticulum is an organelle with multiple functions. The synthesis of transmembrane proteins and proteins that are to be secreted occurs in this organelle. Many conditions that impose stress on cells, including hypoxia, starvation, infections and changes in secretory needs, challenge the folding capacity of the cell and promote endoplasmic reticulum stress. The cellular response involves the activation of sensors that transduce signaling cascades with the aim of restoring homeostasis. This is known as the unfolded protein response, which also intersects with the integrated stress response that reduces protein synthesis through inactivation of the initiation factor eIF2α. Central to the unfolded protein response are the sensors PERK, IRE1 and ATF6, as well as other signaling nodes such as c-Jun N-terminal kinase 1 (JNK) and the downstream transcription factors XBP1, ATF4 and CHOP. These proteins aim to restore homeostasis, but they can also induce cell death, which has been shown to occur by necroptosis and, more commonly, through the regulation of Bcl-2 family proteins (Bim, Noxa and Puma) that leads to mitochondrial apoptosis. In addition, endoplasmic reticulum stress and proteotoxic stress have been shown to induce TRAIL receptors and activation of caspase-8. Endoplasmic reticulum stress is a common feature in the pathology of numerous diseases because it plays a role in neurodegeneration, stroke, cancer, metabolic diseases and inflammation. Understanding how cells react to endoplasmic reticulum stress can accelerate discovery of drugs against these diseases. © 2015 FEBS.

Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.

PubMed

Ralevski, Elizabeth; Southwick, Steven; Jackson, Eric; Jane, Jane Serrita; Russo, Melanie; Petrakis, Ismene

2016-08-01

Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the

Stress-Induced Cubic-to-Hexagonal Phase Transformation in Perovskite Nanothin Films.

PubMed

Cao, Shi-Gu; Li, Yunsong; Wu, Hong-Hui; Wang, Jie; Huang, Baoling; Zhang, Tong-Yi

2017-08-09

The strong coupling between crystal structure and mechanical deformation can stabilize low-symmetry phases from high-symmetry phases or induce novel phase transformation in oxide thin films. Stress-induced structural phase transformation in oxide thin films has drawn more and more attention due to its significant influence on the functionalities of the materials. Here, we discovered experimentally a novel stress-induced cubic-to-hexagonal phase transformation in the perovskite nanothin films of barium titanate (BaTiO 3 ) with a special thermomechanical treatment (TMT), where BaTiO 3 nanothin films under various stresses are annealed at temperature of 575 °C. Both high-resolution transmission electron microscopy and Raman spectroscopy show a higher density of hexagonal phase in the perovskite thin film under higher tensile stress. Both X-ray photoelectron spectroscopy and electron energy loss spectroscopy does not detect any change in the valence state of Ti atoms, thereby excluding the mechanism of oxygen vacancy induced cubic-to-hexagonal (c-to-h) phase transformation. First-principles calculations show that the c-to-h phase transformation can be completed by lattice shear at elevated temperature, which is consistent with the experimental observation. The applied bending plus the residual tensile stress produces shear stress in the nanothin film. The thermal energy at the elevated temperature assists the shear stress to overcome the energy barriers during the c-to-h phase transformation. The stress-induced phase transformation in perovskite nanothin films with TMT provides materials scientists and engineers a novel approach to tailor nano/microstructures and properties of ferroelectric materials.

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, Xueqi; Huang, Shengbin; Yu, Qing

Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activitymore » and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.« less

Curcuma longa Linn. extract and curcumin protect CYP 2E1 enzymatic activity against mercuric chloride-induced hepatotoxicity and oxidative stress: A protective approach.

PubMed

Joshi, Deepmala; Mittal, Deepak Kumar; Shukla, Sangeeta; Srivastav, Sunil Kumar; Dixit, Vaibhav A

2017-07-05

The present investigation has been conducted to evaluate the therapeutic potential of Curcuma longa (200mgkg -1 , po) and curcumin (80mgkg -1 , po) for their hepatoprotective efficacy against mercuric chloride (HgCl 2 : 12μmolkg -1 , ip; once only) hepatotoxicity. The HgCl 2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol contents with a concomitant decline in protein and albumin concentration in serum which were restored towards control by therapy of Curcuma longa or curcumin. On the other hand, both treatments showed a protective effect on drug metabolizing enzymes viz. aniline hydroxylase (AH) and amidopyrine-N-demethylase (AND), hexobarbitone induced sleep time and BSP retention. Choleretic, 1,1-diphenyl-2-picryl-hydrazil (DPPH)-free radical scavenging activities and histological studies also supported the biochemical findings. The present study concludes that Curcuma longa extract or curcumin has the ability to alleviate the hepatotoxic effects caused by HgCl 2 in rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

Development of an animal model of nephrocalcinosis via selective dietary sodium and chloride depletion

PubMed Central

Tuchman, Shamir; Asico, Laureano D.; Escano, Crisanto; Bobb, Daniel A.; Ray, Patricio E.

2013-01-01

Background Nephrocalcinosis (NC) is an important clinical problem seen in critically ill pre-term neonates treated with loop diuretics. No reliable animal models are available to study the pathogenesis of NC in preterm infants. The purpose of this study was to develop a reproducible and clinically relevant animal model of NC for these patients, and to explore the impact of extracellular fluid (ECF) volume contraction induced by sodium and chloride depletion in this process. Methods Three-week old weanling Sprague-Dawley rats were fed diets deficient in either chloride or sodium and chloride. A sub-group of rats from each dietary group was injected daily with furosemide (40 mg/kg; i.p.). Results Rats fed a control diet, with or without furosemide, or a chloride depleted diet alone, did not develop NC. In contrast, 50% of the rats injected with furosemide and fed the chloride depleted diet developed NC. Moreover, 94% of the rats fed the combined sodium/chloride depleted diet developed NC, independently of furosemide use. NC was associated with the development of severe ECF volume contraction, hypochloremic, hypokalemic metabolic alkalosis, increased phosphaturia, and growth retardation. Conclusion Severe ECF volume contraction induced by chronic sodium and chloride depletion appears to play an important role in the pathogenesis of NC. PMID:23174703

Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

PubMed

Yosef, Ido; Edgar, Rotem; Qimron, Udi

2016-11-01

Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

Classification of climate-change-induced stresses on biological diversity.

PubMed

Geyer, Juliane; Kiefer, Iris; Kreft, Stefan; Chavez, Veronica; Salafsky, Nick; Jeltsch, Florian; Ibisch, Pierre L

2011-08-01

Conservation actions need to account for and be adapted to address changes that will occur under global climate change. The identification of stresses on biological diversity (as defined in the Convention on Biological Diversity) is key in the process of adaptive conservation management. We considered any impact of climate change on biological diversity a stress because such an effect represents a change (negative or positive) in key ecological attributes of an ecosystem or parts of it. We applied a systemic approach and a hierarchical framework in a comprehensive classification of stresses to biological diversity that are caused directly by global climate change. Through analyses of 20 conservation sites in 7 countries and a review of the literature, we identified climate-change-induced stresses. We grouped the identified stresses according to 3 levels of biological diversity: stresses that affect individuals and populations, stresses that affect biological communities, and stresses that affect ecosystem structure and function. For each stress category, we differentiated 3 hierarchical levels of stress: stress class (thematic grouping with the coarsest resolution, 8); general stresses (thematic groups of specific stresses, 21); and specific stresses (most detailed definition of stresses, 90). We also compiled an overview of effects of climate change on ecosystem services using the categories of the Millennium Ecosystem Assessment and 2 additional categories. Our classification may be used to identify key climate-change-related stresses to biological diversity and may assist in the development of appropriate conservation strategies. The classification is in list format, but it accounts for relations among climate-change-induced stresses. © 2011 Society for Conservation Biology.

Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders.

PubMed

Gu, Simeng; Wang, Wei; Wang, Fushun; Huang, Jason H

2016-01-01

Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the central "stress circuitry," whose major function is to induce "fight or flight" behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty). The reason for this discrepancy might be that NE is not only for flight (fear), but also for fight (anger). Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. "Adrenaline rush or norepinephrine rush" and fear and anger emotion might act as biomarkers for mental disorders.

Attenuation and cross-attenuation in taste aversion learning in the rat: Studies with ionizing radiation, lithium chloride and ethanol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1988-12-01

The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO)more » disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.« less

Attenuation and cross-attenuation in taste aversion learning in the rat: studies with ionizing radiation, lithium chloride and ethanol.

PubMed

Rabin, B M; Hunt, W A; Lee, J

1988-12-01

The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO) disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.

CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety

PubMed Central

McCall, Jordan G.; Al-Hasani, Ream; Siuda, Edward R.; Hong, Daniel Y.; Norris, Aaron J.; Ford, Christopher P.; Bruchas, Michael R.

2015-01-01

Summary The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. PMID:26212712

Protective effects of kolaviron and gallic acid against cobalt-chloride-induced cardiorenal dysfunction via suppression of oxidative stress and activation of the ERK signaling pathway.

PubMed

Akinrinde, Akinleye Stephen; Omobowale, Olutayo; Oyagbemi, Ademola; Asenuga, Ebunoluwa; Ajibade, Temitayo

2016-12-01

Cobalt (Co) toxicity is a potential public health problem due to recent renewed use of Co in orthopedic implants, dietary supplements, and blood doping in athletes and horses. We investigated the protective roles of kolaviron (KV), a bi-flavonoid of Garcinia kola, and gallic acid (GA) on cobalt chloride (CoCl 2 )-induced cardiorenal damage in rats. CoCl 2 caused significant increases (p < 0.05) in serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), xanthine oxidase (XO), urea, creatinine, malondialdehyde, H 2 O 2 , nitric oxide, as well as C-reactive protein expression, along with significant (p < 0.05) reduction in cardiac and renal expression of extracellular signal regulated kinase (ERK) and the activities of superoxide dismutase, catalase, and glutathione S-transferase. KV and GA prevented the toxic effects of CoCl 2 by stimulating ERK expression and reversing Co-induced biochemical changes. Administration of CoCl 2 alone did not significantly alter ECG patterns in the rats, although co-treatment with KV (200 mg/kg) produced QT-segment prolongation and also appeared to potentiate Co hypotension. Histopathology of the heart and kidneys of rats treated with KV and GA confirmed the biochemical data. KV and GA thus protected against cardiac and renal damage in Co intoxication via antioxidant and (or) cell survival mechanisms, possibly involving ERK activation.

Stress fields in soft material induced by injection of highly-focused microjets

NASA Astrophysics Data System (ADS)

Miyazaki, Yuta; Endo, Nanami; Kawamoto, Sennosuke; Kiyama, Akihito; Tagawa, Yoshiyuki

2017-11-01

Needle-free drug injection systems using high-speed microjets are of great importance for medical innovations since they can solve problems of the conventional needle injection systems. However, the mechanical stress acting on the skin/muscle of patients during the penetration of liquid-drug microjets had not been clarified. In this study we investigate the stress caused by the penetration of microjets into soft materials, which is compared with the stress induced by the penetration of needles. In order to capture high-speed temporal evolution of the stress field inside the material, we utilized a high-speed polarized camera and gelatin that resembles human skin. Remarkably we find clear differences in the stress fields induced by microjets and needles. On one hand, high shear stress induced by the microjets is attenuated immediately after the injection, even though the liquid stays inside the soft material. On the other hand, high-shear stress induced by the needles stays and never decays unless the needles are entirely removed from the material. JSPS KAKENHI Grant Numbers 26709007 and 17H01246.

Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest

PubMed Central

Khaperskyy, Denys A.; Emara, Mohamed M.; Johnston, Benjamin P.; Anderson, Paul; Hatchette, Todd F.; McCormick, Craig

2014-01-01

Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5′ caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication. PMID:25010204

Sampling and testing for chloride ion in concrete

DOT National Transportation Integrated Search

1977-08-01

One of the most severe problems facing the highway community is chloride ion-induced reinforcing steel corrosion and the subsequent deterioration of concrete bridge decks and marine structures. This report presents recommended methods for sampling an...

Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72.

PubMed

Lancaster, Graeme I; Febbraio, Mark A

2005-01-01

The heat shock proteins are a family of highly conserved proteins with critical roles in maintaining cellular homeostasis and in protecting the cell from stressful conditions. While the critical intracellular roles of heat shock proteins are undisputed, evidence suggests that the cell possess the necessary machinery to actively secrete specific heat shock proteins in response to cellular stress. In this review, we firstly discuss the evidence that physical exercise induces the release of heat shock protein 72 from specific tissues in humans. Importantly, it appears as though this release is the result of an active secretory process, as opposed to non-specific processes such as cell lysis. Next we discuss recent in vitro evidence that has identified a mechanistic basis for the observation that cellular stress induces the release of a specific subset of heat shock proteins. Importantly, while the classical protein secretory pathway does not seem to be involved in the stress-induced release of HSP72, we discuss the evidence that lipid-rafts and exosomes are important mediators of the stress-induced release of HSP72.

Cellular stress induces cytoplasmic RNA granules in fission yeast.

PubMed

Nilsson, Daniel; Sunnerhagen, Per

2011-01-01

Severe stress causes plant and animal cells to form large cytoplasmic granules containing RNA and proteins. Here, we demonstrate the existence of stress-induced cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known protein components of mammalian processing bodies and stress granules are found in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding protein (Pabp) colocalizes in stress-induced granules with decapping protein. After glucose deprivation, protein kinase A (PKA) is required for accumulation of Pabp-positive granules and translational down-regulation. This is the first demonstration of a role for PKA in RNA granule formation. In mammals, the translation initiation protein eIF2α is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2α does not block but delays granule formation and subsequent clearance after exposure to hyperosmosis. At least two separate pathways in S. pombe appear to regulate stress-induced granules: pka1 mutants are fully proficient to form granules after hyperosmotic shock; conversely, eIF2α does not affect granule formation in glucose starvation. Further, we demonstrate a Pka1-dependent link between calcium perturbation and RNA granules, which has not been described earlier in any organism.

Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress.

PubMed

Kim, Seong Hun; Kim, Kook Hwan; Kim, Hyoung-Kyu; Kim, Mi-Jeong; Back, Sung Hoon; Konishi, Morichika; Itoh, Nobuyuki; Lee, Myung-Shik

2015-04-01

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-diabetic and anti-obesity activity. FGF21 expression is increased in patients with and mouse models of obesity or nonalcoholic fatty liver disease (NAFLD). However, the functional role and molecular mechanism of FGF21 induction in obesity or NAFLD are not clear. As endoplasmic reticulum (ER) stress is triggered in obesity and NAFLD, we investigated whether ER stress affects FGF21 expression or whether FGF21 induction acts as a mechanism of the unfolded protein response (UPR) adaptation to ER stress induced by chemical stressors or obesity. Hepatocytes or mouse embryonic fibroblasts deficient in UPR signalling pathways and liver-specific eIF2α mutant mice were employed to investigate the in vitro and in vivo effects of ER stress on FGF21 expression, respectively. The in vivo importance of FGF21 induction by ER stress and obesity was determined using inducible Fgf21-transgenic mice and Fgf21-null mice with or without leptin deficiency. We found that ER stressors induced FGF21 expression, which was dependent on a PKR-like ER kinase-eukaryotic translation factor 2α-activating transcription factor 4 pathway both in vitro and in vivo. Fgf21-null mice exhibited increased expression of ER stress marker genes and augmented hepatic lipid accumulation after tunicamycin treatment. However, these changes were attenuated in inducible Fgf21-transgenic mice. We also observed that Fgf21-null mice with leptin deficiency displayed increased hepatic ER stress response and liver injury, accompanied by deteriorated metabolic variables. Our results suggest that FGF21 plays an important role in the adaptive response to ER stress- or obesity-induced hepatic metabolic stress.

Substitution effects of a carbonated hydroxyapatite biomaterial against intoxication chloride nickel-exposed rats.

PubMed

Boulila, Salha; Elfeki, Abdelfattah; Oudadesse, Hassane; Elfeki, Hafed

2015-03-01

This study aimed to investigate the potential effects of a synthetic apatite (carbonated hydroxyapatite) on the detoxification of a group of male "Wistar" rats exposed to nickel chloride. Toxicity was evaluated by rats' bioassay of nickel chloride. Wistar rats received this metal daily by gavage for seven days (4 mg/ml nickel chloride/200 g body weight, BW). To detoxify this organism, a subcutaneous implantation of the apatite is made. The results revealed that exposure to nickel induced oxidative stress, disorders in the balances of ferric phosphocalcic, renal failures, liver toxicity and significant increase in nickel rates in the bones of intoxicated rats. The application of the carbonated hydroxyapatite presented in this study restored those disorders back to normal. The synthetic apatite protected the rats against the toxic effects of nickel by lowering the levels of lipid peroxidation markers and improving the activities of defense enzymes. It also amended ferric and phosphocalcic equilibriums, protected liver and kidney functions and reduced the nickel rate in the bones of the rats. Overall, the results provided strong support for the protective role of carbonated hydroxyapatite in the detoxification of rats exposed to nickel. Those beneficial effects were further confirmed by physico-chemical characterization (X-ray diffraction and infrared spectroscopy), which revealed its property of anionic and cationic substitution, thus supporting its promising candidacy for future biomedical application. The hydroxyapatite is an effective biomaterial to solve health problems, particularly detoxification against metals (nickel).

A mouse dry eye model induced by topical administration of benzalkonium chloride.

PubMed

Lin, Zhirong; Liu, Xiaochen; Zhou, Tong; Wang, Yihui; Bai, Li; He, Hui; Liu, Zuguo

2011-01-25

To develop a dry eye model of mouse induced by topical administration of benzalkonium chloride (BAC) and investigate the possible mechanisms. BAC at concentration of 0.2% was applied to the mouse ocular surface for 7 days. Phenol red thread tear test, tear break-up time (BUT) test, corneal inflammatory index scoring, fluorescein and rose bengal test were performed to evaluate the toxic effects of BAC on the ocular surface. Global specimens were collected on day (D) 7 and labeled with a series of antibodies including cytokeratin 10 (K10) and mucin 5AC (MUC5AC). Apoptosis of ocular surface epithelium was evaluated by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Histologic analysis and transmission electron microscopy (TEM) were performed on D7. BAC at a concentration of 0.2% successfully induced a dry eye condition with decreased tear volume and BUTs, increased corneal fluorescein and rose bengal scores. The Inflammatory index was increased in accompaniment with higher tumor necrosis factor-α (TNF-α) expression and more inflammatory infiltration in the cornea. Immunolabeling revealed positive K10 expression in BAC-treated corneal epithelium and fewer MUC5AC-positive cells in the BAC-treated conjunctival fornix. TUNEL assay showed more apoptotic cells in the corneal basal epithelium. TEM showed that the size and intervals of the microvillis were both reduced in the corneal epithelium. Topical administration of 0.2% BAC in mouse induces changes resembling that of dry eye syndrome in humans, and thus, represents a novel model of dry eye.

A mouse dry eye model induced by topical administration of benzalkonium chloride

PubMed Central

Lin, Zhirong; Liu, Xiaochen; Zhou, Tong; Wang, Yihui; Bai, Li; He, Hui

2011-01-01

Purpose To develop a dry eye model of mouse induced by topical administration of benzalkonium chloride (BAC) and investigate the possible mechanisms. Methods BAC at concentration of 0.2% was applied to the mouse ocular surface for 7 days. Phenol red thread tear test, tear break-up time (BUT) test, corneal inflammatory index scoring, fluorescein and rose bengal test were performed to evaluate the toxic effects of BAC on the ocular surface. Global specimens were collected on day (D) 7 and labeled with a series of antibodies including cytokeratin 10 (K10) and mucin 5AC (MUC5AC). Apoptosis of ocular surface epithelium was evaluated by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Histologic analysis and transmission electron microscopy (TEM) were performed on D7. Results BAC at a concentration of 0.2% successfully induced a dry eye condition with decreased tear volume and BUTs, increased corneal fluorescein and rose bengal scores. The Inflammatory index was increased in accompanyment with higher tumor necrosis factor-α (TNF-α) expression and more inflammatory infiltration in the cornea. Immunolabeling revealed positive K10 expression in BAC-treated corneal epithelium and fewer MUC5AC-positive cells in the BAC-treated conjunctival fornix. TUNEL assay showed more apoptotic cells in the corneal basal epithelium. TEM showed that the size and intervals of the microvillis were both reduced in the corneal epithelium. Conclusions Topical administration of 0.2% BAC in mouse induces changes resembling that of dry eye syndrome in humans, and thus, represents a novel model of dry eye. PMID:21283525

The role of ARK in stress-induced apoptosis in Drosophila cells

PubMed Central

Zimmermann, Katja C.; Ricci, Jean-Ehrland; Droin, Nathalie M.; Green, Douglas R.

2002-01-01

The molecular mechanisms of apoptosis are highly conserved throughout evolution. The homologs of genes essential for apoptosis in Caenorhabditis elegans and Drosophila melanogaster have been shown to be important for apoptosis in mammalian systems. Although a homologue for CED-4/apoptotic protease-activating factor (Apaf)-1 has been described in Drosophila, its exact function and the role of the mitochondrial pathway in its activation remain unclear. Here, we used the technique of RNA interference to dissect apoptotic signaling pathways in Drosophila cells. Inhibition of the Drosophila CED-4/Apaf-1–related killer (ARK) homologue resulted in pronounced inhibition of stress-induced apoptosis, whereas loss of ARK did not protect the cells from Reaper- or Grim-induced cell death. Reduction of DIAP1 induced rapid apoptosis in these cells, whereas the inhibition of DIAP2 expression did not but resulted in increased sensitivity to stress-induced apoptosis; apoptosis in both cases was prevented by inhibition of ARK expression. Cells in which cytochrome c expression was decreased underwent apoptosis induced by stress stimuli, Reaper or Grim. These results demonstrate the central role of ARK in stress-induced apoptosis, which appears to act independently of cytochrome c. Apoptosis induced by Reaper or Grim can proceed via a distinct pathway, independent of ARK. PMID:11901172

Salicylic acid-induced abiotic stress tolerance and underlying mechanisms in plants

PubMed Central

Khan, M. Iqbal R.; Fatma, Mehar; Per, Tasir S.; Anjum, Naser A.; Khan, Nafees A.

2015-01-01

Abiotic stresses (such as metals/metalloids, salinity, ozone, UV-B radiation, extreme temperatures, and drought) are among the most challenging threats to agricultural system and economic yield of crop plants. These stresses (in isolation and/or combination) induce numerous adverse effects in plants, impair biochemical/physiological and molecular processes, and eventually cause severe reductions in plant growth, development and overall productivity. Phytohormones have been recognized as a strong tool for sustainably alleviating adverse effects of abiotic stresses in crop plants. In particular, the significance of salicylic acid (SA) has been increasingly recognized in improved plant abiotic stress-tolerance via SA-mediated control of major plant-metabolic processes. However, the basic biochemical/physiological and molecular mechanisms that potentially underpin SA-induced plant-tolerance to major abiotic stresses remain least discussed. Based on recent reports, this paper: (a) overviews historical background and biosynthesis of SA under both optimal and stressful environments in plants; (b) critically appraises the role of SA in plants exposed to major abiotic stresses; (c) cross-talks potential mechanisms potentially governing SA-induced plant abiotic stress-tolerance; and finally (d) briefly highlights major aspects so far unexplored in the current context. PMID:26175738

Methylene chloride protects against cecal ligation and puncture-induced acute lung injury by modulating inflammatory mediators.

PubMed

Pang, Qingfeng; Dou, Lidong; Pan, Xiuhua; Zeng, Si; He, Jun; Xu, Wenli; Zeng, Yinming

2010-08-01

Recent studies suggest that exogenously administered CO is beneficial for the resolution of acute pulmonary inflammation. In this study, we assessed the role of CO donor, methylene chloride (MC), on modulation of lung inflammation during sepsis. Acute lung injury in Sprague-Dawley rats was induced by cecal ligation and perforation (CLP). MC (100mg/kg) was intragastrically administered 2h before CLP induction. Lung tissues and lavage samples were isolated for biochemical determinations and histological measurements 10h after CLP operation. In addition, we investigated survival rate with the other 40 rats. Intragastric administration with MC significantly decreased morbidity and mortality of CLP-induced ALI as confirmed by blinded histological changes, myeloperoxidase activity, mortality, and the content of TNF-alpha and IL-10. This protective effect could be abolished by an MC inhibitor, disulfiram. These results suggested that MC has obvious protective effects against CLP-induced ALI in rats. The mechanism of the protective effects partly involves modulating inflammatory mediators. (c) 2010 Elsevier B.V. All rights reserved.

Efficient micropropagation and chlorocholine chloride induced stevioside production of Stevia rebaudiana Bertoni.

PubMed

Dey, Avishek; Kundu, Sayanti; Bandyopadhyay, Abhijit; Bhattacharjee, Aloke

2013-01-01

A promising method of micropropagation of Stevia rebaudiana Bertoni has been developed with an aim to increase the biomass, survivability of the plantlets and stevioside production, using chlorocholine chloride (CCC). Microshoots transferred to the MS medium containing different combinations CCC and IBA were found to be most effective in terms of growth pattern, hardening ability of the plantlets and stevioside content, compared to MS medium containing either IBA or CCC. Among other combinations tested, MS medium supplemented with 3 mg/l CCC and 3 mg/l IBA was found most effective in inducing significant changes like reduced shoot length, increased number of roots, higher leaf size, increased biomass and chlorophyll retaining capacity, higher survival percentage and most importantly the elevated stevioside content. Collectively, the major observations of this research indicate that application of CCC in micropropagation of S. rebaudiana Bertoni is a promising approach and has commercial prospects. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress.

PubMed

Shireen, Erum; Pervez, Sidra; Masroor, Maria; Ali, Wafa Binte; Rais, Qudsia; Khalil, Samira; Tariq, Anum; Haleem, Darakshan Jabeen

2014-09-01

Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

Redox-induced surface stress of polypyrrole-based actuators.

PubMed

Tabard-Cossa, Vincent; Godin, Michel; Grütter, Peter; Burgess, Ian; Lennox, R B

2005-09-22

We measure the surface stress induced by electrochemical transformations of a thin conducting polymer film. One side of a micromechanical cantilever-based sensor is covered with an electropolymerized dodecyl benzenesulfonate-doped polypyrrole (PPyDBS) film. The microcantilever serves as both the working electrode (in a conventional three-electrode cell configuration) and as the mechanical transducer for simultaneous, in situ, and real-time measurements of the current and interfacial stress changes. A compressive change in surface stress of about -2 N/m is observed when the conducting polymer is electrochemically switched between its oxidized (PPy+) and neutral (PPy0) state by cyclic voltammetry. The surface stress sensor's response during the anomalous first reductive scan is examined. The effect of long-term cycling on the mechanical transformation ability of PPy(DBS) films in both surfactant and halide-based electrolytes is also discussed. We have identified two main competing origins of surface stress acting on the PPy(DBS)/ gold-coated microcantilever: one purely mechanical due to the volume change of the conducting polymer, and a second charge-induced, owing to the interaction of anions of the supporting electrolyte with the gold surface.

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

PubMed

Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective effects of citalopram in a mouse model of stress-induced anhedonia with a control for chronic stress.

PubMed

Strekalova, Tatyana; Gorenkova, Natalia; Schunk, Edward; Dolgov, Oleg; Bartsch, Dusan

2006-05-01

A stress-induced decrease in sucrose preference in rodents is regarded as an analog of anhedonia, a key symptom of depression. We investigated the effects of citalopram, administrated via drinking water (15 mg/kg/day), in a mouse model of stress-induced anhedonia. In this model, chronic stress induces anhedonia in a subset of C57BL/6N mice, while the remaining animals do not show a hedonic deficit or other depressive-like behaviors, although they are exposed to the same stressors as the anhedonic mice. Pre-stress and post-stress treatment with citalopram counteracted the development and maintenance of anhedonia and rescued normal floating in the forced swim test, demonstrating an antidepressant-like action. During the post-stress treatment, citalopram selectively increased sucrose preference and intake on the fourth week of treatment in anhedonic mice without affecting non-anhedonic animals. Citalopram also decreased elevated water consumption in the anhedonic group. Citalopram, administered 1 week before and during a 4-week stress procedure, decreased the percentage of anhedonic mice and reduced the increase of water intake in stressed mice. This study suggests that our chronic stress paradigm can serve as a model of anhedonia, in which antidepressant treatment is selectively effective in animals with a hedonic deficit.

Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders

PubMed Central

Gu, Simeng; Wang, Wei; Huang, Jason H.

2016-01-01

Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty). The reason for this discrepancy might be that NE is not only for flight (fear), but also for fight (anger). Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders. PMID:27051536

Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage.

PubMed

Akıncı, Ayşin; Eşrefoğlu, Mukaddes; Taşlıdere, Elif; Ateş, Burhan

2017-01-01

Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Animal experimentation. Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals' stomachs were arranged for microscopic and biochemical examinations. Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p<0.05). Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05), the stress and stress + standard diet groups (p<0.05), and the stress and stress + LPZ groups (p<0.05). The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05). Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50) and superoxide dismutase (15.18±1.05) and catalase (16.68±2.29) activities. Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system.

Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

PubMed Central

Akıncı, Ayşin; Eşrefoğlu, Mukaddes; Taşlıdere, Elif; Ateş, Burhan

2017-01-01

Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p<0.05). Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05), the stress and stress + standard diet groups (p<0.05), and the stress and stress + LPZ groups (p<0.05). The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05). Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50) and superoxide dismutase (15.18±1.05) and catalase (16.68±2.29) activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system. PMID:28251024

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

PubMed

Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

Chemical castration in cattle with intratesticular injection of sodium chloride: Effects on stress and inflammatory markers.

PubMed

Oliveira, Fernando C; Ferreira, Carlos E R; Haas, Cristina S; Oliveira, Leonardo G; Mondadori, Rafael G; Schneider, Augusto; Rovani, Monique T; Gonçalves, Paulo B D; Vieira, Arnaldo D; Gasperin, Bernardo G; Lucia, Thomaz

2017-03-01

Intratesticular injection (ITI) of sodium chloride (NaCl) is efficient for chemical castration of young calves, but its effects on calves welfare are unknown. Two experiments were conducted to evaluate the effects of ITI of 20% NaCl on stress and inflammatory markers in calves less than 20 days old and to assess the efficiency of ITI of 30% NaCl in 5 months old calves. In Experiment 1, control calves were only restrained and compared to calves submitted to castration through surgery (SC) and ITI with 20% NaCl (n = 9/group). No differences were observed for the eye corner temperature measured by thermography from 60 s before to 60 s after the procedures (P > 0.05). In the SC group, acute serum cortisol levels increased at 30 and 60 min after the procedure, but increased levels in the ITI group occurred only at 30 min (P < 0.05). Chronic discomfort markers were measured at 0, 24, 48, 72 and 96 h after the procedures (D0, D1, D2, D3 and D4, respectively). The serum levels of the paraoxonase 1 (PON1) enzyme and cortisol did not differ among groups (P > 0.05). Scrotal temperature was higher at D1 in the SC group than for the other groups, but lowest at D4 compared to the control (both P < 0.05). In Experiment 2, histological sections of testes were compared after ITI with either 30% NaCl or 30% calcium chloride (CaCl 2 ), to intact calves (control). After 60 days, intact seminiferous tubules and mediastinum were observed after ITI with 30% NaCl, whereas coagulative necrosis, inflammatory infiltration and calcification occurred after ITI with 30% CaCl 2 . Efficient chemical castration through ITI of 20% NaCl in young calves was followed by slight stress and inflammatory responses compared to surgical castration. However, ITI of 30% NaCl was ineffective for chemical castration of 5 months old calves. Copyright © 2016 Elsevier Inc. All rights reserved.

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.

PubMed

McCall, Jordan G; Al-Hasani, Ream; Siuda, Edward R; Hong, Daniel Y; Norris, Aaron J; Ford, Christopher P; Bruchas, Michael R

2015-08-05

The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing, we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin-releasing hormone(+) (CRH(+)) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Autophagy modulates endoplasmic reticulum stress-induced cell death in podocytes: A protective role

PubMed Central

Cheng, Yu-Chi; Chang, Jer-Ming; Chen, Chien-An

2015-01-01

Endoplasmic reticulum stress occurs in a variety of patho-physiological mechanisms and there has been great interest in managing this pathway for the treatment of clinical diseases. Autophagy is closely interconnected with endoplasmic reticulum stress to counteract the possible injurious effects related with the impairment of protein folding. Studies have shown that glomerular podocytes exhibit high rate of autophagy to maintain as terminally differentiated cells. In this study, podocytes were exposed to tunicamycin and thapsigargin to induce endoplasmic reticulum stress. Thapsigargin/tunicamycin treatment induced a significant increase in endoplasmic reticulum stress and of cell death, represented by higher GADD153 and GRP78 expression and propidium iodide flow cytometry, respectively. However, thapsigargin/tunicamycin stimulation also enhanced autophagy development, demonstrated by monodansylcadaverine assay and LC3 conversion. To evaluate the regulatory effects of autophagy on endoplasmic reticulum stress-induced cell death, rapamycin (Rap) or 3-methyladenine (3-MA) was added to enhance or inhibit autophagosome formation. Endoplasmic reticulum stress-induced cell death was decreased at 6 h, but was not reduced at 24 h after Rap+TG or Rap+TM treatment. In contrast, endoplasmic reticulum stress-induced cell death increased at 6 and 24 h after 3-MA+TG or 3-MA+TM treatment. Our study demonstrated that thapsigargin/tunicamycin treatment induced endoplasmic reticulum stress which resulted in podocytes death. Autophagy, which counteracted the induced endoplasmic reticulum stress, was simultaneously enhanced. The salvational role of autophagy was supported by adding Rap/3-MA to mechanistically regulate the expression of autophagy and autophagosome formation. In summary, autophagy helps the podocytes from cell death and may contribute to sustain the longevity as a highly differentiated cell lineage. PMID:25322957

Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.

PubMed

Bülbül, Mehmet; İzgüt-Uysal, V Nimet; Sinen, Osman; Birsen, İlknur; Tanrıöver, Gamze

2016-02-15

Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway. Copyright © 2016 the American Physiological Society.

Shear stress-induced calcium transients in endothelial cells from human umbilical cord veins.

PubMed Central

Schwarz, G; Callewaert, G; Droogmans, G; Nilius, B

1992-01-01

1. Changes of the free cytosolic Ca2+ concentration induced by shear stress were measured in Fura-2 acetoxymethyl ester-loaded endothelial cells from human umbilical cord veins. 2. We were able to induce Ca2+ transients in almost every cell by blowing a stream of physiological solution onto a single endothelial cell thereby inducing shear stress between 0 and 50 dyn cm-2. The Ca2+ response could be graded by varying the shear stress, and reached a half-maximal value at a shear stress of 30 dyn cm-2. 3. The shear stress responses critically depended on the extracellular Ca2+ concentration and were absent in a Ca(2+)-free solution. Repetitive application of short pulses of shear stress induced cumulative effects because of the slow decay of the shear stress Ca2+ responses (time constants 82.3 +/- 17.8 s from twenty-five cells). Application of a depolarizing high potassium solution to reduce the driving force for Ca2+ entry decreased the Ca2+ transients in some of the cells. 4. Application of shear stress in the presence of other divalent cations, such as nickel, cobalt or barium, always produced substantial changes in the ratio of the 390/360 nm fluorescence signal, indicating influx of these cations and subsequent quenching of the Fura-2 fluorescence. 5. Shear stress responses in the presence of 10 mM Ca2+ were completely blocked by application of 1 mM La3+. 6. Incubation of the cells with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) did not alter the shear stress response, but completely blocked histamine-induced Ca2+ transients. 7. Small submaximal shear stress potentiated the Ca2+ transients induced by histamine. 8. We conclude that shear stress-dependent Ca2+ signals are induced by an influx of calcium that is not modulated via protein kinase C and not activated by membrane depolarization. The influx pathway is also permeable to divalent cations such as Ni2+, Co2+ and Ba2+, but is blocked by La3+. PMID:1338792

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribeiro Júnior, Rogério Faustino, E-mail: rogeriofaustinoribeiro@hotmail.com; Marques, Vinicius Bermond; Nunes, Dieli Oliveira

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposuremore » increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT{sub 1} receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O{sub 2}{sup −} production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. �

Effects of the methylene chloride fraction from modified Boyang-Hwan-o-Tang, a polyherbal medicine on transient middle cerebral artery occlusion-induced ischemia in rats.

PubMed

Oh, Tae Woo; Jung, Hyo Won; Shin, Gil Jo; Park, Yong-Ki

2014-01-28

To study the neuroprotective effect of the methylene chloride fraction from modified Boyang-Hwan-o-Tang (mBHT-MC), especially against neuronal apoptosis. mBHT-MC (10, 25 or 50 mg/kg) was orally administered once per day for 7 days in transient middle cerebral artery occlusion (MCAO)-induced ischemic rats. Infarction volumes was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit score and the expression of apoptotic proteins such as Bcl-2, Bax and caspase-3 by Western blot in MCAO-induced ischemic brain. Neuronal apoptosis in ischemic phenumbra was also investigated by staining with hematoxylin and eosin, Nissl and Hoechst 33342. mBHT-MC administration in MCAO rats significantly decreased infarction volume and neurological deficit scores. mBHT-MC significantly enhanced Bcl-2 expression, and inhibited Bax and caspase-3 expression in ischemic brain. In addition, mBHT-MC significantly decreased the number of apoptotic neuronal cells in ischemic brains. mBHT-MC administration inhibits neuronal death induced by cerebral ischemia in rats, suggesting that mBHT-MC has a neuroprotective property in brain ischemia.

The effect of calcium chloride on growth, photosynthesis, and antioxidant responses of Zoysia japonica under drought conditions.

PubMed

Xu, Chengbin; Li, Xuemei; Zhang, Lihong

2013-01-01

Few attempts have been made to study the alleviating effects of signal molecules on zoysiagrass (Zoysiajaponica) under drought stress. Calcium chloride has been shown to ameliorate the adverse effects of drought stress on many plants. It is necessary to investigate how to enhance drought tolerance of zoysiagrass using calcium chloride. The study elucidated the effects of calcium chloride on zoysiagrass under drought conditions by investigating the following parameters: biomass, chlorophyll (Chl) content, net photosynthetic rate (Pn), chlorophyll fluorescence, antioxidant enzymes, proline content, and malondialdehyde (MDA) content. Experimental conditions consisted of an aqueous CaCl2 solution at 5, 10, and 20 mM sprayed on zoysiagrass leaves for 3 d, following by an inducement of drought conditions by withholding water for 16 d. Under drought conditions, all CaCl2 pretreatments were found to increase the above-ground fresh biomass, as well as below-ground fresh and dry biomass. The resulting Chl (a, b, a+b) contents of the 5 and 10 mM CaCl2 pretreatment groups were higher than those of the control. In the later stages of drought conditions, the chlorophyll fluorescence parameter Fv/Fm was higher in leaves treated with 10 mM CaCl2 than in the leaves of the other two treatment groups. Zoysiagrass pretreated with 10 mM CaCl2 possessed both the maximum observed Pn and antioxidant enzyme activities. Meanwhile, lower MDA and proline contents were recorded in the plants pretreated with 5 and 10 mM CaCl2 under drought conditions. As a whole, the drought tolerance of zoysiagrass was improved to some extent by the application of a moderate calcium concentration.

Acute stress induces selective alterations in cost/benefit decision-making.

PubMed

Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

2012-09-01

Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1-3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression.

Acute Stress Induces Selective Alterations in Cost/Benefit Decision-Making

PubMed Central

Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

2012-01-01

Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1–3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression. PMID:22569506

Hyperosmolarity potentiates toxic effects of benzalkonium chloride on conjunctival epithelial cells in vitro.

PubMed

Clouzeau, Chloé; Godefroy, David; Riancho, Luisa; Rostène, William; Baudouin, Christophe; Brignole-Baudouin, Françoise

2012-01-01

Benzalkonium chloride (BAK), the most commonly used preservative in eye drops, is known to induce ocular irritation symptoms and dry eye in long-term treated patients and animal models. As tear film hyperosmolarity is diagnostic of some types of dry eye disease, we determined in vitro on conjunctival epithelial cells the cytoxicity of BAK in hyperosmolar conditions through cell viability, apoptosis, and oxidative stress assays. The Wong Kilbourne derivative of Chang conjunctival epithelial cells were cultured for 24 h or 48 h either in NaCl-induced hyperosmolar conditions (400-425-500 mOsM), in low concentrations of BAK (10(-4)%, 3.10(-4)%, and 5.10(-4)%), or in combination of both. We investigated cell viability through lysosomal integrity evaluation, cell death (cell membrane permeability and chromatin condensation), and oxidative stress (reactive oxygen species, superoxide anion) using spectrofluorimetry. Immunohistochemistry was performed for cytoskeleton shrinkage (phalloidin staining), mitochondrial permeability transition pore (cytochrome c release), the apoptosis effector active caspase-3, and the caspase-independent apoptosis factor AIF. We also observed early effects induced by the experimental conditions on the conjunctival cell layers using phase contrast imaging of live cells. As compared to standard culture solutions, hyperosmolar stress potentiated BAK cytotoxicity on conjunctival cells through the induction of oxidative stress; reduction of cell viability; cell membrane permeability increase; cell shrinkage with cell blebbing, as shown in phase contrast imaging of live cells; and chromatin condensation. Like BAK, but to a much lesser extent, hyperosmolarity increased cell death in a concentration-dependent manner through a caspase-dependent apoptosis characterized by a release of cytochrome c in the cytoplasm from mitochondria and the activation of caspase-3. Moreover, the caspase-independent apoptosis factor AIF was found translocated from

Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats.

PubMed

Sundaram, Bhuvaneshwari; Aggarwal, Aanchal; Sandhir, Rajat

2013-04-01

Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic control. It is a transition metal that exists in various oxidation states and may thereby act as a pro-oxidant. The present study has been designed to examine the effect of chromium picolinate supplementation on hyperglycemia-induced oxidative stress. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50mg/kg body weight) and chromium was administered orally as chromium picolinate (1mg/kg body weight) daily for a period of four weeks after the induction of diabetes. As is characteristic of diabetic condition, hyperglycemia was associated with an increase in oxidative stress in liver in terms of increased lipid peroxidation and decreased glutathione levels. The activity of antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase were significantly reduced in liver of diabetic animals. Levels of α-tocopherol and ascorbic acid were found to be considerably lower in plasma of diabetic rats. Chromium picolinate administration on the other hand was found to have beneficial effect in normalizing glucose levels, lipid peroxidation and antioxidant status. The results from the present study demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced oxidative stress in experimental diabetes. Copyright © 2012 Elsevier GmbH. All rights reserved.

Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice

PubMed Central

Moon, Minho; Huh, Eugene; Song, Eun Ji; Hwang, Deok-Sang; Lee, Tae Hee; Oh, Myung Sook

2017-01-01

Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa β, tumor necrosis factor-α, and interleukin-1β (IL-1β) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology. PMID:28946610

Analysis on annealing-induced stress of blind-via TSV using FEM

NASA Astrophysics Data System (ADS)

Shao, Jie; Shi, Tielin; Du, Li; Su, Lei; Lu, Xiangning; Liao, Guanglan

2017-07-01

Copper-filled through silicon via (TSV) is a promising material owing to its application in high-density three-dimensional (3D) packaging. However, in TSV manufacturing, thermo-mechanical stress is induced during the annealing process, often causing reliability issues. In this paper, the finite element method is employed to investigate the impacts of via shape and SiO2 liner uniformity on the thermo-mechanical properties of copper- filled blind-via TSV after annealing. Top interface stress analysis on the TSV structure shows that the curvature of via openings releases stress concentration that leads to 60 MPa decrease of normal stresses, σ xx and σ yy , in copper and 70 MPa decrease of σ xx in silicon. Meanwhile, the vertical interface analysis shows that annealing-induced stress at the SiO2/Si interface depends heavily on SiO2 uniformity. By increasing the thickness of SiO2 linear, the stress at the vertical interface can be significantly reduced. Thus, process optimization to reduce the annealing-induced stress becomes feasible. The results of this study help us gain a better understanding of the thermo-mechanical behavior of the annealed TSV in 3D packaging.

Effect of different non-chloride sodium sources on the performance of heat-stressed broiler chickens.

PubMed

Ahmad, T; Mushtaq, T; Mahr-Un-Nisa; Sarwar, M; Hooge, D M; Mirza, M A

2006-06-01

1. One hundred and eighty 1-d-old broiler chicks were used to evaluate the effect upon broiler performance during severely hot summer months of three different sodium salts: sodium bicarbonate (NaHCO3), sodium carbonate (Na2CO3) and sodium sulphate (Na2SO4), in starter and finisher diets having an identical electrolyte balance (DEB) of 250 mEq/kg. 2. The non-chloride sodium salts were added to contribute the same amount of sodium and were substituted at the expense of builder's sand in the basal diets containing common salt (NaCl) as Na and Cl source. 3. Each diet was fed to three experimental units having 15 chicks each until 42 d of age. Severe heat-stress conditions, maintained in the rearing room, were indicated by high average weekly room temperature (minimum 29.3 degrees C; maximum 38.0 degrees C). 4. Diets containing sodium salts gave better body weight gain, feed intake and feed to gain ratio than the control diet. Sodium salts also enhanced water intake as well as water to feed intake ratio. This effect was more pronounced in broilers fed NaHCO3 supplement (with NaCl in the basal diets). 5. The increased water intake resulted in lower body temperature in heat-stressed birds fed NaHCO3 supplemented diet than in birds fed other sodium salts. A lower mortality rate was noted with NaHCO3 (15.15%), Na2CO3 (13.64%) and Na2SO4 (15.15%) supplements than with the control (33.33%) treatment. 6. Better carcase and parts yield were observed in sodium supplemented broilers. Sodium salts reduced the alkalotic pH and enhanced the blood sodium content, which ultimately improved the blood electrolyte balance and overall performance of heat-stressed broilers. 7. Supplementing broiler diets with sodium salts improved the live performance of heat-stressed broilers and better productive performance was noted with NaHCO3 than other sodium supplements.

Cadmium-induced teratogenicity: Association with ROS-mediated endoplasmic reticulum stress in placenta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhen; Wang, Hua; Xu, Zhong Mei

The placenta is essential for sustaining the growth of the fetus. An increased endoplasmic reticulum (ER) stress has been associated with the impaired placental and fetal development. Cadmium (Cd) is a potent teratogen that caused fetal malformation and growth restriction. The present study investigated the effects of maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdCl{sub 2} (4.5 mg/kg) on gestational day 9. As expected, maternal Cd exposure during early limb development significantly increased the incidences of forelimb ectrodactyly in fetuses. An obvious impairment in the labyrinth, a highly developed tissue of bloodmore » vessels, was observed in placenta of mice treated with CdCl{sub 2}. In addition, maternal Cd exposure markedly repressed cell proliferation and increased apoptosis in placenta. An additional experiment showed that maternal Cd exposure significantly upregulated the expression of GRP78, an ER chaperone. Moreover, maternal Cd exposure induced the phosphorylation of placental eIF2α, a downstream molecule of PERK signaling. In addition, maternal Cd exposure significantly increased the level of placental CHOP, another target of PERK signaling, indicating that the unfolded protein response (UPR) signaling was activated in placenta of mice treated with CdCl{sub 2}. Interestingly, alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, significantly alleviated Cd-induced placental ER stress and UPR. Taken together, these results suggest that reactive oxygen species (ROS)-mediated ER stress might be involved in Cd-induced impairment on placental and fetal development. Antioxidants may be used as pharmacological agents to protect against Cd-induced fetal malformation and growth restriction. -- Highlights: ► Cd induces fetal malformation and growth restriction. ► Cd induced placental ER stress and UPR. ► PBN alleviates Cd-induced ER stress and UPR in placenta. ► ROS

NADPH oxidase mediates depressive behavior induced by chronic stress in mice.

PubMed

Seo, Ji-Seon; Park, Jin-Young; Choi, Juli; Kim, Tae-Kyung; Shin, Joo-Hyun; Lee, Ja-Kyeong; Han, Pyung-Lim

2012-07-11

Stress is a potent risk factor for depression, yet the underlying mechanism is not clearly understood. In the present study, we explored the mechanism of development and maintenance of depression in a stress-induced animal model. Mice restrained for 2 h daily for 14 d showed distinct depressive behavior, and the altered behavior persisted for >3 months in the absence of intervention. Acute restraint induced a surge of oxidative stress in the brain, and stress-induced oxidative stress progressively increased with repetition of stress. In vitro, the stress hormone glucocorticoid generated superoxide via upregulation of NADPH oxidase. Consistently, repeated restraints increased the expression of the key subunits of NADPH oxidase, p47phox and p67phox, in the brain. Moreover, stressed brains markedly upregulated the expression of p47phox to weak restress evoked in the poststress period, and this molecular response was reminiscent of amplified ROS surge to restress. Pharmacological inhibition of NADPH oxidase by the NADPH oxidase inhibitor apocynin during the stress or poststress period completely blocked depressive behavior. Consistently, heterozygous p47phox knock-out mice (p47phox(+/-)) or molecular inhibition of p47phox with Lenti shRNA-p47phox in the hippocampus suppressed depressive behavior. These results suggest that repeated stress promotes depressive behavior through the upregulation of NADPH oxidase and the resultant metabolic oxidative stress, and that the inhibition of NADPH oxidase provides beneficial antidepression effects.

Prefrontal Cortex Corticotropin-Releasing Factor Receptor 1 Conveys Acute Stress-Induced Executive Dysfunction.

PubMed

Uribe-Mariño, Andrés; Gassen, Nils C; Wiesbeck, Maximilian F; Balsevich, Georgia; Santarelli, Sara; Solfrank, Beate; Dournes, Carine; Fries, Gabriel R; Masana, Merce; Labermeier, Christiana; Wang, Xiao-Dong; Hafner, Kathrin; Schmid, Bianca; Rein, Theo; Chen, Alon; Deussing, Jan M; Schmidt, Mathias V

2016-11-15

The medial prefrontal cortex (mPFC) subserves complex cognition and is impaired by stress. Corticotropin-releasing factor (CRF), through CRF receptor 1 (CRFR1), constitutes a key element of the stress response. However, its contribution to the effects of stress in the mPFC remains unclear. Mice were exposed to acute social defeat stress and subsequently to either the temporal order memory (n = 11-12) or reversal learning (n = 9-11) behavioral test. Changes in mPFC Crhr1 messenger RNA levels were measured in acutely stressed mice (n = 12). Crhr1 loxP/loxP mice received either intra-mPFC adeno-associated virus-Cre or empty microinjections (n = 17-20) and then were submitted to acute stress and later to the behavioral tests. Co-immunoprecipitation was used to detect activation of the protein kinase A (PKA) signaling pathway in the mPFC of acutely stressed mice (n = 8) or intra-mPFC CRF injected mice (n = 7). Finally, mice received intra-mPFC CRF (n = 11) and/or Rp-isomer cyclic adenosine 3',5' monophosphorothioate (Rp-cAMPS) (n = 12) microinjections and underwent behavioral testing. We report acute stress-induced effects on mPFC-mediated cognition, identify CRF-CRFR1-containing microcircuits within the mPFC, and demonstrate stress-induced changes in Crhr1 messenger RNA expression. Importantly, intra-mPFC CRFR1 deletion abolishes acute stress-induced executive dysfunction, whereas intra-mPFC CRF mimics acute stress-induced mPFC dysfunction. Acute stress and intra-mPFC CRF activate the PKA signaling pathway in the mPFC, leading to cyclic AMP response element binding protein phosphorylation in intra-mPFC CRFR1-expressing neurons. Finally, PKA blockade reverses the intra-mPFC CRF-induced executive dysfunction. Taken together, these results unravel a molecular mechanism linking acute stress to executive dysfunction via CRFR1. This will aid in the development of novel therapeutic targets for stress-induced cognitive dysfunction. Copyright © 2016 Society of Biological

Calcium-mediated responses and glutamine synthetase expression in greater duckweed (Spirodela polyrhiza L.) under diethyl phthalate-induced stress.

PubMed

Cheng, Lee-Ju; Hung, Meng-Ju; Cheng, Yen-I; Cheng, Tai-Sheng

2013-11-15

This study was carried out to assess the influence of diethyl phthalate (DEP) alone or associated with calcium chloride (CaCl2) on greater duckweed plants, emphasizing the implications of calcium in amelioration of DEP-induced stress on plant growth. Greater duckweed were treated with DEP in variable concentrations, as 0, 0.25, 0.5, 1.0 and 2.0mM for 7 days, or treated with the same concentration either 2mM DEP or 2mM DEP plus 10mM CaCl2·2H2O in different duration 0-7 days. Treatment with 2mM DEP resulted in increasing proline content, protease activity, and ammonia accumulation in duckweed tissues. NADH-glutamate dehydrogenase (NADH-GDH; EC 1.4.1.2) and Δ(1)-pyrroline-5-carboxylate reductase (P5CR; EC 1.5.1.2), two key enzymes in the glutamate pathway of proline synthesis, showed increase in activity with DEP treatment and positively correlated with proline accumulation. No further increase in proline accumulation was observed with addition of calcium chloride to the DEP-treated cultures. However, supplementation of Ca(2+) can mitigate the adverse effect of DEP, at least in part to decrease the DEP-induced superoxide accumulation and increase in GDH activity for ammonia assimilation in duckweed fronds. In addition, effects of calcium on mitigation of DEP injury were also observed in glutamine synthetase (GS; EC 6.3.1.2) expression. Both GS1 and GS2 polypeptide accumulation and the level of total GS activity were nearly equivalent to the control. Exogenous proline protects GS2 from DEP-modulated redox damage in the chloroplast lysates but there is no remarkable protection effects on D1 (the 32kDa protein in photosystem II reaction center) degradation. In conclusion, the glutamate pathway of proline synthesis might be involved in mitigation of DEP-induced injury, and calcium plays an important role in increasing GDH, P5CR, and GS expression. Copyright © 2013 Elsevier B.V. All rights reserved.

Blue light-induced oxidative stress in live skin.

PubMed

Nakashima, Yuya; Ohta, Shigeo; Wolf, Alexander M

2017-07-01

Skin damage from exposure to sunlight induces aging-like changes in appearance and is attributed to the ultraviolet (UV) component of light. Photosensitized production of reactive oxygen species (ROS) by UVA light is widely accepted to contribute to skin damage and carcinogenesis, but visible light is thought not to do so. Using mice expressing redox-sensitive GFP to detect ROS, blue light could produce oxidative stress in live skin. Blue light induced oxidative stress preferentially in mitochondria, but green, red, far red or infrared light did not. Blue light-induced oxidative stress was also detected in cultured human keratinocytes, but the per photon efficacy was only 25% of UVA in human keratinocyte mitochondria, compared to 68% of UVA in mouse skin. Skin autofluorescence was reduced by blue light, suggesting flavins are the photosensitizer. Exposing human skin to the blue light contained in sunlight depressed flavin autofluorescence, demonstrating that the visible component of sunlight has a physiologically significant effect on human skin. The ROS produced by blue light is probably superoxide, but not singlet oxygen. These results suggest that blue light contributes to skin aging similar to UVA. Copyright © 2017 Elsevier Inc. All rights reserved.

Metal Chloride Induced Formation of Porous Polyhydroxybutyrate (PHB) Films: Morphology, Thermal Properties and Crystallinity

NASA Astrophysics Data System (ADS)

Tan, W. L.; Yaakob, N. N.; Zainal Abidin, A.; Abu Bakar, M.; Abu Bakar, N. H. H.

2016-06-01

Polyhydroxybutyrate (PHB) films with highly porous structures were synthesized using a one phase system comprising of metal chloride/methanol/PHB/chloroform (MCl2/CH3OH/PHB/CHCl3). SEM analyses confirmed that the MCl2 (where M = Cu2+ or Ni2+) induced porous structures with pore sizes ranging from 0.3 - 2.0 μm. The average pore size increased with the increasing MCl2 content. There existed weak physical interactions between the PHB chains and MCl2 as revealed by FTIR and NMR spectroscopies. The residue of MCl2 in the porous PHB film does not exert significant influence on the thermal stability of PHB. Nevertheless, the crystallinity of the prepared film is enhanced, as MCl2 acts as the nucleation sites to promote the growth of spherullites.

Stress-state effects on the stress-induced martensitic transformation of carburized 4320 steels

NASA Astrophysics Data System (ADS)

Karaman, I.; Balzer, M.; Sehitoglu, Huseyin; Maier, H. J.

1998-02-01

The effect of different stress states on the stress-induced martensitic transformation of retained austenite was investigated in carburized 4320 steels with an initial retained austenite content of 15 pct. Experiments were conducted utilizing a specialized pressure rig and comparison between stress-strain behaviors of specimens with different austenitization and tempering histories was performed under these stress states. Experimental results indicated considerable asymmetry between tension and compression, with triaxial stress states resulting in the highest strength levels for the untempered material. Fine carbide precipitates due to low-temperature tempering increased the strength and ductility of the specimens and also changed the austenite-to-martensite transformation behavior. Numerical simulations of stress-strain behaviors under different stress states were obtained, with an existing micromechanical self-consistent framework utilizing the crystallographic theory of austenite/martensite transformation and the minimum complementary free-energy principle. The model was modified for carburized steels upon microstructural investigation and predicted the same trends in effective stress-effective strain behavior as observed experimentally.

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

PubMed

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Decreased contraction induced by endothelium-derived contracting factor in prolonged treatment of rat renal artery with endoplasmic reticulum stress inducer.

PubMed

Ando, Makoto; Matsumoto, Takayuki; Taguchi, Kumiko; Kobayashi, Tsuneo

2018-05-04

Recent evidence suggests that endoplasmic reticulum (ER) stress is involved in the regulation of various physiological functions, including those of the vascular system. However, the relationship between ER stress and vascular function is poorly understood. The endothelial cells control the vascular tone by releasing endothelium-derived relaxing factors and contracting factors (EDCFs). We hypothesized that tunicamycin, an inducer of ER stress, modifies endothelium-dependent contraction and prostaglandins (PGs), a major class of EDCFs, induced contractions in the rat renal artery in rats. An organ-culture technique was used to purely investigate the effects of ER stress on the vascular tissue. We observed that tunicamycin treatment (20 μg/mL for 23 ± 1 h) did not affect acetylcholine (ACh)-induced relaxation and decreased EDCF-mediated contractions under nitric oxide synthase (NOS) inhibition induced by ACh, ATP, or A23187 (a calcium ionophore) in the renal arteries. Under NOS inhibition, U46619 (a thromboxane A 2 mimetic)- and beraprost (a prostacyclin analog)-induced contractions were also decreased in the renal arteries of the tunicamycin-treated group (vs. vehicle), while PGE 2 - and PGF 2α -induced contractions were similar between the groups. Tunicamycin treatment slightly enhanced the contractions induced by phenylephrine, an α 1 adrenoceptor ligand. Isotonic high-K + -induced contractions were similar between the vehicle- and tunicamycin-treated groups. Another ER stress inducer, thapsigargin (4 μmol/L for 23 ± 1 h), also caused substantial reduction of ACh-induced EDCF-mediated contraction (vs. vehicle-treated group). In the cultured renal arteries, tunicamycin and thapsigargin increased the expression of binding immunoglobulin protein (BiP), an ER stress marker. In conclusion, ER stress induction directly affects renal arterial function, especially in reducing EDCF-mediated contractions.

Hydrocracking with molten zinc chloride catalyst containing 2-12% ferrous chloride

DOEpatents

Zielke, Clyde W.; Bagshaw, Gary H.

1981-01-01

In a process for hydrocracking heavy aromatic polynuclear carbonaceous feedstocks to produce hydrocarbon fuels boiling below about 475.degree. C. by contacting the feedstocks with hydrogen in the presence of a molten zinc chloride catalyst and thereafter separating at least a major portion of the hydrocarbon fuels from the spent molten zinc chloride catalyst, an improvement comprising: adjusting the FeCl.sub.2 content of the molten zinc chloride to from about 2 to about 12 mol percent based on the mixture of ferrous chloride and molten zinc chloride.

Abiotic stresses affect Trichoderma harzianum T39-induced resistance to downy mildew in grapevine.

PubMed

Roatti, Benedetta; Perazzolli, Michele; Gessler, Cesare; Pertot, Ilaria

2013-12-01

Enhancement of plant defense through the application of resistance inducers seems a promising alternative to chemical fungicides for controlling crop diseases but the efficacy can be affected by abiotic factors in the field. Plants respond to abiotic stresses with hormonal signals that may interfere with the mechanisms of induced systemic resistance (ISR) to pathogens. In this study, we exposed grapevines to heat, drought, or both to investigate the effects of abiotic stresses on grapevine resistance induced by Trichoderma harzianum T39 (T39) to downy mildew. Whereas the efficacy of T39-induced resistance was not affected by exposure to heat or drought, it was significantly reduced by combined abiotic stresses. Decrease of leaf water potential and upregulation of heat-stress markers confirmed that plants reacted to abiotic stresses. Basal expression of defense-related genes and their upregulation during T39-induced resistance were attenuated by abiotic stresses, in agreement with the reduced efficacy of T39. The evidence reported here suggests that exposure of crops to abiotic stress should be carefully considered to optimize the use of resistance inducers, especially in view of future global climate changes. Expression analysis of ISR marker genes could be helpful to identify when plants are responding to abiotic stresses, in order to optimize treatments with resistance inducers in field.

Sequential development of hepatocellular carcinoma and liver angiosarcoma in a vinyl chloride-exposed worker.

PubMed

Guido, Maria; Sarcognato, Samantha; Pelletti, Guido; Fassan, Matteo; Murer, Bruno; Snenghi, Rossella

2016-11-01

Strong experimental and clinical evidences have definitely linked occupational vinyl chloride exposure to development of angiosarcoma of the liver. In contrast, despite the International Agency for Research on Cancer having included vinyl chloride among the causes of hepatocellular carcinoma, the association between vinyl chloride exposure and hepatocellular carcinoma remains debated. This issue is relevant, because occupational exposure to high levels of vinyl chloride may still occur. We report a unique case of sequential occurrences of hepatocellular carcinoma and angiosarcoma of the liver, in a vinyl chloride-exposed worker without cirrhosis and any known risk factor for chronic liver disease. Both the hepatocellular carcinoma and the surrounding normal liver showed micronucleus formation, which reflects genotoxic effect of vinyl chloride. Angiosarcoma showed a KRAS G12D point mutation, which is considered to be characteristic of vinyl chloride-induced angiosarcoma. This case supports the pathogenic role of vinyl chloride in both hepatocellular carcinoma and angiosarcoma development. Copyright © 2016 Elsevier Inc. All rights reserved.

Penfluridol induces endoplasmic reticulum stress leading to autophagy in pancreatic cancer.

PubMed

Ranjan, Alok; German, Nadezhda; Mikelis, Constantinos; Srivenugopal, Kalkunte; Srivastava, Sanjay K

2017-06-01

Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression. In this study, we demonstrated that penfluridol induced endoplasmic reticulum stress in BxPC-3, AsPC-1, and Panc-1 pancreatic cancer cell lines as indicated by upregulation of endoplasmic reticulum stress markers such as binding protein (BIP), C/EBP homologous protein (CHOP) and inositol requiring 1α (IRE1α) after treatment with penfluridol in a concentration-dependent manner. Inhibiting endoplasmic reticulum stress by pretreatment with pharmacological inhibitors such as sodium phenylbutyrate and mithramycin or by silencing CHOP using CHOP small interfering RNA, blocked penfluridol-induced autophagy. These results clearly indicate that penfluridol-induced endoplasmic reticulum stress lead to autophagy in our model. Western blot analysis of subcutaneously implanted AsPC-1 and BxPC-3 tumors as well as orthotopically implanted Panc-1 tumors demonstrated upregulation of BIP, CHOP, and IRE1α expression in the tumor lysates from penfluridol-treated mice as compared to tumors from control mice. Altogether, our study establishes that penfluridol-induced endoplasmic reticulum stress leads to autophagy resulting in reduced pancreatic tumor growth. Our study opens a new therapeutic target for advanced chemotherapies against pancreatic cancer.

The influence of deformation-induced residual stresses on the post-forming tensile stress/strain behavior of dual-phase steels

NASA Astrophysics Data System (ADS)

Hance, Brandon Michael

It was hypothesized that, in dual-phase (DP) steels, strain partitioning between ferrite (alpha) and martensite (alpha') during deformation results in a distribution of post-deformation residual stresses that, in turn, affects the subsequent strength, work hardening behavior and formability when the strain path is changed. The post-forming deformation-induced residual stress state was expected to depend upon the microstructure, the amount of strain and the prestrain path. The primary objective of this research program was to understand the influence of deformation-induced residual stresses on the post-forming tensile stress/strain behavior of DP steels. Three commercially produced sheet steels were considered in this analysis: (1) a DP steel with approximately 15 vol. % martensite, (2) a conventional high-strength, low-alloy (HSLA) steel, and (3) a conventional, ultra-low-carbon interstitial-free (IF) steel. Samples of each steel were subjected to various prestrain levels in various plane-stress forming modes, including uniaxial tension, plane strain and balanced biaxial stretching. Neutron diffraction experiments confirmed the presence of large post-forming deformation-induced residual stresses in the ferrite phase of the DP steel. The deformation-alphainduced residual stress state varied systematically with the prestrain mode, where the principal residual stress components are proportional to the principal strain components of the prestrain mode, but opposite in sign. For the first time, and by direct experimental correlation, it was shown that deformation-induced residual stresses greatly affect the post-forming tensile stress/strain behavior of DP steels. As previously reported in the literature, the formability (residual tensile ductility) of the IF steel and the HSLA steel was adversely affected by strain path changes. The DP steel presents a formability advantage over the conventional IF and HSLA steels, and is expected to be particularly well suited for

Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells.

PubMed

Choi, Min Jung; Park, Eun Jung; Min, Kyoung Jin; Park, Jong-Wook; Kwon, Taeg Kyu

2011-04-01

The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in cellular stress that initiates a specialized response designated as the unfolded protein response. ER stress has been implicated in a variety of common diseases, such as diabetes, ischemia and neurodegenerative disorders. Withaferin A, a major chemical constituent of Withania somnifera, has been reported to inhibit tumor cell growth. We show that withaferin A induced a dose-dependent apoptotic cell death in several types of human cancer cells, as measured by FACS analysis and PARP cleavage. Treatment of Caki cells with withaferin A induced a number of signature ER stress markers, including phosphorylation of eukaryotic initiation factor-2α (eIF-2 α), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78. In addition, withaferin A caused up-regulation of CAAT/enhancer-binding protein-homologous protein (CHOP), suggesting the induction of ER stress. Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress. Furthermore, CHOP siRNA or inhibition of caspase-4 activity attenuated withaferin A-induced apoptosis. Taken together, the present study provides strong evidence supporting an important role of the ER stress response in mediating withaferin A-induced apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stress Drop and Depth Controls on Ground Motion From Induced Earthquakes

NASA Astrophysics Data System (ADS)

Baltay, A.; Rubinstein, J. L.; Terra, F. M.; Hanks, T. C.; Herrmann, R. B.

2015-12-01

Induced earthquakes in the central United States pose a risk to local populations, but there is not yet agreement on how to portray their hazard. A large source of uncertainty in the hazard arises from ground motion prediction, which depends on the magnitude and distance of the causative earthquake. However, ground motion models for induced earthquakes may be very different than models previously developed for either the eastern or western United States. A key question is whether ground motions from induced earthquakes are similar to those from natural earthquakes, yet there is little history of natural events in the same region with which to compare the induced ground motions. To address these problems, we explore how earthquake source properties, such as stress drop or depth, affect the recorded ground motion of induced earthquakes. Typically, due to stress drop increasing with depth, ground motion prediction equations model shallower events to have smaller ground motions, when considering the same absolute hypocentral distance to the station. Induced earthquakes tend to occur at shallower depths, with respect to natural eastern US earthquakes, and may also exhibit lower stress drops, which begs the question of how these two parameters interact to control ground motion. Can the ground motions of induced earthquakes simply be understood by scaling our known source-ground motion relations to account for the shallow depth or potentially smaller stress drops of these induced earthquakes, or is there an inherently different mechanism in play for these induced earthquakes? We study peak ground-motion velocity (PGV) and acceleration (PGA) from induced earthquakes in Oklahoma and Kansas, recorded by USGS networks at source-station distances of less than 20 km, in order to model the source effects. We compare these records to those in both the NGA-West2 database (primarily from California) as well as NGA-East, which covers the central and eastern United States and Canada

Chloride channels mediate sodium sulphide-induced relaxation in rat uteri

PubMed Central

Mijušković, Ana; Kokić, Aleksandra Nikolić; Dušić, Zorana Oreščanin; Slavić, Marija; Spasić, Mihajlo B; Blagojević, Duško

2015-01-01

Background and Purpose Hydrogen sulphide reduces uterine contractility and is of potential interest as a treatment for uterine disorders. The aim of this study was to explore the mechanism of sodium sulphide (Na2S)-induced relaxation of rat uterus, investigate the importance of redox effects and ion channel-mediated mechanisms, and any interactions between these two mechanisms. Experimental Approach Organ bath studies were employed to assess the pharmacological effects of Na2S in uterine strips by exposing them to Na2S with or without Cl− channel blockers (DIDS, NFA, IAA-94, T16Ainh-A01, TA), raised KCl (15 and 75 mM), K+ channel inhibitors (glibenclamide, TEA, 4-AP), L-type Ca2+ channel activator (S-Bay K 8644), propranolol and methylene blue. The activities of antioxidant enzymes were measured in homogenates of treated uteri. The expression of bestrophin channel 1 (BEST-1) was determined by Western blotting and RT-PCR. Key Results Na2S caused concentration-dependent reversible relaxation of spontaneously active and calcium-treated uteri, affecting both amplitude and frequency of contractions. Uteri exposed to 75 mM KCl were less sensitive to Na2S compared with uteri in 15 mM KCl. Na2S-induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular HCO3−, suggesting the involvement of chloride ion channels. Na2S in combination with different modulators provoked specific changes in the anti-oxidant profiles of uteri. The expression of BEST-1, both mRNA and protein, was demonstrated in rat uteri. Conclusions and Implications The relaxant effects of Na2S in rat uteri are mediated mainly via a DIDS-sensitive Cl−-pathway. Components of the relaxation are redox- and Ca2+-dependent. PMID:25857480

Chloride channels mediate sodium sulphide-induced relaxation in rat uteri.

PubMed

Mijušković, Ana; Kokić, Aleksandra Nikolić; Dušić, Zorana Oreščanin; Slavić, Marija; Spasić, Mihajlo B; Blagojević, Duško

2015-07-01

Hydrogen sulphide reduces uterine contractility and is of potential interest as a treatment for uterine disorders. The aim of this study was to explore the mechanism of sodium sulphide (Na2 S)-induced relaxation of rat uterus, investigate the importance of redox effects and ion channel-mediated mechanisms, and any interactions between these two mechanisms. Organ bath studies were employed to assess the pharmacological effects of Na2 S in uterine strips by exposing them to Na2 S with or without Cl(-) channel blockers (DIDS, NFA, IAA-94, T16Ainh-A01, TA), raised KCl (15 and 75 mM), K(+) channel inhibitors (glibenclamide, TEA, 4-AP), L-type Ca(2+) channel activator (S-Bay K 8644), propranolol and methylene blue. The activities of antioxidant enzymes were measured in homogenates of treated uteri. The expression of bestrophin channel 1 (BEST-1) was determined by Western blotting and RT-PCR. Na2 S caused concentration-dependent reversible relaxation of spontaneously active and calcium-treated uteri, affecting both amplitude and frequency of contractions. Uteri exposed to 75 mM KCl were less sensitive to Na2 S compared with uteri in 15 mM KCl. Na2 S-induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular HCO3 (-) , suggesting the involvement of chloride ion channels. Na2 S in combination with different modulators provoked specific changes in the anti-oxidant profiles of uteri. The expression of BEST-1, both mRNA and protein, was demonstrated in rat uteri. The relaxant effects of Na2 S in rat uteri are mediated mainly via a DIDS-sensitive Cl(-) -pathway. Components of the relaxation are redox- and Ca(2+) -dependent. © 2015 The British Pharmacological Society.

Pressure-Induced Structural Evolution and Band Gap Shifts of Organometal Halide Perovskite-Based Methylammonium Lead Chloride.

PubMed

Wang, Lingrui; Wang, Kai; Xiao, Guanjun; Zeng, Qiaoshi; Zou, Bo

2016-12-15

Organometal halide perovskites are promising materials for optoelectronic devices. Further development of these devices requires a deep understanding of their fundamental structure-property relationships. The effect of pressure on the structural evolution and band gap shifts of methylammonium lead chloride (MAPbCl 3 ) was investigated systematically. Synchrotron X-ray diffraction and Raman experiments provided structural information on the shrinkage, tilting distortion, and amorphization of the primitive cubic unit cell. In situ high pressure optical absorption and photoluminescence spectra manifested that the band gap of MAPbCl 3 could be fine-tuned to the ultraviolet region by pressure. The optical changes are correlated with pressure-induced structural evolution of MAPbCl 3 , as evidenced by band gap shifts. Comparisons between Pb-hybrid perovskites and inorganic octahedra provided insights on the effects of halogens on pressure-induced transition sequences of these compounds. Our results improve the understanding of the structural and optical properties of organometal halide perovskites.

AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress.

PubMed

Liu, Yu; Fares, Matthew; Dunham, Noah P; Gao, Zi; Miao, Kun; Jiang, Xueyuan; Bollinger, Samuel S; Boal, Amie K; Zhang, Xin

2017-07-17

Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Social stress in mice induces voiding dysfunction and bladder wall remodeling

PubMed Central

Chang, Andy; Butler, Stephan; Sliwoski, Joanna; Valentino, Rita; Canning, Douglas

2009-01-01

Several studies have anecdotally reported the occurrence of altered urinary voiding patterns in rodents exposed to social stress. A recent study characterized the urodynamic and central changes in a rat model of social defeat. Here, we describe a similar voiding phenotype induced in mice by social stress and in addition we describe potential molecular mechanisms underlying the resulting bladder wall remodeling. The mechanism leading to the altered voiding habits and underlying bladder phenotype may be relevant to the human syndrome of dysfunctional voiding which is thought to have a psychological component. To better characterize and investigate social stress-induced bladder wall hypertrophy, FVB mice (6 wk old) were randomized to either social stress or control manipulation. The stress involved repeated cycles of a 1-h direct exposure to a larger aggressive C57Bl6 breeder mouse followed by a 23-h period of barrier separation over 4 wk. Social stress resulted in altered urinary voiding patterns suggestive of urinary retention and increased bladder mass. In vivo cystometry revealed an increased volume at micturition with no change in the voiding pressure. Examination of these bladders revealed increased nuclear expression of the transcription factors MEF-2 and NFAT, as well as increased expression of the myosin heavy chain B isoform mRNA. BrdU uptake was increased within the urothelium and lamina propria layers in the social stress group. We conclude that social stress induces urinary retention that ultimately leads to shifts in transcription factors, alterations in myosin heavy chain isoform expression, and increases in DNA synthesis that mediate bladder wall remodeling. Social stress-induced bladder dysfunction in rodents may provide insight into the underlying mechanisms and potential treatment of dysfunctional voiding in humans. PMID:19587139

Exercise-induced heat stress disrupts the shear-dilatory relationship.

PubMed

Ives, Stephen J; Lefferts, Wesley K; Wharton, Margret; Fehling, Patricia C; Smith, Denise L

2016-12-01

What is the central question of this study? Although heat stress is known to increase cardiovascular strain, no study, to date, had explored the potential impact of exercise-induced heat stress on vascular function. What is the main finding and its importance? We found that acute exercise tended to reduce flow-mediated dilatation (FMD), owing in part to reduced reactive hyperaemia/shear stimulus; thus, when FMD is normalized to shear no postexercise deficit exists. Exercise-induced heat stress increased reactive hyperaemia, shear rate, coupled with a sustained FMD postexercise, suggests that exercise-induced heat stress increases the amount of shear stimulus to elicit a similar response, indicating reduced vascular responsiveness, or reserve, which might increase cardiovascular susceptibility. Heat stress increases cardiovascular strain and is of particular concern in occupations, such as firefighting, in which individuals are required to perform strenuous work while wearing personal protective equipment. Sudden cardiac events are associated with strenuous activity and are the leading cause of duty-related death among firefighters, accounting for ∼50% of duty-related fatalities per year. Understanding the acute effects of exercise-induced heat stress (EIHS) on vascular endothelial function may provide insight into the mechanisms precipitating acute coronary events in firefighters. The purpose of this study, therefore, was to determine the effects of EIHS on vascular endothelial function. Using a balanced crossover design, 12 healthy men performed 100 min of moderate-intensity, intermittent exercise with and without EIHS (personal protective equipment or cooling vest, respectively). Measurements of flow-mediated dilatation (FMD), reactive hyperaemia and shear rate area under the curve (SR AUC ) were performed pre- and postexercise. During EIHS, core temperature was significantly higher (38 ± 0.1 versus 37 ± 0.1°C). Postexercise FMD tended to be suppressed

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring

PubMed Central

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring. PMID:28553167

Lateralized sex differences in stress-induced dopamine release in the rat.

PubMed

Sullivan, Ron M; Dufresne, Marc M; Waldron, Jay

2009-02-18

This study examined the possibility that hemispheric differences in stress-induced brain activation vary as a function of sex. Using in-vivo voltammetry, increases in extracellular dopamine release in response to predator odour and tail pinch stress were recorded bilaterally and simultaneously in either the infralimbic cortex or basolateral amygdala. In both stress-sensitive brain regions, significant sex x hemisphere interactions were observed, with males and females showing greater dopamine activation in right-brain and left-brain structures, respectively. Cortical asymmetries in dopamine release also showed sex-specific correlations with stress-induced neuroendocrine activation. Given the intriguing human parallels, we suggest that differential cerebral lateralization may be highly relevant to the disproportionately high incidence of stress-related disorders such as depression and anxiety seen in women.

RNA Seq analysis of the role of calcium chloride stress and electron transport in mitochondria for malachite green decolorization by Aspergillus niger.

PubMed

Gomaa, Ola M; Selim, Nabila S; Wee, Josephine; Linz, John E

2017-08-01

Aspergillus niger was previously demonstrated to decolorize the commercial dye malachite green (MG) and this process was enhanced under calcium chloride (CaCl 2 ) treatment. Previous data also suggested that the decolorization process is related to mitochondrial cytochrome c. In the current work, we analyzed in depth the specific relationship between CaCl 2 treatment and MG decolorization. Gene expression analysis (RNA Seq) using Next Generation Sequencing (NGS) revealed up-regulation of 28 genes that are directly or indirectly associated with stress response functions as early as 30min of CaCl 2 treatment; these data further strengthen our previous findings that CaCl 2 treatment induces a stress response in A. niger which enhances the ability to decolorize MG. A significant increase in fluorescence observed by MitoTracker dye suggests that CaCl 2 treatment also increased mitochondrial membrane potential. Isolated mitochondrial membrane protein fractions obtained from A. niger grown under standard growth conditions decolorized MG in the presence of NADH and decolorization was enhanced in samples isolated from CaCl 2 -treated A. niger cultures. Treatment of whole mitochondrial fraction with KCN which inhibits electron transport by cytochrome c oxidase and Triton-X 100 which disrupts mitochondrial membrane integrity suggests that cyanide sensitive cytochrome c oxidase activity is a key biochemical step in MG decolorization. This suggestion was confirmed by the addition of palladium α-lipoic acid complex (PLAC) which resulted in an initial increase in decolorization. Although the role of cytochrome c and cytochrome c oxidase was confirmed at the biochemical level, changes in levels of transcripts encoding these enzymes after CaCl 2 treatment were not found to be statistically significant in RNA Seq analysis. These data suggest that the regulation of cytochrome c enzymes occur predominantly at the post-transcriptional level under CaCl 2 stress. Thus, using global

Psychological Stress Induces Temporary Masticatory Muscle Mechanical Sensitivity in Rats

PubMed Central

Huang, Fei; Zhang, Min; Chen, Yong-Jin; Li, Qiang; Wu, An-Zhen

2011-01-01

To explore the relationship between psychological stress and masticatory muscle pain, we created a communication stress animal model to determine whether psychological stress could induce increased mechanical sensitivity in masticatory muscles and to study the changes of mechanical nociceptive thresholds after stress removal. Forty-eight male Sprague-Dawley rats were divided into a control group (CON), a foot-shocked group (FS, including 3 subgroups recorded as FS-1, FS-2, and FS-3), a psychological stress group (PS), and a drug treatment group (DT). PS and DT rats were confined in a communication box for one hour a day to observe the psychological responses of neighboring FS rats.Measurements of the mechanical nociceptive thresholds of the bilateral temporal and masseter muscles showed a stimulus-response relationship between psychological stress and muscle mechanical sensitivity. The DT rats, who received a diazepam injection, showed almost the same mechanical sensitivity of the masticatory muscles to that of the control in response to psychological stress. Fourteen days after the psychological stressor was removed, the mechanical nociceptive thresholds returned to normal. These findings suggest that psychological stress is directly related to masticatory muscle pain. Removal of the stressor could be a useful method for relieving mechanical sensitivity increase induced by psychological stress. PMID:21331360

Physiological effects of potassium chloride, formalin and handling stress on bonytail

USGS Publications Warehouse

Sykes, Catherine L.; Caldwell, Colleen A.; Gould, William R.

2011-01-01

We characterized the sublethal physiological changes in bonytail Gila elegans subjected to consecutive 750-mg/L potassium chloride (KCl) and 25-mg/L formalin treatments for the removal of zebra mussel Dreissena polymorpha and quagga mussel D. bugensis veligers. Plasma cortisol, glucose, and osmolality were measured over 24 h and at 14 d posthandling after exposing bonytail to KCl and one net stressor (capture with a net), KCl plus formalin and two net stressors, and one or two net stressors without chemicals. Elevated plasma cortisol (322–440 ng/mL) and glucose (254–399 mg/dL) concentrations were observed in all treatments compared with the concentrations in control fish (plasma cortisol, 56 ng/mL; glucose, 43 mg/dL). While there were no detectable differences in plasma osmolality among the treatment and control fish, a difference was observed between fish that were handled once versus twice. Chemical effects of stress were not observed in any of the physiological responses when the KCl treatment was compared with the one-net stressor treatment or when the KCl plus formalin treatment was compared with the two-net stressor treatment. Cumulative responses, however, were observed between one net stressor and two net stressors for plasma glucose and osmolality but not for plasma cortisol. Plasma cortisol and glucose levels remained elevated at 24 h posthandling, indicating that bonytail had not completely recovered from the handling stressors and would benefit from a recovery period in protected refugia before being released.

Anti-hypertensive effects of the methanol/methylene chloride stem bark extract of Mammea africana in l-NAME-induced hypertensive rats.

PubMed

Nguelefack-Mbuyo, P E; Nguelefack, T B; Dongmo, A B; Afkir, S; Azebaze, A G B; Dimo, T; Legssyer, A; Kamanyi, A; Ziyyat, A

2008-05-22

The methanol/methylene chloride (CH(3)OH/CH(2)Cl(2)) extract from the stem bark of Mammea africana was showed to possess vasodilating effect in the presence and the absence of N(omega)-nitro-l-arginine methyl ester (l-NAME). The present study was designed to evaluate the effects of the methanol/methylene chloride from the stem bark of Mammea africana. The extract (200 mg/(kg day)) was administered orally in rats treated concurrently with l-NAME (40 mg/(kg day)). l-Arginine (100 mg/(kg day)) and captopril (20 mg/(kg day))were used as positive controls. Bodyweight, systolic arterial blood pressure and heart rate were measured weekly throughout the experiment period (28 days). At the end of treatment, animals were killed and the cardiac mass index evaluated. The aorta was used to evaluate the endothelium-dependant relaxation to carbachol. The aorta contraction induced by noradrenalin was also examined and expressed as a percentage of that induced by KCl. The extract neither affected the body weight nor the heart rate. The extract as captopril completely prevented the development of arterial hypertension. Both the substances failed to restore the endothelium-dependent vascular relaxation and increased the vascular contraction to norepinephrine in relation to KCl contraction. They also significantly reduced the left ventricular hypertrophy induced by l-NAME. These findings are in agreement with the traditional use of Mammea africana in the treatment of arterial hypertension and indicate that it may have a beneficial effect in patients with NO deficiency but will be unable to improve their endothelium-dependent vasorelaxation.

Socioeconomic status and stress-induced increases in interleukin-6.

PubMed

Brydon, L; Edwards, S; Mohamed-Ali, V; Steptoe, A

2004-05-01

Coronary artery disease (CAD) is more prevalent in people from a low socioeconomic background, and low socioeconomic status (SES) is associated with an increased exposure to psychological stress. The pro-inflammatory cytokine interleukin-6 (IL-6) plays a central role in CAD development. IL-6 is responsive to psychological stress and could potentially mediate the effect of psychosocial factors on CAD risk. Accordingly, we predicted that people of low SES would have greater and/or more sustained IL-6 responses to acute psychological stress. Based on previous findings, we also predicted that these people would have delayed post-stress cardiovascular recovery. Thirty-eight male civil servants were tested, with participants divided into high and low SES groups according to employment grade. There were no differences between the groups at baseline. However there were significant differences in IL-6 and heart rate responses to stress. Stress induced increases in plasma IL-6 in all participants. However, in the low SES group, IL-6 continued to increase between 75 min and 2h post-stress, whereas IL-6 levels stabilised at 75 min in the high SES group. Heart rate increased to the same extent following stress in both groups, however by 2h post-stress, it had returned to baseline in 75% of the high SES group compared with only 38.1% of the low SES group. These results suggest that low SES people are less able to adapt to stress than their high SES counterparts. Prolonged stress-induced increases in IL-6 in low SES groups represents a novel mechanism potentially linking socioeconomic position and heart disease.

Stress induced magnetic-domain evolution in magnetoelectric composites

NASA Astrophysics Data System (ADS)

Trivedi, Harsh; Shvartsman, Vladimir V.; Lupascu, Doru C.; Medeiros, Marco S. A.; Pullar, Robert C.

2018-06-01

Local observation of the stress mediated magnetoelectric (ME) effect in composites has gained a great deal of interest over the last decades. However, there is an apparent lack of rigorous methods for a quantitative characterization of the ME effect at the local scale, especially in polycrystalline microstructures. In the present work, we address this issue by locally probing the surface magnetic state of barium titante–hexagonal barium ferrite (BaTiO3–BaFe12O19) ceramic composites using magnetic force microscopy (MFM). The effect of the piezoelectrically induced local stress on the magnetostrictive component (BaFe12O19, BaM) was observed in the form of the evolution of the magnetic domains. The local piezoelectric stress was induced by applying a voltage to the neighboring BaTiO3 grains, using a conductive atomic force microscopy tip. The resulting stochastic evolution of magnetic domains was studied in the context of the induced magnetoelastic anisotropy. In order to overcome the ambiguity in the domain changes observed by MFM, certain generalizations about the observed MFM contrast are put forward, followed by application of an algorithm for extracting the average micromagnetic changes. An average change in domain wall thickness of 50 nm was extracted, giving a lower limit on the corresponding induced magnetoelastic anisotropy energy. Furthermore, we demonstrate that this induced magnetomechanical energy is approximately equal to the K1 magnetocrystalline anisotropy constant of BaM, and compare it with a modeled value of applied elastic energy density. The comparison allowed us to judge the quality of the interfaces in the composite system, by roughly gauging the energy conversion ratio.

Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

PubMed

Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

2016-05-23

The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity

PubMed Central

Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

2016-01-01

Background/Objectives: The uroguanylin-GUCY2C gut–brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Subjects/Methods: Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ERT2-Rosa-STOPloxP/loxP-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. Results: DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. Conclusions: These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression

Parallel activation of Ca(2+)-induced survival and death pathways in cardiomyocytes by sorbitol-induced hyperosmotic stress.

PubMed

Chiong, M; Parra, V; Eisner, V; Ibarra, C; Maldonado, C; Criollo, A; Bravo, R; Quiroga, C; Contreras, A; Vicencio, J M; Cea, P; Bucarey, J L; Molgó, J; Jaimovich, E; Hidalgo, C; Kroemer, G; Lavandero, S

2010-08-01

Hyperosmotic stress promotes rapid and pronounced apoptosis in cultured cardiomyocytes. Here, we investigated if Ca(2+) signals contribute to this response. Exposure of cardiomyocytes to sorbitol [600 mosmol (kg water)(-1)] elicited large and oscillatory intracellular Ca(2+) concentration increases. These Ca(2+) signals were inhibited by nifedipine, Cd(2+), U73122, xestospongin C and ryanodine, suggesting contributions from both Ca(2+) influx through voltage dependent L-type Ca(2+) channels plus Ca(2+) release from intracellular stores mediated by IP(3) receptors and ryanodine receptors. Hyperosmotic stress also increased mitochondrial Ca(2+) levels, promoted mitochondrial depolarization, reduced intracellular ATP content, and activated the transcriptional factor cyclic AMP responsive element binding protein (CREB), determined by increased CREB phosphorylation and electrophoretic mobility shift assays. Incubation with 1 mM EGTA to decrease extracellular [Ca(2+)] prevented cardiomyocyte apoptosis induced by hyperosmotic stress, while overexpression of an adenoviral dominant negative form of CREB abolished the cardioprotection provided by 1 mM EGTA. These results suggest that hyperosmotic stress induced by sorbitol, by increasing Ca(2+) influx and raising intracellular Ca(2+) concentration, activates Ca(2+) release from stores and causes cell death through mitochondrial function collapse. In addition, the present results suggest that the Ca(2+) increase induced by hyperosmotic stress promotes cell survival by recruiting CREB-mediated signaling. Thus, the fate of cardiomyocytes under hyperosmotic stress will depend on the balance between Ca(2+)-induced survival and death pathways.

Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats

PubMed Central

Aricioglu, Feyza; Regunathan, Soundar

2010-01-01

Physiological stress evokes a number of responses, including a rise in body temperature, which has been suggested to be the result of an elevation in the thermoregulatory set point. This response seems to share similar mechanisms with infectious fever. The aim of the present study was to investigate the effect of agmatine on different models of stressors [(restraint and lipopolysaccaride (LPS)] on body temperature. Rats were either restrained for 4 h or injected with LPS, both of these stressors caused an increase in body temperature. While agmatine itself had no effect on body temperature, treatment with agmatine (20, 40, 80 mg/kg intraperitoneally) dose dependently inhibited stress- and LPS-induced hyperthermia. When agmatine (80 mg/kg) was administered 30 min later than LPS (500 μg/kg) it also inhibited LPS-induced hyperthermia although the effect became significant only at later time points and lower maximal response compared to simultaneous administration. To determine if the decrease in body temperature is associated with an anti-inflammatory effect of agmatine, the nitrite/nitrate levels in plasma was measured. Agmatine treatment inhibited LPS-induced production of nitrates dose dependently. As an endogenous molecule, agmatine has the capacity to inhibit stress- and LPS-induced increases in body temperature. PMID:15936786

Aneuploidy-induced cellular stresses limit autophagic degradation

PubMed Central

Santaguida, Stefano; Vasile, Eliza; White, Eileen; Amon, Angelika

2015-01-01

An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Aneuploid cells experience a number of stresses that are caused by aneuploidy-induced proteomic changes. How the aneuploidy-associated stresses affect cells and whether cells respond to them are only beginning to be understood. Here we show that autophagosomal cargo such as protein aggregates accumulate within lysosomes in aneuploid cells. This causes a lysosomal stress response. Aneuploid cells activate the transcription factor TFEB, a master regulator of autophagic and lysosomal gene expression, thereby increasing the expression of genes needed for autophagy-mediated protein degradation. Accumulation of autophagic cargo within the lysosome and activation of TFEB-responsive genes are also observed in cells in which proteasome function is inhibited, suggesting that proteotoxic stress causes TFEB activation. Our results reveal a TFEB-mediated lysosomal stress response as a universal feature of the aneuploid state. PMID:26404941

Exercise-Induced Oxidative Stress Responses in the Pediatric Population

PubMed Central

Avloniti, Alexandra; Chatzinikolaou, Athanasios; Deli, Chariklia K.; Vlachopoulos, Dimitris; Gracia-Marco, Luis; Leontsini, Diamanda; Draganidis, Dimitrios; Jamurtas, Athanasios Z.; Mastorakos, George; Fatouros, Ioannis G.

2017-01-01

Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty. PMID:28106721

Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

PubMed

Wang, Yongfu; Wu, Jing; Zhu, Bi; Li, Chaocui; Cai, Jing-Xia

2012-03-01

It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

The histaminergic system is involved in psychological stress-induced hyperthermia in rats.

PubMed

Lkhagvasuren, Battuvshin; Oka, Takakazu

2017-04-01

The histaminergic system modulates numerous physiological functions such as wakefulness, circadian rhythm, feeding, and thermoregulation. However, it is not yet known if this system is also involved in psychological stress-induced hyperthermia (PSH) and, if so, which histamine (H) receptor subtype mediates the effect. Therefore, we investigated the effects of pretreatments with intraperitoneal injections of mepyramine (an H1 receptor inverse agonist), cimetidine (an H2 receptor antagonist), and ciproxifan (an H3 receptor inverse agonist) on cage-exchange stress-induced hyperthermia (a model of PSH) by monitoring core body temperature ( T c ) during both light (10:00 am-12:00 pm) and dark (10:00 pm-12:00 am) phases in conscious, freely moving rats. We also investigated the effects of these drugs on stress-induced changes in locomotor activity ( L a ) to rule out the possibility that effects on T c are achieved secondary to altered L a Cage-exchange stress increased T c within 20 min followed by a gradual decrease back to baseline T c during both phases. In the light phase, mepyramine and cimetidine markedly attenuated PSH, whereas ciproxifan did not affect it. In contrast, in the dark phase, mepyramine dropped T c by 1 °C without affecting cage-exchange stress-induced hyperthermia, whereas cimetidine and ciproxifan did not affect both postinjection T c and PSH Cage-exchange stress induced an increase in L a , especially in the light phase, but none of these drugs altered cage-exchange stress-induced L a in either circadian rhythm phase. These results suggest that the histaminergic system is involved in the physiological mechanisms underlying PSH, particularly through H1 and H2 receptors, without influencing locomotor activity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride.

PubMed

Xiong, Cuiju; Chen, Dong; Liu, Jingbo; Liu, Bingqian; Li, Naiyang; Zhou, Yang; Liang, Xuanwei; Ma, Ping; Ye, Chengtian; Ge, Jian; Wang, Zhichong

2008-05-01

To establish a rabbit dry eye model with topical medication of the ocular preparation preservative benzalkonium chloride (BAC). Sixteen white rabbits were used. One eye of each rabbit was chosen randomly for topical administration of 0.1% BAC twice daily for 14 days. The other untreated eyes served as controls. Schirmer test, fluorescein, and rose bengal staining were performed before and after BAC treatment on days 3, 5, 7, and 14. Conjunctiva impression cytology specimens were collected on days 0, 7, and 14. The rabbits were killed after day 14. Immunofluorescence staining was performed to detect mucin-5 subtype AC (MUC5AC) on conjunctival cryosections. Cornea and conjunctiva structures were evaluated by light and electron microscopy. Compared with untreated controls, BAC-treated eyes showed significant decreases in Schirmer scores (P = 0.01) and increases in fluorescein scores (P < 0.001) on days 5, 7, and 14. A significant increase in rose bengal scores was noticed as early as day 3 (P = 0.001). Decreases in goblet cell density occurred on days 7 and 14 (P = 0.001). Decreased MUC5AC and histopathologic and ultrastructural disorders of the cornea and conjunctiva were also observed in the BAC group. These findings demonstrated that an ophthalmic preservative, benzalkonium chloride, induced a dry eye syndrome in rabbits with damage to the cornea and conjunctiva, decreased aqueous tear basal secretion, goblet cell loss, and MUC5AC deficiency. This rabbit model was consistent with human dry eye syndrome in both aqueous tear and mucin deficiency and may be appropriate for studying dry eye syndrome.

Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

PubMed

Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

2013-01-01

In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

PubMed

Ji, Cheng

2014-01-01

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation.

PubMed

Liu, W; Xu, Z; Li, H; Guo, M; Yang, T; Feng, S; Xu, B; Deng, Yu

2017-09-01

Mercury (Hg) represents a ubiquitous environmental heavy metal that could lead to severe toxic effects in a variety of organs usually at a low level. The present study focused on the liver oxidative stress, one of the most important roles playing in Hg hepatotoxicity, by evaluation of different concentrations of mercuric chloride (HgCl 2 ) administration. Moreover, the protective potential of curcumin against Hg hepatotoxic effects was also investigated. Eighty-four rats were randomly divided into six groups for a three-days experiment: control, dimethyl sulfoxide control, HgCl 2 treatment (0.6, 1.2, and 2.4 mg kg -1 day -1 ), and curcumin pretreatment (100 mg kg -1 day -1 ) groups. Exposure of HgCl 2 resulted in acute dose-dependent hepatotoxic effects. Administration of 2.4 mg kg -1 HgCl 2 significantly elevated total Hg, nonprotein sulfhydryl, reactive oxygen species formation, malondialdehyde, apoptosis levels, serum lactate dehydrogenase, and alanine transaminase activities, with an impairment of superoxide dismutase and glutathione peroxidase in the liver. Moreover, HgCl 2 treatment activated nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in further investigation, with a significant upregulation of Nrf2, heme oxygenase-1, and γ-glutamylcysteine synthetase heavy subunit expression, relative to control. Pretreatment with curcumin obviously prevented HgCl 2 -induced liver oxidative stress, which may be due to its free radical scavenging or Nrf2-ARE pathway-inducing properties. Taking together these data suggest that curcumin counteracts HgCl 2 hepatotoxicity through antagonizing liver oxidative stress.

Pentoxifylline prevents post-traumatic stress disorder induced memory impairment.

PubMed

Alzoubi, Karem H; Khabour, Omar F; Ahmed, Mohammed

2018-05-01

Posttraumatic stress disorder (PTSD) is a disabling prevalent and difficult-to-treat psychiatric disorder, which can develop after the exposure to severe traumatic events such as those occurring during wars and natural disasters. Pentoxifylline (PTX) is a potent antioxidant, which has an important role in prevention of cognitive dysfunctions. In the present study, the effect of PTX on memory impairment induced by PTSD was investigated using the rat animal model. PTSD-like behavior was induced in animals using a single-prolonged stress (SPS) rat model of PTSD (2 h restrain, 20 min forced swimming, 15 min rest, 1-2 min diethyl ether exposure). PTX was administered intraperitoneally at a dose of 100 mg/kg/day. Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers, brain derived neuroptrophic factor (BDNF), and epigenetics (histones) in the hippocampus following treatments were measured using enzymatic assays. The result revealed that SPS impaired both short- and long- term memory (P < 0.05). Use of PTX prevented memory impairment induced by SPS. Furthermore, PTX normalized SPS induced changes in the hippocampus GSH/GSSG ratio, activity of catalase, and glutathione peroxidase (GPx), BDNF, and certain histones levels. In conclusion, the SPS model of PTSD-like behavior induced memory impairment, whereas PTX prevented this impairment possibly through normalizing antioxidant mechanisms, BDNF and epigenetic changes in the hippocampus. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Cynodon dactylon on Stress-Induced Infertility in Male Rats

PubMed Central

Chidrawar, VR; Chitme, HR; Patel, KN; Patel, NJ; Racharla, VR; Dhoraji, NC; Vadalia, KR

2011-01-01

Cynodon dactylon (Family: Poaceae) is known to be a tackler in Indian mythology and is offered to Lord Ganesha. It is found everywhere, even on waste land, road side, dry places, and spreads vigorously on cultivated ground. This study was carried out with an objective to test if the constituents of this plant are useful in coping stress-induced sexual In this study, we considered immobilization stress to induce male infertility and the effect of C. dactylon in restoration of the dysfunction was evaluated by considering sexual behavioral observations, sexual performance, fructose content of the seminal vesicles, epididymal sperm concentration and histopathological examinations as parameters. Treatment of rats under stress with methanolic extract of C. dactylon has shown a promising effect in overcoming stress-induced sexual dysfunction, sexual performance, fructose content, sperm concentration and its effect on accessory sexual organs and body weight. We conclude that active constituents of C. dactylon present in methanolic extract have a potent aphrodisiac and male fertility activity. PMID:21607051

Time-course analysis of the Shewanella amazonensis SB2B proteome in response to sodium chloride shock.

PubMed

Parnell, J Jacob; Callister, Stephen J; Rompato, Giovanni; Nicora, Carrie D; Paša-Tolić, Ljiljana; Williamson, Ashley; Pfrender, Michael E

2011-01-01

Shewanellae are microbial models for environmental stress response; however, the sequential expression of mechanisms in response to stress is poorly understood. Here we experimentally determine the response mechanisms of Shewanella amazonensis SB2B during sodium chloride stress using a novel liquid chromatography and accurate mass-time tag mass spectrometry time-course proteomics approach. The response of SB2B involves an orchestrated sequence of events comprising increased signal transduction associated with motility and restricted growth. Following a metabolic shift to branched chain amino acid degradation, motility and cellular replication proteins return to pre-perturbed levels. Although sodium chloride stress is associated with a change in the membrane fatty acid composition in other organisms, this is not the case for SB2B as fatty acid degradation pathways are not expressed and no change in the fatty acid profile is observed. These findings suggest that shifts in membrane composition may be an indirect physiological response to high NaCl stress.

[Jejunal myenteric denervation induced by benzalkonium chloride].

PubMed

Ramalho, F S; Santos, G C; Ramalho, L N; Kajiwara, J K; Zucoloto, S

1994-01-01

The effects of benzalkonium chloride (BAC) on the number of myenteric neurons, muscle thickness and external perimeter after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied along the time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase. Myenteric denervation increased the thickness of the propria muscle layer, especially in the longitudinal muscle layer, suggesting a higher sensitivity of this layer to myenteric denervation.

Stress reduction in an isotropic plate with a hole by applied induced strains

NASA Technical Reports Server (NTRS)

Sensharma, Pradeep K.; Palantera, Markku J.; Haftka, Raphael T.

1992-01-01

Recently there has been much interest in adaptive structures that can respond to a varying environment by changing their properties. Shape memory alloys and piezoelectric materials can be used as induced strain actuators to reduce stresses in the regions of stress concentration. The objective of the work was to find the maximum possible reduction in the stress concentration factor in an isotropic plate with a hole by applying induced strains in a small area near the hole. Induced strains were simulated by thermal expansion.

Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome.

PubMed

Alcocer-Gómez, Elísabet; Ulecia-Morón, Cristina; Marín-Aguilar, Fabiola; Rybkina, Tatyana; Casas-Barquero, Nieves; Ruiz-Cabello, Jesús; Ryffel, Bernhard; Apetoh, Lionel; Ghiringhelli, François; Bullón, Pedro; Sánchez-Alcazar, José Antonio; Carrión, Angel M; Cordero, Mario D

2016-09-01

Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients.

Effect of chloride contamination in MON-1 propellant on crack growth properties of metals

NASA Technical Reports Server (NTRS)

Moran, C. M.; Toth, L. R.

1981-01-01

The effect of a high level of chloride content (800 ppm) in MON-1 propellant on the crack growth properties of seven materials was investigated. Sustained load tests were conducted at 49 C (120 F) temperature with thin gauge tensile specimens having a semi-elliptical surface flaw. Alloys included aluminum 1100, 3003, 5086 and 6061; corrosion resistant steel types A286 and 347; and titanium 6Al-4V. The configurations tested with precracked flaws exposed to MON-1 were: parent or base metal, center weld, and heat affected zone. It was concluded that this chloride level in MON-1 does not affect the stress corrosion, crack growth properties of these alloys after 1000 hour exposure duration under high stresses.

Modified natural porcine surfactant modulates tobacco smoke-induced stress response in human monocytes.

PubMed

Pinot, F; Bachelet, M; François, D; Polla, B S; Walti, H

1999-01-01

Tobacco smoke (TS) is a potent source of oxidants and oxidative stress is an important mechanism by which TS exerts its toxicity in the lung. We have shown that TS induces heat shock (HS)/stress protein (HSP) synthesis in human monocytes. Pulmonary surfactant (PS) whose major physiological function is to confer mechanical stability to alveoli, also modulates oxidative metabolism and other pro-inflammatory functions of monocytes-macrophages. In order to determine whether PS alters the stress response induced by TS, we incubated human peripheral blood monocytes overnight with modified natural porcine surfactant (Curosurf) (1 mg/ml) before exposure to TS. Curosurf decreased TS-induced, but not HS-induced, expression of the major cytosolic, inducible 72 kD HSP (Hsp70). Furthermore, TS-generated superoxide anions production was significantly decreased by Curosurf in an acellular system, suggesting a direct scavenging effect of PS. We also examined the effects of TS and PS on monocytes ultrastructure. Monocytes incubated with Curosurf presented smoother cell membranes than control monocytes, while TS-induced monocyte vacuolization was, at least in part, prevented by Curosurf. Taken together, our data suggest that PS plays a protective role against oxygen radical-mediated, TS-induced cellular stress responses.

Attenuation and cross-attenuation in taste-aversion learning in the rat: Studies with ionizing radiation, lithium chloride, and ethanol. Scientific report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1989-01-01

The pre-exposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride, and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired pre-exposures to lithium chloride blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiationmore » or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.« less

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

PubMed

Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

2015-01-01

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

Efficient sweat reduction of three different antiperspirant application forms during stress-induced sweating.

PubMed

Schmidt-Rose, T; Lehmbeck, F; Bürger, A; Windisch, B; Keyhani, R; Max, H

2013-12-01

Stress sweating can occur in everyday situations independently of thermally-induced perspiration. It is triggered by emotionally challenging situations and leads to underarm wetness and a characteristic unpleasant malodor. In this study, we aimed to determine the long-term efficacy of three unperfumed antiperspirant (AP) formulas for different application forms (roll-on, stick, aerosol) against stress-induced sweating and malodor formation. We utilized the widely accepted Trier Social Stress Test (TSST) to induce psychosocial stress in female and male volunteers (18 - 40 years) and determined physiological stress parameters. To additionally assess the efficacy of the test AP roll-on against thermally-induced sweating, a hot room study was performed. Increasing heart rates and an augmentation of saliva cortisol levels during the TSST indicated a substantial stress reaction which was paralleled by a pronounced sweat production in the untreated axillae of both males and females. Forty-eight hours after application, all three test APs significantly decreased the amount of sweat in the treated axillae independent of gender. With respect to AP effects on malodor production, trained sniffers assessed sweat samples collected during the TSST from the untreated axillae as significantly more malodorous than comparable samples from the AP-treated axillae. Also, independent of gender the test AP roll-on significantly decreased the thermally-induced sweat in the AP-treated axilla. We show for the first time a highly effective reduction of emotionally-induced axillary sweating and malodor production for three different application forms 48 h after the last product use. The specially developed roll-on, stick, and aerosol AP provide long-term protection against stress-induced sweat which is of high relevance in everyday life. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Acute Stress-Induced Epigenetic Modulations and Their Potential Protective Role Toward Depression.

PubMed

Rusconi, Francesco; Battaglioli, Elena

2018-01-01

Psychiatric disorders entail maladaptive processes impairing individuals' ability to appropriately interface with environment. Among them, depression is characterized by diverse debilitating symptoms including hopelessness and anhedonia, dramatically impacting the propensity to live a social and active life and seriously affecting working capability. Relevantly, besides genetic predisposition, foremost risk factors are stress-related, such as experiencing chronic psychosocial stress-including bullying, mobbing and abuse-, and undergoing economic crisis or chronic illnesses. In the last few years the field of epigenetics promised to understand core mechanisms of gene-environment crosstalk, contributing to get into pathogenic processes of many disorders highly influenced by stressful life conditions. However, still very little is known about mechanisms that tune gene expression to adapt to the external milieu. In this Perspective article, we discuss a set of protective, functionally convergent epigenetic processes induced by acute stress in the rodent hippocampus and devoted to the negative modulation of stress-induced immediate early genes (IEGs) transcription, hindering stress-driven morphostructural modifications of corticolimbic circuitry. We also suggest that chronic stress damaging protective epigenetic mechanisms, could bias the functional trajectory of stress-induced neuronal morphostructural modification from adaptive to maladaptive, contributing to the onset of depression in vulnerable individuals. A better understanding of the epigenetic response to stress will be pivotal to new avenues of therapeutic intervention to treat depression, especially in light of limited efficacy of available antidepressant drugs.

Inheritance of stress-induced, ATF-2-dependent epigenetic change.

PubMed

Seong, Ki-Hyeon; Li, Dong; Shimizu, Hideyuki; Nakamura, Ryoichi; Ishii, Shunsuke

2011-06-24

Atf1, the fission yeast homolog of activation transcription factor-2 (ATF-2), contributes to heterochromatin formation. However, the role of ATF-2 in chromatin assembly in higher organisms remains unknown. This study reveals that Drosophila ATF-2 (dATF-2) is required for heterochromatin assembly, whereas the stress-induced phosphorylation of dATF-2, via Mekk1-p38, disrupts heterochromatin. The dATF-2 protein colocalized with HP1, not only on heterochromatin but also at specific loci in euchromatin. Heat shock or osmotic stress induced phosphorylation of dATF-2 and resulted in its release from heterochromatin. This heterochromatic disruption was an epigenetic event that was transmitted to the next generation in a non-Mendelian fashion. When embryos were exposed to heat stress over multiple generations, the defective chromatin state was maintained over multiple successive generations, though it gradually returned to the normal state. The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure. Copyright © 2011 Elsevier Inc. All rights reserved.

Dynamic [Cl-]i measurement with chloride sensing quantum dots nanosensor in epithelial cells

NASA Astrophysics Data System (ADS)

Wang, Yuchi; Mao, Hua; Wong, Lid B.

2010-02-01

We have synthesized a chloride sensing quantum dots (QD) nanosensor, Cl-QD, for the dynamic measurements of chloride ion concentration in the millimolar range, a sensitivity that is applicable to most physiological intracellular chloride ion concentration ([Cl-]i) measurements in epithelial cells. The Cl-QD is synthesized by conjugating an anion receptor, 1-(2-mercapto-ethyl)-3-phenyl-thiourea (MEPTU) to a water soluble CdSe/ZnS QD at an emission wavelength of 620 nm. Upon binding of chloride ions to the Cl-QD, a photo-induced electron transfer mechanism caused the fluorescence of the QD to quench. This resulted in an inversely proportional relationship between the chloride ion concentration and the fluorescence intensity of the Cl-QD. We have utilized this Cl-QD to measure [Cl-]i in T84 and CF-PAC cultured cells, with either the C1C-2 or CFTR chloride channels being manipulated by pharmacological chloride channel activators and inhibitors. Activations of C1C-2 and CFTR chloride channels in T84 by the respective lubiprostone and genistein caused predictive increases in the fluorescence of the Cl-QD, i.e., a decrease of [Cl-]i. Conversely, glibenclamide, a chloride channel inhibitor, applied to the CF-PAC cells caused a predictable decrease in the fluorescence of Cl-QD due to the increase of [Cl-]i. These are the first data in using QD-based chloride ion sensors for dynamic measurements of intracellular chloride ion concentrations in epithelial cells.

Potato plants (Solanum tuberosum L.) are chloride-sensitive: Is this dogma valid?

PubMed

Hütsch, Birgit W; Keipp, Katrin; Glaser, Ann-Kathrin; Schubert, Sven

2018-06-01

Chloride sensitivity of the potato (Solanum tuberosum L.) cultivars Marabel and Désirée was investigated in two pot experiments (soil/sand mixture and hydroponics). It was tested whether there are differential effects of KCl and K 2 SO 4 application on tuber yield and tuber quality, and whether both potato cultivars differ in their chloride sensitivity. Tuber yield, dry matter percentage of the tubers, starch concentration and starch yield were not significantly affected by potassium source (K 2 SO 4 or KCl). After exposure to salt stress in hydroponics (100 mmol L -1 NaCl, 50 mmol L -1 Na 2 SO 4 , 50 mmol L -1 CaCl 2 ) for 5 days, 3-week-old potato plants had significantly reduced shoot dry mass after NaCl and Na 2 SO 4 application. However, CaCl 2 treatment did not significantly affect shoot growth, although the chloride concentration reached 65 to 74 mg Cl - mg -1 dry matter, similar to the NaCl treatment. In contrast, growth reductions were closely related to sodium concentrations, thus plants suffered sodium toxicity and not chloride toxicity. Both potato cultivars are chloride-resistant and can be fertilised with KCl instead of K 2 SO 4 without the risk of depression in tuber yield or tuber quality. The statement that potatoes are chloride-sensitive and that chloride has negative effects on yield performance needs reconsideration. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence.

PubMed

Potenza, Marc N; Hong, Kwang-ik Adam; Lacadie, Cheryl M; Fulbright, Robert K; Tuit, Keri L; Sinha, Rajita

2012-04-01

Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.

Electrically-induced stresses and deflection in multiple plates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Jih-Perng; Tichler, P.R.

Thermohydraulic tests are being planned at the High Flux Beam Reactor of Brookhaven National Laboratory, in which direct electrical heating of metal plates will simulate decay heating in parallel plate-type fuel elements. The required currents are high if plates are made of metal with a low electrical resistance, such as aluminum. These high currents will induce either attractive or repulsive forces between adjacent current-carrying plates. Such forces, if strong enough, will cause the plates to deflect and so change the geometry of the coolant channel between the plates. Since this is undesirable, an analysis has been made to evaluate themore » magnitude of the deflection and related stresses. In contrast to earlier publications in which either a concentrated or a uniform load was assumed, in this paper an exact force distribution on the plate is analytically solved and then used for stress and deflection calculations, assuming each plate to be a simply supported beam. Results indicate that due to superposition of the induced forces between plates in a multiple-and-parallel plate array, the maximum deflection and bending stress occur at the midpoint of the outermost plate. The maximum shear stress, which is inversely proportional to plate thickness, occurs at both ends of the outermost plate.« less

Electrically-induced stresses and deflection in multiple plates

NASA Astrophysics Data System (ADS)

Hu, Jih-Perng; Tichler, P. R.

1992-04-01

Thermohydraulic tests are being planned at the High Flux Beam Reactor of Brookhaven National Laboratory, in which direct electrical heating of metal plates will simulate decay heating in parallel plate-type fuel elements. The required currents are high if plates are made of metal with a low electrical resistance, such as aluminum. These high currents will induce either attractive or repulsive forces between adjacent current-carrying plates. Such forces, if strong enough, will cause the plates to deflect and so change the geometry of the coolant channel between the plates. Since this is undesirable, an analysis was made to evaluate the magnitude of the deflection and related stresses. In contrast to earlier publications in which either a concentrated or a uniform load was assumed, in this paper an exact force distribution on the plate is analytically solved and then used for stress and deflection calculations, assuming each plate to be a simply supported beam. Results indicate that due to superposition of the induced forces between plates in a multiple-and-parallel plate array, the maximum deflection and bending stress occur at the midpoint of the outermost plate. The maximum shear stress, which is inversely proportional to plate thickness, occurs at both ends of the outermost plate.

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

PubMed

Jangra, Ashok; Sriram, Chandra Shaker; Dwivedi, Shubham; Gurjar, Satendra Singh; Hussain, Md Iftikar; Borah, Probodh; Lahkar, Mangala

2017-01-01

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

Patterns of Sympathetic Responses Induced by Different Stress Tasks

PubMed Central

Fechir, M; Schlereth, T; Purat, T; Kritzmann, S; Geber, C; Eberle, T; Gamer, M; Birklein, F

2008-01-01

Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks. Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and – as a control – neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale. All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction. Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research. PMID:19018304

Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced mouse dry eye model.

PubMed

Zhang, Zhen; Yang, Wen-Zhao; Zhu, Zhen-Zhen; Hu, Qian-Qian; Chen, Yan-Feng; He, Hui; Chen, Yong-Xiong; Liu, Zu-Guo

2014-05-06

We investigated the therapeutic effects and underlying mechanisms of topical doxycycline in a benzalkonium chloride (BAC)-induced mouse dry eye model. Eye drops containing 0.025%, 0.1% doxycycline or solvent were administered to a BAC-induced dry eye model four times daily. The clinical evaluations, including tear break-up time (BUT), fluorescein staining, inflammatory index, and tear volume, were performed on days 0, 1, 4, 7, and 10. Global specimens were collected on day 10 and processed for immunofluorescent staining, TUNEL, and periodic acid-Schiff assay. The levels of inflammatory mediators in the corneas were determined by real-time PCR. The total and phosphorylated nuclear factor-κB (NF-κB) were detected by Western blot. Both 0.025% and 0.1% doxycycline treatments resulted in increased BUT, lower fluorescein staining scores, and inflammatory index on days 4, 7, and 10, while no significant change in tear volume was observed. The 0.1% doxycycline-treated group showed more improvements in decreasing fluorescein staining scores, increasing Ki-67-positive cells, and decreasing TUNEL- and keratin-10-positive cells than other groups. The mucin-filled goblet cells in conjunctivas were increased, and the expression of CD11b and levels of matrix metalloproteinase-9, IL-1β, IL-6, TNF-α, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant in corneas were decreased in both doxycycline-treated groups. In addition, doxycycline significantly reduced the phosphorylation of NF-κB activated in the BAC-treated corneas. Topical doxycycline showed clinical improvements and alleviated ocular surface inflammation on BAC-induced mouse dry eye, suggesting a potential as an anti-inflammatory agent in the clinical treatment of dry eye.

Chronic mild stress facilitates melanoma tumor growth in mouse lines selected for high and low stress-induced analgesia.

PubMed

Ragan, Agnieszka R; Lesniak, Anna; Bochynska-Czyz, Marta; Kosson, Anna; Szymanska, Hanna; Pysniak, Kazimiera; Gajewska, Marta; Lipkowski, Andrzej W; Sacharczuk, Mariusz

2013-09-01

Both chronic stress conditions and hyperergic reaction to environmental stress are known to enhance cancer susceptibility. We described two mouse lines that displayed high (HA) and low (LA) swim stress-induced analgesia (SSIA) to investigate the relationship between inherited differences in sensitivity to stress and proneness to an increased growth rate of subcutaneously inoculated melanoma. These lines display several genetic and physiological differences, among which distinct sensitivity to mutagens and susceptibility to cancer are especially noticeable. High analgesic mice display high proneness both to stress and a rapid local spread of B16F0 melanoma. However, stress-resistant LA mice do not develop melanoma tumors after inoculation, or if so, tumors regress spontaneously. We found that the chronic mild stress (CMS) procedure leads to enhanced interlinear differences in melanoma susceptibility. Tumors developed faster in stress conditions in both lines. However, LA mice still displayed a tendency for spontaneous regression, and 50% of LA mice did not develop a tumor, even under stressed conditions. Moreover, we showed that chronic stress, but not tumor progression, induces depressive behavior, which may be an important clue in cancer therapy. Our results clearly indicate how the interaction between genetic susceptibility to stress and environmental stress determine the risk and progression of melanoma. To our knowledge, HA/LA mouse lines are the first animal models of distinct melanoma progression mediated by inherited differences in stress reactivity.

Individual differences in the locus coeruleus-norepinephrine system: relevance to stress-induced cardiovascular vulnerability

PubMed Central

Wood, Christopher S.; Valentino, Rita J.; Wood, Susan K.

2016-01-01

Repeated exposure to psychosocial stress is a robust sympathomimetic stressor and as such has adverse effects on cardiovascular health. While the neurocircuitry involved remains unclear, the physiological and anatomical characteristics of the locus coeruleus (LC)-norepinephrine (NE) system suggest that it is poised to contribute to stress-induced cardiovascular vulnerability. A major theme throughout is to review studies that shed light on the role that the LC may play in individual differences in vulnerability to social stress-induced cardiovascular dysfunction. Recent findings are discussed that support a unique plasticity in afferent regulation of the LC, resulting in either excitatory or inhibitory input to the LC during establishment of different stress coping strategies. This contrasting regulation of the LC by either afferent regulation, or distinct differences in stress-induced neuroinflammation would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The goal of this review is to highlight recent developments in the interplay between the LC-NE and cardiovascular systems during repeated stress in an effort to advance therapeutic treatments for the development of stress-induced cardiovascular vulnerability. PMID:27423323

Surface aspects of pitting and stress corrosion cracking

NASA Technical Reports Server (NTRS)

Truhan, J. S., Jr.; Hehemann, R. F.

1977-01-01

The pitting and stress corrosion cracking of a stable austenitic stainless steel in aqueous chloride environments were investigated using a secondary ion mass spectrometer as the primary experimental technique. The surface concentration of hydrogen, oxygen, the hydroxide, and chloride ion, magnesium or sodium, chromium and nickel were measured as a function of potential in both aqueous sodium chloride and magnesium chloride environments at room temperature and boiling temperatures. It was found that, under anodic conditions, a sharp increase in the chloride concentration was observed to occur for all environmental conditions. The increase may be associated with the formation of an iron chloride complex. Higher localized chloride concentrations at pits and cracks were also detected with an electron microprobe.

Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.

PubMed

Lombardi, Angela; Inabnet, William Barlow; Owen, Randall; Farenholtz, Kaitlyn Ellen; Tomer, Yaron

2015-01-01

Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

PubMed Central

Riad, Sandra; Bougherara, Habiba

2015-01-01

Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

Bicarbonate secretion and chloride absorption by rabbit cortical collecting ducts. Role of chloride/bicarbonate exchange.

PubMed Central

Star, R A; Burg, M B; Knepper, M A

1985-01-01

Cortical collecting ducts (CCD) from rabbits treated with deoxycorticosterone (DOC) actively secrete bicarbonate at high rates. To investigate the mechanism of bicarbonate secretion, we measured bicarbonate and chloride transport in CCD from rabbits treated with DOC for 9-24 d. Removal of chloride (replaced with gluconate) from both perfusate and bath inhibited bicarbonate secretion without changing transepithelial voltage. Removal of chloride only from the bath increased bicarbonate secretion, while removal of chloride only from the perfusate inhibited secretion. In contrast to the effect of removing chloride, removal of sodium from both the perfusate and bath (replacement with N-methyl-D-glucamine) did not change the rate of bicarbonate secretion. The rate of bicarbonate secretion equaled the rate of chloride absorption in tubules bathed with 0.1 mM ouabain to inhibit any cation-dependent chloride transport. Under these conditions, chloride absorption occurred against an electrochemical gradient. Removal of bicarbonate from both the perfusate and bath inhibited chloride absorption. Removal of bicarbonate only from the bath inhibited chloride absorption, while removal of bicarbonate from the lumen stimulated chloride absorption. We conclude that CCD from DOC-treated rabbits actively secrete bicarbonate and actively absorb chloride by an electroneutral mechanism involving 1:1 chloride/bicarbonate exchange. The process is independent of sodium. PMID:3930570

Cobalt chloride administration in athletes: a new perspective in blood doping?

PubMed

Lippi, G; Franchini, M; Guidi, G C

2005-11-01

Blood doping is an illegal and unfair way of enhancing athletic performance by increasing the oxygen carrying capacity of the blood. Currently used methods usually involve stimulation of erythropoiesis. Gene therapy targeting the hypoxia inducible factor pathway may be an attractive alternative to traditional blood doping techniques. Hypoxia activates a large number of genes with essential roles in cell and tissue adaptation to low oxygen. Cobalt chloride is a well established chemical inducer of hypoxia-like responses such as erythropoiesis. Cobalt supplementation is not banned and therefore would not be detected by current anti-doping testing. Although there is as yet no direct or anecdotal evidence of cobalt chloride administration to athletes, its use should be warned against as being not only unfair but potentially dangerous.

Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

PubMed