Blood pressure, magnesium and other mineral balance in two rat models of salt-sensitive, induced hypertension: effects of a non-peptide angiotensin II receptor type 1 antagonist.

Science.gov (United States)

Rondón, Lusliany Josefina; Marcano, Eunice; Rodríguez, Fátima; del Castillo, Jesús Rafael

2014-01-01

The renin-angiotensin system is critically involved in regulating arterial blood pressure (BP). Inappropriate angiotensin type-1 receptor activation by angiotensin-II (Ang-II) is related to increased arterial BP. Mg has a role in BP; it can affect cardiac electrical activity, myocardial contractility, and vascular tone. To evaluate the relationship between high BP induced by a high sodium (Na) diet and Mg, and other mineral balances, two experimental rat models of salt-sensitive, induced-hypertension were used: Ang-II infused and Dahl salt-sensitive (SS) rats. We found that: 1) Ang-II infusion progressively increased BP, which was accompanied by hypomagnesuria and signs of secondary hyperaldosteronism; 2) an additive effect between Ang-II and a high Na load may have an effect on strontium (Sr), zinc (Zn) and copper (Cu) balances; 3) Dahl SS rats fed a high Na diet had a slow pressor response, accompanied by altered Mg, Na, potassium (K), and phosphate (P) balances; and 4) losartan prevented BP increases induced by Ang II-NaCl, but did not modify mineral balances. In Dahl SS rats, losartan attenuated high BP and ameliorated magnesemia, Na and K balances. Mg metabolism maybe considered a possible defect in this strain of rat that may contribute to hypertension.

Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study

Energy Technology Data Exchange (ETDEWEB)

Rodríguez-Pérez, A.S.; López-Rodríguez, J.F.; Calvo-Turrubiartes, M.Z. [Integrative Physiology Laboratory, Department of Physiology and Biophysics, San Luis Potosí (Mexico); Saavedra-Alanís, V.M. [Molecular Biology Laboratory, Department of Biochemistry, San Luis Potosí (Mexico); Llamazares-Azuara, L. [Autonomous University of San Luis Potosí, Renal Laboratory, Faculty of Medicine, San Luis Potosí (Mexico); Rodríguez-Martínez, M. [Integrative Physiology Laboratory, Department of Physiology and Biophysics, San Luis Potosí (Mexico)

2013-10-02

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

GPER activation ameliorates aortic remodeling induced by salt-sensitive hypertension.

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Liu, Liu; Kashyap, Shreya; Murphy, Brennah; Hutson, Dillion D; Budish, Rebecca A; Trimmer, Emma H; Zimmerman, Margaret A; Trask, Aaron J; Miller, Kristin S; Chappell, Mark C; Lindsey, Sarah H

2016-04-15

The mRen2 female rat is an estrogen- and salt-sensitive model of hypertension that reflects the higher pressure and salt sensitivity associated with menopause. We previously showed that the G protein-coupled estrogen receptor (GPER) mediates estrogenic effects in this model. The current study hypothesized that GPER protects against vascular injury during salt loading. Intact mRen2 female rats were fed a normal (NS; 0.5% Na(+)) or high-salt diet (HS; 4% Na(+)) for 10 wk, which significantly increased systolic blood pressure (149 ± 5 vs. 224 ± 8 mmHg;PTreatment with the selective GPER agonist G-1 for 2 wk did not alter salt-sensitive hypertension (216 ± 4 mmHg;P> 0.05) or ex vivo vascular responses to angiotensin II or phenylephrine (P> 0.05). However, G-1 significantly attenuated salt-induced aortic remodeling assessed by media-to-lumen ratio (NS: 0.43; HS+veh: 0.89; HS+G-1: 0.61;P< 0.05). Aortic thickening was not accompanied by changes in collagen, elastin, or medial proliferation. However, HS induced increases in medial layer glycosaminoglycans (0.07 vs. 0.42 mm(2);P< 0.001) and lipid peroxidation (0.11 vs. 0.51 mm(2);P< 0.01), both of which were reduced by G-1 (0.20 mm(2)and 0.23 mm(2); both P< 0.05). We conclude that GPER's beneficial actions in the aorta of salt-loaded mRen2 females occur independently of changes in blood pressure and vasoreactivity. GPER-induced attenuation of aortic remodeling was associated with a reduction in oxidative stress and decreased accumulation of glycosaminoglycans. Endogenous activation of GPER may protect females from salt- and pressure-induced vascular damage. Copyright © 2016 the American Physiological Society.

Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

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Takakura, Kentaro; Ito, Shogo; Sonoda, Junya; Tabata, Koji; Shiozaki, Motoko; Nagai, Kaoru; Shibata, Masahiro; Koike, Masato; Uchiyama, Yasuo; Gotow, Takahiro

2017-01-01

The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to â¼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of ...

Hydronephrosis causes salt-sensitive hypertension and impaired renal concentrating ability in mice

DEFF Research Database (Denmark)

Carlström, M; Sällström, J; Skøtt, O

2007-01-01

AIM: Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms...... are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension. METHODS: PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate...... salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 +/- 1 mmHg on normal salt diet to 120 +/- 2 mmHg on high salt diet, compared with 103 +/- 1 to 104 +/- 1 in controls. Hydronephrotic animals showed increased...

Free radical scavenging reverses fructose-induced salt-sensitive hypertension

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Zenner ZP

2017-12-01

Full Text Available Zachary P Zenner, Kevin L Gordish, William H Beierwaltes Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA Abstract: We have previously reported that a moderate dietary supplementation of 20% fructose but not glucose leads to a salt-sensitive hypertension related to increased proximal sodium–hydrogen exchanger activity and increased renal sodium retention. We also found that while high salt increased renal nitric oxide formation, this was retarded in the presence of fructose intake. We hypothesized that at least part of the pathway leading to fructose-induced salt-sensitive hypertension could be due to fructose-induced formation of reactive oxygen species and inappropriate stimulation of renin secretion, all of which would contribute to an increase in blood pressure. We found that both 20% fructose intake and a high-salt diet stimulated 8-isoprostane excretion. The superoxide dismutase (SOD mimetic tempol significantly reduced this elevated excretion. Next, we placed rats on a high-salt diet (4% for 1 week in combination with normal rat chow or 20% fructose with or without chronic tempol administration. A fructose plus high-salt diet induced a rapid increase (15 mmHg in systolic blood pressure and reversed high salt suppression of plasma renin activity. Tempol treatment reversed the pressor response and restored high salt suppression of renin. We conclude that fructose-induced salt-sensitive hypertension is driven by increased renal reactive oxygen species formation associated with salt retention and an enhanced renin–angiotensin system. Keywords: reactive oxygen species, tempol, sodium, renin, oxidative stress

Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide.

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Gordish, Kevin L; Kassem, Kamal M; Ortiz, Pablo A; Beierwaltes, William H

2017-04-01

Previously, we reported that 20% fructose diet causes salt-sensitive hypertension. In this study, we hypothesized that a high salt diet supplemented with 20% fructose (in drinking water) stimulates salt-sensitive hypertension by increasing salt retention through decreasing renal nitric oxide. Rats in metabolic cages consumed normal rat chow for 5 days (baseline), then either: (1) normal salt for 2 weeks, (2) 20% fructose in drinking water for 2 weeks, (3) 20% fructose for 1 week, then fructose + high salt (4% NaCl) for 1 week, (4) normal chow for 1 week, then high salt for 1 week, (5) 20% glucose for 1 week, then glucose + high salt for 1 week. Blood pressure, sodium excretion, and cumulative sodium balance were measured. Systolic blood pressure was unchanged by 20% fructose or high salt diet. 20% fructose + high salt increased systolic blood pressure from 125 ± 1 to 140 ± 2 mmHg ( P  fructose + high salt than either high salt, or glucose + high salt (114.2 ± 4.4 vs. 103.6 ± 2.2 and 98.6 ± 5.6 mEq/Day19; P  fructose + high salt group compared to high salt only: 5.33 ± 0.21 versus 7.67 ± 0.31 mmol/24 h; P  fructose + high salt group (2139 ± 178  μ mol /24 hrs P  fructose predisposes rats to salt-sensitivity and, combined with a high salt diet, leads to sodium retention, increased blood pressure, and impaired renal nitric oxide availability. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Uninephrectomy in young age or chronic salt loading causes salt-sensitive hypertension in adult rats

DEFF Research Database (Denmark)

Carlström, Mattias; Sällström, Johan; Skøtt, Ole

2007-01-01

animals raised with normal-salt diet (UNX) or high-salt diet (UNX+HS). In the adult animals, renal and cardiovascular functions were evaluated and blood pressure recorded telemetrically under different sodium conditions (normal, high, and low). Hypertension was present in UNX+HS (122+/-9 mm Hg), UNX (101......+/-3 mm Hg), and HS (96+/-1 mm Hg) groups on normal-salt diets compared with the controls (84+/-2 mm Hg), and the blood pressure was salt sensitive (high- versus normal-salt diet; 23+/-3, 9+/-2, 7+/-2, and 1+/-1 mm Hg, respectively). The hypertensive groups (UNX+HS, UNX, and HS) had increased diuresis......The importance of nephron endowment and salt intake for the development of hypertension is under debate. The present study was designed to investigate whether reduced nephron number, after completion of nephrogenesis, or chronic salt loading causes renal injury and salt-sensitive hypertension...

High salt loading induces urinary storage dysfunction via upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt-sensitive rats

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Seiji Yamamoto

2017-11-01

Full Text Available We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC by using Dahl salt-resistant (DR and salt-sensitive (DS rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period. Cystometrogram showed the intercontraction intervals (ICI were significantly shorter in DS + HS group than in DR + HS group during infusion of saline. Subsequent infusion of amiloride significantly prolonged ICI in DS + HS group, while no intra-group difference in ICI was observed in DR + HS group. No intra- or inter-group differences in maximum intravesical pressure were observed. Protein expression levels of ENaCα in the bladder were significantly higher in DS + HS group than in DR + HS group. ENaCα protein was localized at bladder epithelium in both groups. In conclusion, high salt intake is considered to cause urinary storage dysfunction via upregulation of ENaC in the bladder epithelium with salt-sensitive hypertension, suggesting that ENaC might be a candidate for therapeutic target for urinary storage dysfunction.

High-Salt Intake Suppressed MicroRNA-133a Expression in Dahl SS Rat Myocardium

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Guo, Tong-Shuai; Zhang, Jie; Mu, Jian-Jun; Liu, Fu-Qiang; Yuan, Zu-Yi; Ren, Ke-Yu; Wang, Dan

2014-01-01

Salt-sensitive individuals show earlier and more serious cardiac damage than nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to investigate the different functions of high-salt intake on salt-sensitive (SS) rats and Sprague-Dawley (SD) rats and the involvement of microRNA-133a in these roles. After high-salt intervention, the left ventricular mass (LVW) and left ventricular mass index (LVMI) of the salt-sensitive high salt (SHS) group were obviously higher than those of the salt-sensitive low salt (SLS) group. However, the difference between the Sprague-Dawley high salt (DHS) group and the Sprague-Dawley low salt (DLS) group was not significant. Compared with SLS group, collagen I and connective tissue growth factor (CTGF) in the heart of SHS group were significantly higher, whereas no statistical difference was observed between the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in the heart of both strains were significantly decreased, but that in the SHS group decreased more significantly. These results suggest that high salt intervention could down-regulate the expression of myocardial microRNA-133a, which may be one of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension. PMID:24937684

High-Salt Intake Suppressed MicroRNA-133a Expression in Dahl SS Rat Myocardium

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Tong-Shuai Guo

2014-06-01

Full Text Available Salt-sensitive individuals show earlier and more serious cardiac damage than nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to investigate the different functions of high-salt intake on salt-sensitive (SS rats and Sprague-Dawley (SD rats and the involvement of microRNA-133a in these roles. After high-salt intervention, the left ventricular mass (LVW and left ventricular mass index (LVMI of the salt-sensitive high salt (SHS group were obviously higher than those of the salt-sensitive low salt (SLS group. However, the difference between the Sprague-Dawley high salt (DHS group and the Sprague-Dawley low salt (DLS group was not significant. Compared with SLS group, collagen I and connective tissue growth factor (CTGF in the heart of SHS group were significantly higher, whereas no statistical difference was observed between the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in the heart of both strains were significantly decreased, but that in the SHS group decreased more significantly. These results suggest that high salt intervention could down-regulate the expression of myocardial microRNA-133a, which may be one of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension.

Sodium pump activity and calcium relaxation in vascular smooth muscle of deoxycorticosterone acetate-salt rats

International Nuclear Information System (INIS)

Soltis, E.E.; Field, F.P.

1986-01-01

The Na + -K + pump activity was determined in femoral arterial smooth muscle from deoxycorticosterone acetate (DOCA)-salt hypertensive rats using potassium relaxation and ouabain-sensitive 86 Rb uptake as indices. The membrane-stabilizing effect of calcium and its relation to Na + -K + pump activity also were examined. Femoral arteries from DOCA-salt rats exhibited a greater relaxation in response to potassium addition after contraction with norepinephrine in a low potassium (0.6 mM) Krebs solution. The concentration of potassium required to produce a 50% relaxation was significantly less in DOCA-salt rats. Ouabain-sensitive 86 Rb uptake was significantly greater at 3, 10, and 20 minutes of 86 Rb incubation in femoral arteries from DOCA-salt rats. Linear regression analysis revealed a significant correlation between the uptake of 86 Rb and time of incubation in both control and DOCA-salt rats. A significant difference in the slopes of the regression lines showed that the rate of uptake was greater in DOCA-salt rats. No difference was observed in ouabain-insensitive 86 Rb uptake. A dose-dependent relaxation in response to increasing concentrations of calcium following contraction to norepinephrine was observed in femoral arteries from control and DOCA-salt rats. The relaxation was directly dependent on the level of extracellular potassium and was blocked by ouabain. Femoral arteries from DOCA-salt rats relaxed to a significantly greater extent in response to calcium at each level of potassium when compared with controls. These results provide further evidence for an increase in Na + -K + pump activity in vascular smooth muscle from DOCA-salt hypertensive rats

Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.

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Decano, Julius L; Pasion, Khristine A; Black, Nicole; Giordano, Nicholas J; Herrera, Victoria L; Ruiz-Opazo, Nelson

2016-01-11

Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and

Involvement of ENaC in the development of salt-sensitive hypertension.

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Pavlov, Tengis S; Staruschenko, Alexander

2017-08-01

Salt-sensitive hypertension is associated with renal and vascular dysfunctions, which lead to impaired fluid excretion, increased cardiac output, and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron that plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions. In this mini-review, we summarize recent studies investigating the role of ENaC in the development of salt-sensitive hypertension. On the basis of experimental data obtained from the Dahl salt-sensitive rats, we and others have demonstrated that abnormal ENaC activation in response to a dietary NaCl load contributes to the development of high blood pressure in this model. The role of different humoral factors, such as the components of the renin-angiotensin-aldosterone system, members of the epidermal growth factors family, arginine vasopressin, and oxidative stress mediating the effects of dietary salt on ENaC are discussed in this review to highlight future research directions and to determine potential molecular targets for drug development. Copyright © 2017 the American Physiological Society.

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

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Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

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Zhengxiu Su

Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

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Brunner Sabine

2011-10-01

Full Text Available Abstract Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF. Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28% or a high-salt diet (5.5% starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food (ZDF+S+E, hydralazine (25 mg/kg per day (ZDF+S+H, or no treatment (ZDF+S. Rats on normal salt-diet were assigned to eplerenone (ZDF+E or no treatment (ZDF. Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL or high-salt diet (ZL+S serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio and vascular stiffness (strain and stress were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition

Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

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Sandra Geschka

Full Text Available A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

Dissection of Chromosome 18 Blood Pressure and Salt-Sensitivity Quantitative Trait Loci in the Spontaneously Hypertensive Rat

Czech Academy of Sciences Publication Activity Database

Johnson, M.D.; He, L.; Herman, D.; Wakimoto, H.; Wallace, C. A.; Zídek, Václav; Mlejnek, Petr; Musilová, Alena; Šimáková, Miroslava; Vorlíček, Jaroslav; Křen, Vladimír; Vyklický, O.; Qi, N.R.; Wang, J.; Seidman, Ch. E.; Seidman, J.; Kurtz, T. W.; Aitman, T. J.; Pravenec, Michal

2009-01-01

Roč. 54, č. 3 (2009), s. 639-645 ISSN 0194-911X R&D Projects: GA MŠk(CZ) 1M0520; GA MŠk(CZ) 1P05ME791; GA ČR(CZ) GA301/08/0166 Grant - others:EC(XE) LSHG-CT-2005-019015; Howard Hughes Medical Institute(US) HHMI 55005624; Transatlantic network of excellence(US) Foundation Leducq Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneously hypertensive rat * salt sensitivity * gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.614, year: 2009

Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

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Kentaro Takakura

2017-11-01

Full Text Available The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM, which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS, heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life

Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions.

Science.gov (United States)

Takakura, Kentaro; Ito, Shogo; Sonoda, Junya; Tabata, Koji; Shiozaki, Motoko; Nagai, Kaoru; Shibata, Masahiro; Koike, Masato; Uchiyama, Yasuo; Gotow, Takahiro

2017-11-01

The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS), heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life extension of these

The ontogeny of salt hunger in the rat.

Science.gov (United States)

Leshem, M

1999-05-01

Salt hunger is the behaviour of an animal suffering sodium deficiency. It is characterised by an increased motivation to seek and ingest sodium, and the ability to distinguish between sodium and other salts. Here I review the development of salt hunger in the rat. Salt hunger develops rapidly between birth and weaning. It can first be demonstrated 72 h postnatally when an intracerebroventricular injection of renin elicits greater swallowing of NaCl solution than water and greater mouthing of solid fragments of NaCl than of an artificial sweetener. However, sodium deficit per se cannot arouse the hunger at this age, and first elicits increased intake of NaCl only at 12 days-of-age. The next landmark is at 17 days-of-age when the hormonal synergy of aldosterone and central angiotensin II first elicits salt hunger, as it does in the adult. The specificity of the hunger for the sodium ion also develops postnatally: the 72 h-old sodium-hungry neonate does not distinguish between NaCl and other mono- and di-valent chloride salts but, increasingly during development, the sodium hungry pup distinguishes salts and by weaning age NaCl is clearly preferred to other salts almost as it is in adults. Early development may also be a sensitive period for determining lifelong preferences, and indeed, acute perinatal sodium depletion induces a lifelong enhancement of salt intake. Taken together, these findings demonstrate how a behaviour develops precociously and how, when the behaviour becomes important at weaning, the rat pup is competent to meet its sodium requirements, and may be adapted to anticipate sodium deficit.

Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease.

Science.gov (United States)

Koelfat, Kiran V K; Schaap, Frank G; Hodin, Caroline M J M; Visschers, Ruben G J; Svavarsson, Björn I; Lenicek, Martin; Shiri-Sverdlov, Ronit; Lenaerts, Kaatje; Olde Damink, Steven W M

2017-10-01

Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This

ALLOPURINOL DOES NOT DECREASE BLOOD PRESSURE OR PREVENT THE DEVELOPMENT OF HYPERTENSION IN THE DOCA-SALT RAT MODEL

Science.gov (United States)

Szasz, Theodora; Linder, A. Elizabeth; Davis, Robert P.; Burnett, Robert; Fink, Gregory D.; Watts, Stephanie W.

2010-01-01

Reactive oxygen species (ROS) play an important role in the pathogenesis of hypertension, disease in which ROS levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a ROS-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on BP have yielded controversial results. We hypothesized that XO inhibition would decrease BP or attenuate the development of DOCA-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg/day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by HPLC measurements of XO metabolites in urine, serum and tissues demonstrating decrease in products, increase in substrates and detection of the active metabolite of allopurinol, oxypurinol. We monitored BP continuously via radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension, regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. PMID:20881613

Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

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Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat.

Science.gov (United States)

Alwasel, Saleh H; Barker, David J P; Ashton, Nick

2012-03-01

Sodium retention has been proposed as the cause of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero) model of developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co-transporter 2) expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed on either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink, LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and water to drink, the total volume of fluid ingested by LP rats fell to control levels, but the volume of saline taken was significantly larger [3.8±0.1 compared with 8.8±1.3 ml/24 h per 100 g of body weight in control and LP rats respectively; Psodium content and ECF (extracellular fluid) volumes were greater in LP rats. These results show that prenatal programming of renal sodium wasting leads to a compensatory increase in salt appetite in LP rats. We speculate that the need to maintain salt homoeostasis following malnutrition in utero stimulates greater food intake, leading to accelerated growth and raised BP (blood pressure).

Low-Salt Intake during Mating or Gestation in Rats Is Associated with Low Birth and Survival Rates of Babies

Directory of Open Access Journals (Sweden)

Ranna Chou

2014-01-01

Full Text Available We investigated the influence of maternal salt restriction during mating or gestation on birth rate and offspring growth in Dahl salt-sensitive rats (DS. DS were divided into 5 groups: DS fed a low-salt (0.3% NaCl, w/w (DS-low or high-salt (4% NaCl, w/w diet (DS-high during mating and DS-high or DS-low during gestation, and DS fed regular chow (0.75% NaCl, w/w (DS-regular throughout mating and gestation. During the unspecified periods, the rats were given regular chow. DS-low during mating delivered fewer infants than high-salt mothers (P<0.05. The birth rate on regular chow was 87%. Six out of 11 DS-low rats during pregnancy produced pups while the rats fed a high-salt diet all delivered pups (P<0.025. The pup survival rate was 67% for high-salt mothers during mating and 54% for mothers on a low-salt diet. The pup survival rate was 95% for mothers on a high-salt diet during pregnancy and 64% for mothers on a low-salt diet (P<0.0001. Seven out of 8 DS-regular rats during mating delivered 59 neonates. However, 66% of the neonates survived. A low-salt diet during mating or pregnancy lowers birth rate and the neonates from low-salt mothers during pregnancy were more likely to die than those from high-salt mothers.

Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

Science.gov (United States)

Navidi, Meena; Wolinsky, Ira; Fung, Paul; Arnaud, Sara B.

1995-01-01

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

Context-driven Salt Seeking Test (Rats)

Science.gov (United States)

Chang, Stephen E.; Smith, Kyle S.

2018-01-01

Changes in reward seeking behavior often occur through incremental learning based on the difference between what is expected and what actually happens. Behavioral flexibility of this sort requires experience with rewards as better or worse than expected. However, there are some instances in which behavior can change through non-incremental learning, which requires no further experience with an outcome. Such an example of non-incremental learning is the salt appetite phenomenon. In this case, animals such as rats will immediately seek out a highly-concentrated salt solution that was previously undesired when they are put in a novel state of sodium deprivation. Importantly, this adaptive salt-seeking behavior occurs despite the fact that the rats never tasted salt in the depleted state, and therefore never tasted it as a highly desirable reward. The following protocol is a method to investigate the neural circuitry mediating adaptive salt seeking using a conditioned place preference (CPP) procedure. The procedure is designed to provide an opportunity to discover possible dissociations between the neural circuitry mediating salt seeking and salt consumption to replenish the bodily deficit after sodium depletion. Additionally, this procedure is amenable to incorporating a number of neurobiological techniques for studying the brain basis of this behavior.

Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model.

Science.gov (United States)

Szasz, Theodora; Linder, A Elizabeth; Davis, Robert P; Burnett, Robert; Fink, Gregory D; Watts, Stephanie W

2010-12-01

Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model.

Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

Directory of Open Access Journals (Sweden)

Victoria L M Herrera

Full Text Available Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs affecting blood pressure (BP in 16-month old post-menopausal F2 (Dahl S×R-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001 and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001 F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50 and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65, four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5 were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Effects of Clofibrate on Salt Loading-Induced Hypertension in Rats

Science.gov (United States)

Cruz, Antonio; Rodríguez-Gómez, Isabel; Pérez-Abud, Rocío; Vargas, Miguel Ángel; Wangensteen, Rosemary; Quesada, Andrés; Osuna, Antonio; Moreno, Juan Manuel

2011-01-01

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T4 (FT4) and tissue FT4 and FT3 versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels. PMID:20981147

The American Heart Association Scientific Statement on salt sensitivity of blood pressure: Prompting consideration of alternative conceptual frameworks for the pathogenesis of salt sensitivity?

Science.gov (United States)

Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal; Morris, R Curtis

2017-11-01

: Recently, the American Heart Association (AHA) published a scientific statement on salt sensitivity of blood pressure which emphasized a decades old conceptual framework for the pathogenesis of this common disorder. Here we examine the extent to which the conceptual framework for salt sensitivity emphasized in the AHA Statement accommodates contemporary findings and views of the broader scientific community on the pathogenesis of salt sensitivity. In addition, we highlight alternative conceptual frameworks and important contemporary theories of salt sensitivity that are little discussed in the AHA Statement. We suggest that greater consideration of conceptual frameworks and theories for salt sensitivity beyond those emphasized in the AHA Statement may help to advance understanding of the pathogenesis of salt-induced increases in blood pressure and, in consequence, may lead to improved approaches to preventing and treating this common disorder.

Salt Sensitivity: Challenging and Controversial Phenotype of Primary Hypertension.

Science.gov (United States)

Iatrino, Rossella; Manunta, Paolo; Zagato, Laura

2016-09-01

Increases in life expectancy and cardiovascular adverse events in patients with hypertension highlight the need for new risk-reduction strategies to reduce the burden of degenerative diseases. Among the environmental factors, high salt consumption is currently considered the most important risk factor of hypertension. However, while high salt intake significantly raises blood pressure in some individuals, others do not show variation or even decrease their blood pressure. This heterogeneity is respectively classified as salt sensitivity and salt resistance. In this review, we propose salt sensitivity as a useful phenotype to unravel the mechanistic complexity of primary hypertension. The individual variability in blood pressure modification in response to salt intake changes derives from the combination of genetic and environmental determinants. This combination of random and non random determinants leads to the development of a personal index of sensitivity to salt. However, those genes involved in susceptibility to salt are still not completely identified, and the triggering mechanisms underlying the following development of hypertension still remain uncovered. One reason might be represented by the absence of a specific protocol, universally followed, for a standard definition of salt sensitivity. Another reason may be linked to the absence of common criteria for patient recruitment during clinical studies. Thus, the generation of a reliable approach for a proper recognition of this personal index of sensitivity to salt, and through it the identification of novel therapeutic targets for primary hypertension, should be one of the aspirations for the scientific community.

Where Does Road Salt Go - a Static Salt Model

Science.gov (United States)

Yu, C. W.; Liu, F.; Moriarty, V. W.

2017-12-01

Each winter, more than 15 million tons of road salt is applied in the United States for the de-icing purpose. Considerable amount of chloride in road salt flows into streams/drainage systems with the snow melt runoff and spring storms, and eventually goes into ecologically sensitive low-lying areas in the watershed, such as ponds and lakes. In many watersheds in the northern part of US, the chloride level in the water body has increased significantly in the past decades, and continues an upward trend. The environmental and ecological impact of the elevated chloride level can no longer be ignored. However although there are many studies on the biological impact of elevated chloride levels, there are few investigations on how the spatially distributed road salt application affects various parts of the watershed. In this presentation, we propose a static road salt model as a first-order metric to address spacial distribution of salt loading. Derived from the Topological Wetness Index (TWI) in many hydrological models, this static salt model provides a spatial impact as- sessment of road salt applications. To demonstrate the effectiveness of the static model, National Elevation Dataset (NED) of ten-meter resolution of Lake George watershed in New York State is used to generate the TWI, which is used to compute a spatially dis- tributed "salt-loading coefficient" of the whole watershed. Spatially varying salt applica- tion rate is then aggregated, using the salt-loading coefficients as weights, to provide salt loading assessments of streams in the watershed. Time-aggregated data from five CTD (conductivity-temperature-depth) sensors in selected streams are used for calibration. The model outputs and the sensor data demonstrate a strong linear correlation, with the R value of 0.97. The investigation shows that the static modeling approach may provide an effective method for the understanding the input and transport of road salt to within watersheds.

Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump.

Science.gov (United States)

Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Stieger, Bruno; Meier, Peter J; Hofmann, Alan F; Sugiyama, Yuichi

2005-01-01

Bile salts are predominantly taken up by hepatocytes via the basolateral Na(+)-taurocholate cotransporting polypeptide (NTCP/SLC10A1) and secreted into the bile by the bile salt export pump (BSEP/ABCB11). In the present study, we transfected rat Ntcp and rat Bsep into polarized Madin-Darby canine kidney cells and characterized the transport properties of these cells for eight bile salts. Immunohistochemical staining demonstrated that Ntcp was expressed at the basolateral domains, whereas Bsep was expressed at the apical domains. Basal-to-apical transport of taurocholate across the monolayer expressing only Ntcp and that coexpressing Ntcp/Bsep was observed, whereas the flux across the monolayer of control and Bsep-expressing cells was symmetrical. Basal-to-apical transport of taurocholate across Ntcp/Bsep-coexpressing monolayers was significantly higher than that across monolayers expressing only Ntcp. Kinetic analysis of this vectorial transport of taurocholate gave an apparent K(m) value of 13.9 +/- 4.7 microM for cells expressing Ntcp alone, which is comparable with 22.2 +/- 4.5 microM for cells expressing both Ntcp and Bsep and V(max) values of 15.8 +/- 4.2 and 60.8 +/- 9.0 pmol.min(-1).mg protein(-1) for Ntcp alone and Ntcp and Bsep-coexpressing cells, respectively. Transcellular transport of cholate, glycocholate, taurochenodeoxycholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, ursodeoxycholate, and glycoursodeoxycholate, but not that of lithocholate was also observed across the double transfectant. This double-expressing system can be used as a model to clarify vectorial transport of bile salts across hepatocytes under physiological conditions.

Complete Sensitivity/Uncertainty Analysis of LR-0 Reactor Experiments with MSRE FLiBe Salt and Perform Comparison with Molten Salt Cooled and Molten Salt Fueled Reactor Models

Energy Technology Data Exchange (ETDEWEB)

Brown, Nicholas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Powers, Jeffrey J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mueller, Don [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Patton, Bruce W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-12-01

In September 2016, reactor physics measurements were conducted at Research Centre Rez (RC Rez) using the FLiBe (2 ⁷LiF + BeF₂) salt from the Molten Salt Reactor Experiment (MSRE) in the LR-0 low power nuclear reactor. These experiments were intended to inform on neutron spectral effects and nuclear data uncertainties for advanced reactor systems using FLiBe salt in a thermal neutron energy spectrum. Oak Ridge National Laboratory (ORNL), in collaboration with RC Rez, performed sensitivity/uncertainty (S/U) analyses of these experiments as part of the ongoing collaboration between the United States and the Czech Republic on civilian nuclear energy research and development. The objectives of these analyses were (1) to identify potential sources of bias in fluoride salt-cooled and salt-fueled reactor simulations resulting from cross section uncertainties, and (2) to produce the sensitivity of neutron multiplication to cross section data on an energy-dependent basis for specific nuclides. This report provides a final report on the S/U analyses of critical experiments at the LR-0 Reactor relevant to fluoride salt-cooled high temperature reactor (FHR) and liquid-fueled molten salt reactor (MSR) concepts. In the future, these S/U analyses could be used to inform the design of additional FLiBe-based experiments using the salt from MSRE. The key finding of this work is that, for both solid and liquid fueled fluoride salt reactors, radiative capture in ⁷Li is the most significant contributor to potential bias in neutronics calculations within the FLiBe salt.

The American Heart Association Scientific Statement on salt sensitivity of blood pressure: Prompting consideration of alternative conceptual frameworks for the pathogenesis of salt sensitivity?

Czech Academy of Sciences Publication Activity Database

Kurtz, T. W.; DiCarlo, S. E.; Pravenec, Michal; Morris Jr., R. C.

2017-01-01

Roč. 35, č. 11 (2017), s. 2214-2225 ISSN 0263-6352 Grant - others:AV ČR(CZ) AP1502 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985823 Keywords : blood pressure * hypertension * salt * salt resistence * salt sensitivity * sodium * sodium sensitivity Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 4.085, year: 2016

Dynamic autoregulation and renal injury in Dahl rats

DEFF Research Database (Denmark)

Karlsen, F M; Andersen, C B; Leyssac, P P

1997-01-01

of hypertension, a gradual impairment of autoregulatory control of renal blood flow might expose the glomerular circulation to periods of elevated pressure, resulting in renal injuries in Dahl S rats. Dynamic autoregulatory capacity was assessed in Dahl S and Dahl salt-resistant (Dahl R) rats, SHR, and Sprague......-Dawley rats by inducing broad-band fluctuations in the arterial blood pressure and simultaneously measuring renal blood flow. Dynamic autoregulation was estimated by the transfer function using blood pressure as the input and renal blood flow as the output. Renal morphological injuries were evaluated in Dahl......The Dahl salt-sensitive (Dahl S) rat develops hypertension and renal injuries when challenged with a high salt diet and has been considered to be a model of chronic renal failure. Renal injuries appear very early in life compared with the spontaneously hypertensive rat (SHR). During the course...

Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet.

Science.gov (United States)

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2017-01-01

Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa.

Physalis minima Leaves Extract Induces Re-Endothelialization in Deoxycorticosterone Acetate-Salt-Induced Endothelial Dysfunction in Rats

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Dian Nugrahenny

2018-02-01

Full Text Available The administration of deoxy-corticosterone acetate (DOCA-salt can induce oxidative stress leading to decrease the bioavailability of nitric oxide (NO, increase senescence of circulating endothelial progenitor cells (EPCs, thus contributing to endothelial dysfunction. This study was aimed to investigate the effects of Physalis minima L. leaves extract on serum NO levels, circulating EPCs number, and histopathology of tail artery endothelial cells in DOCA-salt-induced endothelial dysfunction in rats. Twenty-five male Wistar rats were randomly divided into five groups: rats without any treatment (normal, rats treated with DOCA (10 mg/kgBW s.c. twice weekly and given 0.9% NaCl to drink ad libitum for 6 weeks, and DOCA-salt-induced rats orally supplemented with P. minima leaves extract at doses of 500, 1500, or 2500 mg/kgBW for 4 weeks. Serum NO levels were measured by colorimetry. The number of circulating EPCs (CD34+/CD133+ cells was determined by flow cytometry. The tail artery sections were histologically processed with hematoxylin-eosin staining. DOCA-salt-induced rats showed significantly (p<0.05 decrease in serum NO levels and circulating EPCs number compared to the normal. There was also more detached tail artery endothelial cells in DOCA-salt-induced rats. P. minima leaves extract at a dose of 500 mg/kgBW significantly (p<0.05 increased serum NO level and circulating EPCs number, and also induced an optimal re-endothelialization in DOCA-salt-induced rats. P. minima leave extract dose-dependently increases NO bioavailability contributing to enhanced EPCs mobilization, thereby promoting re-endothelialization in DOCA-salt-induced endothelial dysfunction in rats.

Neurogenic pulmonary edema induced by spinal cord injury in spontaneously hypertensive and Dahl salt hypertensive rats

Czech Academy of Sciences Publication Activity Database

Šedý, Jiří; Kuneš, Jaroslav; Zicha, Josef

2011-01-01

Roč. 60, č. 6 (2011), s. 975-979 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/09/0336; GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypertension * neurogenic pulmonary edema * Dahl salt-sensitive rats * SHR Subject RIV: ED - Physiology Impact factor: 1.555, year: 2011

Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.

Science.gov (United States)

Carey, Robert M; Schoeffel, Cynthia D; Gildea, John J; Jones, John E; McGrath, Helen E; Gordon, Lindsay N; Park, Min Jeong; Sobota, Rafal S; Underwood, Patricia C; Williams, Jonathan; Sun, Bei; Raby, Benjamin; Lasky-Su, Jessica; Hopkins, Paul N; Adler, Gail K; Williams, Scott M; Jose, Pedro A; Felder, Robin A

2012-11-01

Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.

Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

Science.gov (United States)

Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

2017-04-16

An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

Effect of Consuming Iodized Salt on Fertility Indices in Male Adult Rats

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M. Mehrabani Natanzi

2017-06-01

Full Text Available Introduction: Today about 27.4 percent of female 15-44 years and 1 percent of female in fertility age are affected by infertility. Iodine is a rare element that is essential for the synthesis of thyroid hormones. Concentration of the thyroid hormones in blood under the influence of iodine intake and changes in thyroid hormones levels interact with reproductive system. Today, all the people of Iran consuming iodized salt regardless of iodine status in their body. In this study according to high prevalence of the infertility among young couples, iodized salt intake on fertility in male rats were investigated. Materials and Methods: In this study 20 male and 20 female adult Wistar rats were used. Twenty male adult Wistar rats were randomly divided into 2 groups. Including the control group and treatment group that received iodine and female adult Wistar were fed with a regular diet. Five male rats from each group were killed at the end of the fourth weeks in order to evaluate the possible effect of iodized salt on sperm analysis and weight of testis. After a month, male and female rats were placed in pairs in separate cages and their offspring were investigated in terms of number, gender and health. Results: The result of this study showed that the number of healthy offspring of treated male rats was significantly lower than the control group. Conclusion: Due to the negative effect of excessive iodine intake on fertility rate, it is recommended to couples to perform functional tests of their thyroid glands before intake of iodized salts.

Curative effect of sesame oil in a rat model of chronic kidney disease.

Science.gov (United States)

Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

2015-12-01

Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

Genetic predisposition to salt-sensitivity : a systematic review

NARCIS (Netherlands)

Beeks, Esther; Kessels, Alfons G H; Kroon, Abraham A; van der Klauw, Melanie M; de Leeuw, Peter W

PURPOSE: To assess the role of genetic polymorphisms in salt sensitivity of blood pressure. DATA IDENTIFICATION: We conducted a systematic review by searching the Medline literature from March 1993 to June 2003. Each paper was scrutinized and data concerning study population, method of salt

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

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Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet

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Mariona Camps-Bossacoma

2017-01-01

Full Text Available Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa.

Cocoa Diet Prevents Antibody Synthesis and Modifies Lymph Node Composition and Functionality in a Rat Oral Sensitization Model

OpenAIRE

Camps-Bossacoma, Mariona; Abril-Gil, Mar; Salda?a-Ruiz, Sandra; Franch, ?ngels; P?rez-Cano, Francisco J.; Castell, Margarida

2016-01-01

Cocoa powder, a rich source of polyphenols, has shown immunomodulatory properties in both the intestinal and systemic immune compartments of rats. The aim of the current study was to establish the effect of a cocoa diet in a rat oral sensitization model and also to gain insight into the mesenteric lymph nodes (MLN) activities induced by this diet. To achieve this, three-week-old Lewis rats were fed either a standard diet or a diet with 10% cocoa and were orally sensitized with ovalbumin (OVA)...

Biochemical Changes Associated With Giving PALUDAL Salt In The Drinking Water Of Rats

International Nuclear Information System (INIS)

ABD-EL-MONEIM, A.E.; LOTFI, S.A.

2010-01-01

Three groups of adult male albino rats were given either tap water (control) or saline water (1 % unrefined paludal salt dissolved in tap water or 1 % pure chemically synthesized NaCl in tap water). The experiment was carried out under hot summer conditions. At the end of 28 days of the treatment, blood samples were collected to follow up the biochemical alterations induced by paludal salt intake in kidney, liver and thyroid function tests besides serum electrolytes since unrefined paludal salt is being used extensively nowadays by Egyptian people as a table salt which comprises risks to human health.The results revealed that drinking water containing high level of either pure or unrefined crude salts led to significant elevation of serum urea, creatinine, sodium, potassium, aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP). Serum triiodothyronine (T3) and thyroxine (T4) were significantly depressed in both groups received high levels of salt in their drinking water. The level of serum total protein was decreased and albumin was negatively affected by salinity of water especially in paludal group while serum globulin was significantly increased in the other two groups. The biochemical alterations observed in rats as a result of drinking water containing paludal salt were more pronounced than those occurred in rats drank tap water plus pure NaCl.

The mobilisation model and parameter sensitivity

International Nuclear Information System (INIS)

Blok, B.M.

1993-12-01

In the PRObabillistic Safety Assessment (PROSA) of radioactive waste in a salt repository one of the nuclide release scenario's is the subrosion scenario. A new subrosion model SUBRECN has been developed. In this model the combined effect of a depth-dependent subrosion, glass dissolution, and salt rise has been taken into account. The subrosion model SUBRECN and the implementation of this model in the German computer program EMOS4 is presented. A new computer program PANTER is derived from EMOS4. PANTER models releases of radionuclides via subrosion from a disposal site in a salt pillar into the biosphere. For uncertainty and sensitivity analyses the new subrosion model Latin Hypercube Sampling has been used for determine the different values for the uncertain parameters. The influence of the uncertainty in the parameters on the dose calculations has been investigated by the following sensitivity techniques: Spearman Rank Correlation Coefficients, Partial Rank Correlation Coefficients, Standardised Rank Regression Coefficients, and the Smirnov Test. (orig./HP)

Assessment of visceral sensitivity using radio telemetry in a rat model of maternal separation

NARCIS (Netherlands)

Welting, O.; van den Wijngaard, R. M.; de Jonge, W. J.; Holman, R.; Boeckxstaens, G. E.

2005-01-01

Stress plays an important role in the development of visceral hypersensitivity, a key mechanism underlying the pathophysiology of the irritable bowel syndrome. Visceral sensitivity in rats is generally assessed under restrain conditions. To avoid this potential stress factor, we developed a model

Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats.

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Lemon, Christian H; Wilson, David M; Brasser, Susan M

2011-12-01

In randomly bred rats, orally applied ethanol stimulates neural substrates for appetitive sweet taste. To study associations between ethanol's oral sensory characteristics and genetically mediated ethanol preference, we made electrophysiological recordings of oral responses (spike density) by taste-sensitive nucleus tractus solitarii neurons in anesthetized selectively bred ethanol-preferring (P) rats and their genetically heterogeneous Wistar (W) control strain. Stimuli (25 total) included ethanol [3%, 5%, 10%, 15%, 25%, and 40% (vol/vol)], a sucrose series (0.01, 0.03, 0.1, 0.3, 0.5, and 1 M), and other sweet, salt, acidic, and bitter stimuli; 50 P and 39 W neurons were sampled. k-means clustering applied to the sucrose response series identified cells showing high (S(1)) or relatively low (S(0)) sensitivity to sucrose. A three-way factorial analysis revealed that activity to ethanol was influenced by a neuron's sensitivity to sucrose, ethanol concentration, and rat line (P = 0.01). Ethanol produced concentration-dependent responses in S(1) neurons that were larger than those in S(0) cells. Although responses to ethanol by S(1) cells did not differ between lines, neuronal firing rates to ethanol in S(0) cells increased across concentration only in P rats. Correlation and multivariate analyses revealed that ethanol evoked responses in W neurons that were strongly and selectively associated with activity to sweet stimuli, whereas responses to ethanol by P neurons were not easily associated with activity to representative sweet, sodium salt, acidic, or bitter stimuli. These findings show differential central neural representation of oral ethanol between genetically heterogeneous rats and P rats genetically selected to prefer alcohol.

Sensitivity to deliberate sea salt seeding of marine clouds – observations and model simulations

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K. Alterskjær

2012-03-01

Full Text Available Sea salt seeding of marine clouds to increase their albedo is a proposed technique to counteract or slow global warming. In this study, we first investigate the susceptibility of marine clouds to sea salt injections, using observational data of cloud droplet number concentration, cloud optical depth, and liquid cloud fraction from the MODIS (Moderate Resolution Imaging Spectroradiometer instruments on board the Aqua and Terra satellites. We then compare the derived susceptibility function to a corresponding estimate from the Norwegian Earth System Model (NorESM. Results compare well between simulations and observations, showing that stratocumulus regions off the west coast of the major continents along with large regions over the Pacific and the Indian Oceans are susceptible. At low and mid latitudes the signal is dominated by the cloud fraction.

We then carry out geo-engineering experiments with a uniform increase over ocean of 10⁻⁹ kg m⁻² s⁻¹ in emissions of sea salt particles with a dry modal radius of 0.13 μm, an emission strength and areal coverage much greater than proposed in earlier studies. The increased sea salt concentrations and the resulting change in marine cloud properties lead to a globally averaged forcing of −4.8 W m⁻² at the top of the atmosphere, more than cancelling the forcing associated with a doubling of CO₂ concentrations. The forcing is large in areas found to be sensitive by using the susceptibility function, confirming its usefulness as an indicator of where to inject sea salt for maximum effect.

Results also show that the effectiveness of sea salt seeding is reduced because the injected sea salt provides a large surface area for water vapor and gaseous sulphuric acid to condense on, thereby lowering the maximum supersaturation and suppressing the formation and lifetime of sulphate particles. In some areas, our simulations show an

Features of metabolic reactions to various water-salt loads in female rats

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Anatoliy I Gozhenko

2018-04-01

Full Text Available Background. In the previous article we reported that screening registered parameters of water-salt, nitrous and lipid metabolism as well as the neuroendocrine-immune complex found 42 among them who in rats subjected to various water-salt loads, significantly different from that of intact rats, but on average the same group of animals that received liquids with different mineralization and chemical composition. The purpose of this article is to find out the features of the reactions of the parameters of metabolism. Materials and methods. Experiment was performed on 58 healthy female Wistar rats 240-290 g divided into 6 groups. Animals of the first group remained intact, using tap water from drinking ad libitum. Instead, the other rats received the same tap water as well as waters Sophiya, Naftussya, Gertsa and its artificial salt analogue through the probe at a dose of 1,5 mL/100 g of body mass for 6 days. The day after the completion of the drinking course in all rats the parameters of water-salt, nitrous and lipid metabolism were registered. Results. Found that 16 metabolic parameters the maximum deviates from the level of intact rats under the influence of the salt analogue of Gertsa water, a smaller, but tangible effect is made by the Gertsa native water, even less effective waters Sofiya and Naftussya, instead of ordinary water is almost ineffective in relation to these metabolic parameters. The other 19 parameters deviates to a maximum extent from the reference level after the use of water Naftussya, fresh water is less effective, whereas quasi-isotonic liquids are practically inactive for these parameters. The remaining 13 parameters in animals that use normal water, deviates from intact control to the same extent as in the previous pattern, which, apparently, is also due to the stressful effects of the load course. Both Naftussya and Gertsa water and its salt analogue prevent the stress deviations of these parameters. Instead, by

Salt sensitivity: a review with a focus on non-Hispanic blacks and Hispanics

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Richardson, Safiya I.; Freedman, Barry I.; Ellison, David H.; Rodriguez, Carlos J.

2015-01-01

The purpose of this review is to summarize the available information regarding salt sensitivity particularly as it relates to non-Hispanic blacks and Hispanics and to clarify possible etiologies, especially those that might shed light on potential treatment options. In non-Hispanic blacks, there is evidence that endothelial dysfunction, reduced potassium intake, decreased urinary kallikrein excretion, upregulation of sodium channel activity, dysfunction in atrial natriuretic peptide (ANP) production, and APOL1 gene nephropathy risk variants may cause or contribute to salt sensitivity. Supported treatment avenues include diets high in potassium and soybean protein, the components of which stimulate nitric oxide production. Racial heterogeneity complicates the study of salt sensitivity in Hispanic populations. Caribbean Hispanics, who have a higher proportion of African ancestry, may respond to commonly prescribed anti-hypertensive agents in a way that is characteristic of non-Hispanic black hypertensives. The low-renin hypertensive phenotype commonly seen in non-Hispanic blacks has been linked to salt sensitivity and may indicate an increased risk for salt sensitivity in a portion of the Hispanic population. In conclusion, increased morbidity and mortality associated with salt sensitivity mandates further studies evaluating the efficacy of tailored dietary and pharmacologic treatment in non-Hispanic blacks and determining the prevalence of low renin hypertension and salt sensitivity within the various subgroups of Hispanic Americans. PMID:23428408

Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats.

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Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2014-06-01

We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment. Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress. We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats. Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

Science.gov (United States)

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2016-08-05

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

Long-term inhibition of xanthine oxidase by febuxostat does not decrease blood pressure in deoxycorticosterone acetate (DOCA-salt hypertensive rats.

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Theodora Szasz

Full Text Available Xanthine oxidase and its products, uric acid and ROS, have been implicated in the pathogenesis of cardiovascular disease, such as hypertension. We have previously reported that allopurinol inhibition of XO does not alter the progression of deoxycorticosterone acetate (DOCA-salt hypertension in rats. However other researchers have observed a reduction in blood pressure after allopurinol treatment in the same model. To resolve this controversy, in this study we used the newer and more effective XO inhibitor febuxostat, and hypothesized that a more complete XO blockade might impair hypertension development and its end-organ consequences. We used DOCA-salt hypertensive rats and administered vehicle (salt water or febuxostat (orally, 5 mg/kg/day in salt water in a short-term "reversal" experiment (2 weeks of treatment 3 weeks after DOCA-salt beginning and a long-term "prevention" experiment (treatment throughout 4 weeks of DOCA-salt. We confirmed XO inhibition by febuxostat by measuring circulating and tissue levels of XO metabolites. We found an overall increase in hypoxanthine (XO substrate and decrease in uric acid (XO product levels following febuxostat treatment. However, despite a trend for reduced blood pressure in the last week of long-term febuxostat treatment, no statistically significant difference in hemodynamic parameters was observed in either study. Additionally, no change was observed in relative heart and kidney weight. Aortic media/lumen ratio was minimally improved by long-term febuxostat treatment. Additionally, febuxostat incubation in vitro did not modify contraction of aorta or vena cava to norepinephrine, angiotensin II or endothelin-1. We conclude that XO inhibition is insufficient to attenuate hypertension in the rat DOCA-salt model, although beneficial vascular effects are possible.

Long-term inhibition of xanthine oxidase by febuxostat does not decrease blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.

Science.gov (United States)

Szasz, Theodora; Davis, Robert Patrick; Garver, Hannah S; Burnett, Robert J; Fink, Gregory D; Watts, Stephanie W

2013-01-01

Xanthine oxidase and its products, uric acid and ROS, have been implicated in the pathogenesis of cardiovascular disease, such as hypertension. We have previously reported that allopurinol inhibition of XO does not alter the progression of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. However other researchers have observed a reduction in blood pressure after allopurinol treatment in the same model. To resolve this controversy, in this study we used the newer and more effective XO inhibitor febuxostat, and hypothesized that a more complete XO blockade might impair hypertension development and its end-organ consequences. We used DOCA-salt hypertensive rats and administered vehicle (salt water) or febuxostat (orally, 5 mg/kg/day in salt water) in a short-term "reversal" experiment (2 weeks of treatment 3 weeks after DOCA-salt beginning) and a long-term "prevention" experiment (treatment throughout 4 weeks of DOCA-salt). We confirmed XO inhibition by febuxostat by measuring circulating and tissue levels of XO metabolites. We found an overall increase in hypoxanthine (XO substrate) and decrease in uric acid (XO product) levels following febuxostat treatment. However, despite a trend for reduced blood pressure in the last week of long-term febuxostat treatment, no statistically significant difference in hemodynamic parameters was observed in either study. Additionally, no change was observed in relative heart and kidney weight. Aortic media/lumen ratio was minimally improved by long-term febuxostat treatment. Additionally, febuxostat incubation in vitro did not modify contraction of aorta or vena cava to norepinephrine, angiotensin II or endothelin-1. We conclude that XO inhibition is insufficient to attenuate hypertension in the rat DOCA-salt model, although beneficial vascular effects are possible.

RAS1, a quantitative trait locus for salt tolerance and ABA sensitivity in Arabidopsis

KAUST Repository

Ren, Zhonghai

2010-03-08

Soil salinity limits agricultural production and is a major obstacle for feeding the growing world population. We used natural genetic variation in salt tolerance among different Arabidopsis accessions to map a major quantitative trait locus (QTL) for salt tolerance and abscisic acid (ABA) sensitivity during seed germination and early seedling growth. A recombinant inbred population derived from Landsberg erecta (Ler; salt and ABA sensitive) x Shakdara (Sha; salt and ABA resistant) was used for QTL mapping. High-resolution mapping and cloning of this QTL, Response to ABA and Salt 1 (RAS1), revealed that it is an ABA- and salt stress-inducible gene and encodes a previously undescribed plant-specific protein. A premature stop codon results in a truncated RAS1 protein in Sha. Reducing the expression of RAS1 by transfer-DNA insertion in Col or RNA interference in Ler leads to decreased salt and ABA sensitivity, whereas overexpression of the Ler allele but not the Sha allele causes increased salt and ABA sensitivity. Our results suggest that RAS1 functions as a negative regulator of salt tolerance during seed germination and early seedling growth by enhancing ABA sensitivity and that its loss of function contributes to the increased salt tolerance of Sha.

High-Salt Intake Ameliorates Hyperglycemia and Insulin Resistance in WBN/Kob-Leprfa/fa Rats: A New Model of Type 2 Diabetes Mellitus

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Yoshiichi Takagi

2018-01-01

Full Text Available High-salt intake is a major risk factor for developing hypertension in type 2 diabetes mellitus, but its effects on glucose homeostasis are controversial. We previously found that high-salt intake induces severe hypertension in WBN/Kob diabetic fatty (WBKDF rats. In the present study, we examined the effects of a high-salt intake on glucose homeostasis in WBKDF rats. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (NS, 0.26% diet or high-sodium (HS, 8% diet for 7 weeks. Systolic blood pressure and urine volume were increased in WBKDF-HS and Wistar-HS. Body weight gain and food consumption were comparable between NS and HS in both strains. Plasma and urine glucose levels were significantly increased in WBKDF-NS but not in WBKDF-HS. HOMA-IR in WBKDF-HS was significantly lower compared with that in WBKDF-NS. The high plasma adiponectin level in WBKDF-NS compared with that in Wistar-NS was further enhanced in WBKDF-HS. Glycogen deposits and fat droplets in the livers of WBKDF-HS were reduced compared with those of WBKDF-NS. The present study demonstrated that HS intake ameliorated hyperglycemia and insulin resistance in WBKDF rats, which may be due to increased plasma levels of adiponectin.

Salivary Proteome Patterns Affecting Human Salt Taste Sensitivity.

Science.gov (United States)

Stolle, Theresa; Grondinger, Freya; Dunkel, Andreas; Meng, Chen; Médard, Guillaume; Kuster, Bernhard; Hofmann, Thomas

2017-10-25

To investigate the role of perireceptor events in inter-individual variability in salt taste sensitivity, 31 volunteers were monitored in their detection functions for sodium chloride (NaCl) and classified into sensitive (0.6-1.7 mmol/L), medium-sensitive (1.8-6.9 mmol/L), and nonsensitive (7.0-11.2 mmol/L) subjects. Chemosensory intervention of NaCl-sensitive (S + ) and nonsensitive (S - ) panellists with potassium chloride, ammonium chloride, and sodium gluconate showed the salt taste sensitivity to be specific for NaCl. As no significant differences were found between S + and S - subjects in salivary sodium and protein content, salivary proteome differences and their stimulus-induced dynamic changes were analyzed by tryptic digestion, iTRAQ labeling, and liquid chromatography-tandem mass spectrometry analysis. Differences in the salivary proteome between S + and S - subjects were found primarily in resting saliva and were largely independent of the dynamic alterations observed upon salt stimulation. Gene ontology enrichment analysis of key proteins, i.e., immunoglobulin heavy constant y1, myeloblastin, cathepsin G, and kallikrein, revealed significantly increased serine-type endopeptidase activity for the S + group, while the S - group exhibited augmented cysteine-type endopeptidase inhibitor activity by increased abundances in lipocalin-1 and cystatin-D, -S, and -SN, respectively. As proteases have been suggested to facilitate transepithelial sodium transport by cleaving the y-subunit of the epithelial sodium channel (ENaC) and protease inhibitors have been shown to reduce ENaC-mediated sodium transport, the differentially modulated proteolytic activity patterns observed in vivo for S + and S - subjects show evidence of them playing a crucial role in affecting human NaCl sensitivity.

Sensitivity of Disease Parameters to Flexible Budesonide/Formoterol Treatment in an Allergic Rat Model

OpenAIRE

Brange , Charlotte; Smailagic , Amir; Jansson , Anne-Helene; Middleton , Brian; Miller-Larsson , Anna; Taylor , John D.; Silberstein , David S.; Lal , Harbans

2009-01-01

Sensitivity of Disease Parameters to Flexible Budesonide/Formoterol Treatment in an Allergic Rat Model correspondance: Corresponding author. Tel.: +46 46 33 6256; fax: +46 46 33 6624. (Brange, Charlotte) (Brange, Charlotte) AstraZeneca R&D Lund--> , Lund--> - SWEDEN (Brange, Charlotte) AstraZeneca R&D Lund--> , Lund--> - SWEDEN (Brange, Charlotte) AstraZeneca R&D Lun...

Sensitivity of storage field performance to geologic and cavern design parameters in salt domes.

Energy Technology Data Exchange (ETDEWEB)

Ehgartner, Brian L. (Sandia National Laboratories, Albuquerque, NM); Park, Byoung Yoon

2009-03-01

A sensitivity study was performed utilizing a three dimensional finite element model to assess allowable cavern field sizes for strategic petroleum reserve salt domes. A potential exists for tensile fracturing and dilatancy damage to salt that can compromise the integrity of a cavern field in situations where high extraction ratios exist. The effects of salt creep rate, depth of salt dome top, dome size, caprock thickness, elastic moduli of caprock and surrounding rock, lateral stress ratio of surrounding rock, cavern size, depth of cavern, and number of caverns are examined numerically. As a result, a correlation table between the parameters and the impact on the performance of storage field was established. In general, slower salt creep rates, deeper depth of salt dome top, larger elastic moduli of caprock and surrounding rock, and a smaller radius of cavern are better for structural performance of the salt dome.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

Science.gov (United States)

Oktar, Süleyman; Ilhan, Selçuk; Meydan, Sedat; Aydin, Mehmet; Yönden, Zafer; Gökçe, Ahmet

2010-01-01

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Effects of Lactobacillus plantarum TWK10-Fermented Soymilk on Deoxycorticosterone Acetate-Salt-Induced Hypertension and Associated Dementia in Rats

Directory of Open Access Journals (Sweden)

Te-Hua Liu

2016-05-01

Full Text Available Oxidative stress resulting from excessive production of reactive oxygen species is the major mediator of neuronal cell degeneration observed in neurodegenerative diseases, such as Alzheimer’s disease (AD and vascular dementia (VaD. Additionally, hypertension has been shown to be a positive risk factor for VaD. Therefore, the objective of this study was to investigate the effects of Lactobacillus plantarum strain TWK10 (TWK10-fermented soymilk on the protection of PC-12 cells in H2O2-, oxygen-glucose deprivation (OGD- and deoxycorticosterone acetate (DOCA-salt-induced rat models of VaD. Notably, the viabilities of H2O2-treated PC-12 cells and OGD model were significantly increased by treatment with TWK10-fermented soymilk ethanol extract (p < 0.05. In addition, oral administration of TWK10-fermented soymilk extract in DOCA-salt hypertension-induced VaD rats resulted in a significant decrease in blood pressure (p < 0.05, which was regulated by inhibiting ACE activity and promoting NO production, in addition to decreased escape latency and increased target crossing (p < 0.05. In conclusion, these results demonstrated that TWK10-fermented soymilk extract could improve learning and memory in DOCA-salt hypertension-induced VaD rats by acting as a blood pressure-lowering and neuroprotective agent.

Cocoa Diet Prevents Antibody Synthesis and Modifies Lymph Node Composition and Functionality in a Rat Oral Sensitization Model

Directory of Open Access Journals (Sweden)

Mariona Camps-Bossacoma

2016-04-01

Full Text Available Cocoa powder, a rich source of polyphenols, has shown immunomodulatory properties in both the intestinal and systemic immune compartments of rats. The aim of the current study was to establish the effect of a cocoa diet in a rat oral sensitization model and also to gain insight into the mesenteric lymph nodes (MLN activities induced by this diet. To achieve this, three-week-old Lewis rats were fed either a standard diet or a diet with 10% cocoa and were orally sensitized with ovalbumin (OVA and with cholera toxin as a mucosal adjuvant. Specific antibodies were quantified, and lymphocyte composition, gene expression, and cytokine release were established in MLN. The development of anti-OVA antibodies was almost totally prevented in cocoa-fed rats. In addition, this diet increased the proportion of TCRγδ+ and CD103+CD8+ cells and decreased the proportion of CD62L+CD4+ and CD62L+CD8+ cells in MLN, whereas it upregulated the gene expression of OX40L, CD11c, and IL-1β and downregulated the gene expression of IL-17α. In conclusion, the cocoa diet induced tolerance in an oral sensitization model accompanied by changes in MLN that could contribute to this effect, suggesting its potential implication in the prevention of food allergies.

Cocoa Diet Prevents Antibody Synthesis and Modifies Lymph Node Composition and Functionality in a Rat Oral Sensitization Model.

Science.gov (United States)

Camps-Bossacoma, Mariona; Abril-Gil, Mar; Saldaña-Ruiz, Sandra; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

2016-04-23

Cocoa powder, a rich source of polyphenols, has shown immunomodulatory properties in both the intestinal and systemic immune compartments of rats. The aim of the current study was to establish the effect of a cocoa diet in a rat oral sensitization model and also to gain insight into the mesenteric lymph nodes (MLN) activities induced by this diet. To achieve this, three-week-old Lewis rats were fed either a standard diet or a diet with 10% cocoa and were orally sensitized with ovalbumin (OVA) and with cholera toxin as a mucosal adjuvant. Specific antibodies were quantified, and lymphocyte composition, gene expression, and cytokine release were established in MLN. The development of anti-OVA antibodies was almost totally prevented in cocoa-fed rats. In addition, this diet increased the proportion of TCRγδ+ and CD103+CD8+ cells and decreased the proportion of CD62L+CD4+ and CD62L+CD8+ cells in MLN, whereas it upregulated the gene expression of OX40L, CD11c, and IL-1β and downregulated the gene expression of IL-17α. In conclusion, the cocoa diet induced tolerance in an oral sensitization model accompanied by changes in MLN that could contribute to this effect, suggesting its potential implication in the prevention of food allergies.

Crushed Salt Constitutive Model

International Nuclear Information System (INIS)

Callahan, G.D.

1999-01-01

The constitutive model used to describe the deformation of crushed salt is presented in this report. Two mechanisms -- dislocation creep and grain boundary diffusional pressure solution -- are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. Upon complete consolidation, the crushed-salt model reproduces the Multimechanism Deformation (M-D) model typically used for the Waste Isolation Pilot Plant (WIPP) host geological formation salt. New shear consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on WIPP and southeastern New Mexico salt. Nonlinear least-squares model fitting to the database produced two sets of material parameter values for the model -- one for the shear consolidation tests and one for a combination of the shear and hydrostatic consolidation tests. Using the parameter values determined from the fitted database, the constitutive model is validated against constant strain-rate tests. Shaft seal problems are analyzed to demonstrate model-predicted consolidation of the shaft seal crushed-salt component. Based on the fitting statistics, the ability of the model to predict the test data, and the ability of the model to predict load paths and test data outside of the fitted database, the model appears to capture the creep consolidation behavior of crushed salt reasonably well

Partial Restoration Of Skeletal Strength In Ovariectomized Rats By Treatment With Strontium Salts

DEFF Research Database (Denmark)

Andersen, Jens Enevold Thaulov; Andersen, Pernille/Høegh; Christgau, Stephan

AIM Ovariectomy of female rats induces significant bone-loss by depriving endogenous estrogen production. We assessed whether administration of strontium salts had a therapeutic benefit in this animal model of postmenopausal osteoporosis. INTRODUCTION In most women after menopause, the rate of bone...... loss exceeds the rate of bone formation, resulting in a net decrease in bone mass and ultimately in development of osteoporosis and elevated risk of sustaining fragility fracture. Most approved osteoporosis treatments work by decreasing the rate of bone resorption, however, these treatments also......-M and S-G respectively compared to 671 mg/cm3 in vehicle treated OVX and 750 mg/cm3 SHAM rats). Bone strength analysis revealed a significant increase (p...

Study of the thermal and mechanical sensitivity of bitumen/oxygen salt mixtures

International Nuclear Information System (INIS)

Backof, E.; Diepold, W.

1975-07-01

The safe handling characteristics of radioactive wastes containing nitrate salts to be fixed in bitumen for ultimate storage in salt mines according to a process developed at the Karlsruhe Nuclear Research Center have been examined with respect to their combustibility and shock sensitivity in tests of inactive bitumen/salt mixtures. Samples containing 40% bitumen and 60% nitrates of alkali, alkaline earth, and heavy metals, organic acids and rare earths were used to determine the thermal sensitivity (ignition temperature, duration of burning, heating under contained conditions), the mechanical sensitivity (shock sensitivity) and, in order to simulate major shock stresses, the sensitivity against detonation stresses. A few basic experiments were also performed on some beta-irradiated inactive samples. It appeared that although the addition of nitrates increased the combustibility of bitumen, neither the high thermal nor the detonation stresses resulted in any explosion-type reaction. (orig.) [de

Effects of salicylic acid on wheat salt sensitivity | Erdal | African ...

African Journals Online (AJOL)

In this study, investigations on the effects of foliar-applied SA on salt sensitivity, hydrogen peroxide (H2O2) generation and activities of antioxidant enzymes like peroxidase (POX) and catalase (CAT) in plant tissues under salt stress was performed. SA treatment significantly increased the fresh and dry weights in both root ...

Iron intake by rats using peroral administration of /sup 55/Fe-salts of phosphatidic acids

Energy Technology Data Exchange (ETDEWEB)

Rauch, P.; Kas, J. (Inst. of Chemical Technology, Prague (Czechoslovakia)); Tykva, R. (Ceskoslovenska Akademie Ved, Prague. Ustav Organicke Chemie a Biochemie)

1984-03-15

The utilization of /sup 55/Fe and its incorporation into rat organs was investigated after peroral administration of various salts of phosphatidic acids (PA). Iron of PA salts is utilized up to 58-94% comparing to /sup 55/Fe/sup 2 +/. The degree of iron utilization depends on the type of PA salts administered. 16 refs.

Auxotrophy-stimulated sensitivity to quaternary ammonium salts and its relation to active transport in yeast

International Nuclear Information System (INIS)

Lachowicz, T.M.; Oblak, E.; Piatkowski, J.

1992-01-01

In previous studies we have observed that auxotrophic mutants of yeast were much more sensitive to quaternary ammonium salts than the corresponding isogenic wild type strains. The super sensitivity of the auxotrophs seems to be a characteristic feature of yeast and yeast-like microorganisms: the level of sensitivity of the quaternary ammonium salts of the bacterial auxotrophs and their original prototrophic forms appeared to be the same. The super sensitivity of yeast auxotrophs disappeared on minimal media with ammonium as a nitrogen source. In this report there are presented the data indicating that enrichment of the minimal medium with arginine restores the super sensitivity of auxotrophic yeast mutants to the quaternary ammonium salts. The results of amino-acid transport into the auxotrophic yeast cells treated with a quaternary ammonium salt in the presence and absence of arginine are given. A working hypothesis of the mechanism of these salts action as a specific inhibition of nutrient transport is discussed. (author). 19 refs, 3 figs, 8 figs

[Effects of total glucosides of paeony on enhancing insulin sensitivity and antagonizing nonalcoholic fatty liver in rats].

Science.gov (United States)

Zheng, Lin-Ying; Pan, Jing-Qiang; Lv, Jun-Hua

2008-10-01

To study the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization of total glucosides of paeony on nonalcoholic fatty liver rats caused by insulin resistance and discuss the acting mechanism. Adult SD rats were maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their fasting blood glucose (FBG) and 2-hours blood glucose after oral glucose tolerance test (OGTT-2 hBG) were mensurated, according to which and the weight the rats were divided randomly into nonalcoholic fatty liver model group, metformin group (0.2 g x kg(-1)) and total glucosides of paeony group (high dosage 0.15 g x kg(-1), low dosage 0.05 g x kg(-1)). All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29th day, all of them were killed and the blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG, fasting insulin (Fins)] and serum lipid [free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)], then the HOMA insulin resistance index (HOMA-IRI, fasting glucosexinsulin) and insulin sensitivity index (ISI) were counted. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) were measured also. Livers were weighed and collected to be observed the pathological changes. Compared with normal group, in nonalcoholic fatty liver model group the levels of Fins and IRI were increased obviously (P insulin resistence were resisted (P insulin resistance, and its action mechanism may be concerned with enhancing insulin sensitivity and antioxidative ability, decreasing serum lipid.

Differential effects of 17 alpha-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat

NARCIS (Netherlands)

Koopen, NR; Post, SM; Wolters, H; Havinga, R; Stellaard, F; Boverhof, R; Kuipers, F; Princen, HMG

Effects of 17 alpha-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis, For this purpose, bile salt pool composition,

Differential regulation of renal prostaglandin receptor mRNAs by dietary salt intake in the rat

DEFF Research Database (Denmark)

Jensen, B L; Mann, Birgitte; Skøtt, O

1999-01-01

and cells by ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. Functional correlates were studied by measurement of PGE2-induced cAMP formation and renin secretion in juxtaglomerular (JG) cells isolated from animals on various salt intakes. RESULTS: EP1 and EP3......BACKGROUND: In this study, we tested the hypothesis that prostaglandin (PG) receptor expression in the rat kidney is subject to physiological regulation by dietary salt intake. METHODS: Rats were fed diets with 0.02 or 4% NaCl for two weeks. PG receptor expression was assayed in kidney regions...... did not affect the expression of EP1 or IP receptors, whereas EP4 transcripts in glomeruli were increased twofold by salt deprivation. Consistent with this, we found that PGE2-evoked cAMP production and renin secretion by JG cells from salt-deprived animals were significantly higher compared...

Modeling salt movement and halophytic crop growth on marginal lands with the APEX model

Science.gov (United States)

Goehring, N.; Saito, L.; Verburg, P.; Jeong, J.; Garrett, A.

2016-12-01

Saline soils negatively impact crop productivity in nearly 20% of irrigated agricultural lands worldwide. At these saline sites, cultivation of highly salt-tolerant plants, known as halophytes, may increase productivity compared to conventional salt-sensitive crops (i.e., glycophytes), thereby increasing the economic potential of marginal lands. Through a variety of mechanisms, halophytes are more effective than glycophytes at excluding, accumulating, and secreting salts from their tissues. Each mechanism can have a different impact on the salt balance in the plant-soil-water system. To date, little information is available to understand the long-term impacts of halophyte cultivation on environmental quality. This project utilizes the Agricultural Policy/Environmental Extender (APEX) model, developed by the US Department of Agriculture, to model the growth and production of two halophytic crops. The crops being modeled include quinoa (Chenopodium quinoa), which has utilities for human consumption and forage, and AC Saltlander green wheatgrass (Elymus hoffmannii), which has forage utility. APEX simulates salt movement between soil layers and accounts for the salt balance in the plant-soil-water system, including salinity in irrigation water and crop-specific salt uptake. Key crop growth parameters in APEX are derived from experimental growth data obtained under non-stressed conditions. Data from greenhouse and field experiments in which quinoa and AC Saltlander were grown under various soil salinity and irrigation salinity treatments are being used to parameterize, calibrate, and test the model. This presentation will discuss progress on crop parameterization and completed model runs under different salt-affected soil and irrigation conditions.

Na/K-ATPase Signaling and Salt Sensitivity: The Role of Oxidative Stress

Directory of Open Access Journals (Sweden)

Jiang Liu

2017-03-01

Full Text Available Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.

Effect of prenatal exposure to different salt concentration on the third month's weight and blood pressure in wistar rat

International Nuclear Information System (INIS)

Fereidoun, H.

2009-01-01

In utero alterations in fluid and electrolyte endocrine systems may result in permanent effects on offspring. A low sodium intake during prenatal life jeopardizes growth in young rats, prenatal high-salt diet in Sprague-Dawley rats caused an increase in MAP at postnatal day 30. The objective of this study was to determine the effect of prenatal exposure to different salt concentrations on the third month's weight and blood pressure in Wistar rat. This study was performed at the Department of Physiology, Isfahan University of Medical Science, Isfahan, Iran, over a period from 1998 to 2003. Six groups of rat, 1 male and 5 female in each group were exposed to 0.5, 1, 1.4, 1.6, 1.8 and 2 percent of salt concentrations during pre-pregnancy, pregnancy and lactation period, another test group consumed distilled water and control group used Isfahan tap water, other living conditions for all groups were similar. Exposure to different salt concentrations on the third month's weight and blood pressure was evaluated. Prenatal exposure to 0.5 and 1% salt concentrations gives birth to more alive and healthy infants, and third month's weight increased significantly, but blood pressure was not influenced significantly. Salt concentrations higher than 1% increased the maternal and infant mortality rate and blood pressure significantly, but some concentrations decreased third month's weight significantly. Level of dietary salt during intrauterine development can influence on the number of alive and healthy infants, birth weight, third month' weight and blood pressure significantly. There is no need to introduce a salt restricted diet in prenatal care, a balanced diet in sodium during pregnancy is recommended, high salt diet creates harmful effect. (author)

Behavioral sensitization after repeated formaldehyde exposure in rats.

Science.gov (United States)

Sorg, B A; Hochstatter, T

1999-01-01

Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary

Sensitivity and uncertainty analysis applied to a repository in rock salt

International Nuclear Information System (INIS)

Polle, A.N.

1996-12-01

This document describes the sensitivity and uncertainty analysis with UNCSAM, as applied to a repository in rock salt for the EVEREST project. UNCSAM is a dedicated software package for sensitivity and uncertainty analysis, which was already used within the preceding PROSA project. The use of UNCSAM provides a flexible interface to EMOS ECN by substituting the sampled values in the various input files to be used by EMOS ECN ; the model calculations for this repository were performed with the EMOS ECN code. Preceding the sensitivity and uncertainty analysis, a number of preparations has been carried out to facilitate EMOS ECN with the probabilistic input data. For post-processing the EMOS ECN results, the characteristic output signals were processed. For the sensitivity and uncertainty analysis with UNCSAM the stochastic input, i.e. sampled values, and the output for the various EMOS ECN runs have been analyzed. (orig.)

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

Science.gov (United States)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

2016-01-01

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

SYSNET: A salt-site systems network model for scenario assessments

International Nuclear Information System (INIS)

Reeves, M.; Banda, R.S.

1986-12-01

This document contains a description of the initial version of the systems model SYSNET. This model is being developed to analyze potentially disruptive scenarios of salt repository systems. Currently the model features a general three-dimensional network topology and simulates the processes of flow, heat transport in rock, heat transport in fluid, brine transport, salt creep dissolution, and precipitation. Of necessity, the SYSNET Code uses relatively simple semi-analytic algorithms so that it may be implemented statistically. Uncertain parameters may be sampled with a compatible preprocessor and then analyzed statistically with a compatible postprocessor. When used in this fashion, SYSNET may be caused to calculate distributions of various performance measures and sensitivities of performance measures to uncertain parameters. The ultimate objective of the SYSNET development is to prioritize data needs by computing sensitivities relative to a particular performance measure, namely the 10,000-year cumulative release, and to evaluate repository systems for compliance with the US Environmental Protection Agency (EPA) Standard. 16 refs., 25 figs., 31 tabs

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats.

Science.gov (United States)

Bopda, Orelien Sylvain Mtopi; Longo, Frida; Bella, Thierry Ndzana; Edzah, Protais Marcellin Ohandja; Taïwe, Germain Sotoing; Bilanda, Danielle Claude; Tom, Esther Ngo Lemba; Kamtchouing, Pierre; Dimo, Theophile

2014-04-28

The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties. Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration. Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity. The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

Science.gov (United States)

Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

Modeling and Evaluation of the Global Sea-Salt Aerosol Distribution: Sensitivity to Emission Schemes and Resolution Effects at Coastal/Orographic Sites

Science.gov (United States)

Spada, M.; Jorba, O.; Perez Garcia-Pando, C.; Janjic, Z.; Baldasano, J. M.

2013-01-01

One of the major sources of uncertainty in model estimates of the global sea-salt aerosol distribution is the emission parameterization. We evaluate a new sea-salt aerosol life cycle module coupled to the online multi-scale chemical transport model NMMB/BSC-CTM. We compare 5 year global simulations using five state-of-the-art sea-salt open-ocean emission schemes with monthly averaged coarse aerosol optical depth (AOD) from selected AERONET sun photometers, surface concentration measurements from the University of Miami's Ocean Aerosol Network, and measurements from two NOAA/PMEL cruises (AEROINDOEX and ACE1). Model results are highly sensitive to the introduction of sea-surface-temperature (SST)-dependent emissions and to the accounting of spume particles production. Emission ranges from 3888 teragrams per year to 8114 teragrams per year, lifetime varies between 7.3 hours and 11.3 hours, and the average column mass load is between 5.0 teragrams and 7.2 teragrams. Coarse AOD is reproduced with an overall correlation of around 0.5 and with normalized biases ranging from +8.8 percent to +38.8 percent. Surface concentration is simulated with normalized biases ranging from minus 9.5 percent to plus 28 percent and the overall correlation is around 0.5. Our results indicate that SST-dependent emission schemes improve the overall model performance in reproducing surface concentrations. On the other hand, they lead to an overestimation of the coarse AOD at tropical latitudes, although it may be affected by uncertainties in the comparison due to the use of all-sky model AOD, the treatment of water uptake, deposition and optical properties in the model and/or an inaccurate size distribution at emission.

Reactive oxygen species dynamics in roots of salt sensitive and salt tolerant cultivars of rice.

Science.gov (United States)

Saini, Shivani; Kaur, Navdeep; Pati, Pratap Kumar

2018-06-01

Salinity stress is one of the major constraints for growth and survival of plants that affects rice productivity worldwide. Hence, in the present study, roots of two contrasting salinity sensitive cultivars, IR64 (IR64, salt sensitive) and Luna Suvarna (LS, salt tolerant) were compared with regard to the levels of reactive oxygen species (ROS) to derive clues for their differential salt stress adaptation mechanisms. In our investigation, the tolerant cultivar exhibited longer primary roots, more lateral roots, higher root number leading to increased root biomass, with respect to IR64. It was observed that LS roots maintained higher level of H 2 O 2 in comparison to IR64. The activities of various enzymes involved in enzymatic antioxidant defense mechanism (SOD, CAT, GPX, DHAR and MDHAR) were found to be greater in LS roots. Further, the higher transcript level accumulation of genes encoding ROS generating (RbohA, RbohD and RbohE) and scavenging enzymes (Fe-SOD, Chloroplastic Cu/Zn-SOD, CAT and DHAR) were noticed in the roots of tolerant cultivar, LS. Moreover, the content of other stress markers such as total protein and proline were also elevated in LS roots. While, the expression of proline biosynthesis gene (P5CS) and proline catabolism gene (PDH) was observed to be lower in LS. Copyright © 2018. Published by Elsevier Inc.

Computational analysis of candidate disease genes and variants for Salt-sensitive hypertension in indigenous Southern Africans

KAUST Repository

Tiffin, Nicki

2010-09-27

Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension. © 2010 Tiffin et al.

Sensitivity of disease parameters to flexible budesonide/formoterol treatment in an allergic rat model.

Science.gov (United States)

Brange, Charlotte; Smailagic, Amir; Jansson, Anne-Helene; Middleton, Brian; Miller-Larsson, Anna; Taylor, John D; Silberstein, David S; Lal, Harbans

2009-02-01

Clinical studies show that flexible dosing (maintenance and symptom-driven dose adjustments) of budesonide and formoterol (BUD/FORM) improves control of asthma exacerbations as compared to fixed maintenance dosing protocols (maintenance therapy) even when the latter utilize higher BUD/FORM doses. This suggests that dose-response relationships for certain pathobiologic mechanisms in asthma shift over time. Here, we have conducted animal studies to address this issue. (1) To test in an animal asthma-like model whether it is possible to achieve the same or greater pharmacological control over bronchoconstriction and airway/lung inflammation, and with less total drug used, by flexible BUD/FORM dosing (upward adjustment of doses) in association with allergen challenges. (2) To determine whether the benefit requires adjustment of both drug components. Rats sensitized on days 0 and 7 were challenged intratracheally with ovalbumin on days 14 and 21. On days 13-21, rats were treated intratracheally with fixed maintenance or flexible BUD/FORM combinations. On day 22, rats were challenged with methacholine and lungs were harvested for analysis. A flexible BUD/FORM dosing regimen (using 3.3 times less total drug than the fixed maintenance high dose regimen), delivered the same or greater reductions of excised lung gas volume (a measure of gas trapped in lung by bronchoconstriction) and lung weight (a measure of inflammatory oedema). When either BUD or FORM alone was increased on days of challenge, the benefit of the flexible dose upward adjustment was lost. Flexible dosing of the BUD/FORM combination improves the pharmacological inhibition of allergen-induced bronchoconstriction and an inflammatory oedema in an allergic asthma-like rat model.

USE OF SENSITIVITY ANALYSIS ON A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR CHLOROFORM IN RATS TO DETERMINE AGE-RELATED TOXICITY

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USE OF SENSITIVITY ANALYSIS ON A PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL FOR CHLOROFORM IN RATS TO DETERMINE AGE-RELATED TOXICITY.CR Eklund, MV Evans, and JE Simmons. US EPA, ORD, NHEERL, ETD,PKB, Research Triangle Park, NC. Chloroform (CHCl3) is a disinfec...

Salt stress induces differential regulation of the phenylpropanoid pathway in Olea europaea cultivars Frantoio (salt-tolerant) and Leccino (salt-sensitive).

Science.gov (United States)

Rossi, Lorenzo; Borghi, Monica; Francini, Alessandra; Lin, Xiuli; Xie, De-Yu; Sebastiani, Luca

2016-10-01

Olive tree (Olea europaea L.) is an important crop in the Mediterranean Basin where drought and salinity are two of the main factors affecting plant productivity. Despite several studies have reported different responses of various olive tree cultivars to salt stress, the mechanisms that convey tolerance and sensitivity remain largely unknown. To investigate this issue, potted olive plants of Leccino (salt-sensitive) and Frantoio (salt-tolerant) cultivars were grown in a phytotron chamber and treated with 0, 60 and 120mM NaCl. After forty days of treatment, growth analysis was performed and the concentration of sodium in root, stem and leaves was measured by atomic absorption spectroscopy. Phenolic compounds were extracted using methanol, hydrolyzed with butanol-HCl, and quercetin and kaempferol quantified via high performance liquid-chromatography-electrospray-mass spectrometry (HPLC-ESI-MS) and HPLC-q-Time of Flight-MS analyses. In addition, the transcripts levels of five key genes of the phenylpropanoid pathway were measured by quantitative Real-Time PCR. The results of this study corroborate the previous observations, which showed that Frantoio and Leccino differ in allocating sodium in root and leaves. This study also revealed that phenolic compounds remain stable or are strongly depleted under long-time treatment with sodium in Leccino, despite a strong up-regulation of key genes of the phenylpropanoid pathway was observed. Frantoio instead, showed a less intense up-regulation of the phenylpropanoid genes but overall higher content of phenolic compounds. These data suggest that Frantoio copes with the toxicity imposed by elevated sodium not only with mechanisms of Na + exclusion, but also promptly allocating effective and adequate antioxidant compounds to more sensitive organs. Copyright © 2016 Elsevier GmbH. All rights reserved.

Modeling of waste/near field interactions for a waste repository in bedded salt: the Dynamic Network (DNET) model

International Nuclear Information System (INIS)

Cranwell, R.M.

1983-01-01

The Fuel Cycle Risk Analysis Division of Sandia National Laboratories has been funded by the US Nuclear Regulatory Commission to develop a methodology for use in assessing the long-term risk from the disposal of radioactive wastes in deep geologic formations. As part of this program, the Dynamic Network (DNET) model was developed to investigate waste/near field interactions associated with the disposal of radioactive wastes in bedded salt formations. The model is a quasi-multi-dimensional network model with capabilities for simulating processes such as fluid flow, heat transport, salt dissolution, salt creep, and the effects of thermal expansion and subsedence on the rock units surrounding the repository. The use of DNET has been demonstrated in the analysis of a hypothetical disposal site containing a bedded salt formation as the host medium for the repository. An example of this demonstration analysis is discussed. Furthermore, the outcome of sensitivity analyses performed on the DNET model are presented

Antihypertensive action of non-natriuretic doses of furosemide in Dahl salt-sensitive rats

DEFF Research Database (Denmark)

Haugan, Ketil; Petersen, Jørgen Søberg; Spannow, Jesper

1997-01-01

Farmakologi, blood pressure, Dahl rats, furosemide, sodium balance, total body sodium, non-natriuretic......Farmakologi, blood pressure, Dahl rats, furosemide, sodium balance, total body sodium, non-natriuretic...

Salt acclimation process: a comparison between a sensitive and a tolerant Olea europaea cultivar.

Science.gov (United States)

Pandolfi, Camilla; Bazihizina, Nadia; Giordano, Cristiana; Mancuso, Stefano; Azzarello, Elisa

2017-03-01

Saline soils are highly heterogeneous in time and space, and this is a critical factor influencing plant physiology and productivity. Temporal changes in soil salinity can alter plant responses to salinity, and pre-treating plants with low NaCl concentrations has been found to substantially increase salt tolerance in different species in a process called acclimation. However, it still remains unclear whether this process is common to all plants or is only expressed in certain genotypes. We addressed this question by assessing the physiological changes to 100 mM NaCl in two contrasting olive cultivars (the salt-sensitive Leccino and the salt-tolerant Frantoio), following a 1-month acclimation period with 5 or 25 mM NaCl. The acclimation improved salt tolerance in both cultivars, but activated substantially different physiological adjustments in the tolerant and the sensitive cultivars. In the tolerant Frantoio the acclimation with 5 mM NaCl was more effective in increasing plant salt tolerance, with a 47% increase in total plant dry mass compared with non-acclimated saline plants. This enhanced biomass accumulation was associated with a 50% increase in K+ retention ability in roots. On the other hand, in the sensitive Leccino, although the acclimation process did not improve performance in terms of plant growth, pre-treatment with 5 and 25 mM NaCl substantially decreased salt-induced leaf cell ultrastructural changes, with leaf cell relatively similar to those of control plants. Taken together these results suggest that in the tolerant cultivar the acclimation took place primarily in the root tissues, while in the sensitive they occurred mainly at the shoot level. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increased sensitivity to salt stress in tocopherol-deficient Arabidopsis mutants growing in a hydroponic system

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Ellouzi, Hasna; Hamed, Karim Ben; Cela, Jana; Müller, Maren; Abdelly, Chedly; Munné-Bosch, Sergi

2013-01-01

Recent studies suggest that tocopherols could play physiological roles in salt tolerance but the mechanisms are still unknown. In this study, we analyzed changes in growth, mineral and oxidative status in vte1 and vte4 Arabidopsis thaliana mutants exposed to salt stress. vte1 and vte4 mutants lack α-tocopherol, but only the vte1 mutant is additionally deficient in γ-tocopherol. Results showed that a deficiency in vitamin E leads to reduced growth and increased oxidative stress in hydroponically-grown plants. This effect was observed at early stages, not only in rosettes but also in roots. The vte1 mutant was more sensitive to salt-induced oxidative stress than the wild type and the vte4 mutant. Salt sensitivity was associated with (i) high contents of Na+, (ii) reduced efficiency of PSII photochemistry (Fv/Fm ratio) and (iii) more pronounced oxidative stress as indicated by increased hydrogen peroxide and malondialdeyde levels. The vte 4 mutant, which accumulates γ- instead of α-tocopherol showed an intermediate sensitivity to salt stress between the wild type and the vte1 mutant. Contents of abscisic acid, jasmonic acid and the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid were higher in the vte1 mutant than the vte4 mutant and wild type. It is concluded that vitamin E-deficient plants show an increased sensitivity to salt stress both in rosettes and roots, therefore indicating the positive role of tocopherols in stress tolerance, not only by minimizing oxidative stress, but also controlling Na+/K+ homeostasis and hormonal balance. PMID:23299430

Road salt emissions: A comparison of measurements and modelling using the NORTRIP road dust emission model

Science.gov (United States)

Denby, B. R.; Ketzel, M.; Ellermann, T.; Stojiljkovic, A.; Kupiainen, K.; Niemi, J. V.; Norman, M.; Johansson, C.; Gustafsson, M.; Blomqvist, G.; Janhäll, S.; Sundvor, I.

2016-09-01

De-icing of road surfaces is necessary in many countries during winter to improve vehicle traction. Large amounts of salt, most often sodium chloride, are applied every year. Most of this salt is removed through drainage or traffic spray processes but a certain amount may be suspended, after drying of the road surface, into the air and will contribute to the concentration of particulate matter. Though some measurements of salt concentrations are available near roads, the link between road maintenance salting activities and observed concentrations of salt in ambient air is yet to be quantified. In this study the NORTRIP road dust emission model, which estimates the emissions of both dust and salt from the road surface, is applied at five sites in four Nordic countries for ten separate winter periods where daily mean ambient air measurements of salt concentrations are available. The model is capable of reproducing many of the salt emission episodes, both in time and intensity, but also fails on other occasions. The observed mean concentration of salt in PM10, over all ten datasets, is 4.2 μg/m3 and the modelled mean is 2.8 μg/m3, giving a fractional bias of -0.38. The RMSE of the mean concentrations, over all 10 datasets, is 2.9 μg/m3 with an average R2 of 0.28. The mean concentration of salt is similar to the mean exhaust contribution during the winter periods of 2.6 μg/m3. The contribution of salt to the kerbside winter mean PM10 concentration is estimated to increase by 4.1 ± 3.4 μg/m3 for every kg/m2 of salt applied on the road surface during the winter season. Additional sensitivity studies showed that the accurate logging of salt applications is a prerequisite for predicting salt emissions, as well as good quality data on precipitation. It also highlights the need for more simultaneous measurements of salt loading together with ambient air concentrations to help improve model parameterisations of salt and moisture removal processes.

The Salt Overly Sensitive (SOS) pathway: established and emerging roles.

Science.gov (United States)

Ji, Hongtao; Pardo, José M; Batelli, Giorgia; Van Oosten, Michael J; Bressan, Ray A; Li, Xia

2013-03-01

Soil salinity is a growing problem around the world with special relevance in farmlands. The ability to sense and respond to environmental stimuli is among the most fundamental processes that enable plants to survive. At the cellular level, the Salt Overly Sensitive (SOS) signaling pathway that comprises SOS3, SOS2, and SOS1 has been proposed to mediate cellular signaling under salt stress, to maintain ion homeostasis. Less well known is how cellularly heterogenous organs couple the salt signals to homeostasis maintenance of different types of cells and to appropriate growth of the entire organ and plant. Recent evidence strongly indicates that different regulatory mechanisms are adopted by roots and shoots in response to salt stress. Several reports have stated that, in roots, the SOS proteins may have novel roles in addition to their functions in sodium homeostasis. SOS3 plays a critical role in plastic development of lateral roots through modulation of auxin gradients and maxima in roots under mild salt conditions. The SOS proteins also play a role in the dynamics of cytoskeleton under stress. These results imply a high complexity of the regulatory networks involved in plant response to salinity. This review focuses on the emerging complexity of the SOS signaling and SOS protein functions, and highlights recent understanding on how the SOS proteins contribute to different responses to salt stress besides ion homeostasis.

A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

Science.gov (United States)

Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats.

Directory of Open Access Journals (Sweden)

Michelle B Bales

Full Text Available Recently, we reported that large bilateral gustatory cortex (GC lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX and in sham-operated controls (SHAM. Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p., but postsurgical tests indicated a weak conditioned taste aversion (CTA even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average. For KCl, there was a significant rightward shift (ΔEC50 = 0.57 log10 units; p<0.001 in the GCX psychometric function relative to SHAM, replicating our prior work. There was also a significant lesion-induced impairment (ΔEC50 = 0.41 log10 units; p = 0.006 in quinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and

Biochemical Effects of Aqueous Extract of Persea americana (Mill) on the Myocardium of Left Ventricle of High Salt-Fed Adult Wistar Rats.

Science.gov (United States)

Olushola, Ayoola I; Aderibigbe, Komolafe O; Stephen, Saka O; Ayodeji, Odukoya S

2017-10-01

The cardioprotective effects of Persea americana extract was investigated on biochemical activities of high salt-fed adult Wistar rats in this study. Forty healthy Wistar rats of both sexes weighing 120 to 150 g were randomly assigned into 8 groups of 5 rats each (groups A, B, C, D, E, F, G, and H). Rats in groups A, F, G, and H were fed with standard laboratory pellets, while groups B, C, D, and E were fed on the high-salt diet for 4 weeks. Concomitantly, daily administration of 50, 100, and 150 mg/kg of the P americana extract were given orally to groups C and F, D and G, and E and H, respectively, while rats in groups A and B were administered distilled water. Blood samples were taken by cardiac puncture; concentration of sodium ion, potassium ion, nitric oxide, and activity of lactate dehydrogenase were determined. One-way analysis of variance was used to analyze data, followed by Student-Newman-Keuls (SNK) test for multiple comparison. Results revealed that concentration of potassium ion and nitric oxide was significantly lower ( P < .05) in high salt-fed groups. Sodium ion concentration and activity of lactate dehydrogenase were higher in high salt-fed group while P americana prevented biochemical perturbations in other experimental groups. In conclusion, high salt-diet induced biochemical alterations which were significantly protected by oral administration of P americana extract.

[Correction of isoproterenol-induced myocardial injury with magnesium salts in magnesium-deficient rats].

Science.gov (United States)

Kharitonova, M V; Zheltova, A A; Spasov, A A; Smirnov, A V; Pan'shin, N G; Iezhitsa, I N

2013-01-01

The effect of Mg L-asparaginate (Mg-L-Asp), Mg chloride (MgCl2) and Mg sulfate (MgSO4) on the severity of isoproterenol-induced myocardial injury in Mg-deficient rats has been evaluated. To induce Mg deficiency, twenty-eight rats were placed on a low Mg diet (Mg content water for 10 weeks. Twelve control rats were fed a basal control diet (Mg content = 500 mg/kg) and water (with Mg content 20 mg/l) for equal duration. On day 49 of low Mg diet, Mg-deficient rats were randomly divided into four groups: 1) group that continued to receive low Mg diet; 2) low Mg diet plus oral MgSO4; 3) low Mg diet plus oral Mg-L-Asp and 4) low Mg diet plus oral MgCl2 (50 mg of Mg per kg of body weight). Isoproterenol was injected subcutaneously (30 mg/kg BW, twice, at an interval of 24 hours) on the day 70 of the study, when plasma and erythrocyte Mg level in rats fed a low Mg diet were significantly decreased by 47% and 45% compared to intact animals. Twenty-four hours after second injection of isoproterenol, tests for activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were run and histopathological study was carried out. Administration of isoproterenol to rats resulted in significantly elevated plasma CK, LDH and AST, however analyses in Mg deficient group demonstrated more dramatically increased activity of CK and AST compared to control rats (3,06 and 4,67 fold in Mg-deficient group vs. 1,91 and 3,92 fold in intact group). Increased leakage of cardiac injury markers was concomitant to increased volume of fuchsinophilic cardiomyocytes (54.2 +/- 1.7% in Mg-deficient group and 38.9 +/- 1.9% in intact group, p < 0.05). However, pretreatment with of MgCl2, MgSO4 and Mg-L-Asp during 21 days favorably decreased sensitivity of myocardium to isoproterenol-induced ischemic injury. All evaluated salts significantly decreased myocyte marker enzymes as well as protected myocardium against isoproterenol-induced histopathological perturbations.

Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring

Directory of Open Access Journals (Sweden)

Stephanie A. Segovia

2018-03-01

Full Text Available Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl, high-salt (SD; 10% kcal from fat, 4% NaCl, high-fat (HF; 45% kcal from fat, 1% NaCl or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1. There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2. Gut expression of inflammatory (Il1r1, Tnfα, Il6, and Il6r and renin–angiotensin system (Agtr1a, Agtr1b markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin–angiotensin regulation.

Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.

Science.gov (United States)

Takatsu, Miwa; Nakashima, Chieko; Takahashi, Keiji; Murase, Tamayo; Hattori, Takuya; Ito, Hiromi; Murohara, Toyoaki; Nagata, Kohzo

2013-11-01

Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.

Pulmonary Complications of Gastric Fluid and Bile Salts Aspiration, an Experimental Study in Rat

OpenAIRE

Samareh Fekri, Mitra; Poursalehi, Hamid Reza; Najafipour, Hamid; Dabiri, Shahriar; Shokoohi, Mostafa; Siahposht Khacheki, Ali; Shahrokhi, Nader; Malekpour Afshar, Reza; Lashkarizadeh, Mohammad Reza

2013-01-01

Objective(s): Gastroesophageal Reflux Disease (GERD) is one of the most common digestive disorders that frequently lead to pulmonary complications due to gastric fluid aspiration. In the present experimental study, chronic aspiration of gastric fluid, its components and bile salts in rat lung was performed to find out the main factor(s) causing pulmonary complications of gastric fluid aspiration. Materials and Methods: Forty eight male rats weighted 250-300 g were selected in six groups. Afte...

Comparative miRomics of Salt-Tolerant and Salt-Sensitive Rice

Directory of Open Access Journals (Sweden)

Goswami Kavita

2017-06-01

Full Text Available Increase in soil salt causes osmotic and ionic stress to plants, which inhibits their growth and productivity. Rice production is also hampered by salinity and the effect of salt is most severe at the seedling and reproductive stages. Salainity tolerance is a quantitative property controlled by multiple genes coding for signaling molecules, ion transporters, metabolic enzymes and transcription regulators. MicroRNAs are key modulators of gene-expression that act at the post-transcriptional level by translation repression or transcript cleavage. They also play an important role in regulating plant’s response to salt-stress. In this work we adopted the approach of comparative and integrated data-mining to understand the miRNA-mediated regulation of salt-stress in rice. We profiled and compared the miRNA regulations using natural varieties and transgenic lines with contrasting behaviors in response to salt-stress. The information obtained from sRNAseq, RNAseq and degradome datasets was integrated to identify the salt-deregulated miRNAs, their targets and the associated metabolic pathways. The analysis revealed the modulation of many biological pathways, which are involved in salt-tolerance and play an important role in plant phenotype and physiology. The end modifications of the miRNAs were also studied in our analysis and isomiRs having a dynamic role in salt-tolerance mechanism were identified.

Bladder overdistension with polyuria in a hypertensive rat model.

Science.gov (United States)

Velasquez Flores, Monica; Mossa, Abubakr H; Cammisotto, Philippe; Campeau, Lysanne

2018-03-31

Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology. © 2018 Wiley Periodicals, Inc.

Maternal fructose and/or salt intake and reproductive outcome in the rat: effects on growth, fertility, sex ratio, and birth order.

Science.gov (United States)

Gray, Clint; Long, Sophie; Green, Charlotte; Gardiner, Sheila M; Craigon, Jim; Gardner, David S

2013-09-01

Maternal diet can significantly skew the secondary sex ratio away from the expected value of 0.5 (proportion males), but the details of how diet may do this are unclear. Here, we altered dietary levels of salt (4% salt in the feed) and/or fructose (10% in the drinking water) of pregnant rats to model potential effects that consumption of a "Western diet" might have on maternofetal growth, development, and sex ratio. We demonstrate that excess fructose consumption before and during pregnancy lead to a marked skew in the secondary sex ratio (proportion of males, 0.60; P < 0.006). The effect was not mediated by selective developmental arrest of female embryos or influenced by fetal position in the uterine horn or sex-specific effects on sperm motility, suggesting a direct effect of glycolyzable monosaccharide on the maternal ovary and/or ovulated oocyte. Furthermore, combined excess maternal consumption of salt and fructose-sweetened beverage significantly reduced fertility, reflected as a 50% reduction in preimplantation and term litter size. In addition, we also noted birth order effects in the rat, with sequential implantation sites tending to be occupied by the same sex.

Wholesomeness study of irradiated salted and dried mackerel in rats

International Nuclear Information System (INIS)

Anukarahanonta, T.; Temcharoen, P.; Nagara, B.N.; Chudhabuddhi, C.; Bhamarapravati, N.

1981-01-01

A long-term multigeneration study was performed of the wholesomeness of irradiated salted and dried mackerel fed to the rats of Wistar strain and revealed no significant evidence that would impose a hazard attributable to irradiation with respect to the longevity, carcinogenecity, teratogenicity, dominant lethal, reproductive function and biophysiological function. Some abnormalities that were noted could be explained on the basis of differences in food quality due to the addition of fish protein and minerals rather than the irradiation effect

Crushed-salt constitutive model update

International Nuclear Information System (INIS)

Callahan, G.D.; Loken, M.C.; Mellegard, K.D.; Hansen, F.D.

1998-01-01

Modifications to the constitutive model used to describe the deformation of crushed salt are presented in this report. Two mechanisms--dislocation creep and grain boundary diffusional pressure solutioning--defined previously but used separately are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. New creep consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on Waste Isolation Pilot Plant and southeastern New Mexico salt to determine material parameters for the constitutive model. Nonlinear least-squares model fitting to data from the shear consolidation tests and a combination of the shear and hydrostatic consolidation tests produced two sets of material parameter values for the model. The change in material parameter values from test group to test group indicates the empirical nature of the model but demonstrates improvement over earlier work with the previous models. Key improvements are the ability to capture lateral strain reversal and better resolve parameter values. To demonstrate the predictive capability of the model, each parameter value set was used to predict each of the tests in the database. Based on the fitting statistics and the ability of the model to predict the test data, the model appears to capture the creep consolidation behavior of crushed salt quite well

Crushed-salt constitutive model update

Energy Technology Data Exchange (ETDEWEB)

Callahan, G.D.; Loken, M.C.; Mellegard, K.D. [RE/SPEC Inc., Rapid City, SD (United States); Hansen, F.D. [Sandia National Labs., Albuquerque, NM (United States)

1998-01-01

Modifications to the constitutive model used to describe the deformation of crushed salt are presented in this report. Two mechanisms--dislocation creep and grain boundary diffusional pressure solutioning--defined previously but used separately are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. New creep consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on Waste Isolation Pilot Plant and southeastern New Mexico salt to determine material parameters for the constitutive model. Nonlinear least-squares model fitting to data from the shear consolidation tests and a combination of the shear and hydrostatic consolidation tests produced two sets of material parameter values for the model. The change in material parameter values from test group to test group indicates the empirical nature of the model but demonstrates improvement over earlier work with the previous models. Key improvements are the ability to capture lateral strain reversal and better resolve parameter values. To demonstrate the predictive capability of the model, each parameter value set was used to predict each of the tests in the database. Based on the fitting statistics and the ability of the model to predict the test data, the model appears to capture the creep consolidation behavior of crushed salt quite well.

Zonal corticosteroid hormone biosynthesis in the adrenal cortex in rats exposed to emotional stress combined with salt loading

International Nuclear Information System (INIS)

Shul'ga, V.A.

1987-01-01

The authors study the pattern of biosynthesis of corticosteroid hormones in the zona glomerulosa and the combined zona fasciculata + zona reticularis of the adrenals, which are responsible for the mineralocorticoid and glucocorticoid function of the glands, during simultaneous exposure of animals to salt loading and emotional stress. Experiments were carried out on rats. The adrenals were divided into parts and samples were incubated in vitro with the addition of 3 H-progesterone to each sample. The specific activity of the 3 H-labeled corticosteroids decreased significantly in rats with a normal salt intake exposed to emotional stress

Angiotensin II protects primary rat hepatocytes against bile salt-induced apoptosis.

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Golnar Karimian

Full Text Available UNLABELLED: Angiotensin II (AT-II is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R and thereby activates hepatic stellate cells (HSCs. AT-II receptor blockers (ARBs are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that AT-1R blockers may induce hepatocyte injury. Therefore, we investigated the effect of AT-II and its receptor blockers on cytokine-, oxidative stress- and bile salt-induced cell death in hepatocytes. Primary rat hepatocytes were exposed to TNF-α/Actinomycin D, the ROS-generating agent menadione or the bile salts: glycochenodeoxycholic acid (GCDCA and tauro-lithocholic acid-3 sulfate (TLCS, to induce apoptosis. AT-II (100 nmol/L was added 10 minutes prior to the cell death-inducing agent. AT-1R antagonists (Sartans and the AT-2R antagonist PD123319 were used at 1 µmol/L. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (Sytox green staining were quantified. Expression of CHOP (marker for ER stress and AT-II receptor mRNAs were quantified by Q-PCR. AT-II dose-dependently reduced GCDCA-induced apoptosis of hepatocytes (-50%, p<0.05 without inducing necrosis. In addition, AT-II reduced TLCS-induced apoptosis of hepatocytes (-50%, p<0.05. However, AT-II did not suppress TNF/Act-D and menadione-induced apoptosis. Only the AT-1R antagonists abolished the protective effect of AT-II against GCDCA-induced apoptosis. AT-II increased phosphorylation of ERK and a significant reversal of the protective effect of AT-II was observed when signaling kinases, including ERK, were inhibited. Moreover, AT-II prevented the GCDCA-induced expression of CHOP (the marker of the ER-mediated apoptosis. CONCLUSION: Angiotensin II protects hepatocytes from bile salt-induced apoptosis through a combined activation of PI3-kinase, MAPKs, PKC pathways and inhibition of bile salt-induced ER stress. Our results suggest a mechanism for the observed hepatocyte

An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins

NARCIS (Netherlands)

Knippels, L.M.J.; Houben, G.F.; Spanhaak, S.; Penninks, A.H.

1999-01-01

We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA

An Appraisal of Methods Recently Recommended for Testing Salt Sensitivity of Blood Pressure

Czech Academy of Sciences Publication Activity Database

Kurtz, T. W.; DiCarlo, S. E.; Pravenec, Michal; Morris Jr., R. C.

2017-01-01

Roč. 6, č. 4 (2017), č. článku e005653. ISSN 2047-9980 Grant - others:AV ČR(CZ) AP1502 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985823 Keywords : hypertension * salt intake * salt sensitivity hypertension * sodium Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 4.863, year: 2016

Effect of indomethacin and salt depletion on renal proton MR imaging; An experimental study in the rat

Energy Technology Data Exchange (ETDEWEB)

Heyman, S.N.; Mammen, M. (Harvard Medical School, Boston, MA (United States). Charles A Dana Research Inst. Beth Israel Hospital, Boston, MA (United States))

1991-11-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.).

Influence of prenatal application of angiotensin II and postnatal salt diet on GABAergic and oxytocin system in rat brain steam and cerebellum

International Nuclear Information System (INIS)

Jackova, L.; Olexova, L.; Svitok, P.; Senko, T.; Stefanik, P.

2015-01-01

Our goal was to determinate how gene expression of GABA transporter 1 (GAT1), glutamate decarboxylase 67 (GAD67) and oxytocin receptor (OTR) is influenced with prenatal exposition to angiotensin II (Ang II) and postnatal salt diet in nucleus tractus solitarii (NTS) and cerebellum in rats. In NTS we observed strong tendency in different reaction of OTR gene expression between Ang II prenatal treatment and control rats after high salt diet. We observed significant influence of sex on GAD67 gene expression in cerebellum. Also, sex in combination with salt diet is significant factor in expression of GAT1 gene in cerebellum. (authors)

Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

Science.gov (United States)

Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

2012-04-01

Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

The Importance of G Protein-Coupled Receptor Kinase 4 (GRK4 in Pathogenesis of Salt Sensitivity, Salt Sensitive Hypertension and Response to Antihypertensive Treatment

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Brian Rayner

2015-03-01

Full Text Available Salt sensitivity is probably caused by either a hereditary or acquired defect of salt excretion by the kidney, and it is reasonable to consider that this is the basis for differences in hypertension between black and white people. Dopamine acts in an autocrine/paracrine fashion to promote natriuresis in the proximal tubule and thick ascending loop of Henle. G-protein receptor kinases (or GRKs are serine and threonine kinases that phosphorylate G protein-coupled receptors in response to agonist stimulation and uncouple the dopamine receptor from its G protein. This results in a desensitisation process that protects the cell from repeated agonist exposure. GRK4 activity is increased in spontaneously hypertensive rats, and infusion of GRK4 antisense oligonucleotides attenuates the increase in blood pressure (BP. This functional defect is replicated in the proximal tubule by expression of GRK4 variants namely p.Arg65Leu, p.Ala142Val and p.Val486Ala, in cell lines, with the p.Ala142Val showing the most activity. In humans, GRK4 polymorphisms were shown to be associated with essential hypertension in Australia, BP regulation in young adults, low renin hypertension in Japan and impaired stress-induced Na excretion in normotensive black men. In South Africa, GRK4 polymorphisms are more common in people of African descent, associated with impaired Na excretion in normotensive African people, and predict blood pressure response to Na restriction in African patients with mild to moderate essential hypertension. The therapeutic importance of the GRK4 single nucleotide polymorphisms (SNPs was emphasised in the African American Study of Kidney Disease (AASK where African-Americans with hypertensive nephrosclerosis were randomised to receive amlodipine, ramipril or metoprolol. Men with the p.Ala142Val genotype were less likely to respond to metoprolol, especially if they also had the p.Arg65Leu variant. Furthermore, in the analysis of response to treatment in

Wholesomeness studies of irradiated salted and dried mackerel, using rats. Part of a coordinated programme on the wholesomeness of the process of food irradiation

International Nuclear Information System (INIS)

Anukarahanonta, T.

1978-04-01

Chronic toxicity of irradiated salted and dried mackerel was evaluated by multi-generation rat feeding studies. Salted and dried mackerel samples were irradiated with 200krad, ground and mixed with a standard laboratory animal diet at 28% w/w. Wistar strain rats were used in the experiment and were divided into 3 groups and fed their respective diets, i.e. stock ration, diet containing 28% of non-irradiated salted and dried mackerel and diet containing 28% of irradiated salted and dried mackerel. The test was carried out for 3 generations. The results revealed no significant difference that would impose a hazard attributable to consumption of irradiated salted and dried mackerel with respect to longevity, carcinogenicity, teratogenicity, dominant lethal, reproductive function and biophysiological function in animals tested

Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

International Nuclear Information System (INIS)

Sawant, Sharmilee P.; Dnyanmote, Ankur V.; Warbritton, Alan; Latendresse, John R.; Mehendale, Harihara M.

2006-01-01

Previously, we reported high hepatotoxic sensitivity of type 2 diabetic (DB) rats to three dissimilar hepatotoxicants. Additional work revealed that a normally nonlethal dose of CCl 4 was lethal in DB rats due to inhibited compensatory tissue repair. The present study was conducted to investigate the importance of compensatory tissue repair in determining the final outcome of hepatotoxicity in diabetes, using another structurally and mechanistically dissimilar hepatotoxicant, thioacetamide (TA), to initiate liver injury. A normally nonlethal dose of TA (300 mg/kg, ip), caused 100% mortality in DB rats. Time course studies (0 to 96 h) showed that in the non-DB rats, liver injury initiated by TA as assessed by plasma alanine or aspartate aminotransferase and hepatic necrosis progressed up to 48 h and regressed to normal at 96 h resulting in 100% survival. In the DB rats, liver injury rapidly progressed resulting in progressively deteriorating liver due to rapidly expanding injury, hepatic failure, and 100% mortality between 24 and 48 h post-TA treatment. Covalent binding of 14 C-TA-derived radiolabel to liver tissue did not differ from that observed in the non-DB rats, indicating similar bioactivation-based initiation of hepatotoxicity. S-phase DNA synthesis measured by [ 3 H]-thymidine incorporation, and advancement of cells through the cell division cycle measured by PCNA immunohistochemistry, were substantially inhibited in the DB rats compared to the non-DB rats challenged with TA. Thus, inhibited cell division and compromised tissue repair in the DB rats resulted in progressive expansion of liver injury culminating in mortality. In conclusion, it appears that similar to type 1 diabetes, type 2 diabetes also increases sensitivity to dissimilar hepatotoxicants due to inhibited compensatory tissue repair, suggesting that sensitivity to hepatotoxicity in diabetes occurs in the absence as well as presence of insulin

Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats.

Science.gov (United States)

Martino-Andrade, Anderson J; Morais, Rosana N; Spercoski, Katherinne M; Rossi, Stefani C; Vechi, Marina F; Golin, Munisa; Lombardi, Natália F; Greca, Cláudio S; Dalsenter, Paulo R

2010-01-08

Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

Science.gov (United States)

Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

2016-03-01

Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest

The expression of Millettia pinnata chalcone isomerase in Saccharomyces cerevisiae salt-sensitive mutants enhances salt-tolerance.

Science.gov (United States)

Wang, Hui; Hu, Tangjin; Huang, Jianzi; Lu, Xiang; Huang, Baiqu; Zheng, Yizhi

2013-04-24

The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full length cDNA (666 bp) was obtained by 3'-end and 5'-end Rapid Amplification of cDNA Ends (RACE). The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%-86%). Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa), whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1) showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata.

Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.

Science.gov (United States)

Brand, Sarel Jacobus; Harvey, Brian Herbert

2017-08-01

Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

Pulmonary Complications of Gastric Fluid and Bile Salts Aspiration, an Experimental Study in Rat

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Mitra Samareh Fekri

2013-06-01

Full Text Available   Objective(s: Gastroesophageal Reflux Disease (GERD is one of the most common digestive disorders that frequently lead to pulmonary complications due to gastric fluid aspiration. In the present experimental study, chronic aspiration of gastric fluid, its components and bile salts in rat lung was performed to find out the main factor(s causing pulmonary complications of gastric fluid aspiration.   Materials and Methods: Forty eight male rats weighted 250-300 g were selected in six groups. After anesthesia and tracheal cannulation, the animals received 0.5 ml/kg normal saline, 0.5 ml/kg of whole gastric fluid, 0.5 ml/kg pepsin (2.5 μg/ml, 0.5 ml/kg hydrochloric acid (pH=1.5 or 0.5 ml/kg bile salts (2.5 μg/ml by injection into their trachea and lungs. In sham group nothing was injected. Results: Parenchymal and airways inflammation and fibrosis of bronchi, bronchioles and parenchyma were significantly more in the test groups compared to saline and sham groups (P

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

Science.gov (United States)

Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

Modeling Episodic Ephemeral Brine Lake Evaporation and Salt Crystallization on the Bonneville Salt Flats, Utah

Science.gov (United States)

Liu, T.; Harman, C. J.; Kipnis, E. L.; Bowen, B. B.

2017-12-01

Public concern about apparent reductions in the areal extent of the Bonneville Salt Flat (BSF) and perceived changes in inundation frequency has motivated renewed interest in the hydrologic and geochemical behavior of this salt playa. In this study, we develop a numerical modeling framework to simulate the relationship between hydrometeorologic variability, brine evaporation and salt crystallization processes on BSF. The BSF, locates in Utah, is the remnant of paleo-lake Bonneville, and is capped by up to 1 meter of salt deposition over a 100 km2 area. The BSF has two distinct hydrologic periods each year: a winter wet periods with standing surface brine and the summer dry periods when the brine is evaporated, exposing the surface salt crust. We develop a lumped non-linear dynamical models coupling conservation expressions from water, dissolved salt and thermal energy to investigate the seasonal and diurnal behavior of brine during the transition from standing brine to exposed salt at BSF. The lumped dynamic models capture important nonlinear and kinetic effects introduced by the high ionic concentration of the brine, including the pronounced effect of the depressed water activity coefficient on evaporation. The salt crystallization and dissolution rate is modeled as a kinetic process linearly proportional to the degree of supersaturation of brine. The model generates predictions of the brine temperature and the solute and solvent masses controlled by diurnal net radiation input and aerodynamic forcing. Two distinct mechanisms emerge as potential controls on salt production and dissolution: (1) evapo-concentration and (2) changes in solubility related to changes in brine temperature. Although the evaporation of water is responsible for ultimate disappearance of the brine each season ,variation in solubility is found to be the dominant control on diurnal cycles of salt precipitation and dissolution in the BSF case. Most salt is crystallized during nighttime, but the

Compound list: imatinib, methanesulfonate salt [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available imatinib, methanesulfonate salt IMA 00186 ftp://ftp.biosciencedbc.jp/archive/open-t...ggates/LATEST/Rat/in_vivo/Liver/Single/imatinib%2C_methanesulfonate_salt.Rat.in_vivo.Liver.Single.zip ...

Selective Loss of Podoplanin Protein Expression Accompanies Proteinuria and Precedes Alterations in Podocyte Morphology in a Spontaneous Proteinuric Rat Model

Science.gov (United States)

Koop, Klaas; Eikmans, Michael; Wehland, Markus; Baelde, Hans; Ijpelaar, Daphne; Kreutz, Reinhold; Kawachi, Hiroshi; Kerjaschki, Dontscho; de Heer, Emile; Bruijn, Jan Anthonie

2008-01-01

To evaluate changes during the development of proteinuria, podocyte morphology and protein expression were evaluated in spontaneously proteinuric, Dahl salt-sensitive (Dahl SS) rats. Dahl SS rats on a low-salt diet were compared with spontaneously hypertensive rats (SHR) at age 2, 4, 6, 8, and 10 weeks. Blood pressure, urinary protein excretion, urinary albumin excretion, and podocyte morphology were evaluated. In addition, the expression of 11 podocyte-related proteins was determined by analyzing protein and mRNA levels. In Dahl SS rats, proteinuria became evident around week 5, increasing thereafter. SHR rats remained non-proteinuric. Dahl SS rats showed widespread foot process effacement at 10 weeks. At ≤8 weeks, expression and distribution of the podocyte proteins was similar between the two strains, except for the protein podoplanin. At 4 weeks, podoplanin began decreasing in the glomeruli of Dahl SS rats in a focal and segmental fashion. Podoplanin loss increased progressively and correlated with albuminuria (r = 0.8, P < 0.001). Double labeling experiments revealed increased expression of the podocyte stress marker desmin in glomerular areas where podoplanin was lost. Dahl SS rats did not show podoplanin gene mutations or decreased mRNA expression. Thus, podocyte morphology and the expression and distribution of most podocyte-specific proteins were normal in young Dahl SS rats, despite marked proteinuria. Our study suggests that decreased expression of podoplanin plays a role in the decrease of glomerular permselectivity. PMID:18599604

Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

Science.gov (United States)

Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

2016-01-01

Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

Science.gov (United States)

Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

Beta-adrenoceptor changes in hypertension: cause or consequence of the elevation in blood pressure?

NARCIS (Netherlands)

Kanczik, R.; Khamssi, M.; Michel, M. C.; Brodde, O. E.

1988-01-01

Cardiac, pulmonary and renal beta-adrenoceptor density and subtype distribution were measured by radioligand binding in three rat models of acquired hypertension. Dahl salt-sensitive (DS) rats on a high-sodium diet, renal hypertensive rats and DOCA-salt rats. The results were compared with

Biliary albumin excretion induced by bile salts in rats is a pathological phenomenon

International Nuclear Information System (INIS)

Ohta, M.; Kitani, K.; Kanai, S.

1989-01-01

The bile to plasma 125I-albumin concentration ratio (B/P ratio) was examined before and during various bile salt infusions in male Wistar rats that had previously received iv injection of 125I-albumin. Endogenous rat albumin and IgG concentrations in the bile were also determined by a single radial immunodiffusion method. Taurocholate (TC) infusion (1.0 mumol/min/100 g body wt) significantly increased the bile flow rate in the first hr but the flow began to decline in the second hr. The B/P ratio as well as rat albumin (and IgG) excretion into the bile significantly increased as early as 15 min after the start of TC infusion, and the increase became more pronounced in the second hr, when the bile flow began to decrease. Infusion of taurochenodeoxycholate (TCDC, 0.4 mumol/min/100 g) caused a reduction in bile flow 15 min after the start of infusion but the B/P ratio increased 40 times at its peak compared with the basal value before the bile salt infusion. Simultaneous infusion of tauroursodeoxycholate (TUDC, 0.6 mumol/min/100 g) and TCDC not only abolished the cholestasis induced by TCDC but maintained stable choleresis as long as for 2 hr. During this choleretic period, the B/P ration never exceeded the basal value. The choleresis induced by either taurodehydrocholate (TDHC) or bucolome was not accompanied by enhanced albumin excretion. In rats given TDHC infusion, albumin excretion started to increase only after the bile flow began to decline following the initial choleretic period. The enhanced excretion of albumin induced by TC and TCDC is therefore suggested to be caused not by the choleresis per se but by a possible concomitant increase in the communication between sinusoids and bile canaliculi, which eventually leads to cholestasis

Thermodynamics of the interaction of γ-cyclodextrin and tauro- and glyco-conjugated bile salts

DEFF Research Database (Denmark)

Schönbeck, Jens Christian Sidney; Westh, Peter; Holm, René

2013-01-01

The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ-cyclodextrin was ......The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ...

Comparison of antibody responses to hen's egg and cow's milk proteins in orally sensitized rats and food-allergic patients

NARCIS (Netherlands)

Knippels, L.M.J.; Kleij, H.P.M. van der; Koppelman, S.J.; Houben, G.F.; Penninks, A.H.; Felius, A.A.

2000-01-01

Background: No adequate enteral sensitization models are available to study food allergy and the allergenicity of food proteins. To further validate an enteral brown Norway (BN) rat sensitization model under development, we studied specific protein recognition to determine whether a comparable

DNA methylation changes detected by methylation-sensitive amplified polymorphism in two contrasting rice genotypes under salt stress.

Science.gov (United States)

Wang, Wensheng; Zhao, Xiuqin; Pan, Yajiao; Zhu, Linghua; Fu, Binying; Li, Zhikang

2011-09-20

DNA methylation, one of the most important epigenetic phenomena, plays a vital role in tuning gene expression during plant development as well as in response to environmental stimuli. In the present study, a methylation-sensitive amplified polymorphism (MSAP) analysis was performed to profile DNA methylation changes in two contrasting rice genotypes under salt stress. Consistent with visibly different phenotypes in response to salt stress, epigenetic markers classified as stable inter-cultivar DNA methylation differences were determined between salt-tolerant FL478 and salt-sensitive IR29. In addition, most tissue-specific DNA methylation loci were conserved, while many of the growth stage-dependent DNA methylation loci were dynamic between the two genotypes. Strikingly, salt stress induced a decrease in DNA methylation specifically in roots at the seedling stage that was more profound in IR29 than in the FL478. This result may indicate that demethylation of genes is an active epigenetic response to salt stress in roots at the seedling stage, and helps to further elucidate the implications of DNA methylation in crop growth and development. Copyright © 2011. Published by Elsevier Ltd.

Status Report on Scoping Reactor Physics and Sensitivity/Uncertainty Analysis of LR-0 Reactor Molten Salt Experiments

Energy Technology Data Exchange (ETDEWEB)

Brown, Nicholas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Mueller, Donald E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Patton, Bruce W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Powers, Jeffrey J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division

2016-08-31

Experiments are being planned at Research Centre Rež (RC Rež) to use the FLiBe (2 ⁷LiF-BeF₂) salt from the Molten Salt Reactor Experiment (MSRE) to perform reactor physics measurements in the LR-0 low power nuclear reactor. These experiments are intended to inform on neutron spectral effects and nuclear data uncertainties for advanced reactor systems utilizing FLiBe salt in a thermal neutron energy spectrum. Oak Ridge National Laboratory (ORNL) is performing sensitivity/uncertainty (S/U) analysis of these planned experiments as part of the ongoing collaboration between the United States and the Czech Republic on civilian nuclear energy research and development. The objective of these analyses is to produce the sensitivity of neutron multiplication to cross section data on an energy-dependent basis for specific nuclides. This report provides a status update on the S/U analyses of critical experiments at the LR-0 Reactor relevant to fluoride salt-cooled high temperature reactor (FHR) and liquid-fueled molten salt reactor (MSR) concepts. The S/U analyses will be used to inform design of FLiBe-based experiments using the salt from MSRE.

Status Report on Scoping Reactor Physics and Sensitivity/Uncertainty Analysis of LR-0 Reactor Molten Salt Experiments

International Nuclear Information System (INIS)

Brown, Nicholas R.; Mueller, Donald E.; Patton, Bruce W.; Powers, Jeffrey J.

2016-01-01

Experiments are being planned at Research Centre Rež (RC Rež) to use the FLiBe (2 "7LiF-BeF_2) salt from the Molten Salt Reactor Experiment (MSRE) to perform reactor physics measurements in the LR-0 low power nuclear reactor. These experiments are intended to inform on neutron spectral effects and nuclear data uncertainties for advanced reactor systems utilizing FLiBe salt in a thermal neutron energy spectrum. Oak Ridge National Laboratory (ORNL) is performing sensitivity/uncertainty (S/U) analysis of these planned experiments as part of the ongoing collaboration between the United States and the Czech Republic on civilian nuclear energy research and development. The objective of these analyses is to produce the sensitivity of neutron multiplication to cross section data on an energy-dependent basis for specific nuclides. This report provides a status update on the S/U analyses of critical experiments at the LR-0 Reactor relevant to fluoride salt-cooled high temperature reactor (FHR) and liquid-fueled molten salt reactor (MSR) concepts. The S/U analyses will be used to inform design of FLiBe-based experiments using the salt from MSRE.

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

Science.gov (United States)

Hodges, Matthew R; Echert, Ashley E; Puissant, Madeleine M; Mouradian, Gary C

2013-04-01

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (peffects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (pCO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (peffective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

Energy Technology Data Exchange (ETDEWEB)

Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

2011-11-15

There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

International Nuclear Information System (INIS)

Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

2011-01-01

There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

The Expression of Millettia pinnata Chalcone Isomerase in Saccharomyces cerevisiae Salt-Sensitive Mutants Enhances Salt-Tolerance

Directory of Open Access Journals (Sweden)

Baiqu Huang

2013-04-01

Full Text Available The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR analyses. Its full length cDNA (666 bp was obtained by 3'-end and 5'-end Rapid Amplification of cDNA Ends (RACE. The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%–86%. Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa, whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1 showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata.

Evaluation of constitutive models for crushed salt

International Nuclear Information System (INIS)

Callahan, G.D.; Loken, M.C.; Hurtado, L.D.; Hansen, F.D.

1996-01-01

Three constitutive models are recommended as candidates for describing the deformation of crushed salt. These models are generalized to three-dimensional states of stress to include the effects of mean and deviatoric stress and modified to include effects of temperature, grain size, and moisture content. A database including hydrostatic consolidation and shear consolidation tests conducted on Waste Isolation Pilot Plant (WIPP) and southeastern New Mexico salt is used to determine material parameters for the models. To evaluate the capability of the models, parameter values obtained from fitting the complete database are used to predict the individual tests. Finite element calculations of a WIPP shaft with emplaced crushed salt demonstrate the model predictions

Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep.

Science.gov (United States)

Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Hayashi, Hisamitsu; Onuki, Reiko; Hofmann, Alan F; Sugiyama, Yuichi

2006-03-01

Na(+)-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a K(m) value of 20 microM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.

The water balance of the urban Salt Lake Valley: a multiple-box model validated by observations

Science.gov (United States)

Stwertka, C.; Strong, C.

2012-12-01

A main focus of the recently awarded National Science Foundation (NSF) EPSCoR Track-1 research project "innovative Urban Transitions and Arid-region Hydro-sustainability (iUTAH)" is to quantify the primary components of the water balance for the Wasatch region, and to evaluate their sensitivity to climate change and projected urban development. Building on the multiple-box model that we developed and validated for carbon dioxide (Strong et al 2011), mass balance equations for water in the atmosphere and surface are incorporated into the modeling framework. The model is used to determine how surface fluxes, ground-water transport, biological fluxes, and meteorological processes regulate water cycling within and around the urban Salt Lake Valley. The model is used to evaluate the hypotheses that increased water demand associated with urban growth in Salt Lake Valley will (1) elevate sensitivity to projected climate variability and (2) motivate more attentive management of urban water use and evaporative fluxes.

Sensitivity to apomorphine-induced yawning and hypothermia in rats eating standard or high-fat chow.

Science.gov (United States)

Baladi, Michelle G; Thomas, Yvonne M; France, Charles P

2012-07-01

Feeding conditions modify sensitivity to indirect- and direct-acting dopamine receptor agonists as well as the development of sensitization to these drugs. This study examined whether feeding condition affects acute sensitivity to apomorphine-induced yawning or changes in sensitivity that occur over repeated drug administration. Quinpirole-induced yawning was also evaluated to see whether sensitization to apomorphine confers cross-sensitization to quinpirole. Drug-induced yawning was measured in different groups of male Sprague Dawley rats (n = 6/group) eating high (34.3%) fat or standard (5.7% fat) chow. Five weeks of eating high-fat chow rendered otherwise drug-naïve rats more sensitive to apomorphine- (0.01-1.0 mg/kg, i.p.) and quinpirole- (0.0032-0.32 mg/kg, i.p.) induced yawning, compared with rats eating standard chow. In other rats, tested weekly with apomorphine, sensitivity to apomorphine-induced yawning increased (sensitization) similarly in rats with free access to standard or high-fat chow; conditioning to the testing environment appeared to contribute to increased yawning in both groups of rats. Food restriction decreased sensitivity to apomorphine-induced yawning across five weekly tests. Rats with free access to standard or high-fat chow and sensitized to apomorphine were cross-sensitized to quinpirole-induced yawning. The hypothermic effects of apomorphine and quinpirole were not different regardless of drug history or feeding condition. Eating high-fat chow or restricting access to food alters sensitivity to direct-acting dopamine receptor agonists (apomorphine, quinpirole), although the relative contribution of drug history and dietary conditions to sensitivity changes appears to vary among agonists.

Sensitivity of modeled atmospheric nitrogen species and nitrogen deposition to variations in sea salt emissions in the North Sea and Baltic Sea regions

Directory of Open Access Journals (Sweden)

D. Neumann

2016-03-01

Full Text Available Coarse sea salt particles are emitted ubiquitously from the ocean surface by wave-breaking and bubble-bursting processes. These particles impact the atmospheric chemistry by affecting the condensation of gas-phase species and, thus, indirectly the nucleation of new fine particles, particularly in regions with significant air pollution. In this study, atmospheric particle concentrations are modeled for the North Sea and Baltic Sea regions in northwestern Europe using the Community Multiscale Air Quality (CMAQ modeling system and are compared to European Monitoring and Evaluation Programme (EMEP measurement data. The sea salt emission module is extended by a salinity-dependent scaling of the sea salt emissions because the salinity in large parts of the Baltic Sea is very low, which leads to considerably lower sea salt mass emissions compared to other oceanic regions. The resulting improvement in predicted sea salt concentrations is assessed. The contribution of surf zone emissions is considered separately. Additionally, the impacts of sea salt particles on atmospheric nitrate and ammonium concentrations and on nitrogen deposition are evaluated. The comparisons with observational data show that sea salt concentrations are commonly overestimated at coastal stations and partly underestimated farther inland. The introduced salinity scaling improves the predicted Baltic Sea sea salt concentrations considerably. The dates of measured peak concentrations are appropriately reproduced by the model. The impact of surf zone emissions is negligible in both seas. Nevertheless, they might be relevant because surf zone emissions were cut at an upper threshold in this study. Deactivating sea salt leads to minor increases in NH3 +  NH4+ and HNO3 +  NO3− and a decrease in NO3− concentrations. However, the overall effect on NH3 +  NH4+ and HNO3 +  NO3− concentrations is smaller than the deviation from the measurements. Nitrogen wet deposition is

Lecithin inhibits fatty acid and bile salt absorption from rat small intestine in vivo.

Science.gov (United States)

Saunders, D R; Sillery, J

1976-12-01

During digestion of a fatty meal, long chain free fatty acids (FFA) and lecithin are among the lipids solubilized in intestinal contents as mixed micelles with bile salts. We hypothesized that if lecithin were not hydrolyzed, the mixed micelles would be abnormal, and absorption of FFA and bile salts would be depressed. To test this hypothesis, isolated segments of rat small intestine were infused in vivo with micellar solutions of 2 mMolar linoleic acid and 10 mMolar taurocholate to which was added 3 mMolar 1-palmitoyl, 2-oleoyl lecithin (a common lecithin in bile and food), or 1-palmitoyl lysolecithin (the hydrolytic product of lecithin). Absorption of FFA and bile salt was measured under steady state conditions using a single-pass technique. Lecithin depressed the rate of FFA absorption by 40% (p less than 0.025) in jejunal and ileal segments whereas lysolecithin was associated with normal rates of FFA absorption. Lecithin also reduced taurocholate absorption from the ileum by 30% (p less than 0.05). These data support the idea that lecithin may depress FFA and bile salt absorption from the small intestine in pancreatic insufficiency.

The Effect of KIO3 and KI Salt towards Iodium Levels (I2 in Urine, Malondialdehyde (MDA and Histological Thyroid Gland of The Goitrogenic Rat

Directory of Open Access Journals (Sweden)

Chanif Mahdi

2014-04-01

Full Text Available Goitrogenic a substance that can inhibit the taking of iodine by the thyroid gland, so that the concentration of iodine in the thyroid to be low., is characterized by the inflammation in the gland thyroid area caused an excessive of free radicals. An excessive of free radicals in the body cause oxidative stress, That increasing the levels of malondialdehyde (MDA as an indicator of lipid peroxidation and decreased levels of urinary iodine excretion levels (EIU. The treated to give KIO3 and KI salt was intended to determine the level of supplementation of iodine (I2, the level of MDA in serum and histological rat thyroid gland. MDA levels are determined through a TBA test (Thio Barbituric acid, meanwhile the histological of the rat thyroid gland was determined by Hematoxylen-Eosin staining (HE. The results showed the KIO3 and KI salt was significantly (p<0.05 reduce levels of MDA in the serum of treatment with KIO3 salt (33.62% and KI salt (37,02% and improving histological of the thyroid gland rats.

Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats.

Science.gov (United States)

Szasz, Theodora; Watts, Stephanie W

2010-06-01

Uric acid (UA) results from xanthine oxidase (XO) catabolism of xanthine and is the final product of purine catabolism in humans. In this species, hyperuricemia is associated with gout, nephropathy, and increased cardiovascular disease risk. Although the effects of hyperuricemia in vascular biology are overall controversial, UA has been described as an antioxidant and as potentially improving endothelial function. Hypertension is associated with endothelial dysfunction. We hypothesized that UA improves the endothelial function of aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. UA (100 microM) in the presence of the uricase inhibitor oxonic acid (10 microM) did not modify relaxation to acetylcholine (ACh) (1 nM-10 microM) in the aorta from nontreated, sham normotensive, and DOCA-salt hypertensive rats [response to 10 microM ACh for UA versus vehicle, respectively: nontreated = 37 +/- 7 versus 48 +/- 7%, sham = 53 +/- 15 versus 57 +/- 20%, DOCA = 81 +/- 4 versus 85 +/- 2% from 20 microM prostaglandin 2alpha (PGF(2alpha))-induced contraction]. Allopurinol (100 microM), a XO inhibitor, did not significantly alter the ACh-induced relaxation of sham and DOCA aortic rings (response to 10 microM ACh for allopurinol versus vehicle, respectively: sham = 61 +/- 5 versus 68 +/- 9%, DOCA = 87 +/- 6 versus 88 +/- 3% from 20 microM PGF(2alpha)-induced contraction). Uricemia, ranging from unmeasurable to 547 microM in sham and to 506 microM in DOCA rats, was not significantly different between these two groups. The expression and activity of XO, as well as the expression of uricase, were not different between sham and DOCA rat aorta. We conclude that, at least in vitro, UA does not affect the ACh-induced relaxation of normotensive and DOCA-salt hypertensive rats.

Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

Science.gov (United States)

Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

2016-01-01

One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

DEFF Research Database (Denmark)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting

2016-01-01

Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX......) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal...

Histomorphometric, biochemical and ultrastructural changes in the aorta of salt-loaded stroke-prone spontaneously hypertensive rats fed a Japanese-style diet.

Science.gov (United States)

Baccarani Contri, M; Taparelli, F; Miselli, M; Bacchelli, B; Biagini, G

2003-02-01

It is demonstrated that dietary habits play a role in cardiovascular diseases. In stroke-prone spontaneously hypertensive rats (SHRsp), concomitant salt loading and a Japanese-style diet greatly accelerate hypertension and the appearance of cerebrovascular lesions by directly damaging arterial vessels. A number of studies have characterised medium and small vessel lesions in SHRsp, but little attention has been paid to the changes in the wall structure of large arteries induced by exposure to a salt-enriched diet. The aim of this study was to investigate the effects of a Japanese-style diet and salt loading on the thoracic aorta. Two-month-old SHRsp were kept on a Japanese-style diet with 1% sodium chloride solution replacing tap water. Two months later, they were sacrificed and compared with age-matched or two-month-old control SHRsp kept on a standard diet and tap water in terms of the histomorphometry, ultrastructure and biochemical composition of the thoracic aorta. The vessel was consistently thicker in the four-month-old SHRsp (+20%, p vs two-month-old rats) regardless of diet. The salt-loaded SHRsp showed a significant reduction in elastic fibre density (-20%, p vs two-month-old rats) and an increase in the other matrix components (%), whereas the four-month-old controls showed preserved elastic fibres and a significant increase in the other matrix components (+65%, p vs two-month-old rats). There was a considerable increase in the amounts of 4-OH-proline (+147%), 5-OH-lysine (+174%) and desmosines (+360%) in the four-month-old controls vs their two-month-old counterparts (p two months of treatment.

Mathematical model of salt cavern leaching for gas storage in high-insoluble salt formations.

Science.gov (United States)

Li, Jinlong; Shi, Xilin; Yang, Chunhe; Li, Yinping; Wang, Tongtao; Ma, Hongling

2018-01-10

A mathematical model is established to predict the salt cavern development during leaching in high-insoluble salt formations. The salt-brine mass transfer rate is introduced, and the effects of the insoluble sediments on the development of the cavern are included. Considering the salt mass conservation in the cavern, the couple equations of the cavern shape, brine concentration and brine velocity are derived. According to the falling and accumulating rules of the insoluble particles, the governing equations of the insoluble sediments are deduced. A computer program using VC++ language is developed to obtain the numerical solution of these equations. To verify the proposed model, the leaching processes of two salt caverns of Jintan underground gas storage are simulated by the program, using the actual geological and technological parameters. The same simulation is performed by the current mainstream leaching software in China. The simulation results of the two programs are compared with the available field data. It shows that the proposed software is more accurate on the shape prediction of the cavern bottom and roof, which demonstrates the reliability and applicability of the model.

The concentration of kynurenine in rat model of asthma.

Directory of Open Access Journals (Sweden)

Barbara Mroczko

2008-06-01

Full Text Available Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN. To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC. In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01. In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma.

Modeling of Salt Solubilities in Mixed Solvents

DEFF Research Database (Denmark)

Chiavone-Filho, O.; Rasmussen, Peter

2000-01-01

A method to correlate and predict salt solubilities in mixed solvents using a UNIQUAC+Debye-Huckel model is developed. The UNIQUAC equation is applied in a form with temperature-dependent parameters. The Debye-Huckel model is extended to mixed solvents by properly evaluating the dielectric...... constants and the liquid densities of the solvent media. To normalize the activity coefficients, the symmetric convention is adopted. Thermochemical properties of the salt are used to estimate the solubility product. It is shown that the proposed procedure can describe with good accuracy a series of salt...

(−-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

Directory of Open Access Journals (Sweden)

Douglas Jackson

2018-06-01

Full Text Available (−-Epicatechin (E is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-α-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day on the cardiovascular function of deoxycorticosterone acetate (DOCA-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX, UNX + E, DOCA, DOCA + E. DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05. Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts.

Derivatization of peptides as quaternary ammonium salts for sensitive detection by ESI-MS.

Science.gov (United States)

Cydzik, Marzena; Rudowska, Magdalena; Stefanowicz, Piotr; Szewczuk, Zbigniew

2011-06-01

A series of model peptides in the form of quaternary ammonium salts at the N-terminus was efficiently prepared by the solid-phase synthesis. Tandem mass spectrometric analysis of the peptide quaternary ammonium derivatives was shown to provide sequence confirmation and enhanced detection. We designed the 2-(1,4-diazabicyclo[2.2.2] octylammonium)acetyl quaternary ammonium group which does not suffer from neutral losses during MS/MS experiments. The presented quaternization of 1,4-diazabicyclo[2.2.2]octane (DABCO) by iodoacetylated peptides is relatively easy and compatible with standard solid-phase peptide synthesis. This methodology offers a novel sensitive approach to analyze peptides and other compounds. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

Energy Technology Data Exchange (ETDEWEB)

Snodin, Benedict E. K., E-mail: benedict.snodin@chem.ox.ac.uk; Mosayebi, Majid; Schreck, John S.; Romano, Flavio; Doye, Jonathan P. K., E-mail: jonathan.doye@chem.ox.ac.uk [Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ (United Kingdom); Randisi, Ferdinando [Life Sciences Interface Doctoral Training Center, South Parks Road, Oxford OX1 3QU (United Kingdom); Rudolf Peierls Centre for Theoretical Physics, 1 Keble Road, Oxford OX1 3NP (United Kingdom); Šulc, Petr [Center for Studies in Physics and Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065 (United States); Ouldridge, Thomas E. [Department of Mathematics, Imperial College, 180 Queen’s Gate, London SW7 2AZ (United Kingdom); Tsukanov, Roman; Nir, Eyal [Department of Chemistry and the Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer Sheva (Israel); Louis, Ard A. [Rudolf Peierls Centre for Theoretical Physics, 1 Keble Road, Oxford OX1 3NP (United Kingdom)

2015-06-21

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na{sup +}] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

International Nuclear Information System (INIS)

Snodin, Benedict E. K.; Mosayebi, Majid; Schreck, John S.; Romano, Flavio; Doye, Jonathan P. K.; Randisi, Ferdinando; Šulc, Petr; Ouldridge, Thomas E.; Tsukanov, Roman; Nir, Eyal; Louis, Ard A.

2015-01-01

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na + ] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA

Constitutive modeling of salt behavior: State of the technology

International Nuclear Information System (INIS)

Munson, D.E.; Wawersik, W.R.

1992-01-01

The modern investigation of the thermomechanical behavior of salt started in the mid-1930's and, for what appears to be a very narrow discipline, ''salt mechanics'' has acquired considerable technical depth and sophistication. The last three decades have been especially productive in constitutive model development and laboratory investigations of time-dependent creep behavior. This has been largely due ot anticipated use of domal or bedded salt deposits as sites for radioactive waste repositories and to expanded need for hydrocarbon and feedback storage caverns. Salt is an interesting material, in that it is ''metal-like''; and, therefore, constitutive modeling can draw upon a large body of metal deformation information to arrive at appropriate models of behavior. Testing apparatus and methods have centered on either uniaxial or triaxial compression to obtain steady state and transient creep responses. Flow and fracture potentials have been defined. Validation attempts of the models against field data, although limited, have proved promising. The objective here is to summarize the state-of-the-technology of the constitutive modeling of salt behavior or ''salt mechanics.''

Mechanical modeling of the growth of salt structures

Energy Technology Data Exchange (ETDEWEB)

Alfaro, Ruben Alberto Mazariegos [Texas A & M Univ., College Station, TX (United States)

1993-05-01

A 2D numerical model for studying the morphology and history of salt structures by way of computer simulations is presented. The model is based on conservation laws for physical systems, a fluid marker equation to keep track of the salt/sediments interface, and two constitutive laws for rocksalt. When buoyancy alone is considered, the fluid-assisted diffusion model predicts evolution of salt structures 2.5 times faster than the power-law creep model. Both rheological laws predict strain rates of the order of 4.0 x 10^-15 s^-1 for similar structural maturity level of salt structures. Equivalent stresses and viscosities predicted by the fluid-assisted diffusion law are 10² times smaller than those predicted by the power-law creep rheology. Use of East Texas Basin sedimentation rates and power-law creep rheology indicate that differential loading is an effective mechanism to induce perturbations that amplify and evolve to mature salt structures, similar to those observed under natural geological conditions.

Salt-Induced Hypertension in a Mouse Model of Liddle's Syndrome is Mediated by Epithelial Sodium Channels in the Brain

Science.gov (United States)

Van Huysse, James W.; Amin, Md. Shahrier; Yang, Baoli; Leenen, Frans H. H.

2012-01-01

Neural precursor cell expressed and developmentally downregulated 4-2 protein (Nedd4-2) facilitates the endocytosis of epithelial Na channels (ENaC). Both mice and humans with a loss of regulation of ENaC by Nedd4-2 have salt-induced hypertension. ENaC is also expressed in the brain, where it is critical for hypertension on high salt diet in salt-sensitive rats. In the present studies we assessed whether Nedd4-2 knockout (−/−) mice have: 1) increased brain ENaC; 2) elevated CSF sodium on high salt diet; and 3) enhanced pressor responses to CSF sodium and hypertension on high salt diet, both mediated by brain ENaC. Prominent choroid plexus and neuronal ENaC staining was present in −/− but not in wild-type (W/T) mice. In chronically instrumented mice, intracerebroventricular (icv) infusion of Na-rich aCSF increased MAP 3-fold higher in −/− than W/T. Icv infusion of the ENaC blocker benzamil abolished this enhancement. In telemetered −/− mice on high salt diet (8% NaCl), CSF [Na+], MAP and HR increased significantly, MAP by 30-35 mmHg. These MAP and HR responses were largely prevented by icv benzamil, but only to a minor extent by sc benzamil at the icv rate. We conclude that increased ENaC expression in the brain of Nedd 4-2 −/− mice mediates their hypertensive response to high salt diet, by causing increased sodium levels in the CSF as well as hyper-responsiveness to CSF sodium. These findings highlight the possible causative contribution of CNS ENaC in the etiology of salt-induced hypertension. PMID:22802227

Evaluation of potential crushed-salt constitutive models

International Nuclear Information System (INIS)

Callahan, G.D.; Loken, M.C.; Sambeek, L.L. Van; Chen, R.; Pfeifle, T.W.; Nieland, J.D.; Hansen, F.D.

1995-12-01

Constitutive models describing the deformation of crushed salt are presented in this report. Ten constitutive models with potential to describe the phenomenological and micromechanical processes for crushed salt were selected from a literature search. Three of these ten constitutive models, termed Sjaardema-Krieg, Zeuch, and Spiers models, were adopted as candidate constitutive models. The candidate constitutive models were generalized in a consistent manner to three-dimensional states of stress and modified to include the effects of temperature, grain size, and moisture content. A database including hydrostatic consolidation and shear consolidation tests conducted on Waste Isolation Pilot Plant and southeastern New Mexico salt was used to determine material parameters for the candidate constitutive models. Nonlinear least-squares model fitting to data from the hydrostatic consolidation tests, the shear consolidation tests, and a combination of the shear and hydrostatic tests produces three sets of material parameter values for the candidate models. The change in material parameter values from test group to test group indicates the empirical nature of the models. To evaluate the predictive capability of the candidate models, each parameter value set was used to predict each of the tests in the database. Based on the fitting statistics and the ability of the models to predict the test data, the Spiers model appeared to perform slightly better than the other two candidate models. The work reported here is a first-of-its kind evaluation of constitutive models for reconsolidation of crushed salt. Questions remain to be answered. Deficiencies in models and databases are identified and recommendations for future work are made. 85 refs

Responses to cholinergic agonists of rats selectively bred for differential sensitivity to ethanol.

Science.gov (United States)

de Fiebre, C M; Romm, E; Collins, J T; Draski, L J; Deitrich, R A; Collins, A C

1991-03-01

Alcoholics are almost invariably heavy users of tobacco. Both alcoholism and smoking appear to be influenced by genetic factors but it is not known whether the same or different genes regulate the abuse of ethanol and nicotine. Recent studies have demonstrated that the long-sleep (LS) and short-sleep (SS) mouse lines, which were selectively bred for differences in ethanol-induced anesthesia ("sleep-time"), also differ in several effects of nicotine and the muscarinic agonist, oxotremorine. In order to determine whether or not these differences are due to chance, the relative sensitivities of rat lines which were selectively bred for differences in ethanol-induced sleep-time were determined. The high alcohol sensitivity (HAS) rat line was more sensitive to the locomotor and body temperature depressant effects of nicotine than was the low alcohol sensitivity (LAS) rat line. The control line (CAS) was intermediate in sensitivity. The rat lines did not differ in sensitivity to oxotremorine's hypothermia-producing effects. The numbers and affinities of two classes of brain nicotinic receptors were measured in eight brain regions. No differences among the rat lines were detected. These results suggest that ethanol elicits some of its depressant actions via an effect on brain nicotinic systems, but the differences in sensitivity to ethanol and nicotine are probably not due to differences in the number of brain nicotinic receptors. Perhaps this interaction explains the high correlation between alcoholism and smoking in humans.

Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model

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Yusuke Kemmochi

2013-01-01

Full Text Available Spontaneously Diabetic Torii Leprfa (SDT fatty rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

Eating high-fat chow enhances sensitization to the effects of methamphetamine on locomotion in rats.

Science.gov (United States)

McGuire, Blaine A; Baladi, Michelle G; France, Charles P

2011-05-11

Eating high-fat chow can modify the effects of drugs acting directly or indirectly on dopamine systems and repeated intermittent drug administration can markedly increase sensitivity (i.e., sensitization) to the behavioral effects of indirect-acting dopamine receptor agonists (e.g., methamphetamine). This study examined whether eating high-fat chow alters the sensitivity of male Sprague Dawley rats to the locomotor stimulating effects of acute or repeated administration of methamphetamine. The acute effects of methamphetamine on locomotion were not different between rats (n=6/group) eating high-fat or standard chow for 1 or 4 weeks. Sensitivity to the effects of methamphetamine (0.1-10mg/kg, i.p.) increased progressively across 4 once per week tests; this sensitization developed more rapidly and to a greater extent in rats eating high-fat chow as compared with rats eating standard chow. Thus, while eating high-fat chow does not appear to alter sensitivity of rats to acutely-administered methamphetamine, it significantly increases the sensitization that develops to repeated intermittent administration of methamphetamine. These data suggest that eating certain foods influences the development of sensitization to drugs acting on dopamine systems. Copyright © 2011 Elsevier B.V. All rights reserved.

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

Science.gov (United States)

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.

Science.gov (United States)

de Fiebre, NancyEllen C; Dawson, Ralph; de Fiebre, Christopher M

2002-06-01

Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.

Sensitivity to deliberate sea salt seeding of marine clouds - observations and model simulations

OpenAIRE

Alterskjaer, K.; Kristjansson, J. E.; Seland, O.

2012-01-01

Sea salt seeding of marine clouds to increase their albedo is a proposed technique to counteract or slow global warming. In this study, we first investigate the susceptibility of marine clouds to sea salt injections, using observational data of cloud droplet number concentration, cloud optical depth, and liquid cloud fraction from the MODIS (Moderate Resolution Imaging Spectroradiometer) instruments on board the Aqua and Terra satellites. We then compare the derived susceptibility function to...

Modification of thermal sensitivity of Chinese hamster cells by exposure to solutions of monovalent and divalent cationic salts

International Nuclear Information System (INIS)

Raaphorst, G.P.; Azzam, E.I.; Vadasz, J.

1984-06-01

Chinese hamster V79 cells were heated in culture medium or in 0.155-mol.dm -3 solutions of LiCl, NaCl, KCl, MgCl 2 , CaCl 2 and BaCl 2 . The presence of any one of these ionic solutions during heating increased the thermal sensitivity of the cells. The order of increased thermal sensitivity was KCl > LiCl > NaCl for the monovalent salts and BaCl 2 > MgCl 2 > CaCl 2 for the divalent cation salts. The addition of glucose to LiCl or NaCl solutions did not reduce the thermal sensitization caused by these solutions. When cells were sensitized by LiCl or NaCl treatment, a change in pH from 7.2 to 6.6 did not further increase thermal sensitivity. These data show that nutrient and ionic factors and their interplay are involved in cellular thermal sensitivity

The relation of Cx43 and NMDA to visceral sensitization in rats with irritable bowel syndrome

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Jing-yu ZHANG

2016-01-01

Full Text Available Objective 　To study the relationship between connexin 43 (Cx43 and N-methyl-D-aspartate (NMDA receptors and visceral sensitization in the rats with irritable bowel syndrome (IBS. Methods 　Thirty rats were gavaged with Triehinella spiralis to reproduce the IBS model. These rats were randomly divided into IBS group, IBS+colon distension group, and IBS+STI-571+colon distension group, and other groups of normal rats were randomized into normal group and normal+colon distension group, with 10 rats in each group. Immunofluorescent double staining were used to observe the expressions of intestine Cx43 and sacral NMDA re ceptors of rats in all the groups. Results 　The Cx43 and sacral NMDA expressions in the normal group, normal+colon distension group and IBS group showed no significant changes (P>0.05, however, Cx43 and sacral NMDA expressions were significantly higher in IBS rats with colon distension as compared with those in normal group, normal+colon distension group, and IBS group (P<0.05, while they were significantly lower in the IBS+STI-571+colon distension group after STI-571 intervention (P<0.05. Conclusion 　Cx43 and sacral NMDA may be the most important factor of visceral sensitization in IBS rats. DOI: 10.11855/j.issn.0577-7402.2015.12.02

Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.

Science.gov (United States)

Omerbašić, Damir; Smith, Ewan St J; Moroni, Mirko; Homfeld, Johanna; Eigenbrod, Ole; Bennett, Nigel C; Reznick, Jane; Faulkes, Chris G; Selbach, Matthias; Lewin, Gary R

2016-10-11

The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat

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Damir Omerbašić

2016-10-01

Full Text Available The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF, an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.

Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt Seeking.

Science.gov (United States)

Chang, Stephen E; Smedley, Elizabeth B; Stansfield, Katherine J; Stott, Jeffrey J; Smith, Kyle S

2017-06-07

Salt appetite, in which animals can immediately seek out salt when under a novel state of sodium deprivation, is a classic example of how homeostatic systems interface with learned associations to produce an on-the-fly updating of motivated behavior. Neural activity in the ventral pallidum (VP) has been shown to encode changes in the value of salt under such conditions, both the value of salt itself (Tindell et al., 2006) and the motivational value of its predictive cues (Tindell et al., 2009; Robinson and Berridge, 2013). However, it is not known whether the VP is necessary for salt appetite in terms of seeking out salt or consuming salt following sodium depletion. Here, we used a conditioned place-preference procedure to investigate the effects of optogenetically inhibiting the VP on context-driven salt seeking and the consumption of salt following deprivation. Male rats learned to associate one context with sucrose and another context with less-desirable salt. Following sodium depletion, and in the absence of either sucrose or salt, we found that inhibiting the VP selectively reduced the elevation in time spent in the salt-paired context. VP inhibition had minimal effects on the consumption of salt once it was made available. To our knowledge, this is the first evidence that the VP or any brain region is necessary for the ability to use contextual cues to guide salt seeking. These results highlight a dissociation between deficit-driven reward seeking and reward consumption to replenish those deficits, with the former process being particularly sensitive to on-line VP activity. SIGNIFICANCE STATEMENT Salt appetite, in which rats will immediately seek out a once-undesirable concentrated salt solution after being depleted of bodily sodium despite never having tasted salt as a positive reward, is a phenomenon showing how animals can update their motivational goals without any new learning or conditioning. This salt-seeking behavior is also observed when the animal

Cardiosphere-Derived Cells Reverse Heart Failure With Preserved Ejection Fraction in Rats by Decreasing Fibrosis and Inflammation

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Romain Gallet, MD

2016-01-01

Full Text Available The pathogenesis of heart failure with a preserved ejection fraction (HFpEF is unclear. Myocardial fibrosis, inflammation, and cardiac hypertrophy have been suggested to contribute to the pathogenesis of HFpEF. Cardiosphere-derived cells (CDCs are heart-derived cell products with antifibrotic and anti-inflammatory properties. This study tested whether rat CDCs were sufficient to decrease manifestations of HFpEF in hypertensive rats. Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6 to 7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. High-salt rats developed hypertension, left ventricular (LV hypertrophy, and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion, and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed that CDCs reversed changes in numerous transcripts associated with HFpEF, including many involved in inflammation and/or fibrosis. These studies suggest that CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF.

Intestinal inflammation in TNBS sensitized rats as a model of chronic inflammatory bowel disease

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N. Selve

1992-01-01

Full Text Available An enteritis, based on a delayed-type hypersensitivity reaction, was induced in TNBS (2,4,4-trinitrobenzenesulphonic acid sensitized rats by multiple intrajejunal challenge with TNBS via an implanted catheter. This treatment induced chronic inflammation of the distal small intestine characterized by intense hyperaemia, oedema and gut wall thickening as assessed by macroscopic scoring and weighing a defined part of the dissected intestine. Histologically, the inflammatory response included mucosal and submucosal cell infiltration by lymphocytes and histiocytes, transmural granulomatous inflammation with multinucleated cells and activated mesenteric lymph nodes. Ex vivo stimulated release of the inflammatory mediator LTB4 in the dissected part of the intestine was increased following TNBS treatment. Drug treatment with sulphasalazine or 5-aminosalicylic acid improved the enteritis score and attenuated TNBS induced oedema formation and LTB4 production. The applicability and relevance of this new model are discussed with respect to drug development and basic research of inflammatory bowel diseases.

A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

Science.gov (United States)

Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

2016-06-01

The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats.

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Eiichiro Yamamoto

Full Text Available The combination therapy of an angiotensin receptor blocker (ARB with a calcium channel blocker (CCB or with a diuretic is favorably recommended for the treatment of hypertension. However, the difference between these two combination therapies is unclear. The present work was undertaken to examine the possible difference between the two combination therapies in vascular protection. Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP were divided into 6 groups, and they were orally administered (1 vehicle, (2 olmesartan, an ARB, (3 azelnidipine, a CCB, (4 hydrochlorothiazide, a diuretic, (5 olmesartan combined with azelnidipine, or (6 olmesartan combined with hydrochlorothiazide. Olmesartan combined with either azelnidipine or hydrochlorothiazide ameliorated vascular endothelial dysfunction and remodeling in SHRSP more than did monotherapy with either agent. However, despite a comparable blood pressure lowering effect between the two treatments, azelnidipine enhanced the amelioration of vascular endothelial dysfunction and remodeling by olmesartan to a greater extent than did hydrochlorothiazide in salt-loaded SHRSP. The increased enhancement by azelnidipine of olmesartan-induced vascular protection than by hydrochlorothiazide was associated with a greater amelioration of vascular nicotinamide adenine dinucleotide phosphate (NADPH oxidase activation, superoxide, mitogen-activated protein kinase activation, and with a greater activation of the Akt/endothelial nitric oxide synthase (eNOS pathway. These results provided the first evidence that a CCB potentiates the vascular protective effects of an ARB in salt-sensitive hypertension, compared with a diuretic, and provided a novel rationale explaining the benefit of the combination therapy with an ARB and a CCB.

Modelling of the thermomechanical behaviour of salt rock

International Nuclear Information System (INIS)

Albers, G.; Graefe, V.; Korthaus, E.; Pudewillis, A.; Prij, J.

1986-01-01

The modelling of the thermomechanical behaviour of salt rock is examined, with respect to the disposal of radioactive waste in salt formations. The calculation methods and programmes currently available for the modelling are described. Some examples are given of calculations carried out in parallel with tests. Some results of modelling calculations for a repository are presented by way of illustration. (U.K.)

Early life stress sensitizes the renal and systemic sympathetic system in rats.

Science.gov (United States)

Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P renal and systemic sympathetic system ultimately impairing blood pressure regulation.

The γ-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens.

Science.gov (United States)

Fu, Zhenyu; Yang, Hongfa; Xiao, Yuqiang; Zhao, Gang; Huang, Haiyan

2012-07-10

Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.

Mitochondria from rat uterine smooth muscle possess ATP-sensitive potassium channel

Directory of Open Access Journals (Sweden)

Olga B. Vadzyuk

2018-03-01

Full Text Available The objective of this study was to detect ATP-sensitive K+ uptake in rat uterine smooth muscle mitochondria and to determine possible effects of its activation on mitochondrial physiology. By means of fluorescent technique with usage of K+-sensitive fluorescent probe PBFI (potassium-binding benzofuran isophthalate we showed that accumulation of K ions in isolated mitochondria from rat myometrium is sensitive to effectors of KATP-channel (ATP-sensitive K+-channel – ATP, diazoxide, glibenclamide and 5HD (5-hydroxydecanoate. Our data demonstrates that K+ uptake in isolated myometrium mitochondria results in a slight decrease in membrane potential, enhancement of generation of ROS (reactive oxygen species and mitochondrial swelling. Particularly, the addition of ATP into incubation medium led to a decrease in mitochondrial swelling and ROS production, and an increase in membrane potential. These effects were eliminated by diazoxide. If blockers of KATP-channel were added along with diazoxide, the effects of diazoxide were removed. So, we postulate the existence of KATP-channels in rat uterus mitochondria and assume that their functioning may regulate physiological conditions of mitochondria, such as matrix volume, ROS generation and polarization of mitochondrial membrane. Keywords: ATP-sensitive potassium channel, Diazoxide, 5-hydroxydecanoate, Myometrium, Mitochondria, Mitochondrial swelling, Mitochondrial membrane potential, ROS

A universal salt model based on under-ground precipitation of solid salts due to supercritical water `out-salting'

Science.gov (United States)

Rueslåtten, H.; Hovland, M. T.

2010-12-01

One of the common characteristics of planets Earth and Mars is that both host water (H2O) and large accumulations of salt. Whereas Earth’s surface-environment can be regarded as ‘water-friendly’ and ‘salt hostile’, the reverse can be said for the surface of Mars. This is because liquid water is stable on Earth, and the atmosphere transports humidity around the globe, whereas on planet Mars, liquid water is unstable, rendering the atmosphere dry and, therefore, ‘salt-friendly’. The riddle as to how the salt accumulated in various locations on those two planets, is one of long-lasting and great debate. The salt accumulations on Earth are traditionally termed ‘evaporites’, meaning that they formed as a consequence of the evaporation of large masses of seawater. How the accumulations on Mars formed is much harder to explain, as an ocean only existed briefly. Although water molecules and OH-groups may exist in abundance in bound form (crystal water, adsorbed water, etc.), the only place where free water is expected to be stable on Mars is within underground faults, fractures, and crevices. Here it likely occurs as brine or in the form of ice. Based on these conditions, a key to understanding the accumulation of large deposits of salt on both planets is linked to how brines behave in the subsurface when pressurized and heated beyond their supercritical point. At depths greater than about 3 km (P>300 bars) water will no longer boil in a steam phase. Rather, it becomes supercritical and will attain the phase of supercritical water vapor (SCRIW) with a specific gravity of typically 0.3 g/cm3. An important characteristic of SCRIW is its inability to dissolve the common sea salts. The salt dissolved in the brines will therefore precipitate as solid particles when brines (seawater on the Earth) move into the supercritical P&T-domain (T>400°C, P>300 bars). Numerical modeling of a hydrothermal system in the Atlantis II Deep of the Red Sea indicates that a

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Energy Technology Data Exchange (ETDEWEB)

Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

2014-05-09

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

International Nuclear Information System (INIS)

Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.

2014-01-01

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations

Energy Technology Data Exchange (ETDEWEB)

Kirman, C.R., E-mail: ckirman@summittoxicology.com [Summit Toxicology, PO Box 3209, Bozeman, MT 59715 (United States); Suh, M.; Proctor, D.M. [ToxStrategies, Mission Viejo, CA (United States); Hays, S.M. [Summit Toxicology, PO Box 3209, Bozeman, MT 59715 (United States)

2017-06-15

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. - Highlights: • An improved version of the PBPK model for Cr(VI) toxicokinetics was developed. • The model incorporates data collected to fill important data gaps. • Model predictions for specific age groups and sensitive subpopulations are provided. • Implications to human health risk assessment are discussed.

Chronic exposure to MDMA (Ecstasy elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

Directory of Open Access Journals (Sweden)

Swann Alan C

2006-01-01

Full Text Available Abstract Background The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA. Methods The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg and a saline control group (N = 9/group. All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13. Rats were then given an additional 25-day washout period, and re-challenged (day 38 with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39. Open-field locomotor activity was recorded using a computerized automated activity monitoring system. Results Acute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group, while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change

Improvements of Spiers model for compaction creep of crushed rock salt

International Nuclear Information System (INIS)

Poley, A.D.

1996-10-01

This report describes a number of improvements to the existing model for the process of compaction creep of rock salt developed by Spiers and co-workers. The process of compaction creep determines the behaviour of the seals of crushed rock salt, the last engineered barriers of a repository in rock salt for (radioactive) wastes. In Chapter 2 the derivation of the original model of Spiers and co-workers is followed except for some simplifying approximations. A comparison of the model results is made with experimental data and a number of model adjustments are suggested. In Chapter 3 one of these suggested model adjustments is explored, and an alternative model is developed. The results obtained with this model compare favourably with the experimental data without the use of adjustable shape functions as for the original model. Preliminary investigations of the impact of the new model on estimated releases to the geosphere of radionuclides form a repository in rock salt revealed striking differences: with the new model the compaction of the rock salt seals was so rapid that no releases could occur. The striking differences between the results - in terms of releases form a rock salt repository to the geosphere after groundwater intrusion - obtained using the two models clearly indicate the need for further experimental research into the end-compaction behaviour of rock salt backfill. (orig.)

Oral sensitization to food proteins: A Brown Norway rat model

NARCIS (Netherlands)

Knippels, L.M.J.; Penninks, A.H.; Spanhaak, S.; Houben, G.F.

1998-01-01

Background: Although several in vivo antigenicity assays using parenteral immunization are operational, no adequate enteral sensitization models are available to study food allergy and allergenicity of food proteins. Objective: This paper describes the development of an enteral model for food

Salting our landscape: An integrated catchment model using readily accessible data to assess emerging road salt contamination to streams

International Nuclear Information System (INIS)

Jin Li; Whitehead, Paul; Siegel, Donald I.; Findlay, Stuart

2011-01-01

A new integrated catchment model for salinity has been developed to assess the transport of road salt from upland areas in watersheds to streams using readily accessible landscape, hydrologic, and meteorological data together with reported salt applications. We used Fishkill Creek (NY) as a representative watershed to test the model. Results showed good agreement between modeled and measured stream water chloride concentrations. These results suggest that a dominant mode of catchment simulation that does not entail complex deterministic modeling is an appropriate method to model salinization and to assess effects of future applications of road salt to streams. We heuristically increased and decreased salt applications by 100% and results showed that stream chloride concentrations increased by 13% and decreased by 7%, respectively. The model suggests that future management of salt application can reduce environmental concentrations, albeit over some time. - Highlights: → A new Integrated Catchment Model (INCA-Cl) is developed to simulate salinity. → Road salt application is important in controlling stream chloride concentration. → INCA-Cl can be used to manage and forecast the input and transport of chloride to the rivers. - A newly developed integrated catchment model for salinity can be used to manage and forecast the inputs and transport of chloride to streams.

Salting our landscape: An integrated catchment model using readily accessible data to assess emerging road salt contamination to streams

Energy Technology Data Exchange (ETDEWEB)

Jin Li, E-mail: li.jin@ouce.ox.ac.uk [Earth Sciences Department, Syracuse University, Syracuse, NY 13210 (United States); School of Geography and the Environment, University of Oxford, Oxford, OX1 3QY (United Kingdom); Whitehead, Paul [School of Geography and the Environment, University of Oxford, Oxford, OX1 3QY (United Kingdom); Siegel, Donald I. [Earth Sciences Department, Syracuse University, Syracuse, NY 13210 (United States); Findlay, Stuart [Cary Institute of Ecosystem Studies, 2801 Sharon Turnpike, Millbrook, NY 12545 (United States)

2011-05-15

A new integrated catchment model for salinity has been developed to assess the transport of road salt from upland areas in watersheds to streams using readily accessible landscape, hydrologic, and meteorological data together with reported salt applications. We used Fishkill Creek (NY) as a representative watershed to test the model. Results showed good agreement between modeled and measured stream water chloride concentrations. These results suggest that a dominant mode of catchment simulation that does not entail complex deterministic modeling is an appropriate method to model salinization and to assess effects of future applications of road salt to streams. We heuristically increased and decreased salt applications by 100% and results showed that stream chloride concentrations increased by 13% and decreased by 7%, respectively. The model suggests that future management of salt application can reduce environmental concentrations, albeit over some time. - Highlights: > A new Integrated Catchment Model (INCA-Cl) is developed to simulate salinity. > Road salt application is important in controlling stream chloride concentration. > INCA-Cl can be used to manage and forecast the input and transport of chloride to the rivers. - A newly developed integrated catchment model for salinity can be used to manage and forecast the inputs and transport of chloride to streams.

Application of rat mast cell incubates as a possible short-time test for sensitizing occupational chemicals

Energy Technology Data Exchange (ETDEWEB)

Diel, F.; Neidhart, B.; Opree, W.

1981-08-01

The direct action of sensitizing occupational chemicals (formaldehyde, phenol, phenylhydrazine, p-aminophenol) on rat mast cells was investigated by determination of histamine using HPLC separation and fluorimetric detection. It turned out that dispersed mast cells from immunized and non-immunized Wistar-rats are more sensitive than small-cut lung tissue slices. Passive cutaneous anaphylaxis was negative after a fortnight sensitizing experiment with the here described occupational chemicals. Short-time tests with rat mast cells reflect anaphylactoid response and are suitable for the screening of sensitizing chemicals.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Directory of Open Access Journals (Sweden)

M.F. Souza

2014-06-01

Full Text Available Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL, estradiol (0.05 mg/mL, progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

Science.gov (United States)

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

Science.gov (United States)

Almey, Anne; Arena, Lauren; Oliel, Joshua; Shams, Waqqas M; Hafez, Nada; Mancinelli, Cynthia; Henning, Lukas; Tsanev, Aleks; Brake, Wayne G

2017-03-01

There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

Science.gov (United States)

Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

2013-09-01

Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Copyright © 2013 Wiley Periodicals, Inc.

Importance of associative learning processes for one-trial behavioral sensitization of preweanling rats.

Science.gov (United States)

McDougall, Sanders A; Pothier, Alexandria G; Der-Ghazarian, Taleen; Herbert, Matthew S; Kozanian, Olga O; Castellanos, Kevin A; Flores, Ana T

2011-10-01

During adulthood, associative learning is necessary for the expression of one-trial behavioral sensitization; however, it is uncertain whether the same associative processes are operative during the preweanling period. Two strategies were used to assess the importance of associative learning for one-trial behavioral sensitization of preweanling rats. In the initial experiments, we varied both the sequence and time interval between presentation of the conditioned stimulus (CS, novel environment) and unconditioned stimulus (US, cocaine). In the final experiment, we determined whether electroconvulsive shock-induced retrograde amnesia would disrupt one-trial behavioral sensitization. Results showed that robust-sensitized responding was apparent regardless of the sequence in which cocaine and the novel environment (the presumptive CS) were presented. Varying the time between CS and US presentation (0, 3, or 6 h) was also without effect. Results from experiment 3 showed that single or multiple electroconvulsive shock treatments did not alter the expression of the sensitized response. Therefore, these data indicated that one-trial behavioral sensitization of preweanling rats was exclusively mediated by nonassociative mechanisms and that associative processes did not modulate sensitized responding. These findings are in contrast to what is observed during adulthood, as adult rats exhibit one-trial behavioral sensitization only when associative processes are operative.

The sensitivity of male rat reproductive organs to monosodium glutamate

Directory of Open Access Journals (Sweden)

Sitthichai Iamsaard

2014-05-01

Full Text Available Objective. This study aimed to investigate the sensitivity of the testis, epididymis, seminal vesicle, and sperm acrosome reaction (AR to monosodium L- glutamate (MSG in rats. Materials and methods. Rats were divided into four groups and fed with non-acidic MSG at 0.25, 3 or 6 g/kg body weight for 30 days or without MSG. The morphological changes in the reproductive organs were studied. The plasma testosterone level, epididymal sperm concentration, and sperm AR status were assayed. Results. Compared to the control, no significant changes were discerned in the morphology and weight of the testes, or the histological structures of epididymis, vas deferens and seminal vesicle. In contrast, significant decreases were detected in the weight of the epididymis, testosterone levels, and sperm concentration of rats treated with 6 g/kg body weight of MSG. The weight loss was evident in the seminal vesicle in MSG-administered rats. Moreover, rats treated with MSG 3 and 6 g/kg exhibited partial testicular damage, characterized by sloughing of spermatogenic cells into the seminiferous tubular lumen, and their plasma testosterone levels were significantly decreased. In the 6 g/kg MSG group, the sperm concentration was significantly decreased compared with the control or two lower dose MSG groups. In AR assays, there was no statistically significant difference between MSG-rats and normal rats. Conclusion. Testicular morphological changes, testosterone level, and sperm concentration were sensitive to high doses of MSG while the rate of AR was not affected. Therefore, the consumption of high dose MSG must be avoided because it may cause partial infertility in male.

Computational analysis of candidate disease genes and variants for Salt-sensitive hypertension in indigenous Southern Africans

KAUST Repository

Tiffin, Nicki; Meintjes, Ayton; Ramesar, Rajkumar; Bajic, Vladimir B.; Rayner, Brian

2010-01-01

appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select

Neuroprotective and antioxidant activities of bamboo salt soy sauce against H2O2-induced oxidative stress in rat cortical neurons.

Science.gov (United States)

Jeong, Jong Hee; Noh, Min-Young; Choi, Jae-Hyeok; Lee, Haiwon; Kim, Seung Hyun

2016-04-01

Bamboo salt (BS) and soy sauce (SS) are traditional foods in Asia, which contain antioxidants that have cytoprotective effects on the body. The majority of SS products contain high levels of common salt, consumption of which has been associated with numerous detrimental effects on the body. However, BS may be considered a healthier substitute to common salt. The present study hypothesized that SS made from BS, known as bamboo salt soy sauce (BSSS), may possess enhanced cytoprotective properties; this was evaluated using a hydrogen peroxide (H 2 O 2 )-induced neuronal cell death rat model. Rat neuronal cells were pretreated with various concentrations (0.001, 0.01, 0.1, 1 and 10%) of BSSS, traditional soy sauce (TRSS) and brewed soy sauce (BRSS), and were subsequently exposed to H 2 O 2 (100 µM). The viability of neuronal cells, and the occurrence of DNA fragmentation, was subsequently examined. Pretreatment of neuronal cells with TRSS and BRSS reduced cell viability in a concentration-dependent manner, whereas neuronal cells pretreated with BSSS exhibited increased cell viability, as compared with non-treated neuronal cells. Furthermore, neuronal cells pretreated with 0.01% BSSS exhibited the greatest increase in viability. Exposure of neuronal cells to H 2 O 2 significantly increased the levels of reactive oxygen species (ROS), B-cell lymphoma 2-associated X protein, poly (ADP-ribose), cleaved poly (ADP-ribose) polymerase, cytochrome c , apoptosis-inducing factor, cleaved caspase-9 and cleaved caspase-3, in all cases. Pretreatment of neuronal cells with BSSS significantly reduced the levels of ROS generated by H 2 O 2 , and increased the levels of phosphorylated AKT and phosphorylated glycogen synthase kinase-3β. Furthermore, the observed effects of BSSS could be blocked by administration of 10 µM LY294002, a phosphatidylinositol 3-kinase inhibitor. The results of the present study suggested that BSSS may exert positive neuroprotective effects against H 2 O 2

Amnesia induced by morphine in spatial memory retrieval inhibited in morphine-sensitized rats.

Science.gov (United States)

Farahmandfar, Maryam; Naghdi, Nasser; Karimian, Seyed Morteza; Kadivar, Mehdi; Zarrindast, Mohammad-Reza

2012-05-15

The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Compost and residues from biogas plant as potting substrates for salt-tolerant and salt-sensitive plants

Energy Technology Data Exchange (ETDEWEB)

Cam Van, Do Thi

2013-08-01

Compost and residues from biogas plant have been increasingly recognized as potting substrates in horticulture. To investigate the suitability of both materials to grow salt tolerant plants in 2010 a pot experiment was conducted in the greenhouse of INRES-Plant nutrition, University of Bonn. Ryegrass (Lolium perenne L.), rape (Brassica napus) and sunflower (Helianthus annuus) were chosen as experimental plants. To reduce the high salt content compost and residues from biogas plant were leached. To improve physical characteristics of raw materials, additives including Perlite, Styromull, Hygromull, Lecaton, Peat, Cocofiber were incorporated into compost or residues from biogas plant with the volumetric ratio of 4:1. Plant growth (DM) and nutrient uptake (N, P, K, Mg, Ca, Na and S) of the experimental plants grown in compost-based or residue-based substrates with and without additives and standard soil as a control were determined. Preliminary results reveal that origin compost and residues from biogas plant without leaching are suitable potting substrates for those plants. For compost leaching may not be recommended while for residues from biogas plant the effect of leaching was not distinct and needs further investigations. The incorporation of additives into the basic materials partially resulted in higher plant dry matter yield and nutrient uptake. However, differences between the additives on both parameters were mainly insignificant. Incorporation of Hygromull or Peat, especially into residues from biogas plant favored plant growth and enhanced total nutrient uptake. In 2011, pot experiments were continued with the salt-sensitive ornamental plants, Pelargonium (Pelargonium zonale Toro) and Salvia (Salvia splendens). Two separate experiments were carried out for the mixtures of compost and additives (SPS standard soil type 73 based on Peat, Hygromull or Cocofiber) with different volumetric ratios (4:1, 1:1, 1:4) and the mixtures of Peat incorporated with small

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats

OpenAIRE

Hodges, Matthew R.; Echert, Ashley E.; Puissant, Madeleine M.; Mouradian, Gary C.

2013-01-01

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7 % CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10 mg/kg/day) in adult male BN and SD rats. Fluoxetine had minimal ...

Isoflurane Anesthesia Interferes with the Expression of Cocaine-Induced Sensitization in Female Rats

OpenAIRE

Siegal, Nora; Dow-Edwards, Diana

2009-01-01

Repeated cocaine administration results in a progressive sensitization of behavior which typically occurs more readily in female rats than in males. Our recent studies of rats undergoing surgical procedures revealed that following anesthesia, females sensitized less than males receiving identical repeated cocaine injections. Since isoflurane acts primarily by increasing the effects of the inhibitory neurotransmitter γ-amino butyric acid (GABA) and reducing the effects of the excitatory amino ...

Two planets: Earth and Mars - One salt model: The Hydrothermal SCRIW-Model

Science.gov (United States)

Hovland, M. T.; Rueslaatten, H.; Johnsen, H. K.; Indreiten, T.

2011-12-01

One of the common characteristics of planets Earth and Mars is that both host water (H2O) and large accumulations of salt. Whereas Earth's surface-environment can be regarded as 'water-friendly' and 'salt hostile', the reverse can be said for the surface of Mars. This is because liquid water is stable on Earth, and the atmosphere transports humidity around the globe, whereas on planet Mars, liquid water is unstable, rendering the atmosphere dry and, therefore, 'salt-friendly'. The riddle as to how the salt accumulated in various locations on those two planets is one of long-lasting and great debate. The salt accumulations on Earth are traditionally termed 'evaporites', meaning that they formed by the evaporation of large masses of seawater. How the accumulations on Mars formed is much harder to explain, with a similar model, as surface water, representing a large ocean only existed briefly. Although water molecules and OH-groups may exist in abundance in bound form (crystal water, adsorbed water, etc.), the only place where free water is expected to be stable on Mars is within underground faults, fractures, and crevices. Here it likely occurs as brine or in the form of ice. Based on these conditions, a key to understanding the accumulation of large deposits of salt on both planets is linked to how brines behave in the subsurface when pressurized and heated beyond their supercritical point. At depths greater than about 3 km (i.e., a pressure, P>300 bars) water will no longer boil in a steam phase. Rather, it becomes supercritical and will form a supercritical water 'vapor' (SCRIW) with a specific gravity of typically 0.3 g/cm3. An important characteristic of SCRIW is its inability to dissolve the common sea salts. The salt dissolved in the brines will therefore precipitate as solid particles when brines (seawater on the Earth) move into the supercritical P&T-domain (above 400 C and 300 bars). Numerical modeling of a hydrothermal system in the Atlantis II Deep of the

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

Science.gov (United States)

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P hearts demonstrated prolonged action potentials ( P hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

Comparative 2D-DIGE analysis of salinity responsive microsomal proteins from leaves of salt-sensitive Arabidopsis thaliana and salt-tolerant Thellungiella salsuginea.

Science.gov (United States)

Vera-Estrella, Rosario; Barkla, Bronwyn J; Pantoja, Omar

2014-12-05

Halophytes have evolved unique molecular strategies to overcome high soil salinity but we still know very little about the main mechanisms that these plants use to complete their lifecycle under salinity stress. One useful approach to further our understanding in this area is to directly compare the response to salinity of two closely related species which show diverse levels of salt tolerance. Here we present a comparative proteomic study using DIGE of leaf microsomal proteins to identify salt-responsive membrane associated proteins in Arabidopsis thaliana (a glycophyte) and Thellungiella salsuginea (a halophyte). While a small number of distinct protein abundance changes were observed upon salt stress in both species, the most notable differences were observed between species and specifically, in untreated plants with a total of 36 proteins displaying significant abundance changes. Gene ontology (GO) term enrichment analysis showed that the majority of these proteins were distributed into two functional categories; transport (31%) and carbohydrate metabolism (17%). Results identify several novel salt responsive proteins in this system and support the theory that T. salsuginea shows a high degree of salt-tolerance because molecular mechanisms are primed to deal with the stress. This intrinsic ability to anticipate salinity stress distinguishes it from the glycophyte A. thaliana. There is significant interest in understanding the molecular mechanisms that plants use to tolerate salinity as soil salinization is becoming an increasing concern for agriculture with high soil Na(+) levels leading to reduced yields and economic loss. Much of our knowledge on the molecular mechanisms employed by plants to combat salinity stress has come from work on salt-sensitive plants, but studies on naturally occurring highly salt-resistant plants, halophytes, and direct comparisons between closely related glycophytes and halophytes, could help to further our understanding of salinity

User's manual and guide to SALT3 and SALT4: two-dimensional computer codes for analysis of test-scale underground excavations for the disposal of radioactive waste in bedded salt deposits

International Nuclear Information System (INIS)

Lindner, E.N.; St John, C.M.; Hart, R.D.

1984-02-01

SALT3 and SALT4 are two-dimensional analytical/displacement-discontinuity codes designed to evaluate temperatures, deformation, and stresses associated with underground disposal of radioactive waste in bedded salt. These codes were developed by the University of Minnesota for the Office of Nuclear Waste Isolation in 1979. The present documentation describes the mathematical equations of the physical system being modeled, the numerical techniques utilized, and the organization of these computer codes. The SALT3 and SALT4 codes can simulate: (a) viscoelastic behavior in pillars adjacent to excavations; (b) transversely isotropic elastic moduli such as those exhibited by bedded or stratified rock; and (c) excavation sequence. Major advantages of these codes are: (a) computational efficiency; (b) the small amount of input data required; and (c) a creep law based on laboratory experimental data for salt. The main disadvantage is that some of the assumptions in the formulation of the codes, i.e., the homogeneous elastic half-space and temperature-independent material properties, render it unsuitable for canister-scale analysis or analysis of lateral deformation of the pillars. The SALT3 and SALT4 codes can be used for parameter sensitivity analyses of two-dimensional, repository-scale, thermomechanical response in bedded salt during the excavation, operational, and post-closure phases. It is especially useful in evaluating alternative patterns and sequences of excavation or waste canister placement. SALT3 is a refinement of an earlier code, SALT, and includes a fully anelastic creep model and thermal stress routine. SALT4 is a later version, and incorporates a revised creep model which is strain-hardening

Immune-mediated effects upon oral challenge of ovalbumin-sensitized Brown Norway rats: Further characterization of a rat food allergy model

NARCIS (Netherlands)

Knippels, L.M.J.; Penninks, A.H.; Smit, J.J.; Houben, G.F.

1999-01-01

Although several in vivo antigenicity assays using parenteral immunization are operational, no full validated enteral models are available to study food allergy and allergenicity of food proteins. To further validate a developed enteral Brown Norway (BN) rat food allergy model, systemic and local

DYE-SENSITIZED PHOTOPOLYMERIZATION OF METHYL METHACRYLATE INITIATED BY COUMARIN DYE/IODONIUM SALT SYSTEM

Institute of Scientific and Technical Information of China (English)

Fang Gao; Yong-yuan Yang

1999-01-01

The photosensitive initiating system composed of 7-diethylamino-3-(2'-benzimidazolyl)coumarin dye (DEDC) and diphenyliodonium hexafluorophosphate (DIHP) which act as the sensitizer and the initiator respectively, can be used to initiate the polymerization of methyl methacrylate (MMA). The results showed that when exposed to visible light, coumarin dye/iodonium salt undergoes quick electron transfer from DEDC to DIHP and free radicals are produced. The visible light photoinduced reaction between DEDC and DIHP is mainly through the excited singlet state of DEDC and thus it is a little sensitive to O2. The influence of concentration of DEDC, DIHP and MMA on the rate of photopolymerization of MMA was also investigated.

Mechanical stratification of autochthonous salt: Implications from basin-scale numerical models of rifted margin salt tectonics

Science.gov (United States)

Ings, Steven; Albertz, Markus

2014-05-01

Deformation of salt and sediments owing to the flow of weak evaporites is a common phenomenon in sedimentary basins worldwide, and the resulting structures and thermal regimes have a significant impact on hydrocarbon exploration. Evaporite sequences ('salt') of significant thickness (e.g., >1km) are typically deposited in many cycles of seawater inundation and evaporation in restricted basins resulting in layered autochthonous evaporite packages. However, analogue and numerical models of salt tectonics typically treat salt as a homogeneous viscous material, often with properties of halite, the weakest evaporite. In this study, we present results of two-dimensional plane-strain numerical experiments designed to illustrate the effects of variable evaporite viscosity and embedded frictional-plastic ('brittle') sediment layers on the style of salt flow and associated deformation of the sedimentary overburden. Evaporite viscosity is a first-order control on salt flow rate and the style of overburden deformation. Near-complete evacuation of low-viscosity salt occurs beneath expulsion basins, whereas significant salt is trapped when viscosity is high. Embedded frictional-plastic sediment layers (with finite yield strength) partition salt flow and develop transient contractional structures (folds, thrust faults, and folded faults) in a seaward salt-squeeze flow regime. Multiple internal sediment layers reduce the overall seaward salt flow during sediment aggradation, leaving more salt behind to be re-mobilized during subsequent progradation. This produces more seaward extensive allochthonous salt sheets. If there is a density difference between the embedded layers and the surrounding salt, then the embedded layers 'fractionate' during deformation and either float to the surface or sink to the bottom (depending on density), creating a thick zone of pure halite. Such a process of 'buoyancy fractionation' may partially explain the apparent paradox of layered salt in

4D modeling of salt-sediment interactions during diapir evolution

Energy Technology Data Exchange (ETDEWEB)

Callot, J.P.; Rondon, D.; Letouzey, J. [IFP, Rueil Malmaison (France); Krajewski, P. [Gaz de France-PEG, Lingen (Germany); Rigollet, C. [Gaz de France, St. Denis la Plaine (France)

2007-09-13

We performed sand/silicon models imaged with X-ray tomography and reconstructed by 3D geomodelling for the study of (1) the interaction between host rock and salt diapir during diapir growth, and (2) the evolution of intra salt brittle rocks during diapir ascent. X-ray tomography is a non destructive imaging technique which allows us to follow the 4D evolution of the analogue model. Salt is modelled by Newtonian silicone putty and the internal rock layer, as well as the sedimentary host rock, by a granular Mohr-Coulomb material, generally coryndon. The analogue models are then compared to natural examples, the evolution of which is obtained through 3D restoration of the structures. (1) A 4D evolutionary scenario for a salt diapir development was originally proposed by Trusheim (1960) and discussed later on by Vendeville (1999) among others (Ge et al., 1997; Zirngast et al., 1996). This scenario is reproduced through analogue models to test the relative importance of (1) extensional tectonics, (2) sediment progradations, and (3) source layer depletion and rim-syncline touchdown, in the evolution of a diapir. The comparison of our results with the restored natural analogue shows that the main parameter remains (1) the rim-syncline touchdown and (2) the unloading of the diapir due to erosion. The latter accounts for a drop in strength necessary to allow for the flank rotation and down building of the diapir. Extensional stresses and sediment progradations will also amplify the halokinesis. (2) Salt diapirs from the Middle East or in Southern Permian Basin petroleum province show exotic blocks at outcrop and in salt mines, known as 'stringers' in subsurface data, usually composed of anhydrite, dolomite, marls or carbonates. These stringers, which constitute major structures inside the salt diapir, can reach a few km in size and originate from pre-existing brittle rock layers embedded in the salt layer. Stringers of the Ara carbonate within the Precambrian

Aluminium sensitized spectrofluorimetric determination of fluoroquinolones in milk samples coupled with salting-out assisted liquid-liquid ultrasonic extraction

Science.gov (United States)

Xia, Qinghai; Yang, Yaling; Liu, Mousheng

2012-10-01

An aluminium sensitized spectrofluorimetric method coupled with salting-out assisted liquid-liquid ultrasonic extraction for the determination of four widely used fluoroquinolones (FQs) namely norfloxacin (NOR), ofloxacin (OFL), ciprofloxacin (CIP) and gatifloxacin (GAT) in bovine raw milk was described. The analytical procedure involves the fluorescence sensitization of aluminium (Al3+) by complexation with FQs, salting-out assisted liquid-liquid ultrasonic extraction (SALLUE), followed by spectrofluorometry. The influence of several parameters on the extraction (the salt species, the amount of salt, pH, temperature and phase volume ratio) was investigated. Under optimized experimental conditions, the detection limits of the method in milk varied from 0.009 μg/mL for NOR to 0.016 μg/mL for GAT (signal-to-noise ratio (S/N) = 3). The relative standard deviations (RSD) values were found to be relatively low (0.54-2.48% for four compounds). The calibration graph was linear from 0.015 to 2.25 μg/mL with coefficient of determinations not less than 0.9974. The methodology developed was applied to the determination of FQs in bovine raw milk samples. The main advantage of this method is simple, accurate and green. The method showed promising applications for analyzing polar analytes especially polar drugs in various sample matrices.

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

Science.gov (United States)

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity

International Nuclear Information System (INIS)

Corley, R.A.; Wilson, D.M.; Hard, G.C.; Stebbins, K.E.; Bartels, M.J.; Soelberg, J.J.; Dryzga, M.D.; Gingell, R.; McMartin, K.E.; Snellings, W.M.

2008-01-01

Male Wistar rats have been shown to be the most sensitive sex, strain and species to ethylene glycol-induced nephrotoxicity in subchronic studies. A chronic toxicity and dosimetry study was therefore conducted in male Wistar rats administered ethylene glycol via the diet at 0, 50, 150, 300, or 400 mg/kg/day for up to twelve months. Subgroups of animals were included for metabolite analysis and renal clearance studies to provide a quantitative basis for extrapolating dose-response relationships from this sensitive animal model in human health risk assessments. Mortality occurred in 5 of 20 rats at 300 mg/kg/day (days 111-221) and 4 of 20 rats at 400 mg/kg/day (days 43-193), with remaining rats at this dose euthanized early (day 203) due to excessive weight loss. Increased water consumption and urine volume with decreased specific gravity occurred at 300 mg/kg/day presumably due to osmotic diuresis. Calculi (calcium oxalate crystals) occurred in the bladder or renal pelvis at ≥ 300 mg/kg/day. Rats dying early at ≥ 300 mg/kg/day had transitional cell hyperplasia with inflammation and hemorrhage of the bladder wall. Crystal nephropathy (basophilic foci, tubule or pelvic dilatation, birefringent crystals in the pelvic fornix, or transitional cell hyperplasia) affected most rats at 300 mg/kg/day, all at 400 mg/kg/day, but none at ≤ 150 mg/kg/day. No significant differences in kidney oxalate levels, the metabolite responsible for renal toxicity, were observed among control, 50 and 150 mg/kg/day groups. At 300 and 400 mg/kg/day, oxalate levels increased proportionally with the nephrotoxicity score supporting the oxalate crystal-induced nephrotoxicity mode of action. No treatment-related effects on the renal clearance of intravenously infused 3 H-inulin, a marker for glomerular filtration, and 14 C-oxalic acid were observed in rats surviving 12 months of exposure to ethylene glycol up to 300 mg/kg/day. In studies with naive male Wistar and F344 rats (a less sensitive

Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading

Directory of Open Access Journals (Sweden)

Ratnayake Walisundera MN

2010-02-01

Full Text Available Abstract Background There are safety concerns regarding widespread consumption of phytosterol and phytostanol supplemented food products. The aim of this study was to determine, in the absence of excess dietary salt, the individual effects of excess accumulation of dietary phytosterols and phytostanols on blood pressure in Wistar Kyoto (WKY inbred rats that have a mutation in the Abcg5 gene and thus over absorb phytosterols and phytostanols. Methods Thirty 35-day old male WKY inbred rats (10/group were fed a control diet or a diet containing phytosterols or phytostanols (2.0 g/kg diet for 5 weeks. The sterol composition of the diets, plasma and tissues were analysed by gas chromatography. Blood pressure was measured by the tail cuff method. mRNA levels of several renal blood pressure regulatory genes were measured by real-time quantitative PCR. Results Compared to the control diet, the phytosterol diet resulted in 3- to 4-fold increases in the levels of phytosterols in plasma, red blood cells, liver, aorta and kidney of WKY inbred rats (P 9-fold the levels of phytostanols in plasma, red blood cells, liver, aorta and kidney of these rats (P P P P P angiotensinogen mRNA levels of these rats. Conclusion These data suggest that excessive accumulation of dietary phytosterols and phytostanols in plasma and tissues may contribute to the increased blood pressure in WKY inbred rats in the absence of excess dietary salt. Therefore, even though phytosterols and phytostanols lower cholesterol levels, prospective clinical studies testing the net beneficial effects of dietary phytosterols and phytostanols on cardiovascular events for subgroups of individuals that have an increased incorporation of these substances are needed.

Relative deficiency of nitric oxide-dependent vasodilation in salt hypertensive Dahl rats: the possible role of superoxide anions

Czech Academy of Sciences Publication Activity Database

Zicha, Josef; Dobešová, Zdenka; Kuneš, Jaroslav

2001-01-01

Roč. 19, č. 2 (2001), s. 247-254 ISSN 0263-6352 R&D Projects: GA AV ČR IAA7011805; GA AV ČR IAA7011711; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : blood pressure * salt hypertension * Dahl rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.210, year: 2001

Simple and Sensitive Colorimetric Assay for Pb2+ Based on Glutathione Protected Ag Nanoparticles by Salt Amplification.

Science.gov (United States)

Chen, Zhang; Li, Huidong; Chu, Lin; Liu, Chenbin; Luo, Shenglian

2015-02-01

A simple and sensitive colorimetric assay for Pb2+ detection has been reported using glutathione protected silver nanoparticles (AgNPs) by salt amplification. The naked AgNPs aggregate under the influence of salt. Glutathione (GSH) can bind to AgNPs via Ag-S bond, helping AgNPs to against salt-induced aggregation. However, GSH binding to AgNPs can be compromised by the interaction between Pb2+ and GSH. As a result, Pb2+-mediated aggregation of AgNPs under the influence of salt is reflected by the UV-Visible spectrum, and the qualitative and quantitative detection for Pb2+ is accomplished, with the detection range 0.5-4 µM and a detection limit of 0.5 µM. At the same time, Pb2+ in real water sample is detected. Furthermore, the high selectivity and low cost of the assay means it is promising for enviromental applications.

Statistical methods for mechanistic model validation: Salt Repository Project

International Nuclear Information System (INIS)

Eggett, D.L.

1988-07-01

As part of the Department of Energy's Salt Repository Program, Pacific Northwest Laboratory (PNL) is studying the emplacement of nuclear waste containers in a salt repository. One objective of the SRP program is to develop an overall waste package component model which adequately describes such phenomena as container corrosion, waste form leaching, spent fuel degradation, etc., which are possible in the salt repository environment. The form of this model will be proposed, based on scientific principles and relevant salt repository conditions with supporting data. The model will be used to predict the future characteristics of the near field environment. This involves several different submodels such as the amount of time it takes a brine solution to contact a canister in the repository, how long it takes a canister to corrode and expose its contents to the brine, the leach rate of the contents of the canister, etc. These submodels are often tested in a laboratory and should be statistically validated (in this context, validate means to demonstrate that the model adequately describes the data) before they can be incorporated into the waste package component model. This report describes statistical methods for validating these models. 13 refs., 1 fig., 3 tabs

Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

DEFF Research Database (Denmark)

Mumme, Karen; Gray, Clint; Reynolds, Clare M.

2016-01-01

: Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats...

Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486.

Science.gov (United States)

Nagasawa, K; Matsuura, N; Takeshita, Y; Ito, S; Sano, Y; Yamada, Y; Uchinaka, A; Murohara, T; Nagata, K

2016-04-25

Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We have now investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology as well as on metabolic parameters in this model. DS/obese rats were exposed to cold stress (immersion in ice-cold water to a depth of 1-2 cm for 2 h per day) with or without subcutaneous injection of the GR antagonist RU486 (2 mg kg(-1)day(-1)) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+)) littermates served as a control. Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction in DS/obese rats in a manner sensitive to RU486 treatment. Cold stress with or without RU486 did not affect body weight or fat mass. In contrast, cold stress further increased cardiac oxidative stress as well as macrophage infiltration and proinflammatory gene expression in LV and visceral fat tissue, with all of these effects being attenuated by RU486. Cold stress also further increased GR and 11β-hydroxysteroid dehydrogenase type 1 mRNA and protein abundance in LV and visceral adipose tissue, and these effects were again inhibited by RU486. In addition, RU486 ameliorated the stress-induced aggravation of dyslipidemia, glucose intolerance and insulin resistance in DS/obese rats. Our results implicate GR signaling in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as of abnormal glucose and lipid metabolism in a rat model of MetS.

Mixing Modeling Analysis For SRS Salt Waste Disposition

International Nuclear Information System (INIS)

Lee, S.

2011-01-01

Nuclear waste at Savannah River Site (SRS) waste tanks consists of three different types of waste forms. They are the lighter salt solutions referred to as supernate, the precipitated salts as salt cake, and heavier fine solids as sludge. The sludge is settled on the tank floor. About half of the residual waste radioactivity is contained in the sludge, which is only about 8 percentage of the total waste volume. Mixing study to be evaluated here for the Salt Disposition Integration (SDI) project focuses on supernate preparations in waste tanks prior to transfer to the Salt Waste Processing Facility (SWPF) feed tank. The methods to mix and blend the contents of the SRS blend tanks were evalutaed to ensure that the contents are properly blended before they are transferred from the blend tank such as Tank 50H to the SWPF feed tank. The work consists of two principal objectives to investigate two different pumps. One objective is to identify a suitable pumping arrangement that will adequately blend/mix two miscible liquids to obtain a uniform composition in the tank with a minimum level of sludge solid particulate in suspension. The other is to estimate the elevation in the tank at which the transfer pump inlet should be located where the solid concentration of the entrained fluid remains below the acceptance criterion (0.09 wt% or 1200 mg/liter) during transfer operation to the SWPF. Tank 50H is a Waste Tank that will be used to prepare batches of salt feed for SWPF. The salt feed must be a homogeneous solution satisfying the acceptance criterion of the solids entrainment during transfer operation. The work described here consists of two modeling areas. They are the mixing modeling analysis during miscible liquid blending operation, and the flow pattern analysis during transfer operation of the blended liquid. The modeling results will provide quantitative design and operation information during the mixing/blending process and the transfer operation of the blended

Effect of SO/sub 2/ upon the sensitization with albumin through the airway in rats

Energy Technology Data Exchange (ETDEWEB)

Matsumura, Y

1968-01-01

Rats were exposed to 400 ppM SO/sub 2/ for 30 min and then to 90 min of nebulized egg albumin and bovine serum albumin sensitizing antigens 7 times at intervals of a few days. Serum analysis was done 4 wk after final exposure-treatment. There was enhanced sensitization of rats exposed to SO/sub 2/ by 2 of 4 tests (hemagglutination and radioimmunoelectrophoresis) while other 2 tests showed no antibodies in any rat (insensitive tests). Results were possible due to slowed clearance.

Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

Science.gov (United States)

Tsao, L I; Su, T P

1997-02-01

A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

Modeling Coupled THM Processes and Brine Migration in Salt at High Temperatures

International Nuclear Information System (INIS)

Rutqvist, Jonny; Blanco-Martin, Laura; Molins, Sergi; Trebotich, David; Birkholzer, Jens

2015-01-01

In this report, we present FY2015 progress by Lawrence Berkeley National Laboratory (LBNL) related to modeling of coupled thermal-hydrological-mechanical-chemical (THMC) processes in salt and their effect on brine migration at high temperatures. This is a combined milestone report related to milestone Salt R&D Milestone ''Modeling Coupled THM Processes and Brine Migration in Salt at High Temperatures'' (M3FT-15LB0818012) and the Salt Field Testing Milestone (M3FT-15LB0819022) to support the overall objectives of the salt field test planning.

Modeling Coupled THM Processes and Brine Migration in Salt at High Temperatures

Energy Technology Data Exchange (ETDEWEB)

Rutqvist, Jonny [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Blanco-Martin, Laura [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Molins, Sergi [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Trebotich, David [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Birkholzer, Jens [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2015-09-01

In this report, we present FY2015 progress by Lawrence Berkeley National Laboratory (LBNL) related to modeling of coupled thermal-hydrological-mechanical-chemical (THMC) processes in salt and their effect on brine migration at high temperatures. This is a combined milestone report related to milestone Salt R&D Milestone “Modeling Coupled THM Processes and Brine Migration in Salt at High Temperatures” (M3FT-15LB0818012) and the Salt Field Testing Milestone (M3FT-15LB0819022) to support the overall objectives of the salt field test planning.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

Science.gov (United States)

Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes.

Science.gov (United States)

Wilhelm, C J; Mitchell, S H

2008-10-01

Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess 'choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals.

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction.

Science.gov (United States)

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-12-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems.

A novel fluorescence imaging approach to monitor salt stress-induced modulation of ouabain-sensitive ATPase activity in sunflower seedling roots.

Science.gov (United States)

Mukherjee, Soumya; Bhatla, Satish Chander

2014-04-01

Seedlings exposed to salt stress are expected to show modulation of intracellular accumulation of sodium ions through a variety of mechanisms. Using a new methodology, this work demonstrates ouabain (OU)-sensitive ATPase activity in the roots of sunflower seedlings subjected to salt stress (120 mM NaCl). 9-Anthroylouabain (a derivative of ouabain known to inhibit Na(+), K(+) -ATPase activity in animal systems, EC 3.6.3.9) has been used as a probe to analyze OU-sensitive ATPase activity in sunflower (Helianthus annuus) seedling roots by spectrofluorometric estimation and localization of its spatial distribution using confocal laser scanning microscopy. Salt stress for 48 h leads to a significant induction of OU-sensitive ATPase activity in the meristematic region of the seedling roots. Calcium ions (10 mM) significantly inhibit enzyme activity and a parallel accumulation of sodium ions in the cytosol of the columella cells, epidermis and in the cells of the meristematic region of the roots is evident. As a rapid response to NaCl stress, the activity of OU-sensitive ATPase gets localized in the nuclear membrane of root protoplasts and it gets inhibited after treatment with calcium ions. Nuclear membrane localization of the OU-sensitive ATPase activity highlights a possible mechanism to efflux sodium ions from the nucleus. Thus, a correlation between OU-sensitive ATPase activity, its modulation by calcium ions and accumulation of sodium ions in various regions of the seedling roots, has been demonstrated using a novel approach in a plant system. © 2013 Scandinavian Plant Physiology Society.

Thermodynamics and structure of inclusion compounds of tauro- and glyco-conjugated bile salts and beta-cyclodextrin

DEFF Research Database (Denmark)

Holm, Rene; Shi, Wei; Andersen Hartvig, Rune

2009-01-01

The interaction between natural beta-cyclodextrin and bile salts common in rat, dog and man, taurocholate, tauro-beta-muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate and glycochenodeoxycholate, was studied using isothermal titration calorimetry, and the str......The interaction between natural beta-cyclodextrin and bile salts common in rat, dog and man, taurocholate, tauro-beta-muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate and glycochenodeoxycholate, was studied using isothermal titration calorimetry......, and the structural differences in the interaction were investigated by H-1-ROESY NMR and molecular modeling. The beta-cyclodextrin was selected based upon its frequent use in preformulation and drug formulation as oral excipients for the solubilization of drug substances with low aqueous solubility. All...

Potential constitutive models for salt: Survey of phenomenology, micromechanisms, and equations

International Nuclear Information System (INIS)

Senseny, P.E.; Hansen, F.D.

1987-12-01

Results are given of a literature survey performed to document the thermomechanical phenomena and micromechanical processes observed for salt over the ranges of stress and temperature of interest for a high-level nuclear repository. The elastic and thermal expansion behavior of salt can be readily modeled by the generalized Duhamel Neumann form of Hooke's law with temperature-dependent elastic constants and coefficient of thermal expansion. Inelastic deformation is primarily viscoplastic, but also has a brittle component. The observed phenomenological behavior of salt occurs because of micromechanical processes. To the extent that these processes have been studied, a summary of deformation mechanisms in natural salt is included in this report. Eight constitutive models that appear to be capable of modeling the viscoplastic deformation have been selected from the literature. Two models have been selected to model brittle deformation. Insufficient data are available to develop a model for failure. 92 refs., 39 figs., 6 tabs

ROS production is increased in the kidney but not in the brain of Dahl rats with salt hypertension elicited in adulthood

Czech Academy of Sciences Publication Activity Database

Vokurková, Martina; Rauchová, Hana; Řezáčová, Lenka; Vaněčková, Ivana; Zicha, Josef

2015-01-01

Roč. 64, č. 3 (2015), s. 303-312 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : Dahl rats * lipid peroxidation * NADPH oxidase * reactive oxygen species * salt hypertension Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

Food quantity affects the sensitivity of Daphnia to road salt.

Science.gov (United States)

Brown, Arran H; Yan, Norman D

2015-04-07

Road deicing operations have raised chloride (Cl) levels in many temperate lakes in Europe and North America. These lakes vary widely in trophic status, but to date, no one has quantified the interaction between food quantity and road salt toxicity. We examined the effects of food quantity (particulate algal C concentration (C)) on the chronic toxicity of Cl to Daphnia in soft-water bioassays. There was a strong positive linear relationship (r(2) = 0.92 for NaCl and r(2) = 0.96 for CaCl2) between food quantity and Cl LC50. As food quantity increased from 0.2 to 1.0 mg C/L (levels characteristic of oligotrophic to eutrophic lakes, respectively), the chronic Cl LC50 increased from 55.7 to 284.8 mg Cl/L. Salt type (NaCl or CaCl2) did not affect the Cl LC50, Daphnia life history parameters, or the intrinsic rate of population increase (r). The life history parameter most sensitive to Cl was neonate production. Cl did not inhibit egg production, nor was the maternal lipid investment in eggs changed, but egg viability and the subsequent release of live neonates decreased as Cl levels increased and food decreased. Our results suggest the trophic status of lakes should be considered when assessing ecological threat from Cl.

Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

Directory of Open Access Journals (Sweden)

Chiaki Nagai-Okatani

Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

Experiments and Modeling in Support of Generic Salt Repository Science

International Nuclear Information System (INIS)

Bourret, Suzanne Michelle; Stauffer, Philip H.; Weaver, Douglas James; Caporuscio, Florie Andre; Otto, Shawn; Boukhalfa, Hakim; Jordan, Amy B.; Chu, Shaoping; Zyvoloski, George Anthony; Johnson, Peter Jacob

2017-01-01

Salt is an attractive material for the disposition of heat generating nuclear waste (HGNW) because of its self-sealing, viscoplastic, and reconsolidation properties (Hansen and Leigh, 2012). The rate at which salt consolidates and the properties of the consolidated salt depend on the composition of the salt, including its content in accessory minerals and moisture, and the temperature under which consolidation occurs. Physicochemical processes, such as mineral hydration/dehydration salt dissolution and precipitation play a significant role in defining the rate of salt structure changes. Understanding the behavior of these complex processes is paramount when considering safe design for disposal of heat-generating nuclear waste (HGNW) in salt formations, so experimentation and modeling is underway to characterize these processes. This report presents experiments and simulations in support of the DOE-NE Used Fuel Disposition Campaign (UFDC) for development of drift-scale, in-situ field testing of HGNW in salt formations.

Experiments and Modeling in Support of Generic Salt Repository Science

Energy Technology Data Exchange (ETDEWEB)

Bourret, Suzanne Michelle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stauffer, Philip H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Weaver, Douglas James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Caporuscio, Florie Andre [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Otto, Shawn [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Boukhalfa, Hakim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Jordan, Amy B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chu, Shaoping [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zyvoloski, George Anthony [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Johnson, Peter Jacob [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-01-19

Salt is an attractive material for the disposition of heat generating nuclear waste (HGNW) because of its self-sealing, viscoplastic, and reconsolidation properties (Hansen and Leigh, 2012). The rate at which salt consolidates and the properties of the consolidated salt depend on the composition of the salt, including its content in accessory minerals and moisture, and the temperature under which consolidation occurs. Physicochemical processes, such as mineral hydration/dehydration salt dissolution and precipitation play a significant role in defining the rate of salt structure changes. Understanding the behavior of these complex processes is paramount when considering safe design for disposal of heat-generating nuclear waste (HGNW) in salt formations, so experimentation and modeling is underway to characterize these processes. This report presents experiments and simulations in support of the DOE-NE Used Fuel Disposition Campaign (UFDC) for development of drift-scale, in-situ field testing of HGNW in salt formations.

The amphetamine sensitization model of schizophrenia symptoms and its effect on schedule-induced polydipsia in the rat.

Science.gov (United States)

Hawken, Emily R; Beninger, Richard J

2014-05-01

Amphetamine enhances dopamine (DA) transmission and induces psychotic states or exacerbates psychosis in at-risk individuals. Amphetamine sensitization of the DA system has been proposed as a rodent model of schizophrenia-like symptoms. In humans, excessive nonphysiologic drinking or primary polydipsia is significantly associated with a diagnosis of schizophrenia. In rodents, nonphysiologic drinking can be induced by intermittent presentation of food in the presence of a drinking spout to a hungry animal; this phenomenon is termed, "schedule-induced polydipsia" (SIP). This study aims to determine the effects of amphetamine sensitization on SIP. We injected rats with amphetamine (1.5 mg/kg) daily for 5 days. Following 4 weeks of withdrawal, animals were food restricted and exposed to the SIP protocol (noncontingent fixed-time 1-min food schedule) for daily 2-h sessions for 24 days. Results showed that previously amphetamine-injected animals drank more in the SIP protocol and drank more than controls when the intermittent food presentation schedule was removed. These findings suggest that hyperdopaminergia associated with schizophrenia may contribute to the development of polydipsia in this population. Whether animals that develop SIP have DA dysfunction or aberrant activity of other circuits that modulate DA activity has yet to be clearly defined.

Free energy landscape of a minimalist salt bridge model.

Science.gov (United States)

Li, Xubin; Lv, Chao; Corbett, Karen M; Zheng, Lianqing; Wu, Dongsheng; Yang, Wei

2016-01-01

Salt bridges are essential to protein stability and dynamics. Despite the importance, there has been scarce of detailed discussion on how salt bridge partners interact with each other in distinct solvent exposed environments. In this study, employing a recent generalized orthogonal space tempering (gOST) method, we enabled efficient molecular dynamics simulation of repetitive breaking and reforming of salt bridge structures within a minimalist salt-bridge model, the Asp-Arg dipeptide and thereby were able to map its detailed free energy landscape in aqueous solution. Free energy surface analysis shows that although individually-solvated states are more favorable, salt-bridge states still occupy a noticeable portion of the overall population. Notably, the competing forces, e.g. intercharge attractions that drive the formation of salt bridges and solvation forces that pull the charged groups away from each other, are energetically comparable. As the result, the salt bridge stability is highly tunable by local environments; for instance when local water molecules are perturbed to interact more strongly with each other, the population of the salt-bridge states is likely to increase. Our results reveal the critical role of local solvent structures in modulating salt-bridge partner interactions and imply the importance of water fluctuations on conformational dynamics that involves solvent accessible salt bridge formations. © 2015 The Protein Society.

Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

Science.gov (United States)

Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

2017-09-01

The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Eating high-fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning.

Science.gov (United States)

Baladi, Michelle G; France, Charles P

2010-10-01

Discriminative stimulus effects of direct acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high-fat chow increases sensitivity to quinpirole-induced yawning, and this study examined whether eating high-fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high-fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose-response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free-feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high-fat chow is likely because of enhanced sensitivity at D3 receptors. Thus, eating high-fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse.

Eating high fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning

Science.gov (United States)

Baladi, Michelle G; France, Charles P

2010-01-01

Discriminative stimulus effects of directly-acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high fat chow increases sensitivity to quinpirole-induced yawning and the current study examined whether eating high fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose- response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free- feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high fat chow is likely due to enhanced sensitivity at D3 receptors. Thus, eating high fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse. PMID:20729718

Age and radiation sensitivity of rat mammary clonogenic cells

International Nuclear Information System (INIS)

Shimada, Yoshiya; Yasukawa-Barnes, J.; Kim, R.Y.; Gould, M.N.; Clifton, K.H.

1994-01-01

The relative risk of breast cancer is very high among women who were exposed to ionizing radiation during or before puberty. In the current studies, the surviving fractions of clonogenic mammary cells of groups of virgin rats were estimated after single exposures to 137 Cs γ rays at intervals from 1 to 12 weeks after birth. The radiosensitivity of clonogens from prepubertal rats was high and changed with the onset of puberty at between 4 and 6 weeks of age. By this time, the increase in the size of the clonogenic cell subpopulation was slowing and differentiation of terminal mammary end buds and alveolar structures was occurring. Analysis of the relationship of clonogen survival and radiation dose according to the α/β model showed that the exponential αD term predominated at the second and fourth weeks of age. By the eighth week of age, the βD 2 term had come to predominate and the survival curve had a pronounced initial convex shoulder. Further experiments are required to determine whether there is an association between the high sensitivity of the prepubertal and pubertal mammary clonogens to radiation killing and a high susceptibility to radiogenic initiation of cancer. 24 refs., 4 figs., 1 tab

Tubuloglomerular feedback in Dahl rats

DEFF Research Database (Denmark)

Karlsen, F M; Leyssac, P P; Holstein-Rathlou, N H

1998-01-01

in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response...

Spirulina vesicolor Improves Insulin Sensitivity and Attenuates Hyperglycemia-Mediated Oxidative Stress in Fructose-Fed Rats

Directory of Open Access Journals (Sweden)

Walaa Hozayen

2016-03-01

Full Text Available Aim: The current study aimed to investigate the anti-hyperglycemic, anti-hyperlipidemic and insulin sensitizing effects of the cyanobacterium Spirulina vesicolor extract in fructose-fed rats. Materials and Methods: Rats were fed 30% fructose solution in drinking water for 4 weeks. Animals exhibited hyperglycemia and hyperinsulinemia were selected for further investigations. Diabetic and control rats were orally supplemented with 50 mg/kg body weight S. vesicolor extract for 4 weeks. Results: At the end of 8 weeks, fructose-fed rats showed significant increase in serum glucose, insulin, cholesterol, triglycerides, cardiovascular risk indices and insulin resistance. Treatment of the fructose-fed rats with S. vesicolor extract improved this metabolic profile. Fructose feeding produced a significant increase in serum tumor necrosis factor alpha (TNF-α and a decrease in adiponectin levels. In addition, fructose-fed rats exhibited a significant increase in liver, kidney and heart lipid peroxidation levels, and declined antioxidant defenses. Supplementation of the fructose-fed rats with S. vesicolor extract reversed these alterations. Conclusion: S. vesicolor attenuates hyperglycemia-mediated oxidative stress and inflammation, and is thus effective in improving insulin sensitivity in fructose-fed rats. [J Complement Med Res 2016; 5(1.000: 57-64

Hydration patterns and salting effects in sodium chloride solution.

Science.gov (United States)

Li, Weifeng; Mu, Yuguang

2011-10-07

The salting effects of 2M sodium chloride electrolyte are studied based on a series of model solutes with properties ranging from hydrophobic to hydrophilic. Generally, hydrophobic solutes will be salted out and hydrophilic solutes will be salted in by NaCl solution. The solvation free energy changes are highly correlated with Kirkwood-Buff integrals. The underlying mechanism resorts to the preferential binding of ions and water to solutes. Our results demonstrate that the salting effect not only depends on the salt's position in Hofmeister series, but also on the solutes' specifics. Taking the hydration free energies of solutes and ions as independent variables, a schematic diagram of salting effects is suggested. The resolved multifaceted salting effects rely on the sensitive balance of the tripartite interaction among solutes, ions, and water. © 2011 American Institute of Physics

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

Science.gov (United States)

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the

High salt intake increases plasma trimethylamine N-oxide (TMAO) concentration and produces gut dysbiosis in rats.

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Bielinska, Klaudia; Radkowski, Marek; Grochowska, Marta; Perlejewski, Karol; Huc, Tomasz; Jaworska, Kinga; Motooka, Daisuke; Nakamura, Shota; Ufnal, Marcin

2018-03-22

A high-salt diet is considered a cardiovascular risk factor; however, the mechanisms are not clear. Research suggests that gut bacteria-derived metabolites such as trimethylamine N-oxide (TMAO) are markers of cardiovascular diseases. We evaluated the effect of high salt intake on gut bacteria and their metabolites plasma level. Sprague Dawley rats ages 12-14 wk were maintained on either water (controls) or 0.9% or 2% sodium chloride (NaCl) water solution (isotonic and hypertonic groups, respectively) for 2 wk. Blood plasma, urine, and stool samples were analyzed for concentrations of trimethylamine (TMA; a TMAO precursor), TMAO, and indoxyl sulfate (indole metabolite). The gut-blood barrier permeability to TMA and TMA liver clearance were assessed at baseline and after TMA intracolonic challenge test. Gut bacterial flora was analyzed with a 16S ribosomal ribonucleic acid (rRNA) gene sequence analysis. The isotonic and hypertonic groups showed a significantly higher plasma TMAO and significantly lower 24-hr TMAO urine excretion than the controls. However, the TMA stool level was similar between the groups. There was no significant difference between the groups in gut-blood barrier permeability and TMA liver clearance. Plasma indoxyl concentration and 24-hr urine indoxyl excretion were similar between the groups. There was a significant difference between the groups in gut bacteria composition. High salt intake increases plasma TMAO concentration, which is associated with decreased TMAO urine excretion. Furthermore, high salt intake alters gut bacteria composition. These findings suggest that salt intake affects an interplay between gut bacteria and their host homeostasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling an economic evaluation of a salt fluoridation program in Peru.

Science.gov (United States)

Mariño, Rodrigo J; Fajardo, Jorge; Arana, Ana; Garcia, Carlos; Pachas, Flor

2011-01-01

This article models the cost-effectiveness, from a societal viewpoint, of a dental caries prevention program using salt fluoridation for children 12 years of age, compared with non-intervention (or status quo) in Arequipa, Peru. Standard cost-effectiveness analysis methods were used. The costs associated with implementing and operating the salt-fluoridation program were identified and measured using 2009 prices. Health outcomes were measured as dental caries averted over a 6-year period. Clinical effectiveness data was taken from published data. Costs were measured as direct treatment costs, programs costs and costs of productivity losses as a result of dental treatments. The incremental cost-effectiveness ratio was calculated. A hypothetical population of 25,000 12-year-olds living in Arequipa, Peru was used in this analysis. Two-way sensitivity analyses were conducted over a range of values for key parameters. Our primary analysis estimated that if a dental caries prevention program using salt-fluoridation was available for 25,000 6-year-old children for 6 years, the net saving from a societal perspective would total S/. 11.95 [1 US$ = S/. (2009) 3.01] per diseased tooth averted when compared with the status quo group. That is, after 6 years, an investment of S/.0.32 per annum per child would result in a net saving of S/.11.95 per decayed/missing/filled teeth prevented. While the analysis has inherent limitations as a result of its reliance on a range of assumptions, the findings indicate that for the situations prevailing in Peru, there are significant health and economic benefits to be gained from the use of salt fluoridation.

Modeling internal deformation of salt structures targeted for radioactive waste disposal

International Nuclear Information System (INIS)

Chemia, Zurab

2008-01-01

This thesis uses results of systematic numerical models to argue that externally inactive salt structures, which are potential targets for radioactive waste disposal, might be internally active due to the presence of dense layers or blocks within a salt layer. The three papers that support this thesis use the Gorleben salt diapir (NW Germany), which was targeted as a future final repository for high-grade radioactive waste, as a general guideline. The first two papers present systematic studies of the parameters that control the development of a salt diapir and how it entrains a dense anhydrite layer. Results from these numerical models show that the entrainment of a dense anhydrite layer within a salt diapir depends on four parameters: sedimentation rate, viscosity of salt, perturbation width and the stratigraphic location of the dense layer. The combined effect of these four parameters, which has a direct impact on the rate of salt supply (volume/area of the salt that is supplied to the diapir with time), shape a diapir and the mode of entrainment. Salt diapirs down-built with sedimentary units of high viscosity can potentially grow with an embedded anhydrite layer and deplete their source layer (salt supply ceases). However, when salt supply decreases dramatically or ceases entirely, the entrained anhydrite layer/segments start to sink within the diapir. In inactive diapirs, sinking of the entrained anhydrite layer is inevitable and strongly depends on the rheology of the salt, which is in direct contact with the anhydrite layer. During the post-depositional stage, if the effective viscosity of salt falls below the threshold value of around 10 18 -10 19 Pa s, the mobility of anhydrite blocks might influence any repository within the diapir. However, the internal deformation of the salt diapir by the descending blocks decreases with increase in effective viscosity of salt. The results presented in this thesis suggest that it is highly likely that salt structures

Modulation of olfactory sensitivity and glucose sensing by the feeding state in obese Zucker rats.

Directory of Open Access Journals (Sweden)

Pascaline eAimé

2014-09-01

Full Text Available The Zucker fa/fa rat has been widely used as an animal model to study obesity, since it recapitulates most of its behavioral and metabolic dysfunctions, such as hyperphagia, hyperglycemia and insulin resistance. Although it is well established that olfaction is under nutritional and hormonal influences, little is known about the impact of metabolic dysfunctions on olfactory performances and glucose-sensing in the olfactory system of the obese Zucker rat. In the present study, using a behavioral paradigm based on a conditioned olfactory aversion, we have shown that both obese and lean Zucker rats have a better olfactory sensitivity when they are fasted than when they are satiated. Interestingly, the obese Zucker rats displayed a higher olfactory sensitivity than their lean controls. By investigating the molecular mechanisms involved in glucose-sensing in the olfactory system, we demonstrated that sodium-coupled glucose transporters 1 (SGLT1 and insulin dependent glucose transporters 4 (GLUT4 are both expressed in the olfactory bulb (OB. By comparing the expression of GLUT4 and SGLT1 in OB of obese and lean Zucker rats, we found that only SGLT1 is regulated in genotype-dependent manner. Next, we used glucose oxidase biosensors to simultaneously measure in vivo the extracellular fluid glucose concentrations ([Gluc]ECF in the OB and the cortex. Under metabolic steady state, we have determined that the OB contained twice the amount of glucose found in the cortex. In both regions, the [Gluc]ECF was 2 fold higher in obese rats compared to their lean controls. Under induced dynamic glycemia conditions, insulin injection produced a greater decrease of [Gluc]ECF in the OB than in the cortex. Glucose injection did not affect OB [Gluc]ECF in Zucker fa/fa rats. In conclusion, these results emphasize the importance of glucose for the OB network function and provide strong arguments towards establishing the OB glucose-sensing as a key factor for sensory

Bile salts as semiochemicals in fish

Science.gov (United States)

Buchinger, Tyler J.; Li, Weiming; Johnson, Nicholas S.

2014-01-01

Bile salts are potent olfactory stimuli in fishes; however the biological functions driving such sensitivity remain poorly understood. We provide an integrative review of bile salts as semiochemicals in fish. First, we present characteristics of bile salt structure, metabolism, and function that are particularly relevant to chemical communication. Bile salts display a systematic pattern of structural variation across taxa, are efficiently synthesized, and are stable in the environment. Bile salts are released into the water via the intestine, urinary tract, or gills, and are highly water soluble. Second, we consider the potential role of bile salts as semiochemicals in the contexts of detecting nearby fish, foraging, assessing risk, migrating, and spawning. Lastly, we suggest future studies on bile salts as semiochemicals further characterize release into the environment, behavioral responses by receivers, and directly test the biological contexts underlying olfactory sensitivity.

Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats.

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Jerabek, Pavel; Havlickova, Tereza; Puskina, Nina; Charalambous, Chrysostomos; Lapka, Marek; Kacer, Petr; Sustkova-Fiserova, Magdalena

2017-11-01

An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10 mg/kg s.c.). On the experimental day, JMV2959 (3 and 6 mg/kg i.p.) or saline were administered before testing. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5 mg/kg s.c.) with or without JMV2959 (3 and 6 mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10-40 mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dissipation of excess photosynthetic energy contributes to salinity tolerance: a comparative study of salt-tolerant Ricinus communis and salt-sensitive Jatropha curcas.

Science.gov (United States)

Lima Neto, Milton C; Lobo, Ana K M; Martins, Marcio O; Fontenele, Adilton V; Silveira, Joaquim Albenisio G

2014-01-01

The relationships between salt tolerance and photosynthetic mechanisms of excess energy dissipation were assessed using two species that exhibit contrasting responses to salinity, Ricinus communis (tolerant) and Jatropha curcas (sensitive). The salt tolerance of R. communis was indicated by unchanged electrolyte leakage (cellular integrity) and dry weight in leaves, whereas these parameters were greatly affected in J. curcas. The leaf Na+ content was similar in both species. Photosynthesis was intensely decreased in both species, but the reduction was more pronounced in J. curcas. In this species biochemical limitations in photosynthesis were more prominent, as indicated by increased C(i) values and decreased Rubisco activity. Salinity decreased both the V(cmax) (in vivo Rubisco activity) and J(max) (maximum electron transport rate) more significantly in J. curcas. The higher tolerance in R. communis was positively associated with higher photorespiratory activity, nitrate assimilation and higher cyclic electron flow. The high activity of these alternative electron sinks in R. communis was closely associated with a more efficient photoprotection mechanism. In conclusion, salt tolerance in R. communis, compared with J. curcas, is related to higher electron partitioning from the photosynthetic electron transport chain to alternative sinks. Copyright © 2013 Elsevier GmbH. All rights reserved.

Molten Salt Power Tower Cost Model for the System Advisor Model (SAM)

Energy Technology Data Exchange (ETDEWEB)

Turchi, C. S.; Heath, G. A.

2013-02-01

This report describes a component-based cost model developed for molten-salt power tower solar power plants. The cost model was developed by the National Renewable Energy Laboratory (NREL), using data from several prior studies, including a contracted analysis from WorleyParsons Group, which is included herein as an Appendix. The WorleyParsons' analysis also estimated material composition and mass for the plant to facilitate a life cycle analysis of the molten salt power tower technology. Details of the life cycle assessment have been published elsewhere. The cost model provides a reference plant that interfaces with NREL's System Advisor Model or SAM. The reference plant assumes a nominal 100-MWe (net) power tower running with a nitrate salt heat transfer fluid (HTF). Thermal energy storage is provided by direct storage of the HTF in a two-tank system. The design assumes dry-cooling. The model includes a spreadsheet that interfaces with SAM via the Excel Exchange option in SAM. The spreadsheet allows users to estimate the costs of different-size plants and to take into account changes in commodity prices. This report and the accompanying Excel spreadsheet can be downloaded at https://sam.nrel.gov/cost.

Adverse social experiences in adolescent rats result in enduring effects on social competence, pain sensitivity and endocannabinoid signaling

Directory of Open Access Journals (Sweden)

Peggy Schneider

2016-10-01

Full Text Available Social affiliation is essential for many species and gains significant importance during adolescence. Disturbances in social affiliation, in particular social rejection experiences during adolescence, affect an individual’s well-being and are involved in the emergence of psychiatric disorders. The underlying mechanisms are still unknown, partly because of a lack of valid animal models. By using a novel animal model for social peer-rejection, which compromises adolescent rats in their ability to appropriately engage in playful activities, here we report on persistent impairments in social behavior and dysregulations in the endocannabinoid system. From postnatal day (pd 21 to pd 50 adolescent female Wistar rats were either reared with same-strain partners (control or within a group of Fischer 344 rats (inadequate social rearing, ISR, previously shown to serve as inadequate play partners for the Wistar strain. Adult ISR animals showed pronounced deficits in social interaction, social memory, processing of socially transmitted information, and decreased pain sensitivity. Molecular analysis revealed increased CB1 receptor protein levels and CP55,940 stimulated 35SGTPγS binding activity specifically in the amygdala and thalamus in previously peer-rejected rats. Along with these changes, increased levels of the endocannabinoid anandamide and a corresponding decrease of its degrading enzyme fatty acid amide hydrolase were seen in the amygdala. Our data indicate lasting consequences in social behavior and pain sensitivity following peer-rejection in adolescent female rats. These behavioral impairments are accompanied by persistent alterations in CB1 receptor signaling. Finally, we provide a novel translational approach to characterize neurobiological processes underlying social peer-rejection in adolescence.

Nitrogen-detected TROSY yields comparable sensitivity to proton-detected TROSY for non-deuterated, large proteins under physiological salt conditions

Energy Technology Data Exchange (ETDEWEB)

Takeuchi, Koh [National Institute for Advanced Industrial Science and Technology, Molecular Profiling Research Center for Drug Discovery (Japan); Arthanari, Haribabu [Harvard Medical School, Department of Biochemistry and Molecular Pharmacology (United States); Imai, Misaki [Japan Biological Informatics Consortium, Research and Development Department (Japan); Wagner, Gerhard, E-mail: gerhard-wagner@hms.harvard.edu [Harvard Medical School, Department of Biochemistry and Molecular Pharmacology (United States); Shimada, Ichio, E-mail: shimada@iw-nmr.f.u-tokyo.ac.jp [National Institute for Advanced Industrial Science and Technology, Molecular Profiling Research Center for Drug Discovery (Japan)

2016-02-15

Direct detection of the TROSY component of proton-attached {sup 15}N nuclei ({sup 15}N-detected TROSY) yields high quality spectra with high field magnets, by taking advantage of the slow {sup 15}N transverse relaxation. The slow transverse relaxation and narrow line width of the {sup 15}N-detected TROSY resonances are expected to compensate for the inherently low {sup 15}N sensitivity. However, the sensitivity of {sup 15}N-detected TROSY in a previous report was one-order of magnitude lower than in the conventional {sup 1}H-detected version. This could be due to the fact that the previous experiments were performed at low salt (0–50 mM), which is advantageous for {sup 1}H-detected experiments. Here, we show that the sensitivity gap between {sup 15}N and {sup 1}H becomes marginal for a non-deuterated, large protein (τ{sub c} = 35 ns) at a physiological salt concentration (200 mM). This effect is due to the high salt tolerance of the {sup 15}N-detected TROSY. Together with the previously reported benefits of the {sup 15}N-detected TROSY, our results provide further support for the significance of this experiment for structural studies of macromolecules when using high field magnets near and above 1 GHz.

Chronic Blockade of Brain Endothelin Receptor Type-A (ETA Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats

Directory of Open Access Journals (Sweden)

Luis R. Cassinotti

2018-02-01

Full Text Available Overactivity of the sympathetic nervous system and central endothelins (ETs are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA-salt hypertensive rats. Following brain ET receptor type A (ETA blockade by BQ610 (selective antagonist, transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ETA blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein in the right OB of hypertensive animals. However, ETA blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ETA are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats.

Science.gov (United States)

Cassinotti, Luis R; Guil, María J; Schöller, Mercedes I; Navarro, Mónica P; Bianciotti, Liliana G; Vatta, Marcelo S

2018-02-27

Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ET A ) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ET A blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ET A blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ET A are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye.

Science.gov (United States)

Rahman, Mostafeezur; Okamoto, Keiichiro; Thompson, Randall; Katagiri, Ayano; Bereiter, David A

2015-05-01

Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, whereas OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline-evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared with controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline-evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation.

PHOTOPOLYMERIZATION INITIATED BY DIMETHYLAMINOCHALCONE/DIPHENYL-IODONIUM SALT COMBINATION SYSTEM SENSITIVE TO VISIBLE LIGHT

Institute of Scientific and Technical Information of China (English)

LI Jun; LI Miaozhen; SONG Huaihai; YANG Yongyuan; WANG Erjian

1993-01-01

Several dimethylamino-substituted chalcone (I.e.dimethylaminobenzal acetophenone) (DBA) derivatives with intramolecular charge transfer transition character were used as visible light sensitizers for radical photopolymerization initiated by iodonium salt (DPIO). Initiating radical species is produced from DBA sensitized photolysis of DPIO through the single electron transfer,accompanying the bleaching of DBA.The activity of DBA decreases as a function of substituent attached to phenyl ring in the order:DBA-2(OCH3)＞DBA-1(H)＞DBA-3(Cl).The kinetic study on photopolymerization of MMA was carried out in CH3CN solution at 30℃ by dilatometry.The polymerization rate was determined to be proportional to the concentration with exponents of 0.42,0.25 and 0.86 for DPIO,DBA-1and MMA,respectively.

Erythrocyte sodium concentration and 86Rb uptake in weanling Dahl rats

International Nuclear Information System (INIS)

McCormick, C.P.; Hennessy, J.F.; Rauch, A.L.; Buckalew, V.M. Jr.

1989-01-01

Alterations in Na, K ATPase pump activity as well as erythrocyte (RBC) intracellular sodium concentration (Nai) have been demonstrated in humans and rats with established hypertension. The contribution of hypertension itself to these changes is unclear. Accordingly, we investigated RBC ion transport and plasma ouabain-like factor (OLF) in four- to five-week old normotensive Dahl salt-sensitive (DS) and salt-resistant (DR) rats on low salt diet. Although both strains were normotensive, systolic blood pressure (SBP) of DS (123 ± 2 mm Hg) was higher than that of DR (116 ± 1 mm Hg). No interstrain difference was evident in RBC pump activity measured as ouabain-sensitive 86rubidium ( 86 Rb) uptake (DS = 0.277 ± .030 and DR = 0.271 ± .029 mumol/10(9)RBC/h) even though RBC Nai was greater in DS than DR (14.9 ± 2.0 v 10.7 ± 1.0 mEq/L; P less than 0.05). Plasma OLF was higher in DS than DR (28.9 ± 4.7 v 16.5 ± 2.3 pmol/mL; P less than 0.05), but did not correlate with RBC pump activity in either strain. RBC Nai was directly correlated with pump activity in DS (r = 0.84, P less than 0.01) and demonstrated a trend to correlate in DR (r = 0.71, P = 0.07). RBC Nai was also directly correlated with SBP in DR (r = 0.73, P less than 0.05) and DS (r = 0.70, P = 0.05). We conclude that RBC Nai is genetically determined in Dahl rats and is elevated in normotensive DS who are at risk for hypertension development

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.

Science.gov (United States)

Kirman, C R; Suh, M; Proctor, D M; Hays, S M

2017-06-15

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster (Crassostrea gigas) and culture broth under different conditions

Energy Technology Data Exchange (ETDEWEB)

Jung, Pil-Mun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Jae Seok [Korea Food and Drug Administration, Seoul 122-704 (Korea, Republic of); Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Baek, Min [Atomic Energy Policy Division, Ministry of Education, Science and Technology, Gwacheon 427-715 (Korea, Republic of); Chung, Young-Jin [Department of Food and Nutrition, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

2009-07-15

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster (Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D{sub 10} value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster (Crassostrea gigas) and culture broth under different conditions

International Nuclear Information System (INIS)

Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

2009-01-01

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster (Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D 10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster ( Crassostrea gigas) and culture broth under different conditions

Science.gov (United States)

Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

2009-07-01

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster ( Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Damage-induced nonassociated inelastic flow in rock salt

International Nuclear Information System (INIS)

Chan, K.S.; Bodner, S.R.; Brodsky, N.S.; Fossum, A.F.; Munson, D.E.

1993-01-01

The multi-mechanism deformation coupled fracture model recently developed by CHAN, et al. (1992), for describing time-dependent, pressure-sensitive inelastic flow and damage evolution in crystalline solids was evaluated against triaxial creep experiments on rock salt. Guided by experimental observations, the kinetic equation and the flow law for damage-induced inelastic flow in the model were modified to account for the development of damage and inelastic dilatation in the transient creep regime. The revised model was then utilized to obtain the creep response and damage evolution in rock salt as a function of confining pressure and stress difference. Comparison between model calculation and experiment revealed that damage-induced inelastic flow is nonassociated, dilatational, and contributes significantly to the macroscopic strain rate observed in rock salt deformed at low confining pressures. The inelastic strain rate and volumetric strain due to damage decrease with increasing confining pressures, and all are suppressed at sufficiently high confining pressures

Bioelectronic tongue of taste buds on microelectrode array for salt sensing.

Science.gov (United States)

Liu, Qingjun; Zhang, Fenni; Zhang, Diming; Hu, Ning; Wang, Hua; Hsia, K Jimmy; Wang, Ping

2013-02-15

Taste has received great attention for its potential applications. In this work, we combine the biological tissue with micro-chips to establish a novel bioelectronic tongue system for salt taste detection. Before experiment, we established a computational model of action potential in salt taste receptor cell, simulating the responsive results to natural salt stimuli of NaCl solution with various concentrations. Then 36-channel microelectrode arrays (MEA) with the diameter of 30 μm were fabricated on the glass substrate, and taste epithelium was stripped from rat and fixed on MEA. When stimulated by the salt stimuli, electrophysiological activities of taste receptor cells in taste buds were measured through a multi-channel recording system. Both simulation and experiment results showed a dose-dependent increase in NaCl-induced potentials of taste receptor cells, which indicated good applications in salt measurements. The multi-channel analysis demonstrated that different groups of MEA channels were activated during stimulations, indicating non-overlapping populations of receptor cells in taste buds involved in salt taste perception. The study provides an effective and reliable biosensor platform to help recognize and distinguish salt taste components. Copyright © 2012 Elsevier B.V. All rights reserved.

Calibrating a Salt Water Intrusion Model with Time-Domain Electromagnetic Data

DEFF Research Database (Denmark)

Herckenrath, Daan; Odlum, Nick; Nenna, Vanessa

2013-01-01

Salt water intrusion models are commonly used to support groundwater resource management in coastal aquifers. Concentration data used for model calibration are often sparse and limited in spatial extent. With airborne and ground-based electromagnetic surveys, electrical resistivity models can......, we perform a coupled hydrogeophysical inversion (CHI) in which we use a salt water intrusion model to interpret the geophysical data and guide the geophysical inversion. We refer to this methodology as a Coupled Hydrogeophysical Inversion-State (CHI-S), in which simulated salt concentrations...... are transformed to an electrical resistivity model, after which a geophysical forward response is calculated and compared with the measured geophysical data. This approach was applied for a field site in Santa Cruz County, California, where a time-domain electromagnetic (TDEM) dataset was collected...

Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study.

Science.gov (United States)

Chen, Jing; Gu, Dongfeng; Huang, Jianfeng; Rao, Dabeeru C; Jaquish, Cashell E; Hixson, James E; Chen, Chung-Shiuan; Chen, Jichun; Lu, Fanghong; Hu, Dongsheng; Rice, Treva; Kelly, Tanika N; Hamm, L Lee; Whelton, Paul K; He, Jiang

2009-03-07

Since insulin resistance is thought to be the underlying mechanism for metabolic syndrome, affected individuals might be sensitive to a dietary sodium intervention. We aimed to examine the association between metabolic syndrome and salt sensitivity of blood pressure. 1906 Chinese participants without diabetes, aged 16 years or more, were selected to receive a low-sodium diet (51.3 mmol per day) for 7 days followed by a high-sodium diet (307.8 mmol per day) for an additional 7 days. Participants were excluded from the analysis if metabolic risk factor information was missing or if they did not complete their dietary interventions. Blood pressure was measured at baseline and on days 2, 5, 6, and 7 of each intervention. Metabolic syndrome was defined as the presence of three or more of: abdominal obesity, raised blood pressure, high triglyceride concentration, low HDL cholesterol, or high glucose. High salt sensitivity was defined as a decrease in mean arterial blood pressure of more than 5 mm Hg during low-sodium or an increase of more than 5 mm Hg during high-sodium intervention. This study is registered with ClinicalTrials.gov, number NCT00721721. Of the 1881 participants with information regarding metabolic syndrome, 283 had metabolic syndrome. 1853 participants completed the low-sodium diet and 1845 completed the high-sodium diet. Multivariable-adjusted mean changes in blood pressure were significantly greater in participants with metabolic syndrome than in those without on both low-sodium and high-sodium diets (plow-sodium and a 3.13-fold increased odds (1.80-5.43) of high salt-sensitivity during the high-sodium intervention. These results suggest that metabolic syndrome enhances blood pressure response to sodium intake. Reduction in sodium intake could be an especially important component in reducing blood pressure in patients with multiple risk factors for metabolic syndrome.

A SENSITIZED PHOTOINITIATION SYSTEM——BIS (7- DIETHYLAMINO COUMARIN )KETONE- 3 AND DIPHENYLIODONIUM SALT COMBINATION

Institute of Scientific and Technical Information of China (English)

LI Jun; WANG Xiuzhi; YANG Yongyung; LI Miaozhen; WANG Erjian

1993-01-01

Bis (7- diethylaminocoumarin ) ketone- 3(DACK) and diphenyliodonium salt (DPIO)combination as an effective photoinitiation system for radical polymerization has been investigated. The sensitized photolysis of DACK/DPIO leads to bleaching of DACK and decomposition of DPIO to generate initiating radical species. The electron transfer sensitization occurs mainly from the triplet state of DACK. The photobleaching obeyed a second-order kinetics and the rate constant was evaluated to be 31.3mol-1.l.s-1. Photopolymerization of MMA initiated by DACK/DPIO was carried out in acetonitrile solution. The polymerization rate was found to be proportional to the concentration of DACK, DPIO and MMA with the exponents of 0.34, 0.40 and 1.0 respectively. The initiated efficiency is comparable to those of small molecular ketones. The sensitized photoinitiation mechanism has been discussed.

Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the Lou/C rat.

Directory of Open Access Journals (Sweden)

Christelle Veyrat-Durebex

Full Text Available The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3 ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3, known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF and thyrotropin-releasing hormone (TRH.

Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

Directory of Open Access Journals (Sweden)

Zhenzhen Cai

2013-02-01

Full Text Available A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS method was developed for determination of timosaponin AIII (TA-III in rat plasma, using ginsenoside Re as an internal standard (IS. TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ was 11.14 ng/mL. Intra-day and inter-day precisions (RSD were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III.

Characterization of Salt Overly Sensitive 1 (SOS1) gene homoeologs in quinoa (Chenopodium quinoa Willd.).

Science.gov (United States)

Maughan, P J; Turner, T B; Coleman, C E; Elzinga, D B; Jellen, E N; Morales, J A; Udall, J A; Fairbanks, D J; Bonifacio, A

2009-07-01

Salt tolerance is an agronomically important trait that affects plant species around the globe. The Salt Overly Sensitive 1 (SOS1) gene encodes a plasma membrane Na+/H+ antiporter that plays an important role in germination and growth of plants in saline environments. Quinoa (Chenopodium quinoa Willd.) is a halophytic, allotetraploid grain crop of the family Amaranthaceae with impressive nutritional content and an increasing worldwide market. Many quinoa varieties have considerable salt tolerance, and research suggests quinoa may utilize novel mechanisms to confer salt tolerance. Here we report the cloning and characterization of two homoeologous SOS1 loci (cqSOS1A and cqSOS1B) from C. quinoa, including full-length cDNA sequences, genomic sequences, relative expression levels, fluorescent in situ hybridization (FISH) analysis, and a phylogenetic analysis of SOS1 genes from 13 plant taxa. The cqSOS1A and cqSOS1B genes each span 23 exons spread over 3477 bp and 3486 bp of coding sequence, respectively. These sequences share a high level of similarity with SOS1 homologs of other species and contain two conserved domains, a Nhap cation-antiporter domain and a cyclic-nucleotide binding domain. Genomic sequence analysis of two BAC clones (98 357 bp and 132 770 bp) containing the homoeologous SOS1 genes suggests possible conservation of synteny across the C. quinoa sub-genomes. This report represents the first molecular characterization of salt-tolerance genes in a halophytic species in the Amaranthaceae as well as the first comparative analysis of coding and non-coding DNA sequences of the two homoeologous genomes of C. quinoa.

Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

DEFF Research Database (Denmark)

Mathe, A.; Wegener, Gregers; Finger, B.

2010-01-01

Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion....... In selected animals effect of NPS on home cage activity was explored. Finally, brains from separate groups of naive animals were harvested; hippocampi, amygdalae and PVN punched out, and mRNA transcripts measured with the real-time quantitative polymerase chain reaction (rt-qPCR). Results: The most salient...

Preliminary model validation for integral stability behavior in molten salt natural circulation

International Nuclear Information System (INIS)

Cai Chuangxiong; He Zhaozhong; Chen Kun

2017-01-01

Passive safety system is an important characteristic of Fluoride-Salt-Cooled High-Temperature Reactor (FHR). In order to remove the decay heat, a direct reactor auxiliary cooling system (DRACS) which uses the passive safety technology is proposed to the FHR as the ultimate heat sink. The DRACS is relying on the natural circulation, so the study of molten salt natural circulation plays an important role at TMSR. A high-temperature molten salt natural circulation test loop has been designed and constructed at the TMSR center of the Chinese Academy of Sciences (CAS) to understand the characteristics of the natural circulation and verify the design model. It adopts nitrate salt as the working fluid to simulate fluoride salts, and uses air as the ultimate heat sink. The test shows the operation very well and has a very nice performance, the Heat transfer coefficients (salt-salt or salt-air), power of the loop, heat loss of molten salt pool (or molten salt pipe or air cooling tower), starting time of the loop, flow rate that can be verified in this loop. A series of experiments have been done and the results show that the experimental data are well matched with the design data. This paper aims at analyzing the molten salt circulation model, studying the characteristics of the natural circulation, and verifying the Integral stability behavior by three different natural circulation experiments. Also, the experiment is going on, and more experiments will been carry out to study the molten salt natural circulation for optimizing the design. (author)

SALT4: a two-dimensional displacement discontinuity code for thermomechanical analysis in bedded salt deposits

International Nuclear Information System (INIS)

1983-04-01

SALT4 is a two-dimensional analytical/displacement-discontinuity code designed to evaluate temperatures, deformation, and stresses associated with underground disposal of radioactive waste in bedded salt. This code was developed by the University of Minnesota. This documentation describes the mathematical equations of the physical system being modeled, the numerical techniques utilized, and the organization of the computer code, SALT4. The SALT4 code takes into account: (1) viscoelastic behavior in the pillars adjacent to excavations; (2) transversely isotropic elastic moduli such as those exhibited by bedded or stratified rock; and (2) excavation sequence. Major advantages of the SALT4 code are: (1) computational efficiency; (2) the small amount of input data required; and (3) a creep law consistent with laboratory experimental data for salt. The main disadvantage is that some of the assumptions in the formulation of SALT4, i.e., temperature-independent material properties, render it unsuitable for canister-scale analysis or analysis of lateral deformation of the pillars. The SALT4 code can be used for parameter sensitivity analyses of two-dimensional, repository-scale, thermal and thermomechanical response in bedded salt during the excavation, operational, and post-closure phases. It is especially useful in evaluating alternative patterns and sequences of excavation or waste canister placement. SALT4 can also be used to verify fully numerical codes. This is similar to the use of analytic solutions for code verification. Although SALT4 was designed for analysis of bedded salt, it is also applicable to crystalline rock if the creep calculation is suppressed. In Section 1.5 of this document the code custodianship and control is described along with the status of verification, validation and peer review of this report

Model-based studies into ground water movement, with water density depending on salt content. Case studies and model validation with respect to the long-term safety of radwaste repositories. Final report

International Nuclear Information System (INIS)

Schelkes, K.

1995-12-01

Near-to-reality studies into ground water movement in the environment of planned radwaste repositories have to take into account that the flow conditions are influenced by the water density which in turn depends on the salt content. Based on results from earlier studies, computer programs were established that allow computation and modelling of ground water movement in salt water/fresh water systems, and the programs were tested and improved according to progress of the studies performed under the INTRAVAL international project. The computed models of ground water movement in the region of the Gorlebener Rinne showed for strongly simplified model profiles that the developing salinity distribution varies very sensitively in response to the applied model geometry, initial input data for salinity distribution, time frame of the model, and size of the transversal dispersion length. The WIPP 2 INTRAVAL experiment likewise studied a large-area ground water movement system influenced by salt water. Based on the concept of a hydraulically closed, regional ground water system (basin model), a sectional profile was worked out covering all relevant layers of the cap rock above the salt formation planned to serve as a repository. The model data derived to describe the salt water/fresh water movements in this profile resulted in essential enlargements and modifications of the ROCKFLOW computer program applied, (relating to input data for dispersion modelling, particle-tracker, computer graphics interface), and yielded important information for the modelling of such systems (relating to initial pressure data at the upper margin, network enhancement for important concentration boundary conditions, or treatment of permeability contrasts). (orig.) [de

Modeling of Dense Water Production and Salt Transport from Alaskan Coastal Polynyas

Science.gov (United States)

Signorini, Sergio R.; Cavalieri, Donald J.

2000-01-01

The main significance of this paper is that a realistic, three-dimensional, high-resolution primitive equation model has been developed to study the effects of dense water formation in Arctic coastal polynyas. The model includes realistic ambient stratification, realistic bottom topography, and is forced by time-variant surface heat flux, surface salt flux, and time-dependent coastal flow. The salt and heat fluxes, and the surface ice drift, are derived from satellite observations (SSM/I and NSCAT sensors). The model is used to study the stratification, salt transport, and circulation in the vicinity of Barrow Canyon during the 1996/97 winter season. The coastal flow (Alaska coastal current), which is an extension of the Bering Sea throughflow, is formulated in the model using the wind-transport regression. The results show that for the 1996/97 winter the northeastward coastal current exports 13% to 26% of the salt produced by coastal polynyas upstream of Barrow Canyon in 20 to 30 days. The salt export occurs more rapidly during less persistent polynyas. The inclusion of ice-water stress in the model makes the coastal current slightly weaker and much wider due to the combined effects of surface drag and offshore Ekman transport.

Toxicological evaluation of 6'-sialyllactose (6'-SL) sodium salt.

Science.gov (United States)

Gurung, Rit Bahadur; Kim, Dae Hee; Kim, Lila; Lee, Albert W; Wang, Zhenhua; Gao, Yonglin

2018-06-01

We performed a series of toxicity studies on the safety of 6'-sialyllactose (6'-SL) sodium salt as a food ingredient. 6'-SL sodium salt, up to a maximum dose of 5000 μg/plate, did not increase the number of revertant colonies in five strains of Salmonella typhimurium in the presence or absence of S9 metabolic activation. A chromosomal aberration assay (using Chinese hamster lung cells) found no clastogenic effects at any concentration of 6'-SL sodium salt in the presence or absence of S9 metabolic activation. An in vivo bone marrow micronucleus test in Kunming mice showed no clastogenic activities with 6'-SL sodium salt doses up to 2000 mg/kg body weight (bw). In an acute toxicity study, the mean lethal dose of 6'-SL sodium salt was greater than 20 g/kg bw in rats. In a 13-week subchronic toxicity investigation, no effects were found at doses up to 5.0 g/kg bw of 6'-SL sodium salt in food consumption, body weight, clinical signs, blood biochemistry and hematology, urinalysis, or ophthalmic and histological macroscopic examination of organs. The no-observed-adverse-effect level (NOAEL) was 5.0 g/kg bw/day in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

High Salt Intake Attenuates Breast Cancer Metastasis to Lung.

Science.gov (United States)

Xu, Yijuan; Wang, Wenzhe; Wang, Minmin; Liu, Xuejiao; Lee, Mee-Hyun; Wang, Mingfu; Zhang, Hao; Li, Haitao; Chen, Wei

2018-04-04

Diet-related factors are thought to modify the risk of cancers, while the influence of high salt intake remains largely uncharacterized. Breast cancer is the most common cancer in women worldwide. In the present study, we examined the effect of salt intake on breast cancer by using a 4T1 mouse mammary tumor model. Unexpectedly, both the fitness and the survival rate of the tumor-bearing mice were improved by high salt intake. Similarly, high salt intake suppressed the primary tumor growth as well as metastasis to lung in mice. Mechanistically, high salt intake greatly reduced food intake and thus might exert antitumor effect through mimicking calorie restriction. Immunoblotting showed the lower proliferation marker Ki-67 and the higher expression of the tumor suppressor gene p53 in tumors of high salt intake mice. Importantly, high salt intake might induce hyperosmotic stress, which sensitized breast cancer cells to p53-dependent anoikis. Collectively, our findings raise the possibility that endogenous salt deposition might act as the first-line defense system against breast cancer progression as well as metastasis.

Modeling and simulation of a molten salt cavity receiver with Dymola

International Nuclear Information System (INIS)

Zhang, Qiangqiang; Li, Xin; Wang, Zhifeng; Zhang, Jinbai; El-Hefni, Baligh; Xu, Li

2015-01-01

Molten salt receivers play an important role in converting solar energy to thermal energy in concentrating solar power plants. This paper describes a dynamic mathematical model of the molten salt cavity receiver that couples the conduction, convection and radiation heat transfer processes in the receiver. The temperature dependence of the material properties is also considered. The radiosity method is used to calculate the radiation heat transfer inside the cavity. The outlet temperature of the receiver is calculated for 11 sets of transient working conditions. The simulation results compare well with experimental data, thus the model can be further used in system simulations of entire power plants. - Highlights: • A detailed model for molten salt cavity receiver is presented. • The model couples the conduction, convection and thermal radiation. • The simulation results compare well with experimental data. • The model can be further used for many purposes.

Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

DEFF Research Database (Denmark)

Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In CMS model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

Sensitivity of perianal tape impressions to diagnose pinworm (Syphacia spp.) infections in rats (Rattus norvegicus) and mice (Mus musculus).

Science.gov (United States)

Hill, William Allen; Randolph, Mildred M; Mandrell, Timothy D

2009-07-01

We determined the sensitivity of perianal tape impressions to detect Syphacia spp. in rats and mice. We evaluated 300 rat and 200 mouse perianal impressions over 9 wk. Pinworm-positive perianal tape impressions from animals with worm burdens at necropsy were considered as true positives. Conversely, pinworm-negative perianal tape impressions from animals with worm burdens were considered false negatives. The sensitivity of perianal tape impressions for detecting Syphacia muris infections in rats was 100%, and for detecting Syphacia obvelata in mice was 85.5%. Intermittent shedding of Syphacia obvelata ova is the most probable explanation for the decreased sensitivity rate we observed in mice. We urge caution in use of perianal tape impressions alone for Syphacia spp. screening in sentinel mice and rats.

Optical Modeling of Sea Salt Aerosols: The Effects of Nonsphericity and Inhomogeneity

Science.gov (United States)

Bi, Lei; Lin, Wushao; Wang, Zheng; Tang, Xiaoyun; Zhang, Xiaoyu; Yi, Bingqi

2018-01-01

The nonsphericity and inhomogeneity of marine aerosols (sea salts) have not been addressed in pertinent radiative transfer calculations and remote sensing studies. This study investigates the optical properties of nonspherical and inhomogeneous sea salts using invariant imbedding T-matrix simulations. Dry sea salt aerosols are modeled based on superellipsoidal geometries with a prescribed aspect ratio and roundness parameter. Wet sea salt particles are modeled as coated superellipsoids, as spherical particles with a superellipsoidal core, and as homogeneous spheres depending on the level of relative humidity. Aspect ratio and roundness parameters are found to be critical to interpreting the linear depolarization ratios (LDRs) of NaCl crystals from laboratory measurements. The optimal morphology parameters of NaCl necessary to reproduce the measurements are found to be consistent with data gleaned from an electron micrograph. The LDRs of wet sea salts are computed based on inhomogeneous models and compared with the measured data from ground-based LiDAR. The dependence of the LDR on relative humidity is explicitly considered. The increase in the LDR with relative humidity at the initial phase of deliquescence is attributed to both the size increase and the inhomogeneity effect. For large humidity values, the LDR substantially decreases because the overall particle shape becomes more spherical and the inhomogeneity effect in a particle on the LDR is suppressed for submicron sea salts. However, the effect of inhomogeneity on optical properties is pronounced for coarse-mode sea salts. These findings have important implications for atmospheric radiative transfer and remote sensing involving sea salt aerosols.

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

International Nuclear Information System (INIS)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.; Storm, Gert; Arts, Josje H.E.; Kuper, C. Frieke; Bloksma, Nanne; Henricks, Paul A.J.

2006-01-01

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later

Sound sensitivity of neurons in rat hippocampus during performance of a sound-guided task

Science.gov (United States)

Vinnik, Ekaterina; Honey, Christian; Schnupp, Jan; Diamond, Mathew E.

2012-01-01

To investigate how hippocampal neurons encode sound stimuli, and the conjunction of sound stimuli with the animal's position in space, we recorded from neurons in the CA1 region of hippocampus in rats while they performed a sound discrimination task. Four different sounds were used, two associated with water reward on the right side of the animal and the other two with water reward on the left side. This allowed us to separate neuronal activity related to sound identity from activity related to response direction. To test the effect of spatial context on sound coding, we trained rats to carry out the task on two identical testing platforms at different locations in the same room. Twenty-one percent of the recorded neurons exhibited sensitivity to sound identity, as quantified by the difference in firing rate for the two sounds associated with the same response direction. Sensitivity to sound identity was often observed on only one of the two testing platforms, indicating an effect of spatial context on sensory responses. Forty-three percent of the neurons were sensitive to response direction, and the probability that any one neuron was sensitive to response direction was statistically independent from its sensitivity to sound identity. There was no significant coding for sound identity when the rats heard the same sounds outside the behavioral task. These results suggest that CA1 neurons encode sound stimuli, but only when those sounds are associated with actions. PMID:22219030

Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

DEFF Research Database (Denmark)

Isaksson, G L; Stubbe, J; Hansen, Per Lyngs

2014-01-01

We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC...

Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studie

Czech Academy of Sciences Publication Activity Database

Stuchlík, Aleš; Radostová, Dominika; Hatalová, Hana; Valeš, Karel; Nekovářová, Tereza; Kopřivová, J.; Svoboda, Jan; Horáček, J.

2016-01-01

Roč. 10, Oct 26 (2016), č. článku 209. ISSN 1662-5153 R&D Projects: GA MZd(CZ) NV15-34524A Institutional support: RVO:67985823 Keywords : OCD * quinpirole * animal model * brain circuits * rat * human Subject RIV: FH - Neurology Impact factor: 3.104, year: 2016

Mediterranean salt giants beyond the evaporite model: The Sicily perspective

Science.gov (United States)

Carmelo Manuella, Fabio; Scribano, Vittorio; Carbone, Serafina; Hovland, Martin; Johnsen, Hans-Konrad; Rueslåtten, Håkon

2017-04-01

Mediterranean salt giants, occurring both in sub-seafloor and in onshore settings (the "Gessoso Solfifera Group"), are traditionally explained by repeated cycles of desiccation and replenishment of the entire basin. However, such hypotheses are strongly biased by mass balance calculations and geodynamic considerations. In addition, any hypothesis without full desiccation, still based on the evaporite model, should consider that seawater brines start to precipitate halite when 2/3 of the seawater has evaporated, and hence the level of the basin cannot be the same as the adjacent ocean. On the other hand, hydrothermal venting of hot saline brines onto the seafloor can precipitate salt in a deep marine basin if a layer of heavy brine exists along the seafloor. This process, likely related to sub-surface boiling or supercritical out-salting (Hovland et al., 2006), is consistent with geological evidence in the Red Sea "Deeps" (Hovland et al., 2015). Although supercritical out-salting and phase separation can sufficiently explain the formation of several marine salt deposits, even in deep marine settings, the Mediterranean salt giant formations can also be explained by the serpentinization model (Scribano et al., 2016). Serpentinization of abyssal peridotites does not involve seawater salts, and large quantities of saline brines accumulate in pores and fractures of the sub-seafloor serpentinites. If these rocks undergo thermal dehydration, for example, due to igneous intrusions, brines and salt slurries can migrate upwards as hydrothermal plumes, eventually venting at the seafloor, giving rise to giant salt deposits over time. These hydrothermal processes can take place in a temporal sequence, as it occurred in the "Caltanissetta Basin" (Sicily). There, salt accumulation associated with serpentinization started during Triassic times (and even earlier), and venting of heavy brines onto the seafloor eventually occurred in the Messinian via the hydrothermal plume mechanism

Salt intrusion study in Cochin estuary - Using empirical models

Digital Repository Service at National Institute of Oceanography (India)

Jacob, B.; Revichandran, C.; NaveenKumar, K.R.

been applied to the Cochin estuary in the present study to identify the most suitable model for predicting the salt intrusion length. Comparison of the obtained results indicate that the model of Van der Burgh (1972) is the most suitable empirical model...

Effective salt criteria in callus-cultured tomato genotypes.

Science.gov (United States)

Dogan, Mahmut; Tipirdamaz, Rukiye; Demir, Yavuz

2010-01-01

Na+, Cl-, K+, Ca2+, and proline contents, the rate of lipid peroxidation level in terms of malondialdehyde (MDA) and chlorophyll content, and the changes in the activity of antioxidant enzymes, such as superoxide dismutase (SOD: EC 1.15.1.1), catalase (CAT: EC 1.11.1.6), ascorbate peroxidase (APX: EC 1.11.1.11), and glutathione reductase (GR: EC 1.6.4.2), in tissues of five tomato cultivars in salt tolerance were investigated in a callus culture. The selection of effective parameters used in these tomato genotypes and to find out the use of in vitro tests in place of in vivo salt tolerance tests were investigated. As a material, five different tomato genotypes during a 10-day time period were used, and 150 mM NaCl was applied at callus plant tissue. The exposure to NaCl induced a significant increase in MDA content in both salt-resistant and salt-sensitive cultivars. But the MDA content was higher in salt-sensitive cultivars. The chlorophyll content was more decreased in salt-sensitive than in salt-resistant ones. The proline amount was more increased in salt-sensitive than in salt-resistant ones. It has been reported that salt-tolerant plants, besides being able to regulate the ion and water movements, also exhibit a strong antioxidative enzyme system for effective removal of ROS. The degree of damage depends on the balance between the formation of ROS and its removal by the antioxidative scavenging system that protects against them. Exclusion or inclusion of Na+, Cl-, K+, and Ca2+, antioxidant enzymes and MDA concentration play a key protective role against stress, and this feature at the callus plant tissue used as an identifier for tolerance to salt proved to be an effective criterion.

Overexpression of Rat Neurons Nitric Oxide Synthase in Rice Enhances Drought and Salt Tolerance.

Directory of Open Access Journals (Sweden)

Wei Cai

Full Text Available Nitric oxide (NO has been shown to play an important role in the plant response to biotic and abiotic stresses in Arabidopsis mutants with lower or higher levels of endogenous NO. The exogenous application of NO donors or scavengers has also suggested an important role for NO in plant defense against environmental stress. In this study, rice plants under drought and high salinity conditions showed increased nitric oxide synthase (NOS activity and NO levels. Overexpression of rat neuronal NO synthase (nNOS in rice increased both NOS activity and NO accumulation, resulting in improved tolerance of the transgenic plants to both drought and salt stresses. nNOS-overexpressing plants exhibited stronger water-holding capability, higher proline accumulation, less lipid peroxidation and reduced electrolyte leakage under drought and salt conditions than wild rice. Moreover, nNOS-overexpressing plants accumulated less H2O2, due to the observed up-regulation of OsCATA, OsCATB and OsPOX1. In agreement, the activities of CAT and POX were higher in transgenic rice than wild type. Additionally, the expression of six tested stress-responsive genes including OsDREB2A, OsDREB2B, OsSNAC1, OsSNAC2, OsLEA3 and OsRD29A, in nNOS-overexpressing plants was higher than that in the wild type under drought and high salinity conditions. Taken together, our results suggest that nNOS overexpression suppresses the stress-enhanced electrolyte leakage, lipid peroxidation and H2O2 accumulation, and promotes proline accumulation and the expression of stress-responsive genes under stress conditions, thereby promoting increased tolerance to drought and salt stresses.

The altered balance between sympathetic nervous system and nitric oxide in salt hypertensive Dahl rats: ontogenetic and F2 hybrid studies

Czech Academy of Sciences Publication Activity Database

Dobešová, Zdenka; Kuneš, Jaroslav; Zicha, Josef

2002-01-01

Roč. 20, č. 5 (2002), s. 945-955 ISSN 0263-6352 R&D Projects: GA AV ČR IAA7011805; GA AV ČR IAA7011711; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : salt hypertension * sympathetic nervous system * Dahl rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.534, year: 2002

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

Science.gov (United States)

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of the metabolism of 125I orthohippuric acid (sodium salt) in rats

International Nuclear Information System (INIS)

Boegl, W.; Stockhausen, K.; Censori, M.; Jahn, M.; Sander, B.

1977-07-01

100 μCi Iodine-125-labeled Orthoiodohippurate (sodium salt) were applied i.v. to two Wistar rats. Urine and faeces were collected during several days over periods of 24 hours in a metabolic cage. The urine was analysed both directly and after separation of the radioactive substances with an adsorbtive resin by means of TLC and HPLC. The faeces were extracted and then separated like the urine. The two main metabolites of I-125 Orthoiodohippurate (Hipp) were I-125 Orthoiodobenzoic acid (Benz) and J-125 Iodide (I). The mixture of metabolites in the first 24 hours urine urine was composed of: approximately 20% Benz, appeoximately 70% Hipp, approximately 10% I. During the following days, this composition showed a few changes. The most appropriate method for analyzing proved to be the direct HPLC of the metabolic urine and faeces extract. (orig./MG) [de

3D Gravity Modeling of Complex Salt Features in the Southern Gulf of Mexico

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Mauricio Nava-Flores

2016-01-01

Full Text Available We present a three-dimensional (3D gravity modeling and inversion approach and its application to complex geological settings characterized by several allochthonous salt bodies embedded in terrigenous sediments. Synthetic gravity data were computed for 3D forward modeling of salt bodies interpreted from Prestack Depth Migration (PSDM seismic images. Density contrasts for the salt bodies surrounded by sedimentary units are derived from density-compaction curves for the northern Gulf of Mexico’s oil exploration surveys. By integrating results from different shape- and depth-source estimation algorithms, we built an initial model for the gravity anomaly inversion. We then applied a numerically optimized 3D simulated annealing gravity inversion method. The inverted 3D density model successfully retrieves the synthetic salt body ensemble. Results highlight the significance of integrating high-resolution potential field data for salt and subsalt imaging in oil exploration.

Increased BOLD activation to predator stressor in subiculum and midbrain of amphetamine-sensitized maternal rats.

Science.gov (United States)

Febo, Marcelo; Pira, Ashley S

2011-03-25

Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1mg/kg, i.p. ×3days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Research on Dynamic Dissolving Model and Experiment for Rock Salt under Different Flow Conditions

Directory of Open Access Journals (Sweden)

Xinrong Liu

2015-01-01

Full Text Available Utilizing deep rock salt cavern is not only a widely recognized energy reserve method but also a key development direction for implementing the energy strategic reserve plan. And rock salt cavern adopts solution mining techniques to realize building cavity. In view of this, the paper, based on the dissolving properties of rock salt, being simplified and hypothesized the dynamic dissolving process of rock salt, combined conditions between dissolution effect and seepage effect in establishing dynamic dissolving models of rock salt under different flow quantities. Devices were also designed to test the dynamic dissolving process for rock salt samples under different flow quantities and then utilized the finite-difference method to find the numerical solution of the dynamic dissolving model. The artificial intelligence algorithm, Particle Swarm Optimization algorithm (PSO, was finally introduced to conduct inverse analysis of parameters on the established model, whose calculation results coincide with the experimental data.

Salt tolerance at single cell level in giant-celled Characeae

Directory of Open Access Journals (Sweden)

Mary Jane eBeilby

2015-04-01

Full Text Available Characean plants provide an excellent experimental system for electrophysiology and physiology due to: (i very large cell size, (ii position on phylogenetic tree near the origin of land plants and (iii continuous spectrum from very salt sensitive to very salt tolerant species. A range of experimental techniques is described, some unique to characean plants. Application of these methods provided electrical characteristics of membrane transporters, which dominate the membrane conductance under different outside conditions. With this considerable background knowledge the electrophysiology of salt sensitive and salt tolerant genera can be compared under salt and/or osmotic stress. Both salt tolerant and salt sensitive Characeae show a rise in membrane conductance and simultaneous increase in Na+ influx upon exposure to saline medium. Salt tolerant Chara longifolia and Lamprothamnium sp. exhibit proton pump stimulation upon both turgor decrease and salinity increase, allowing the membrane PD to remain negative. The turgor is regulated through the inward K+ rectifier and 2H+/Cl- symporter. Lamprothamnium plants can survive in hypersaline media up to twice seawater strength and withstand large sudden changes in salinity. Salt-sensitive Chara australis succumbs to 50 - 100 mM NaCl in few days. Cells exhibit no pump stimulation upon turgor decrease and at best transient pump stimulation upon salinity increase. Turgor is not regulated. The membrane PD exhibits characteristic noise upon exposure to salinity. Depolarization of membrane PD to excitation threshold sets off trains of action potentials, leading to further loses of K+ and Cl-. In final stages of salt damage the H+/OH- channels are thought to become the dominant transporter, dissipating the proton gradient and bringing the cell PD close to 0. The differences in transporter electrophysiology and their synergy under osmotic and/or saline stress in salt sensitive and salt tolerant characean cells

Extracting structural features of rat sciatic nerve using polarization-sensitive spectral domain optical coherence tomography

NARCIS (Netherlands)

Islam, M.S.; Oliveira, M.C.; Wang, Y.; Henry, F.P.; Randolph, M.A.; Park, B. H.; de Boer, J.F.

2012-01-01

We present spectral domain polarization-sensitive optical coherence tomography (SD PS-OCT) imaging of peripheral nerves. Structural and polarization-sensitive OCT imaging of uninjured rat sciatic nerves was evaluated both qualitatively and quantitatively. OCT and its functional extension, PS-OCT,

Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats.

Science.gov (United States)

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Untersmayr, Eva; Castell, Margarida

2017-04-01

Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer's patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+cells as well. In cocoa-fed animals, we identified a five-time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Revised predictive equations for salt intrusion modelling in estuaries

NARCIS (Netherlands)

Gisen, J.I.A.; Savenije, H.H.G.; Nijzink, R.C.

2015-01-01

For one-dimensional salt intrusion models to be predictive, we need predictive equations to link model parameters to observable hydraulic and geometric variables. The one-dimensional model of Savenije (1993b) made use of predictive equations for the Van der Burgh coefficient $K$ and the dispersion

Improvement of N-phthaloylchitosan based gel polymer electrolyte in dye-sensitized solar cells using a binary salt system.

Science.gov (United States)

Yusuf, S N F; Azzahari, A D; Selvanathan, V; Yahya, R; Careem, M A; Arof, A K

2017-02-10

A binary salt system utilizing lithium iodide (LiI) as the auxiliary component has been introduced to the N-phthaloylchitosan (PhCh) based gel polymer electrolyte consisting of ethylene carbonate (EC), dimethylformamide (DMF), tetrapropylammonium iodide (TPAI), and iodine (I 2 ) in order to improve the performance of dye-sensitized solar cell (DSSC) with efficiency of 6.36%, photocurrent density, J SC of 17.29mAcm -2 , open circuit voltage, V OC of 0.59V and fill factor, FF of 0.62. This efficiency value is an improvement from the 5.00% performance obtained by the DSSC consisting of only TPAI single salt system. The presence of the LiI in addition to the TPAI improves the charge injection rates and increases the iodide contribution to the total conductivity and both factors contribute to the increase in efficiency of the DSSC. The interaction behavior between polymer-plasticizer-salt was thoroughly investigated using EIS, FTIR spectroscopy and XRD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Precipitates/Salts Model Calculations for Various Drift Temperature Environments

International Nuclear Information System (INIS)

Marnier, P.

2001-01-01

The objective and scope of this calculation is to assist Performance Assessment Operations and the Engineered Barrier System (EBS) Department in modeling the geochemical effects of evaporation within a repository drift. This work is developed and documented using procedure AP-3.12Q, Calculations, in support of ''Technical Work Plan For Engineered Barrier System Department Modeling and Testing FY 02 Work Activities'' (BSC 2001a). The primary objective of this calculation is to predict the effects of evaporation on the abstracted water compositions established in ''EBS Incoming Water and Gas Composition Abstraction Calculations for Different Drift Temperature Environments'' (BSC 2001c). A secondary objective is to predict evaporation effects on observed Yucca Mountain waters for subsequent cement interaction calculations (BSC 2001d). The Precipitates/Salts model is documented in an Analysis/Model Report (AMR), ''In-Drift Precipitates/Salts Analysis'' (BSC 2001b)

Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats.

Science.gov (United States)

Zhou, Ming-Sheng; Jaimes, Edgar A; Raij, Leopoldo

2006-07-01

We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.

Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt.

Science.gov (United States)

Sanphui, Palash; Tothadi, Srinu; Ganguly, Somnath; Desiraju, Gautam R

2013-12-02

Sildenafil is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. Because of poor aqueous solubility of the drug, the citrate salt, with improved solubility and pharmacokinetics, has been marketed. However, the citrate salt requires an hour to reach its peak plasma concentration. Thus, to improve solubility and bioavailability characteristics, cocrystals and salts of the drug have been prepared by treating aliphatic dicarboxylic acids with sildenafil; the N-methylated piperazine of the drug molecule interacts with the carboxyl group of the acid to form a heterosynthon. Salts are formed with oxalic and fumaric acid; salt monoanions are formed with succinic and glutaric acid. Sildenafil forms cocrystals with longer chain dicarboxylic acids such as adipic, pimelic, suberic, and sebacic acids. Auxiliary stabilization via C-H···O interactions is also present in these cocrystals and salts. Solubility experiments of sildenafil cocrystal/salts were carried out in 0.1N HCl aqueous medium and compared with the solubility of the citrate salt. The glutarate salt and pimelic acid cocrystal dissolve faster than the citrate salt in a two hour dissolution experiment. The glutarate salt exhibits improved solubility (3.2-fold) compared to the citrate salt in water. Solubilities of the binary salts follow an inverse correlation with their melting points, while the solubilities of the cocrystals follow solubilities of the coformer. Pharmacokinetic studies on rats showed that the glutarate salt exhibits doubled plasma AUC values in a single dose within an hour compared to the citrate salt. The high solubility of glutaric acid, in part originating from the strained conformation of the molecule and its high permeability, may be the reason for higher plasma levels of the drug.

Epac activation sensitizes rat sensory neurons via activation of Ras

Science.gov (United States)

Shariati, Behzad; Thompson, Eric L.; Nicol, Grant D.; Vasko, Michael R.

2015-01-01

Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2′-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. PMID:26596174

Epac activation sensitizes rat sensory neurons through activation of Ras.

Science.gov (United States)

Shariati, Behzad; Thompson, Eric L; Nicol, Grant D; Vasko, Michael R

2016-01-01

Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2'-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. Copyright © 2015 Elsevier Inc. All rights reserved.

Modeling Coupled THMC Processes and Brine Migration in Salt at High Temperatures

Energy Technology Data Exchange (ETDEWEB)

Rutqvist, Jonny; Blanco Martin, Laura; Mukhopadhyay, Sumit; Houseworth, Jim; Birkholzer, Jens

2014-08-14

In this report, we present FY2014 progress by Lawrence Berkeley National Laboratory (LBNL) related to modeling of coupled thermal-hydrological-mechanical-chemical (THMC) processes in salt and their effect on brine migration at high temperatures. LBNL’s work on the modeling of coupled THMC processes in salt was initiated in FY2012, focusing on exploring and demonstrating the capabilities of an existing LBNL modeling tool (TOUGH-FLAC) for simulating temperature-driven coupled flow and geomechanical processes in salt. This work includes development related to, and implementation of, essential capabilities, as well as testing the model against relevant information and published experimental data related to the fate and transport of water. we provide more details on the FY2014 work, first presenting updated tools and improvements made to the TOUGH-FLAC simulator, and the use of this updated tool in a new model simulation of long-term THM behavior within a generic repository in a salt formation. This is followed by the description of current benchmarking and validations efforts, including the TSDE experiment. We then present the current status in the development of constitutive relationships and the dual-continuum model for brine migration. We conclude with an outlook for FY2015, which will be much focused on model validation against field experiments and on the use of the model for the design studies related to a proposed heater experiment.

Rock salt constitutive modeling

International Nuclear Information System (INIS)

Nickell, R.E.

1980-01-01

The Serata model is the best operational model available today because it incorporates: (1) a yield function to demarcate between viscoelastic and viscoplastic behavior of rock salt; (2) a pressure and temperature dependence for yield stresses; and (3) a standard linear solid, which can be readily extended into the non-linear regime, to represent creep behavior. Its only deficiencies appear to be the lack of secondary creep behavior (a free dashpot) and some unsettling arbitrariness about the Poisson's ratio (ν → 0.5) argument for viscoplasticity. The Sandia/WIPP model will have good primary and secondary creep capability, but lacks the viscoplastic behavior. In some cases, estimated inelastic strains may be underpredicted. If a creep acceleration mechanism associated with brine inclusions is observed, this model may require extensive revision. Most of the other models available (SAI, RE-SPEC, etc.) are only useful for short-term calculations, because they employ temporal power law (t/sup n/) primary creep representations. These models are unsatisfactory because they cannot represent dual mechanisms with differing characteristic times. An approach based upon combined creep and plasticity is recommended in order to remove the remaining deficiency in the Serata model. DOE/Sandia/WIPP should be encouraged to move aggressively in this regard

Functionally induced changes in water transport in the proximal tubule segment of rat kidneys

DEFF Research Database (Denmark)

Faarup, Poul; von Holstein-Rathlou, Niels-Henrik; Nørgaard, Tove

2011-01-01

To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the pr......To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure...... segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries....

The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity.

Science.gov (United States)

Kuga, Kazuhiro; Yasuno, Hironobu; Sakai, Yumi; Harada, Yumiko; Shimizu, Fumi; Miyamoto, Yumiko; Takamatsu, Yuki; Miyamoto, Makoto; Sato, Keiichiro

2017-11-01

In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm 2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model. Copyright © 2017 Elsevier Inc. All rights reserved.

Health gain by salt reduction in europe: a modelling study.

Directory of Open Access Journals (Sweden)

Marieke A H Hendriksen

Full Text Available Excessive salt intake is associated with hypertension and cardiovascular diseases. Salt intake exceeds the World Health Organization population nutrition goal of 5 grams per day in the European region. We assessed the health impact of salt reduction in nine European countries (Finland, France, Ireland, Italy, Netherlands, Poland, Spain, Sweden and United Kingdom. Through literature research we obtained current salt intake and systolic blood pressure levels of the nine countries. The population health modeling tool DYNAMO-HIA including country-specific disease data was used to predict the changes in prevalence of ischemic heart disease and stroke for each country estimating the effect of salt reduction through its effect on blood pressure levels. A 30% salt reduction would reduce the prevalence of stroke by 6.4% in Finland to 13.5% in Poland. Ischemic heart disease would be decreased by 4.1% in Finland to 8.9% in Poland. When salt intake is reduced to the WHO population nutrient goal, it would reduce the prevalence of stroke from 10.1% in Finland to 23.1% in Poland. Ischemic heart disease would decrease by 6.6% in Finland to 15.5% in Poland. The number of postponed deaths would be 102,100 (0.9% in France, and 191,300 (2.3% in Poland. A reduction of salt intake to 5 grams per day is expected to substantially reduce the burden of cardiovascular disease and mortality in several European countries.

Food restriction modulates β-adrenergic-sensitive adenylate cyclase in rat liver during aging

International Nuclear Information System (INIS)

Katz, M.S.

1988-01-01

Adenylate cyclase activities were studied in rat liver during postmaturational aging of male Fischer 344 rats fed ad libitum or restricted to 60% of the ad libitum intake. Catecholamine-stimulated adenylate cyclase activity increased by 200-300% between 6 and 24-27 mo of age in ad libitum-fed rats, whereas in food-restricted rats catecholamine response increased by only 58-84% between 6 and 30 mo. In ad libitum-fed rats, glucagon-stimulated enzyme activity also increased by 40% between 6 and 12 mo and in restricted rats a similar age-related increase was delayed until 18 mo. β-Adrenergic receptor density increased by 50% between 6 and 24 mo in livers from ad libitum-fed but not food-restricted rats and showed a highly significant correlation with maximal isoproterenol-stimulated adenylate cyclase activity over the postmaturational life span. Age-related increases in unstimulated (basal) adenylate cyclase activity and nonreceptor-mediated enzyme activation were retarded by food restriction. The results demonstrate that food restriction diminishes a marked age-related increase in β-adrenergic-sensitive adenylate cyclase activity of rat liver. Alterations of adrenergic-responsive adenylate cyclase with age and the modulatory effects of food restriction appear to be mediated by changes in both receptor and nonreceptor components of adenylate cyclase

Attenuated flow‐induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short‐term high salt diet

Science.gov (United States)

Cosic, Anita; Jukic, Ivana; Stupin, Ana; Mihalj, Martina; Mihaljevic, Zrinka; Novak, Sanja; Vukovic, Rosemary

2016-01-01

Key points Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress.The objective of this study was to assess vascular response to flow‐induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS‐fed rats in vitro.The novelty of this study is in demonstrating impaired flow‐induced dilatation of MCAs and down‐regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID.In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake.Recirculation of leukocytes might additionally increase vascular oxidative stress in vivo. Abstract The aim of this study was to determine flow‐induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)‐fed rats. Healthy male Sprague‐Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10–Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N ω‐nitro‐l‐arginine methyl ester (l‐name). mRNA levels of antioxidative enzymes, NAPDH‐oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real‐time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma

Cross-sensitivity of X-ray-hypersensitive cells derived from LEC strain rats to DNA-damaging agents

International Nuclear Information System (INIS)

Okui, T.; Endoh, D.; Arai, S.; Isogai, E.; Hayashi, M.

1996-01-01

The cross-sensitivity of X-ray-hypersensitive lung fibroblasts from LEC strain (LEC) rats to other DNA-damaging agents was examined. The LEC cells were 2- to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks, and to a cross-linking agent, mitomycin C, than the cells from WKAH strain (WKAH) rats, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, but not to UV-irradiation. Although no difference was observed in the initial yields of DNA double-strand breaks induced by BLM between LEC and WKAH cells, the repair process of DNA double-strand breaks was significantly slower in LEC cells than in WKAH cells

Chronic antioxidant therapy lowers blood pressure in adult but not in young Dahl salt hypertensive rats: the role of sympathetic nervous system

Czech Academy of Sciences Publication Activity Database

Vaněčková, Ivana; Vokurková, Martina; Rauchová, Hana; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Vorlíček, Jaroslav; Zicha, Josef

2013-01-01

Roč. 208, č. 4 (2013), s. 340-349 ISSN 1748-1708 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GAP304/12/0259 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : age * Dahl rats * reactive oxygen species * salt hypertension * tempol Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.251, year: 2013

Simulating emission and chemical evolution of coarse sea-salt particles in the Community Multiscale Air Quality (CMAQ) model

OpenAIRE

J. T. Kelly; P. V. Bhave; C. G. Nolte; U. Shankar; K. M. Foley

2009-01-01

Chemical processing of sea-salt particles in coastal environments significantly impacts concentrations of particle components and gas-phase species and has implications for human exposure to particulate matter and nitrogen deposition to sensitive ecosystems. Emission of sea-salt particles from the coastal surf zone is known to be elevated compared to that from the open ocean. Despite the importance of sea-salt emissions and chemical processing, the US EPA's Community Multiscale Air Quality (C...

A daily salt balance model for stream salinity generation processes following partial clearing from forest to pasture

Directory of Open Access Journals (Sweden)

M. A. Bari

2006-01-01

Full Text Available We developed a coupled salt and water balance model to represent the stream salinity generation process following land use changes. The conceptual model consists of three main components with five stores: (i Dry, Wet and Subsurface Stores, (ii a saturated Groundwater Store and (iii a transient Stream zone Store. The Dry and Wet Stores represent the salt and water movement in the unsaturated zone and also the near-stream dynamic saturated areas, responsible for the generation of salt flux associated with surface runoff and interflow. The unsaturated Subsurface Store represents the salt bulge and the salt fluxes. The Groundwater Store comes into play when the groundwater level is at or above the stream invert and quantifies the salt fluxes to the Stream zone Store. In the stream zone module, we consider a 'free mixing' between the salt brought about by surface runoff, interflow and groundwater flow. Salt accumulation on the surface due to evaporation and its flushing by initial winter flow is also incorporated in the Stream zone Store. The salt balance model was calibrated sequentially following successful application of the water balance model. Initial salt stores were estimated from measured salt profile data. We incorporated two lumped parameters to represent the complex chemical processes like diffusion-dilution-dispersion and salt fluxes due to preferential flow. The model has performed very well in simulating stream salinity generation processes observed at Ernies and Lemon experimental catchments in south west of Western Australia. The simulated and observed stream salinity and salt loads compare very well throughout the study period with NSE of 0.7 and 0.4 for Ernies and Lemon catchment respectively. The model slightly over predicted annual stream salt load by 6.2% and 6.8%.

Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

Directory of Open Access Journals (Sweden)

Atrayee Banerjee

Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

Numerical modeling of salt marsh morphological change induced by Hurricane Sandy

Science.gov (United States)

Hu, Kelin; Chen, Qin; Wang, Hongqing; Hartig, Ellen K.; Orton, Philip M.

2018-01-01

The salt marshes of Jamaica Bay serve as a recreational outlet for New York City residents, mitigate wave impacts during coastal storms, and provide habitat for critical wildlife species. Hurricanes have been recognized as one of the critical drivers of coastal wetland morphology due to their effects on hydrodynamics and sediment transport, deposition, and erosion processes. In this study, the Delft3D modeling suite was utilized to examine the effects of Hurricane Sandy (2012) on salt marsh morphology in Jamaica Bay. Observed marsh elevation change and accretion from rod Surface Elevation Tables and feldspar Marker Horizons (SET-MH) and hydrodynamic measurements during Hurricane Sandy were used to calibrate and validate the wind-waves-surge-sediment transport-morphology coupled model. The model results agreed well with in situ field measurements. The validated model was then used to detect salt marsh morphological change due to Sandy across Jamaica Bay. Model results indicate that the island-wide morphological changes in the bay's salt marshes due to Sandy were in the range of −30 mm (erosion) to +15 mm (deposition), and spatially complex and heterogeneous. The storm generated paired deposition and erosion patches at local scales. Salt marshes inside the west section of the bay showed erosion overall while marshes inside the east section showed deposition from Sandy. The net sediment amount that Sandy brought into the bay is only about 1% of the total amount of reworked sediment within the bay during the storm. Numerical experiments show that waves and vegetation played a critical role in sediment transport and associated wetland morphological change in Jamaica Bay. Furthermore, without the protection of vegetation, the marsh islands of Jamaica Bay would experience both more erosion and less accretion in coastal storms.

Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine and enhances ΔFosB expression in adult rats.

Science.gov (United States)

Perondi, María Cecilia; Gutiérrez, María Cecilia; Valdomero, Analía; Cuadra, Gabriel Ricardo

2017-08-30

Previous studies have indicated that neural changes induced by early nutritional insult cause an altered response to pharmacological treatments, including addictive drugs. This study evaluates the influence of perinatal protein malnutrition in developing cross-sensitization to cocaine-induced rewarding effects in animals pre-exposed to morphine. Different groups of well-nourished (C-rats) and protein-deprived animals (D-rats) were treated twice a day for three days with increasing doses of morphine or with saline. After 3days, the incentive motivational effects of cocaine were assessed in a Conditioned Place Preference paradigm in both groups. In saline pre-treated animals, dose-response curves to cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10mg/kg, while this effect was observed in C-rats only with 10 and 15mg/kg. Furthermore, when animals of both groups were pre-treated with escalating doses of morphine, cross-sensitization to the conditioning effect of cocaine was elicited only in D-rats with low doses of cocaine (5 and 7.5mg/kg). In contrast, under the same experimental conditions, C-rats show no cross-sensitization. To correlate this differential rewarding response with a molecular substrate linked to the behavioral changes observed after repeated drug exposure, ΔFosB expression was assessed in different brain regions. D-rats showed a significant increase in this transcription factor in the nucleus accumbens, amygdala and medial prefrontal cortex. These results demonstrated that perinatal protein deprivation facilitates rewarding effects and the development of cross-sensitization to cocaine, which correlates with an upregulation of ΔFosB in brain areas related to the reward circuitry. Copyright © 2017 Elsevier B.V. All rights reserved.

[Establishment of rat model of psychical erectile dysfunction].

Science.gov (United States)

Wang, Qiu-lin; Wang, Shu-ren; Duan, Jin

2006-01-01

To set up a method of establishing the animal model of psychical erectile dysfunction with emotional stress. All thirty-six male rats with normal sexual function were divided into three groups, i. e. normal group, model group and demasculinized group randomly according to their weights. The rats in the model group were suspended upside down in midair over the water and irritated repeatedly. Two weeks later, the sexual abilities of all rats, i. e. the times of mounting and intromitting the estrus female rats, the latent period of mounting, intromission and ejaculation, were recorded, and the number of rats that had sexual activities was also counted. And the hemorheology indices of the rats were measured. Compared with the normal rats, the latency of mounting [(152.5 +/- 24.6) s vs (42.4 +/- 9.6) s] and intromission [(437.0 +/- 67.7) s vs (130.8 +/- 39.1) s] of the model rats were longer (P 0.05). The hemorheology indices, e. g. blood viscosity, hematocrit (Hct) and red cell aggregation (RCA), of the model rats was significant higher than that of the normal and demasculinized rats (P erectile dysfunction can be made ideally with psychical stress.

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

Science.gov (United States)

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

Science.gov (United States)

Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2013-11-01

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

International Nuclear Information System (INIS)

Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

2008-01-01

Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD 10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

Thermo-mechanical modelling of salt caverns due to fluctuating loading conditions.

Science.gov (United States)

Böttcher, N.

2015-12-01

This work summarizes the development and application of a numerical model for the thermo-mechanical behaviour of salt caverns during cyclic gas storage. Artificial salt caverns are used for short term energy storage, such as power-to-gas or compressed air energy storage. Those applications are characterized by highly fluctuating operation pressures due to the unsteady power levels of power plants based on renewable energy. Compression and expansion of the storage gases during loading and unloading stages lead to rapidly changing temperatures in the host rock of the caverns. This affects the material behaviour of the host rock within a zone that extends several meters into the rock mass adjacent to the cavern wall, and induces thermo-mechanical stresses and alters the creep response.The proposed model features the thermodynamic behaviour of the storage medium, conductive heat transport in the host rock, as well as temperature dependent material properties of rock salt using different thermo-viscoplastic material models. The utilized constitutive models are well known and state-of-the-art in various salt mechanics applications. The model has been implemented into the open-source software platform OpenGeoSys. Thermal and mechanical processes are solved using a finite element approach, coupled via a staggered coupling scheme. The simulation results allow the conclusion, that the cavern convergence rate (and thus the efficiency of the cavern) is highly influenced by the loading cycle frequency and the resulting gas temperatures. The model therefore allows to analyse the influence of operation modes on the cavern host rock or on neighbouring facilities.

Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

Science.gov (United States)

Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

2014-01-01

Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

A sensitivity analysis of the WIPP disposal room model: Phase 1

Energy Technology Data Exchange (ETDEWEB)

Labreche, D.A.; Beikmann, M.A. [RE/SPEC, Inc., Albuquerque, NM (United States); Osnes, J.D. [RE/SPEC, Inc., Rapid City, SD (United States); Butcher, B.M. [Sandia National Labs., Albuquerque, NM (United States)

1995-07-01

The WIPP Disposal Room Model (DRM) is a numerical model with three major components constitutive models of TRU waste, crushed salt backfill, and intact halite -- and several secondary components, including air gap elements, slidelines, and assumptions on symmetry and geometry. A sensitivity analysis of the Disposal Room Model was initiated on two of the three major components (waste and backfill models) and on several secondary components as a group. The immediate goal of this component sensitivity analysis (Phase I) was to sort (rank) model parameters in terms of their relative importance to model response so that a Monte Carlo analysis on a reduced set of DRM parameters could be performed under Phase II. The goal of the Phase II analysis will be to develop a probabilistic definition of a disposal room porosity surface (porosity, gas volume, time) that could be used in WIPP Performance Assessment analyses. This report documents a literature survey which quantifies the relative importance of the secondary room components to room closure, a differential analysis of the creep consolidation model and definition of a follow-up Monte Carlo analysis of the model, and an analysis and refitting of the waste component data on which a volumetric plasticity model of TRU drum waste is based. A summary, evaluation of progress, and recommendations for future work conclude the report.

Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein.

Science.gov (United States)

Cichocki, Joseph A; Smith, Gregory J; Morris, John B

2014-11-01

The target site for inhaled vapor-induced injury often differs in mouth-breathing humans compared with nose-breathing rats, thus complicating the use of rat inhalation toxicity data for assessment of human risk. We sought to examine sensitivity of respiratory/transitional nasal (RTM) and tracheobronchial (TBM) mucosa to two electrophilic irritant vapors: diacetyl and acrolein. Computational fluid dynamic physiologically based pharmacokinetic modeling was coupled with biomarker assessment to establish delivered dose-response relationships in RTM and TBM in male F344 rats following 6 h exposure to diacetyl or acrolein. Biomarkers included glutathione status, proinflammatory and antioxidant gene mRNA levels, and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Modeling revealed that 0.0094-0.1653 μg acrolein/min-cm(2) and 3.9-21.6 μg diacetyl/min-cm(2) were deposited into RTM/TBM. Results indicate RTM and TBM were generally of similar sensitivity to diacetyl and acrolein. For instance, both tissues displayed induction of antioxidant and proinflammatory genes, and nuclear accumulation of Nrf2 after electrophile exposure. Hierarchical cellular response patterns were similar in RTM and TBM but differed between vapors. Specifically, diacetyl exposure induced proinflammatory and antioxidant genes concomitantly at low exposure levels, whereas acrolein induced antioxidant genes at much lower exposure levels than that required to induce proinflammatory genes. Generally, diacetyl was less potent than acrolein, as measured by maximal induction of transcripts. In conclusion, the upper and lower extrapulmonary airways are of similar sensitivity to inhaled electrophilic vapors. Dosimetrically based extrapolation of nasal responses in nose-breathing rodents may provide an approach to predict risk to the lower airways of humans during mouth-breathing. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All

LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone.

Science.gov (United States)

Kusaka, Hiroaki; Sueta, Daisuke; Koibuchi, Nobutaka; Hasegawa, Yu; Nakagawa, Takashi; Lin, BoWen; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2015-12-01

LCZ696, an angiotensin receptor-neprilysin inhibitor, has recently been demonstrated to exert more beneficial effects on hypertensive or heart failure patients than conventional renin-angiotensin system blockers. However, the mechanism underlying the benefit of LCZ696 remains to be understood. The present study was undertaken to examine the effect of LCZ696 compared with valsartan on hypertension and cardiovascular injury. (i) Using telemetry, we compared the hypotensive effect of LCZ696 and valsartan in spontaneously hypertensive rats (SHR) that were fed a high-salt diet followed by a low-salt diet. (ii) We also examined the comparative effect of LCZ696 and valsartan on salt loaded SHRcp, a model of metabolic syndrome. (i) LCZ696 exerted a greater blood pressure (BP) lowering effect than valsartan in SHR regardless of high-salt or low-salt intake. Additive BP reduction by LCZ696 was associated with a significant increase in urinary sodium excretion and sympathetic activity suppression. (ii) LCZ696 significantly ameliorated cardiac hypertrophy and inflammation, coronary arterial remodeling, and vascular endothelial dysfunction in high-salt loaded SHRcp compared with valsartan. LCZ696 caused greater BP reduction than valsartan in SHR regardless of the degree of salt intake, which was associated with a significant enhancement in urinary sodium excretion and sympathetic activity suppression. Furthermore, an additive BP lowering effect of LCZ696 led to greater cardiovascular protection in hypertensive rats. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Augmenting the salt tolerance in wheat ( Triticum aestivum ) through ...

African Journals Online (AJOL)

Augmenting the salt tolerance in wheat ( Triticum aestivum ) through exogenously applied silicon. ... African Journal of Biotechnology ... physiology and biochemistry of wheat genotypes (salt sensitive; Auqab-2000 and salt tolerant; SARC-5) ...

Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

Science.gov (United States)

Bigiani, Albertino

2017-05-01

Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels. In heterologous expression systems, these channels mediate outwardly rectifying membrane currents with distinct biophysical and pharmacological properties. I therefore tested whether also salt-detecting taste cells were endowed with these currents. To this aim, I applied the patch-clamp techniques to single cells in isolated taste buds from rat fungiform papillae. Salt-detecting cells were functionally identified by exploiting the effect of amiloride, which induces a current response by shutting down ENaCs. I looked for the presence of outwardly rectifying currents by using appropriate voltage-clamp protocols and specific pharmacological tools. I found that indeed salt-detecting cells possessed these currents with properties consistent with the presence, at least in part, of CALHM1 channels. Unexpectedly, CALHM1-like currents in taste cells were potentiated by known blockers of pannexin, suggesting a possible inhibitory action of this protein on CALMH1. These findings indicate that communication between salt-detecting cells and nerve endings might involve ATP release by CALMH1 channels. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Precipitates/Salts Model Calculations for Various Drift Temperature Environments

Energy Technology Data Exchange (ETDEWEB)

P. Marnier

2001-12-20

The objective and scope of this calculation is to assist Performance Assessment Operations and the Engineered Barrier System (EBS) Department in modeling the geochemical effects of evaporation within a repository drift. This work is developed and documented using procedure AP-3.12Q, Calculations, in support of ''Technical Work Plan For Engineered Barrier System Department Modeling and Testing FY 02 Work Activities'' (BSC 2001a). The primary objective of this calculation is to predict the effects of evaporation on the abstracted water compositions established in ''EBS Incoming Water and Gas Composition Abstraction Calculations for Different Drift Temperature Environments'' (BSC 2001c). A secondary objective is to predict evaporation effects on observed Yucca Mountain waters for subsequent cement interaction calculations (BSC 2001d). The Precipitates/Salts model is documented in an Analysis/Model Report (AMR), ''In-Drift Precipitates/Salts Analysis'' (BSC 2001b).

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

Science.gov (United States)

Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

2011-04-28

Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.