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Sample records for salt-sensitive dahl rats

  1. Effects of Tulbaghia violacea Harv. (Alliaceae) rhizome methanolic extract on kidney function and morphology in Dahl salt-sensitive rats

    National Research Council Canada - National Science Library

    Moodley, Kogi; Naidoo, Yougasphree; Mackraj, Irene

    2014-01-01

    .... It could, therefore, prove beneficial in ameliorating renal pathology associated with hypertension. To evaluate the effects of long-term administration of Tulbaghia violacea on renal function and morphology in the Dahl salt-sensitive (DSS) rat model...

  2. 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...

  3. Dahl salt-sensitive rats develop hypovitaminosis D and hyperparathyroidism when fed a standard diet

    Science.gov (United States)

    Thierry-Palmer, Myrtle; Cephas, Stacy; Sayavongsa, Phouyong; Doherty, Akins; Arnaud, Sara B.

    2005-01-01

    The Dahl salt-sensitive rat (S), a model for salt-sensitive hypertension, excretes protein-bound 25-hydroxyvitamin D (25-OHD) into urine when fed a low salt diet. Urinary 25-OHD increases during high salt intake. We tested the hypothesis that continuous loss of 25-OHD into urine would result in low plasma 25-OHD concentration in mature S rats raised on a standard diet. Dahl S and salt-resistant (R) male rats were raised to maturity (12-month-old) on a commercial rat diet (1% salt) and switched to 0.3% (low) or 2% (high) salt diets 3 weeks before euthanasia. Urine (24 h) was collected at the end of the dietary treatments. Urinary 25-OHD and urinary 25-OHD binding activity of S rats were three times that of R rats, resulting in lower plasma 25-OHD and 24,25-dihydroxyvitamin D concentrations in S rats than in R rats (P rats were twice that of R rats. S rats fed 2% salt had higher plasma 1,25-dihydroxyvitamin D concentrations than those fed 0.3% salt (P = 0.002). S rats excreted more calcium into urine than R rats (P rats was three times that of the R rats, suggesting kidney damage in the S rats. Low plasma 25-OHD and 24,25-dihydroxyvitamin D and high plasma 1,25-dihydroxyvitamin D and PTH concentrations seen in the mature S rats have also been reported for elderly patients with low-renin (salt-induced) hypertension. An implication of this study is that low vitamin D status may occur with age in salt-sensitive individuals, even when salt intake is normal.

  4. Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats.

    Science.gov (United States)

    Fedorova, O V; Kolodkin, N I; Agalakova, N I; Lakatta, E G; Bagrov, A Y

    2001-02-01

    Dahl salt-sensitive rats (DS), which have a mutation in the alpha-1 subunit of Na(+)/K(+)-ATPase, exhibit impaired pressure natriuresis and on a high-salt diet, retain Na(+) and exhibit increased blood pressure. Recently, we have shown that mammalian tissues contain a bufadienolide Na(+)/K(+)-ATPase inhibitory factor, marinobufagenin (MBG), that exhibits greater affinity for the alpha-1 than alpha-3 sodium pump isoform. The present study investigated the possible role of MBG in hypertension in DS on a high NaCl intake. Eight DS and 8 Dahl salt-resistant rats (DR) were placed on an 8% NaCl diet. Within 2 weeks, systolic blood pressure increased in DS (162+/-9 mm Hg at week 2 versus 110+/-2 mm Hg in baseline, Psodium pump isoform of the kidneys, as would be expected of a putative natriuretic hormone.

  5. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat.

    Science.gov (United States)

    Mattson, David L; James, Leilani; Berdan, Elizabeth A; Meister, Carla J

    2006-07-01

    Experiments were performed to determine the importance of activation or infiltration of immune cells in the kidney during the development of hypertension and renal disease in Dahl salt-sensitive rats (SS/Mcw) fed a 4.0% NaCl diet. Compared with vehicle-treated rats, chronic administration of mycophenolate mofetil ([MMF] 30 mg/kg per day, IP), an immunosuppressive agent that has cytostatic effects on T and B cells, decreased cell-specific markers of T and B cells by 50% to 60% in the kidneys of SS/Mcw rats (n=5 per group). Further studies were performed on Dahl SS/Mcw rats, which were instrumented with chronic indwelling catheters and studied after 3 weeks on the 4.0% NaCl diet. Rats were administered MMF or 5% dextrose vehicle daily during the 3-week period of high NaCl intake. Mean arterial blood pressure in the rats administered MMF (122+/-2 mm Hg; n=11) was significantly decreased compared with vehicle-treated rats (139+/-4 mm Hg; n=9). Furthermore, the rate of protein (112+/-13 mg per day) and albumin excretion (15+/-3 mg per day) in the MMF-treated rats was significantly lower than the protein and albumin excretion rate in vehicle-treated rats (167+/-25 and 31+/-7 mg per day, respectively). Creatinine clearance and body weight were not different between the groups, averaging 0.52+/-0.08 mL/min per gram kidney weight and 322+/-10 g, respectively, in the MMF-treated group. These experiments indicate that the activation of the immune system or renal infiltration of immune cells plays an important role in the development of hypertension and renal disease in Dahl SS/Mcw rats consuming an elevated NaCl diet.

  6. High salt-diet reduces SLC14A1 gene expression in the choroid plexus of Dahl salt sensitive rats.

    Science.gov (United States)

    Guo, Lirong; Meng, Jie; Xuan, Chengluan; Ge, Jingyan; Sun, Wenzhu; O'Rourke, Stephen T; Sun, Chengwen

    2015-05-29

    Elevated Na(+) concentration ([Na(+)]) in the cerebrospinal fluid (CSF) contributes to the development of salt-sensitive hypertension. CSF is formed by the choroid plexus (CP) in cerebral ventricles, and [Na(+)] in CSF is controlled by transporters in CP. Here, we examined the effect of high salt diet on the expression of urea transporters (UTs) in the CP of Dahl S vs Dahl R rats using real time PCR. High salt intake (8%, for 2 weeks) did not alter the mRNA levels of UT-A (encoded by SLC14A2 gene) in the CP of either Dahl S or Dahl R rats. In contrast, the mRNA levels of UT-B (encoded by SLC14A1 gene) were significantly reduced in the CP of Dahl S rats on high salt diet as compared with Dahl R rats or Dahl S rats on normal salt diet. Reduced UT-B expression was associated with increased [Na(+)] in the CSF and elevated mean arterial pressure (MAP) in Dahl S rats treated with high salt diet, as measured by radiotelemetry. High salt diet-induced reduction in UT-B protein expression in the CP of Dahl S rats was confirmed by Western blot. Immunohistochemistry using UT-B specific antibodies demonstrated that UT-B protein was expressed on the epithelial cells in the CP. These data indicate that high salt diet induces elevations in CSF [Na(+)] and in MAP, both of which are associated with reduced UT-B expression in the CP of Dahl S rats, as compared with Dahl R rats. The results suggest that altered UT-B expression in the CP may contribute to an imbalance of water and electrolytes in the CSF of Dahl S rats on high salt diet, thereby leading to alterations in MAP. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys.

    Science.gov (United States)

    Hoagland, Kimberly M; Flasch, Averia K; Dahly-Vernon, Annette J; dos Santos, Elisabete Alcantara; Knepper, Mark A; Roman, Richard J

    2004-04-01

    This study compared the expression of enzymes and transport and channel proteins involved in the regulation of sodium reabsorption in the kidney of Dahl salt-sensitive (DS) and salt-resistant Brown-Norway (BN) and consomic rats (SS.BN13), in which chromosome 13 from the BN rat has been introgressed into the DS genetic background. The expression of the Na+/K+/2Cl- (BSC-1) cotransporter, Na+/H+ exchanger (NHE3), and Na+-K+-ATPase proteins were similar in the renal cortex of DS, BN, and SS.BN13 rats fed either a low-salt (0.1% NaCl) or a high-salt (8% NaCl) diet. The expression of the BSC-1 and the renal outer medullary K+ channel (ROMK) were higher, whereas the expression of the cytochrome P4504A proteins responsible for the formation of 20-hydroxyeicosatetraenoic (20-HETE) was lower in the outer medulla of the kidney of DS than in BN or SS.BN13 rats fed either a low-salt or a high-salt diet. In addition, the renal formation and excretion of 20-HETE was lower in DS than in BN and SS.BN13 rats. These results suggest that overexpression of ROMK and BSC-1 in the thick ascending limb combined with a deficiency in renal formation of 20-HETE may predispose Dahl S rats fed a high-salt diet to Na+ retention and hypertension.

  8. Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension.

    Science.gov (United States)

    Tran, Kenneth; Han, June-Chiew; Taberner, Andrew J; Barrett, Carolyn J; Crampin, Edmund J; Loiselle, Denis S

    2016-09-01

    Salt-induced hypertension leads to development of left ventricular hypertrophy in the Dahl salt-sensitive (Dahl/SS) rat. Before progression to left ventricular failure, the heart initially undergoes a compensated hypertrophic response. We hypothesized that changes in myocardial energetics may be an early indicator of transition to failure. Dahl/SS rats and their salt-resistant consomic controls (SS-13(BN)) were placed on either a low- or high-salt diet to generate four cohorts: Dahl-SS rats on a low- (Dahl-LS) or high-salt diet (Dahl-HS), and SS-13(BN) rats on a low- (SSBN-LS) or high-salt diet (SSBN-HS). We isolated left ventricular trabeculae and characterized their mechanoenergetic performance. Our results show, at most, modest effects of salt-induced compensated hypertrophy on myocardial energetics. We found that the Dahl-HS cohort had a higher work-loop heat of activation (estimated from the intercept of the heat vs. relative afterload relationship generated from work-loop contractions) relative to the SSBN-HS cohort and a higher economy of contraction (inverse of the slope of the heat vs. active stress relation) relative to the Dahl-LS cohort. The maximum extent of shortening and maximum shortening velocity of the Dahl/SS groups were higher than those of the SS-13(BN) groups. Despite these differences, no significant effect of salt-induced hypertension was observed for either peak work output or peak mechanical efficiency during compensated hypertrophy. Copyright © 2016 the American Physiological Society.

  9. Blood pressure and proteinuria effects of multiple quantitative trait loci on rat chromosome 9 that differentiate the spontaneously hypertensive rat from the Dahl salt-sensitive rat.

    Science.gov (United States)

    Toland, Edward J; Yerga-Woolwine, Shane; Farms, Phyllis; Cicila, George T; Saad, Yasser; Joe, Bina

    2008-11-01

    A blood pressure (BP) quantitative trait locus (QTL) was previously located within 117 kb on rat chromosome 9 (RNO9) using hypertensive Dahl salt-sensitive and normotensive Dahl salt-resistant rats. An independent study between two hypertensive rat strains, the Dahl salt-sensitive rat and the spontaneously hypertensive rat (SHR), also detected a QTL encompassing this 117 kb region. Dahl salt-sensitive alleles in both of these studies were associated with increased BP. To map SHR alleles that decrease BP in the Dahl salt-sensitive rat, a panel of eight congenic strains introgressing SHR alleles onto the Dahl salt-sensitive genetic background were constructed and characterized. S.SHR(9)x3B, S.SHR(9)x3A and S.SHR(9)x2B, the congenic regions of which span a portion or all of the 1 logarithm of odds (LOD) interval identified by linkage analysis, did not significantly alter BP. However, S.SHR(9), S.SHR(9)x4A, S.SHR(9)x7A, S.SHR(9)x8A and S.SHR(9)x10A, the introgressed segments of which extend distal to the 1 LOD interval, significantly reduced BP. The shortest genomic segment, BP QTL1, to which this BP-lowering effect can be traced is the differential segment of S.SHR(9)x4A and S.SHR(9)x2B, to which an urinary protein excretion QTL also maps. However, the introgressed segment of S.SHR(9)x10A, located outside of this QTL1 region, represented a second BP QTL (BP QTL2) having no detectable effects on urinary protein excretion. In summary, the data suggest that there are multiple RNO9 alleles of the SHR that lower BP of the Dahl salt-sensitive rat with or without detectable effects on urinary protein excretion and that only one of these BP QTLs, QTL1, overlaps with the 117 kb BP QTL region identified using Dahl salt-sensitive and Dahl salt-resistant rats.

  10. Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats.

    Science.gov (United States)

    Hashmat, Shireen; Rudemiller, Nathan; Lund, Hayley; Abais-Battad, Justine M; Van Why, Scott; Mattson, David L

    2016-09-01

    Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl salt-sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T-lymphocytes isolated from the kidney compared with circulating T-lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats (n = 13-14/group) with an IL-6 neutralizing antibody or normal IgG during an 11-day period of high-salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared with control SS. Moreover, the increase in MAP following 11 days of high-NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138 ± 3 vs. 149 ± 3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney (n = 8-9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs. the control group. The total number of T- and B-lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney. Copyright © 2016 the American Physiological Society.

  11. Lack of Effects of Metformin and AICAR Chronic Infusion on the Development of Hypertension in Dahl Salt-Sensitive Rats

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    Tengis S. Pavlov

    2017-04-01

    Full Text Available In the kidney, reabsorption via the epithelial sodium channel (ENaC is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS hypertension in Dahl SS rats. AMP-activated kinase (AMPK, playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP in Dahl SS rats. Blood pressure elevation was accompanied by a short-term decline of heart rate and increased circadian arterial pressure dipping. Metformin and AICAR were delivered intravenously at doses of 200 and 20 mg/kg/day, respectively. However, both control and drug-treated groups had similar development of high blood pressure within 3 weeks of 8% NaCl dietary salt intake. In the metformin-treated animals MAP reached 164.9 ± 9.1 mmHg, which was not significantly different from the control group (171.8 ± 5.6 mmHg. Patch clamp analysis revealed that the metformin-treated rats had no difference in the activity of ENaC. AICAR treatment also did not affect the development of hypertension and kidney injury. MAP reached 182.8 ± 4.8 and 178.0 ± 2.8 mmHg in AICAR and vehicle treated groups, respectively. Of note, we found that high-salt diet activated AMPK in the Dahl SS rats, and treatment with these AMPK activators had no significant further effect on AMPK activity. We conclude that AMPK activators, at least under these conditions, do not affect development of hypertension during high-salt diet in the Dahl SS rat model.

  12. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China); Yang, Z. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Department of Pathology, Xi' an, China, Department of Pathology, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Yuan, Z.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China)

    2014-03-03

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13{sup BN} rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

  13. Amelioration of cardio-renal injury with aging in dahl salt-sensitive rats by H2-enriched electrolyzed water

    Science.gov (United States)

    2013-01-01

    Abstract Recent studies have revealed the biological effects of H2 in suppressing organ injuries due to acute inflammation and oxidative stress. Dahl salt-sensitive (SS) rats naturally develop elevated blood pressure (BP) and kidney injury with aging. The present study examined the effect of long-term supplementation of H2 in drinking water on age-related changes. Four-week-old male Dahl SS rats were fed 3 types of water (n = 30 each) for up to 48 weeks: filtered water (FW), water with a high H2 content (492.5 ppb) obtained with water electrolysis (EW), or dehydrogenated EW (DW). Animals were subjected to histological analysis at 16, 24, and 48 weeks. The FW group showed progressive BP elevation and increases in albuminuria and cardiac remodeling during the course of treatment. Histologically, there were significant changes as a function of aging, i.e., glomerular sclerosis with tubulointerstitial fibrosis in the kidney, and increased cardiomyocyte diameter with interstitial fibrosis in the heart at 48 weeks. These changes were related to the enhanced inflammation and oxidative stress in the respective organs. However, there were no striking differences in BP among the groups, despite histological alterations in the EW group being significantly decreased when compared to FW and DW in both organs, with concurrently lower oxidative stress and inflammatory markers at 48 weeks. Conclusion Long-term ad libitum consumption of H2-enriched electrolyzed water can ameliorate the processes of kidney injury and cardiac remodeling with aging in Dahl SS rats by suppressing, at least partly, elevated inflammation and oxidative stress. PMID:24289332

  14. The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats

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    Fernandez Rayne

    2010-08-01

    Full Text Available Abstract Background Activation of glucagon-like peptide-1 (GLP-1 receptors improves insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide analogue with pharmacologic properties similar to the GLP-1 receptor agonist, exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in Dahl salt-sensitive (DSS rats. Methods DSS rats were fed low salt (LS, 0.3% NaCl or high salt (HS, 8% NaCl diets. HS rats were treated with vehicle, AC3174 (1.7 pmol/kg/min, or GLP-1 (25 pmol/kg/min for 4 weeks via subcutaneous infusion. Other HS rats received captopril (150 mg/kg/day or AC3174 plus captopril. Results HS rat survival was improved by all treatments except GLP-1. Systolic blood pressure (SBP was lower in LS rats and in GLP-1, AC3174, captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p Conclusions Thus, AC3174 had antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal survival, an effect not observed with GLP-1.

  15. HV1 ACTS AS A SODIUM SENSOR AND PROMOTES SUPEROXIDE PRODUCTION IN MEDULLARY THICK ASCENDING LIMB OF DAHL SALT-SENSITIVE RATS

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    Jin, Chunhua; Sun, Jingping; Stilphen, Carly A.; Smith, Susan M. E.; Ocasio, Hiram; Bermingham, Brent; Darji, Sandip; Guha, Avirup; Patel, Roshan; Geurts, Aron M.; Jacob, Howard J.; Lambert, Nevin A.; O’Connor, Paul M.

    2015-01-01

    We previously characterized a H+ transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by NAD(P)H oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13BN) rats, and superoxide production was enhanced in low Na+ media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na+. We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H+ currents. In order to test this hypothesis, we developed HV1−/− null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1−/− rats (P<0.05), and more rapid recovery of intracellular pH in wild-type rats (ΔpHi 0.005U/sec vs. 0.002U/sec, p=0.046 respectively). Superoxide production was enhanced by low intracellular sodium (<10mM) in both thick limb and peritoneal macrophages only when HV1 was present. When fed a high salt diet, blood pressure, outer-medullary renal injury (tubular casts) and oxidative stress (4-Hydroxynonenal staining) were significantly reduced in HV1−/− rats compared to wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na+ is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats. PMID:24935944

  16. Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats.

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    Cowley, Allen W; Yang, Chun; Zheleznova, Nadezhda N; Staruschenko, Alexander; Kurth, Theresa; Rein, Lisa; Kumar, Vikash; Sadovnikov, Katherine; Dayton, Alex; Hoffman, Matthew; Ryan, Robert P; Skelton, Meredith M; Salehpour, Fahimeh; Ranji, Mahsa; Geurts, Aron

    2016-02-01

    This study reports the consequences of knocking out NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4) on the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single-cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4, resulting in a loss of the ≈68 kDa band in Western blot analysis of renal cortical tissue of the knock out of Nox4 in the SS rat (SS(Nox4-/-)) rats. SS(Nox4-/-) rats exhibited a significant reduction of salt-induced hypertension compared with SS rats after 21 days of 4.0% NaCl diet (134±5 versus 151±3 mm Hg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3-dimensional cryoimaging revealed significantly higher redox ratios (NADH/FAD [reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide]) in the kidneys of SS(Nox4-/-) rats even when fed the 0.4% NaCl diet, indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared with SS rats. Before the development of hypertension, RNA expression levels of Nox subunits Nox2, p67(phox), and p22(phox) were found to be significantly lower (P<0.05) in SS(Nox4-/-) compared with SS rats in the renal cortex. Thus, the mutation of Nox4 seems to modify transcription of several genes in ways that contribute to the protective effects observed in the SS(Nox4-/-) rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SS(Nox4-/-) rat could be the result of multiple pathways, including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4. © 2015 American Heart Association, Inc.

  17. EVIDENCE OF THE IMPORTANCE OF NOX4 IN PRODUCTION OF HYPERTENSION IN DAHL SALT-SENSITIVE RATS

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    Cowley, Allen W.; Yang, Chun; Zheleznova, Nadezhda N.; Staruschenko, Alexander; Kurth, Theresa; Rein, Lisa; Kumar, Vikash; Sadovnikov, Katherine; Dayton, Alex; Hoffman, Matthew; Ryan, Robert P.; Skelton, Meredith M.; Salehpour, Fahimeh; Ranji, Mahsa; Geurts, Aron

    2015-01-01

    This study reports the consequences of knocking out NADPH oxidase 4 (Nox4) upon the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4 resulting in a loss of the ~68 kD band in Western blot analysis of renal cortical tissue of the SSNox4−/− rats. SSNox4−/− rats exhibited a significant reduction of salt-induced hypertension compared to SS rats after 21 days of 4.0% NaCl diet (134±5 vs 151±3 mmHg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3D cryoimaging revealed significantly higher redox ratios (NADH/FAD) in the kidneys of SSNox4−/− rats even when fed the 0.4% NaCl diet indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared to SS rats. Prior to the development of hypertension, RNA expression levels of NADPH oxidase subunits Nox2, p67phox, and p22phox were found to be significantly lower (p<0.05) in SSNox4−/− compared to SS rats in the renal cortex. Thus the mutation of Nox4 appears to modify transcription of a number of genes in ways that contribute to the protective effects observed in the SSNox4−/− rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SSNox4−/− rat could be the result of multiple pathways including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4. PMID:26644237

  18. Tubuloglomerular feedback in Dahl rats

    DEFF Research Database (Denmark)

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

    1998-01-01

    We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response...

  19. Impact of High Salt Independent of Blood Pressure on PRMT/ADMA/DDAH Pathway in the Aorta of Dahl Salt-Sensitive Rats

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    Fu-Qiang Liu

    2013-04-01

    Full Text Available Endothelial dysfunction participates in the development and progression of salt-sensitive hypertension. Asymmetric dimethylarginine (ADMA is an endogenous inhibitor of nitric oxide synthase (NOS. The objectives of this study were to investigate the impact of a high salt diet on the PRMT/ADMA/DDAH (protein arginine methyltransferases; dimethylarginine dimethylaminohydrolase pathway in Dahl salt-sensitive (DS rats and SS-13BN consomic (DR rats, and to explore the mechanisms that regulate ADMA metabolism independent of blood pressure reduction. Plasma levels of nitric oxide (NO in DS rats given a high salt diet and subjected to intragastric administration of hydralazine (SH + HYD group were lower than those given a normal salt diet (SN group. There were significant decreases in expression and activity of dimethylarginine dimethylaminohydrolase (DDAH and endothelial NO synthase (eNOS in DS rats given a high diet (SH group in comparison to the SN group. The activity of DDAH and expression of eNOS in the SH + HYD group decreased more significantly than SN group. The mRNA expression of DDAH-1 and DDAH-2 were lowest in the SH group. The results suggest that salt, independent of blood pressure, can affect the PRMT-1/ADMA/DDAH system to a certain degree and lead to endothelial dysfunction in Dahl salt-sensitive rats.

  20. 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.

  1. Sildenafil Treatment Ameliorates the Maternal Syndrome of Preeclampsia and Rescues Fetal Growth in the Dahl Salt-Sensitive Rat.

    Science.gov (United States)

    Gillis, Ellen E; Mooney, Jennifer N; Garrett, Michael R; Granger, Joey P; Sasser, Jennifer M

    2016-03-01

    Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus. There is currently no effective treatment, but sildenafil, a phosphodiesterase-5 inhibitor, has been proposed as a potential therapy to reduce blood pressure and improve uteroplacental perfusion in preeclamptic patients. We hypothesized that sildenafil would improve the maternal syndrome and fetal outcomes in the Dahl S rat model of superimposed preeclampsia. Dahl S rats were mated, and half received sildenafil (50 mg/kg per day, via food) from day 10 through day 20 of pregnancy. The untreated Dahl S rats had a significant rise in blood pressure and a 2-fold increase in urinary protein excretion from baseline to late pregnancy; however, sildenafil-treated Dahl S rats exhibited ≈40 mm Hg drops in blood pressure with no rise in protein excretion. Sildenafil also increased creatinine clearance and reduced nephrinuria and glomerulomegaly. Sildenafil treatment reduced the uterine artery resistance index during late pregnancy in the Dahl S rat and improved fetal outcomes (survival, weight, and litter size). In addition, 19% of all pups were resorbed in untreated rats, with no incidence of resorptions observed in the treated group. Furthermore, tumor necrosis factor-α, endothelin-1, and oxidative stress, which are characteristically increased in women with preeclampsia and in experimental models of the disease, were reduced in treated rats. These data suggest that sildenafil improves the maternal syndrome of preeclampsia and blood flow to the fetoplacental unit, providing preclinical evidence to support the hypothesis that phosphodiesterase type 5 inhibition may be an important therapeutic target for the treatment of preeclampsia. © 2016 American Heart Association, Inc.

  2. Chronic Inhibition of Renal Outer Medullary Potassium Channel Not Only Prevented but Also Reversed Development of Hypertension and End-Organ Damage in Dahl Salt-Sensitive Rats.

    Science.gov (United States)

    Zhou, Xiaoyan; Forrest, Michael J; Sharif-Rodriguez, Wanda; Forrest, Gail; Szeto, Daphne; Urosevic-Price, Olga; Zhu, Yonghua; Stevenson, Andra S; Zhou, Yuchen; Stribling, Sloan; Dajee, Maya; Walsh, Shawn P; Pasternak, Alexander; Sullivan, Kathleen A

    2017-02-01

    The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na+/K+/2Cl- cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc. The present studies were designed to examine the effects of ROMKi B on systemic hemodynamics, renal function and structure, and vascular function in Dahl salt-sensitive rats. Four experimental groups-control, high-salt diet alone; ROMKi B 3 mg·kg-1·d-1; ROMKi B 10 mg·kg-1·d-1; and hydrochlorothiazide 25 mg·kg-1·d-1-were included in prophylactic (from week 1 to week 9 on high-salt diet) and therapeutic studies (from week 5 to week 9 on high-salt diet), respectively. ROMKi B produced sustained blood pressure reduction and improved renal and vascular function and histological alterations induced by a high-salt diet. ROMKi B was superior to hydrochlorothiazide at reducing blood pressure. Furthermore, ROMKi B provided beneficial effects on both the plasma lipid profile and bone mineral density. Chronic ROMK inhibition not only prevented but also reversed the development of hypertension and end-organ damage in Dahl salt-sensitive rats. Our findings suggest a potential utility of ROMKi B as a novel antihypertensive agent, particularly for the treatment of the salt-sensitive hypertension patient population. © 2016 American Heart Association, Inc.

  3. Inhibition of Mammalian Target of Rapamycin Complex 1 Attenuates Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.

    Science.gov (United States)

    Kumar, Vikash; Wollner, Clayton; Kurth, Theresa; Bukowy, John D; Cowley, Allen W

    2017-10-01

    The goal of the present study was to explore the protective effects of mTORC1 (mammalian target of rapamycin complex 1) inhibition by rapamycin on salt-induced hypertension and kidney injury in Dahl salt-sensitive (SS) rats. We have previously demonstrated that H 2 O 2 is elevated in the kidneys of SS rats. The present study showed a significant upregulation of renal mTORC1 activity in the SS rats fed a 4.0% NaCl for 3 days. In addition, renal interstitial infusion of H 2 O 2 into salt-resistant Sprague Dawley rats for 3 days was also found to stimulate mTORC1 activity independent of a rise of arterial blood pressure. Together, these data indicate that the salt-induced increases of renal H 2 O 2 in SS rats activated the mTORC1 pathway. Daily administration of rapamycin (IP, 1.5 mg/kg per day) for 21 days reduced salt-induced hypertension from 176.0±9.0 to 153.0±12.0 mm Hg in SS rats but had no effect on blood pressure salt sensitivity in Sprague Dawley treated rats. Compared with vehicle, rapamycin reduced albumin excretion rate in SS rats from 190.0±35.0 to 37.0±5.0 mg/d and reduced the renal infiltration of T lymphocytes (CD3 + ) and macrophages (ED1 + ) in the cortex and medulla. Renal hypertrophy and cell proliferation were also reduced in rapamycin-treated SS rats. We conclude that enhancement of intrarenal H 2 O 2 with a 4.0% NaCl diet stimulates the mTORC1 pathway that is necessary for the full development of the salt-induced hypertension and kidney injury in the SS rat. © 2017 American Heart Association, Inc.

  4. Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

    Science.gov (United States)

    Salehpour, F; Ghanian, Z; Yang, C; Zheleznova, N N; Kurth, T; Dash, R K; Cowley, A W; Ranji, M

    2015-08-15

    The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. Copyright © 2015 the American Physiological Society.

  5. Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging

    Science.gov (United States)

    Salehpour, F.; Ghanian, Z.; Yang, C.; Zheleznova, N. N.; Kurth, T.; Dash, R. K.; Cowley, A. W.

    2015-01-01

    The goal of the present study was to quantify and correlate the contribution of the cytosolic p67phox subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67phox was rendered functionally inactive by zinc finger nuclease mutation of the gene (SSp67phox-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SSp67phox-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SSp67phox-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SSp67phox rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67phox subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. PMID:26062875

  6. Aortic and carotid arterial stiffness and epigenetic regulator gene expression changes precede blood pressure rise in stroke-prone Dahl salt-sensitive hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV, precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain, blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Regression of glomerular and tubulointerstitial injuries by dietary salt reduction with combination therapy of angiotensin II receptor blocker and calcium channel blocker in Dahl salt-sensitive rats.

    Directory of Open Access Journals (Sweden)

    Kazi Rafiq

    Full Text Available A growing body of evidence indicates that renal tissue injuries are reversible. We investigated whether dietary salt reduction with the combination therapy of angiotensin II type 1 receptor blocker (ARB plus calcium channel blocker (CCB reverses renal tissue injury in Dahl salt-sensitive (DSS hypertensive rats. DSS rats were fed a high-salt diet (HS; 4% NaCl for 4 weeks. Then, DSS rats were given one of the following for 10 weeks: HS diet; normal-salt diet (NS; 0.5% NaCl, NS + an ARB (olmesartan, 10 mg/kg/day, NS + a CCB (azelnidipine, 3 mg/kg/day, NS + olmesartan + azelnidipine or NS + hydralazine (50 mg/kg/day. Four weeks of treatment with HS diet induced hypertension, proteinuria, glomerular sclerosis and hypertrophy, glomerular podocyte injury, and tubulointerstitial fibrosis in DSS rats. A continued HS diet progressed hypertension, proteinuria and renal tissue injury, which was associated with inflammatory cell infiltration and increased proinflammatory cytokine mRNA levels, NADPH oxidase activity and NADPH oxidase-dependent superoxide production in the kidney. In contrast, switching to NS halted the progression of hypertension, renal glomerular and tubular injuries. Dietary salt reduction with ARB or with CCB treatment further reduced blood pressure and partially reversed renal tissues injury. Furthermore, dietary salt reduction with the combination of ARB plus CCB elicited a strong recovery from HS-induced renal tissue injury including the attenuation of inflammation and oxidative stress. These data support the hypothesis that dietary salt reduction with combination therapy of an ARB plus CCB restores glomerular and tubulointerstitial injury in DSS rats.

  9. Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats.

    Science.gov (United States)

    Chi, Liguo; Belardinelli, Luiz; Zeng, Aliya; Hirakawa, Ryoko; Rajamani, Sridharan; Ling, Haiyun; Dhalla, Arvinder K

    2016-05-15

    Late Na(+) current (INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high-salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 ± 96 vs. 891 ± 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 ± 0.5 vs. 18.9 ± 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 ± 1.9 vs. 14.9 ± 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 ± 0.02 from 0.14 ± 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 ± 12 from 68 ± 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 ± 8 vs. 212 ± 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 ± 0.01 and 0.17 ± 0.02 pA/pF, respectively, vs. 0.41 ± 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg·kg(-1)·day(-1) dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure. Copyright © 2016 the American Physiological Society.

  10. A miso (Japanese soybean paste) diet conferred greater protection against hypertension than a sodium chloride diet in Dahl salt-sensitive rats.

    Science.gov (United States)

    Watanabe, Hiromitsu; Kashimoto, Naoki; Kajimura, Junko; Kamiya, Kenji

    2006-09-01

    The purpose of this study was to compare the effects of miso and sodium chloride (NaCl) on blood pressure in both sexes of Dahl and SD rats. The systolic and diastolic blood pressures (SBP/DBP) were measured at 2, 4, 8 and 12 weeks of treatment with a miso diet including 2.3% NaCl, a high-sodium diet including 2.3% or 1.9% NaCl, or a normal diet including 0.3% NaCl (MF diet; Oriental Yeast Co., Tokyo, Japan). The rats were autopsied after 12 weeks on a diet. DBP in male Dahl rats was significantly increased by the 2.3% NaCl diet as compared with that in the MF group (p diet.

  11. Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a rat chromosome 2 QTL region in Dahl salt-sensitive rats.

    Science.gov (United States)

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

    2013-01-01

    Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP) quantitative trait loci (QTLs) that co-localized with navigational performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, Prat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM) task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (Prats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

  12. Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP quantitative trait loci (QTLs that co-localized with navigational performance (Nav-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5, diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5, and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5 compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05. The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

  13. Prestroke proteomic changes in cerebral microvessels in stroke-prone, transgenic[hCETP]-Hyperlipidemic, Dahl salt-sensitive hypertensive rats.

    Science.gov (United States)

    Bergerat, Agnes; Decano, Julius; Wu, Chang-Jiun; Choi, Hyungwon; Nesvizhskii, Alexey I; Moran, Ann Marie; Ruiz-Opazo, Nelson; Steffen, Martin; Herrera, Victoria Lm

    2011-01-01

    Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor-induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non-stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke.

  14. Dynamic autoregulation and renal injury in Dahl rats

    DEFF Research Database (Denmark)

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

    1997-01-01

    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...... S rats and SHR and were scored semiquantitatively. Dynamic autoregulation was efficient and comparable in the low-frequency range (salt diet. Autoregulation...... was preserved during a low salt diet and in rats exposed to a late-onset hypertension of short duration, only partly preserved if the late-onset hypertension was of a longer duration, and abolished in early-onset hypertension. All Dahl S rats on a high salt diet showed severe morphological changes in the kidney...

  15. Mutation of SH2B3 (LNK), a genome-wide association study candidate for hypertension, attenuates Dahl salt-sensitive hypertension via inflammatory modulation.

    Science.gov (United States)

    Rudemiller, Nathan P; Lund, Hayley; Priestley, Jessica R C; Endres, Bradley T; Prokop, Jeremy W; Jacob, Howard J; Geurts, Aron M; Cohen, Eric P; Mattson, David L

    2015-05-01

    Human genome-wide association studies have linked SH2B adaptor protein 3 (SH2B3, LNK) to hypertension and renal disease, although little experimental investigation has been performed to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting mutation was a 6-bp, in-frame deletion within a highly conserved region of the Src homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl SS hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3(em1Mcwi) mutant rats. To determine whether this was because of differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3(em1Mcwi) mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3(em1Mcwi) mutant bone marrow. Rats that received Sh2b3(em1Mcwi) mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. © 2015 American Heart Association, Inc.

  16. A multi-component model of the dynamics of salt-induced hypertension in Dahl-S rats

    Directory of Open Access Journals (Sweden)

    Van Vliet Bruce N

    2009-10-01

    Full Text Available Abstract Background In humans, salt intake has been suggested to influence blood pressure (BP on a wide range of time scales ranging from several hours or days to many months or years. Detailed time course data collected in the Dahl salt-sensitive rat strain suggest that the development of salt-induced hypertension may consist of several distinct phases or components that differ in their timing and reversibility. To better understand these components, the present study sought to model the dynamics of salt-induced hypertension in the Dahl salt sensitive (Dahl-S rat using 3 sets of time course data. Results The first component of the model ("Acute-Reversible" consisted of a linear transfer function to account for the rapid and reversible effects of salt on BP (ie. acute salt sensitivity, corresponding with a depressed slope of the chronic pressure natriuresis relationship. For the second component ("Progressive-Irreversible", an integrator function was used to represent the relatively slow, progressive, and irreversible effect of high salt intake on BP (corresponding with a progressive salt-induced shift of the chronic pressure natriuresis relationship to higher BP levels. A third component ("Progressive-Reversible" consisted of an effect of high salt intake to progressively increase the acute salt-sensitivity of BP (ie. reduce the slope of the chronic pressure natriuresis relationship, amounting to a slow and progressive, yet reversible, component of salt-induced hypertension. While the 3 component model was limited in its ability to follow the BP response to rapid and/or brief transitions in salt intake, it was able to accurately follow the slower steady state components of salt-induced BP changes. This model exhibited low values of mean absolute error (1.92 ± 0.23, 2.13 ± 0.37, 2.03 ± 0.3 mmHg for data sets 1 - 3, and its overall performance was significantly improved over that of an initial model having only 2 components. The 3 component

  17. Evidence for a link between gut microbiota and hypertension in the Dahl rat

    Science.gov (United States)

    Mell, Blair; Jala, Venkatakrishna R.; Mathew, Anna V.; Byun, Jaeman; Waghulde, Harshal; Zhang, Youjie; Haribabu, Bodduluri; Vijay-Kumar, Matam; Pennathur, Subramaniam

    2015-01-01

    The gut microbiota plays a critical role in maintaining physiological homeostasis. This study was designed to evaluate whether gut microbial composition affects hypertension. 16S rRNA genes obtained from cecal samples of Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats were sequenced. Bacteria of the phylum Bacteroidetes were higher in the S rats compared with the R rats. Furthermore, the family S24-7 of the phylum Bacteroidetes and the family Veillonellaceae of the phylum Firmicutes were higher in the S rats compared with the R rats. Analyses of the various phylogenetic groups of cecal microbiota revealed significant differences between S and R rats. Both strains were maintained on a high-salt diet, administered antibiotics for ablation of microbiota, transplanted with S or R rat cecal contents, and monitored for blood pressure (BP). Systolic BP of the R rats remained unaltered irrespective of S or R rat cecal transplantation. Surprisingly, compared with the S rats given S rat cecal content, systolic BP of the S rats given a single bolus of cecal content from R rats was consistently and significantly elevated during the rest of their life, and they had a shorter lifespan. A lower level of fecal bacteria of the family Veillonellaceae and increased plasma acetate and heptanoate were features associated with the increased BP observed in the S rats given R rat microbiota compared with the S rats given S rat microbiota. These data demonstrate a link between microbial content and BP regulation and, because the S and R rats differ in their genomic composition, provide the necessary basis to further examine the relationship between the host genome and microbiome in the context of BP regulation in the Dahl rats. PMID:25829393

  18. Hydronephrosis causes salt-sensitive hypertension in rats

    DEFF Research Database (Denmark)

    Carlström, Mattias; Wåhlin, Nils; Sällström, Johan

    2006-01-01

    hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device was implanted 4-6 weeks later and blood pressure was measured...... on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. RESULTS: All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis......, blood pressure increased from 118 +/- 5 mmHg on low salt to 140 +/- 6 mmHg on high salt intake, compared to control levels of 82 +/- 2 and 84 +/- 2 mmHg, respectively. Plasma renin concentration was increased in the hydronephrotic group of animals compared to controls on all diets, but the difference...

  19. Dr. Lewis Kitchener Dahl, the Dahl Rats and the ‘Inconvenient truth’ abou the Genetics of Hypertension

    Science.gov (United States)

    Joe, Bina

    2014-01-01

    Synopsis Lewis K. Dahl is regarded as an iconic figure in the field of hypertension research. During the 1960s and 1970s he published several seminal articles in the field that shed light on the relationship between salt and hypertension. Further, the Dahl rat models of hypertension that he developed by a selective breeding strategy are among the most widely used models for hypertension research. To this day, genetic studies using this model are ongoing in our laboratory. While Dr. Dahl is known for his contributions to the field of hypertension, very little, if any, of his personal history is documented. This article details a short biography of Dr. Lewis Dahl, the history behind the development of the Dahl rats and presents an overview of the results obtained through the genetic analysis of the Dahl rat as an experimental model to study the inheritance of hypertension. PMID:25646295

  20. The role of chemokine ligand 16 in high salt induced myocardial remodeling in salt sensitive hypertensive rats

    Directory of Open Access Journals (Sweden)

    Mei-li LIU

    2015-11-01

    Full Text Available Objective To investigate the effects of chemokine ligand 16 (CXCL16 in high salt induced myocardial remodeling in salt sensitive hypertensive rats. Methods Sixty-four Dahl salt sensitive (Dahl-SS rats were randomly divided into normal salt (NS, 0.3% NaCl and high salt (HS, 8.0% NaCl group, 32 rats for each group. Blood pressure was measured by tail-cuff method every week. Hearts were harvested and the expression of CXCL16 in heart tissues was detected by Western blotting at the 2nd, 4th, 6th and 8th week after NS or HS feeding. Immunofluorescence double staining was used to detect the colocalization of CXCL16 with both cardiomyocytes and cardiac fibroblasts. Immunofluorescence and immunohistochemical staining were used to detect the expression of CXCL16 and the biomarker of macrophage in the myocardial tissue after 6 week and 8 week of NS or HS feeding. Myocardial fibrosis was evaluated by HE and Masson trichrome staining. Results Compared with that in NS group, the systolic pressure and diastolic pressure in HS group increased significantly after 1 week of HS feeding (147.10±3.67mmHg vs128.57±6.32mmHg, P<0.01 and 110.86±4.24mmHg vs90.69±4.51mmHg, P<0.01, respectively. HS feeding significantly increased the myocardial CXCL16 expression in rats of HS group at the 6th week (1.18±0.05 vs0.58±0.02, P<0.05, and the expression of CXCL16 was further up-regulated at the 8th week (1.43±0.06 vs0.67±0.03, P<0.05. At the 8th week, obvious fibrosis remodeling and macrophage infiltration appeared in the myocardial tissue of the rats in HS group. Conclusion High salt intervention could up-regulate the expression of CXCL16 in salt sensitive hypertensive myocardial remodeling, which may promote macrophage infiltration and participate in the pathological process of myocardial fibrosis accordingly. DOI: 10.11855/j.issn.0577-7402.2015.11.04

  1. Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats

    Directory of Open Access Journals (Sweden)

    Pan Huang

    2016-01-01

    Full Text Available Background. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. Methods. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP, serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected. Results. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and •OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation. Conclusions. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress.

  2. GENETIC VARIANTS IN ARHGEF11 ARE ASSOCIATED WITH KIDNEY INJURY IN THE DAHL S RAT

    Science.gov (United States)

    Williams, Jan M.; Johnson, Ashley C.; Stelloh, Cary; Dreisbach, Albert C.; Franceschini, Nora; Regner, Kevin R.; Townsend, Raymond R.; Roman, Richard J.; Garrett, Michael R.

    2012-01-01

    A previous genetic analysis comparing the Dahl salt-sensitive (S) rat to the spontaneously hypertensive rat (SHR) identified a major locus on chromosome 2 that influences proteinuria in the S rat. In the present study, blood pressure, proteinuria, and renal hemodynamics were evaluated in congenic strains with small segments of the protective SHR genome on the S background. Proteinuria and renal function were significantly improved in the congenic strains compared to the S. The causative locus interval was narrowed to differential expression. Arhgef11, Pear1, and Sh2d2 were identified as important candidate genes that may be linked to kidney injury in the S rat. In particular, Arhgef11 plays an important role in the activation of the Rho-ROCK signaling pathway. Inhibition of this pathway using fasudil resulted in a significant reduction of proteinuria in treated S rats (compared to untreated S). However, no difference was observed between treated or untreated SHR or congenic strains. The homologous region in humans was found to be associated with estimated glomerular filtration rate (eGFR) in the Candidate Gene Association Resource (CARe) population. In summary, these findings demonstrate that allelic variants in Arhgef11, acting through the Rho-ROCK pathway, could influence kidney injury in the S as well as provide insight into human kidney disease. PMID:22987919

  3. Null mutation of the nicotinamide adenine dinucleotide phosphate-oxidase subunit p67phox protects the Dahl-S rat from salt-induced reductions in medullary blood flow and glomerular filtration rate.

    Science.gov (United States)

    Evans, Louise C; Ryan, Robert P; Broadway, Elizabeth; Skelton, Meredith M; Kurth, Theresa; Cowley, Allen W

    2015-03-01

    Null mutations in the p67(phox) subunit of nicotinamide adenine dinucleotide phosphate-oxidase confer protection from salt sensitivity on Dahl salt-sensitive rats. Here, we track the sequential changes in medullary blood flow (MBF), glomerular filtration rate (GFR), urinary protein, and mean arterial pressure in SSp67(phox) null rats and wild-type littermates during 21 days of 4.0% NaCl high-salt (HS) diet. Optical fibers were implanted in the renal medulla and MBF was measured in conscious rats by laser Doppler flowmetry. Separate groups of rats were prepared with femoral venous catheters and GFR was measured by the transcutaneous assessment of fluorescein isothiocyanate-sinistrin disappearance curves. Mean arterial blood pressure was measured by telemetry. In wild-type rats, HS caused a rapid reduction in MBF, which was significantly lower than control values by HS day-6. Reduced MBF was associated with a progressive increase in mean arterial pressure, averaging 170±5 mm Hg by HS salt day-21. A significant reduction in GFR was evident on day-14 HS, after the onset of hypertension and reduced MBF. In contrast, HS had no significant effect on MBF in SSp67(phox) null rats and the pressor response to sodium was blunted, averaging 150±3 mm Hg on day-21 HS. GFR was maintained throughout the study and proteinuria was reduced. In summary, when p67(phox) is not functional in the salt-sensitive rats, HS does not cause reduced MBF and salt-sensitive hypertension is attenuated, and consequently renal injury is reduced and GFR is maintained. © 2014 American Heart Association, Inc.

  4. Endogenous cardiotonic steroids and differential patterns of sodium pump inhibition in NaCl-loaded salt-sensitive and normotensive rats.

    Science.gov (United States)

    Bagrov, Alexei Y; Agalakova, Natalia I; Kashkin, Vladimir A; Fedorova, Olga V

    2009-05-01

    Endogenous sodium pump inhibitors promote sodium excretion in normotensives and contribute to vasoconstriction in NaCl-sensitive hypertension. Marinobufagenin (MBG), an endogenous bufadienolide inhibitor of alpha-1 sodium pump, contributes to hypertension in Dahl salt-sensitive rats (DS). We hypothesized that in NaCl-loaded DS and normotensive Sprague-Dawley rats (S-D), MBG would elicit different patterns of sodium pump inhibition. We compared systolic blood pressure (SBP), renal sodium excretion, activity of the sodium pump in aorta and renal medulla, and levels of MBG, atrial natriuretic peptide (ANP), and cyclic guanosine monophosphate (cGMP) in salt-loaded DS and S-D (20% NaCl, 2.5 ml/kg, intraperitoneally). NaCl loading produced sustained elevations in renal MBG excretion in both DS (2.41 +/- 0.24 vs. 0.79 +/- 0.08 pmol/h/kg, P sodium pump was inhibited by 22% (P sodium pump did not change. NaCl-loaded S-D excreted twice as much sodium as DS; in S-D, renal sodium pump was inhibited by 24% vs. 14% inhibition in DS (P sodium pump in the kidney and in vascular smooth muscle, respectively, resulting in an adaptive natriuresis in S-D but sodium retention and pressor response in DS.

  5. 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

    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...... in adulthood. Rats were operated at 3 weeks of age (after completed nephrogenesis) and then subjected to either normal or high-salt diets for 6 to 8 weeks. Four different experimental groups were used: sham-operated animals raised with normal-salt diet (controls) or high-salt diet (HS) and uninephrectomized...... 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...

  6. Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats

    DEFF Research Database (Denmark)

    Carlström, M.; Wåhlin, N.; Skøtt, Ole

    2007-01-01

    AIM: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have...... shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. METHODS: Partial unilateral ureteral...... obstruction was created in 3-week-old male Sprague-Dawley rats and blood pressure was measured telemetrically 4-6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral...

  7. Base-resolution maps of 5-methylcytosine and 5-hydroxymethylcytosine in Dahl S rats: effect of salt and genomic sequence.

    Science.gov (United States)

    Liu, Yong; Liu, Pengyuan; Yang, Chun; Cowley, Allen W; Liang, Mingyu

    2014-04-01

    Analysis of 5-hydroxymethylcytosine (5hmC) at single-base resolution has been largely limited to studies of stem cells or developmental stages. Given the potential importance of epigenetic events in hypertension, we have analyzed 5hmC and 5-methylcytosine (5mC) at single-base resolution in the renal outer medulla of the Dahl salt-sensitive rat and examined the effect of disease-relevant genetic or environmental alterations on 5hmC and 5mC patterns. Of CpG sites that fell within CpG islands, 11% and 1% contained significant 5mC and 5hmC, respectively. 5mC levels were substantially higher for genes with lower mRNA abundance and showed a prominent nadir around the transcription start site. In contrast, 5hmC levels were higher in genes with higher expression. Substitution of a 12.9-Mbp region of chromosome 13, which attenuates the hypertensive and renal injury phenotypes in salt-sensitive rats, or exposure to a high-salt diet, which accelerates the disease phenotypes, was associated with differential 5mC or 5hmC in several hundred CpG islands. Nearly 80% of the CpG islands that were differentially methylated in response to salt and associated with differential mRNA abundance were intragenic CpG islands. The substituted genomic segment had significant cis effects on mRNA abundance but not on DNA methylation. The study established base-resolution maps of 5mC and 5hmC in an in vivo model of disease and revealed several characteristics of 5mC and 5hmC important for understanding the role of epigenetic modifications in the regulation of organ systems function and complex diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats.

    Science.gov (United States)

    Vilskersts, Reinis; Kuka, Janis; Svalbe, Baiba; Cirule, Helena; Liepinsh, Edgars; Grinberga, Solveiga; Kalvinsh, Ivars; Dambrova, Maija

    2011-01-01

    Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronate, an inhibitor of L-carnitine biosynthesis, or their combination on the development of hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Experimental animals were divided into five groups and treated for 8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at the doses above (n = 10). During the experiment, control group animals continued to consume a diet with normal salt content. Administration of the combination significantly improved the survival rate for 50% of the population. None of the tested compounds or their combination influenced high salt intake-induced hypertension, while treatment with mildronate and the combination for 8 weeks significantly decreased resting heart rate by 12% and 10%, respectively. Feeding with high salt diet had no influence on systolic function of the heart, but it induced thickening of the ventricular walls and development of heart hypertrophy that was not improved by the administration of tested compounds. In addition, administration of the combination attenuated the development of endothelial dysfunction in isolated aortic rings. In conclusion, our results demonstrate that treatment with a combination of L-carnitine and mildronate is protective against hypertension-induced complications in an experimental model of salt-induced hypertension.

  10. The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

    Czech Academy of Sciences Publication Activity Database

    Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

    2017-01-01

    Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

  11. Genetics of hypertensive organ-damage in consomic rat models

    OpenAIRE

    Wendt, Norbert

    2010-01-01

    The clinical importance of hypertension is due to its high prevalence and the resulting hypertensive organ-damage (HOD). Especially salt-sensitive patients tend to develope increased levels of HOD. Aim of this thesis was to investigate the genetic basis of HOD in salt-sensitive hypertension. The salt-sensitive Dahl-rat (SS) was considered a suitable animal-model, which besides severe HOD like left-ventricular hypertrophy with fibrosis-deposition, also developes hypercholesteremia. By expe...

  12. Dahl's Neologisms

    Science.gov (United States)

    Cheetham, Dominic

    2016-01-01

    Roald Dahl is famous for his lexical creativity, for his skill in naming his characters, his ability to create names for a variety of imagined creatures and sweets, and for his most mentioned achievement in creating the language used by the BFG. This paper presents an overview of the development and patterning of Dahl's word creation as found in a…

  13. Infiltrating immune cells in the kidney in salt-sensitive hypertension and renal injury.

    Science.gov (United States)

    Mattson, David L

    2014-09-01

    The importance of the immune system in hypertension, vascular disease, and renal disease has been appreciated for over 50 years. Recent experimental advances have led to a greater appreciation of the mechanisms whereby inflammation and immunity participate in cardiovascular disease. In addition to the experimental data, multiple studies in patients have demonstrated a strong correlation between the observations made in animals and humans. Of great interest is the development of salt-sensitive hypertension in humans with the concurrent increase in albumin excretion rate. Experiments in our laboratory have demonstrated that feeding a high-NaCl diet to Dahl salt-sensitive (SS) rats results in a significant infiltration of T lymphocytes into the kidney that is accompanied by the development of hypertension and renal disease. The development of disease in the Dahl SS closely resembles observations made in patients; studies were therefore performed to investigate the pathological role of infiltrating immune cells in the kidney in hypertension and renal disease. Pharmacological and genetic studies indicate that immune cell infiltration into the kidney amplifies the disease process. Further experiments demonstrated that infiltrating T cells may accentuate the Dahl SS phenotype by increasing intrarenal ANG II and oxidative stress. From these and other data, we hypothesize that infiltrating immune cells, which surround the blood vessels and tubules, can serve as a local source of bioactive molecules which mediate vascular constriction, increase tubular sodium reabsorption, and mediate the retention of sodium and water to amplify sodium-sensitive hypertension. Multiple experiments remain to be performed to refine and clarify this hypothesis. Copyright © 2014 the American Physiological Society.

  14. Differential Effect of Renal Cortical and Medullary Interstitial Fluid Calcium on Blood Pressure Regulation in Salt-Sensitive Hypertension.

    Science.gov (United States)

    Pointer, Mildred A; Eley, Shaleka; Anderson, Lauren; Waters, Brittany; Royall, Brittany; Nichols, Sheena; Wells, Candace

    2015-08-01

    Hypercalciuria is a frequent characteristic of hypertension. In this report we extend our earlier studies investigating the role of renal interstitial fluid calcium (ISF(Ca))(2+) as a link between urinary calcium excretion and blood pressure in the Dahl salt-sensitive (DS) hypertensive model. Dahl salt-sensitive and salt-resistant (DR) rats were placed on control (0.45%) and high (8%) salt diets to determine if changes in renal cortical and medullary ISF(Ca)(2+)correlated with changes in urinary calcium excretion and blood pressure. We observed that renal ISFCa(2+) was predicted by urinary calcium excretion (P blood pressure (P blood pressure in DS rats (P blood pressure in the DR rats under the conditions of this study. We interpret these findings to suggest that decreased renal cortical ISF(Ca)(2+) plays a role in the increase in blood pressure following a high salt diet in salt hypertension perhaps by mediating renal vasoconstriction; the role of medullary calcium remains to be fully understood. Further studies are needed to determine the mechanism of the altered renal ISF(Ca)(2+) and its role in blood pressure regulation. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. 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.

  16. Mutation of SH2B3 (LNK), a GWAS candidate for hypertension, attenuates Dahl SS hypertension via inflammatory modulation

    Science.gov (United States)

    Rudemiller, Nathan P.; Lund, Hayley; Priestley, Jessica R. C.; Endres, Bradley T.; Prokop, Jeremy W.; Jacob, Howard J.; Geurts, Aron M.; Cohen, Eric P.; Mattson, David L.

    2015-01-01

    Human genome wide association studies (GWAS) have linked SH2B3 (LNK) to hypertension and renal disease, though little experimental investigation has been done to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases (ZFN). The resulting mutation was a 6 base-pair, in-frame deletion within a highly-conserved region of the Src Homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl salt-sensitive (SS) hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3em1Mcwi mutant rats. To determine if this was due to differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3em1Mcwi mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3em1Mcwi mutant bone marrow. Rats that received Sh2b3em1Mcwi mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. PMID:25776069

  17. Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

    OpenAIRE

    Hao Yu; Tao Yang; Peng Gao; Xing Wei; Hexuan Zhang; Shiqiang Xiong; Zongshi Lu; Li Li; Xiao Wei; Jing Chen; Yu Zhao; Arendshorst, William J.; Qianhui Shang; Daoyan Liu; Zhiming Zhu

    2016-01-01

    High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dah...

  18. The Role of Natriuretic Agents In the Mechanism of Hypertension in the Dahl Strain of Salt-Sensitive and Salt-Resistant Rats

    Science.gov (United States)

    1986-07-02

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing...and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information...to volume expansion with whole blood, following treatment with probenecid , a blocker of tubular secretion of organic acids. Probenecid (50 mM

  19. Pregnancy prevents hypertensive remodeling and decreases myogenic reactivity in posterior cerebral arteries from Dahl salt-sensitive rats : a role in eclampsia?

    NARCIS (Netherlands)

    Aukes, Annet M.; Vitullo, Lisa; Zeeman, Gerda G.; Cipolla, Marilyn J.

    Previous studies have demonstrated that pregnancy prevents protective hypertension-induced remodeling of cerebral arteries using nitric oxide synthase (NOS) inhibition to raise mean arterial pressure (MAP). In the present study, we investigated whether this effect of pregnancy was specific to NOS

  20. Plasma level of the endogenous sodium pump ligand marinobufagenin is related to the salt-sensitivity in men.

    Science.gov (United States)

    Fedorova, Olga V; Lakatta, Edward G; Bagrov, Alexei Y; Melander, Olle

    2015-03-01

    Salt-induced elevation of the endogenous digitalis like sodium pump ligand marinobufagenin (MBG) in the Dahl salt-sensitive rats resulted in elevated blood pressure (BP). Here, we tested, in humans, whether MBG levels are related to ambulatory 24-h BP (ABP), controlled long-term increase of salt-intake induces changes in MBG and any salt-induced change in MBG is related to salt sensitivity. Thirty-nine healthy individuals (53 ± 11 years old; 20 men and 19 women) had a total daily NaCl intake of 50 mmol (low-salt) and 150 mmol (high-salt) for 4 weeks each, in a random order. ABP and MBG in plasma and urine were measured at baseline (unstandardized salt intake) and after high and low-salt intake. At baseline, plasma MBG (P-MBG) was related to 24-h SBP (r = 0.43, P = 0.007) and DBP (r = 0.32, P = 0.047), whereas 24-h urinary excretion of MBG (UE-MBG) was related to 24-h DBP only (r = 0.42, P = 0.008). Sex-specific analyses revealed that these relationships were significant in men only. Compared with low-salt, high-salt diet increased P-MBG (P = 0.029), mainly driven by results in men. Male P-MBG responders vs. nonresponders (above vs. below median of high-salt induced P-MBG increase) had markedly enhanced SBP (10.4 ± 6.4 vs. 1.0 ± 6.0 mmHg; P = 0.003) and DBP (6.7 ± 5.0 vs. -0.6 ± 3.6 mmHg; P = 0.001) salt sensitivity. In men, MBG increases with 24-h ABP, and similar to Dahl salt-sensitive rats, 4 weeks of high-salt induced MBG response is accompanied by marked salt sensitivity. However, these patterns seem to be sex-specific and are not observed in women.

  1. High dietary salt does not significantly affect plasma 25-hydroxyvitamin D concentrations of Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Bayorh Mohamed A

    2010-12-01

    Full Text Available Abstract Background The Dahl salt-sensitive rat, but not the Dahl salt-resistant rat, develops hypertension and hypovitaminosis D when fed a high salt diet. Since the salt-sensitive rat and salt-resistant rat were bred from the Sprague Dawley rat, the aim of this research was to test the hypothesis that salt-resistant and Sprague Dawley rats would be similar in their vitamin D endocrine system response to high salt intake. Findings Sprague Dawley, salt-sensitive, and salt-resistant rats were fed high (80 g/kg, 8% or low (3 g/kg, 3% salt diets for three weeks. The blood pressure of Sprague Dawley rats increased from baseline to week 3 during both high and low salt intake and the mean blood pressure at week 3 of high salt intake was higher than that at week 3 of low salt intake (P Conclusions These data indicate that the effect of high salt intake on the vitamin D endocrine system of Sprague Dawley rats at week 3 was similar to that of salt-resistant rats. The salt-sensitive rat, thus, appears to be a more appropriate model than the Sprague Dawley rat for assessing possible effects of salt-sensitivity on vitamin D status of humans.

  2. 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...

  3. Multiple susceptibility loci for radiation-induced mammary tumorigenesis in F2[Dahl S x R]-intercross rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Although two major breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified accounting for 20% of breast cancer genetic risk, identification of other susceptibility genes accounting for 80% risk remains a challenge due to the complex, multi-factorial nature of breast cancer. Complexity derives from multiple genetic determinants, permutations of gene-environment interactions, along with presumptive low-penetrance of breast cancer predisposing genes, and genetic heterogeneity of human populations. As with other complex diseases, dissection of genetic determinants in animal models provides key insight since genetic heterogeneity and environmental factors can be experimentally controlled, thus facilitating the detection of quantitative trait loci (QTL. We therefore, performed the first genome-wide scan for loci contributing to radiation-induced mammary tumorigenesis in female F2-(Dahl S x R-intercross rats. Tumorigenesis was measured as tumor burden index (TBI after induction of rat mammary tumors at forty days of age via ¹²⁷Cs-radiation. We observed a spectrum of tumor latency, size-progression, and pathology from poorly differentiated ductal adenocarcinoma to fibroadenoma, indicating major effects of gene-environment interactions. We identified two mammary tumorigenesis susceptibility quantitative trait loci (Mts-QTLs with significant linkage: Mts-1 on chromosome-9 (LOD-2.98 and Mts-2 on chromosome-1 (LOD-2.61, as well as two Mts-QTLs with suggestive linkage: Mts-3 on chromosome-5 (LOD-1.93 and Mts-4 on chromosome-18 (LOD-1.54. Interestingly, Chr9-Mts-1, Chr5-Mts-3 and Chr18-Mts-4 QTLs are unique to irradiation-induced mammary tumorigenesis, while Chr1-Mts-2 QTL overlaps with a mammary cancer susceptibility QTL (Mcs 3 reported for 7,12-dimethylbenz-[α]antracene (DMBA-induced mammary tumorigenesis in F2[COP x Wistar-Furth]-intercross rats. Altogether, our results suggest at least three distinct susceptibility QTLs for

  4. Anti-hypertensive effect of Lycium barbarum L. with down-regulated expression of renal endothelial lncRNA sONE in a rat model of salt-sensitive hypertension.

    Science.gov (United States)

    Zhang, Xinyu; Yang, Xinping; Lin, Yahui; Suo, Miaomiao; Gong, Ling; Chen, Jingzhou; Hui, Rutai

    2015-01-01

    The present study aims to test whether Lycium barbarum L. has anti-hypertensive effect through regulating expression of lncRNA sONE in a rat model of salt-sensitive hypertension. Nine weeks old borderline hypertensive rats (BHRs) were divided into 4 groups receiving high (8% NaCl), medium (0.25% NaCl, as control group), and low salt diet (0.015% NaCl) for 16 weeks, respectively, while the fourth group (high salt + L. barbarum group) fed with high salt diet for 12 weeks, then followed by 8% NaCl and L. barbarum treatment for 4 weeks. Body weight and blood pressure were recorded biweekly. Salt-sensitive hypertension was successfully induced by 12-week high salt diet in BHR model. Blood pressure was significantly increased in the model (P hypertension model rats with the L. barbarum compared with that receiving high salt diet. Our results indicated that L. barbarum L. had anti-hypertensive effect and might lower blood pressure by suppressing the expression of lncRNA sONE in BHR model.

  5. Roald Dahl and Sociology 101.

    Science.gov (United States)

    Royer, Sharon E.

    1998-01-01

    Discusses author Roald Dahl's view of society as revealed through his books for children and adolescents. Describes Dahl's three major works for intermediate readers ("The BFG,""The Witches," and "Matilda"). Discusses Dahl's view of the world and its place in his books. Notes Dahl's positive impact on adolescent readers; and discusses critics'…

  6. Dynamic modeling of renal blood flow in Dahl hypertensive and normotensive rats

    DEFF Research Database (Denmark)

    Knudsen, Torben; Elmer, Henrik; Knudsen, Morten H

    2004-01-01

    A method is proposed in this paper which allows characterization of renal autoregulatory dynamics and efficiency using quantitative mathematical methods. Based on data from rat experiments, where arterial blood pressure and renal blood flow are measured, a quantitative model for renal blood flow...... dynamics is constructed. The mathematical structure for the dynamics is chosen as a "grey-box model," i.e. the model structure is inspired from physiology, but the actual parameters is found by numerical methods. Based on a number of experiments, features are extracted from the estimated parameters, which...

  7. Gene by environment QTL mapping through multiple trait analyses in blood pressure salt-sensitivity: identification of a novel QTL in rat chromosome 5

    Directory of Open Access Journals (Sweden)

    Tôrres César H

    2006-05-01

    Full Text Available Background The genetic mechanisms underlying interindividual blood pressure variation reflect the complex interplay of both genetic and environmental variables. The current standard statistical methods for detecting genes involved in the regulation mechanisms of complex traits are based on univariate analysis. Few studies have focused on the search for and understanding of quantitative trait loci responsible for gene × environmental interactions or multiple trait analysis. Composite interval mapping has been extended to multiple traits and may be an interesting approach to such a problem. Methods We used multiple-trait analysis for quantitative trait locus mapping of loci having different effects on systolic blood pressure with NaCl exposure. Animals studied were 188 rats, the progenies of an F2 rat intercross between the hypertensive and normotensive strain, genotyped in 179 polymorphic markers across the rat genome. To accommodate the correlational structure from measurements taken in the same animals, we applied univariate and multivariate strategies for analyzing the data. Results We detected a new quantitative train locus on a region close to marker R589 in chromosome 5 of the rat genome, not previously identified through serial analysis of individual traits. In addition, we were able to justify analytically the parametric restrictions in terms of regression coefficients responsible for the gain in precision with the adopted analytical approach. Conclusion Future work should focus on fine mapping and the identification of the causative variant responsible for this quantitative trait locus signal. The multivariable strategy might be valuable in the study of genetic determinants of interindividual variation of antihypertensive drug effectiveness.

  8. High Dietary Protein Exacerbates Hypertension and Renal Damage in Dahl SS Rats by Increasing Infiltrating Immune Cells in the Kidney

    National Research Council Canada - National Science Library

    De Miguel, Carmen; Lund, Hayley; Mattson, David L

    2011-01-01

    ...) compared to rats fed normal protein (132±3 mm Hg, 1.2±0.3) or low-protein (132±6 mm Hg, 0.3±0.1) diets. Significantly greater numbers of infiltrating T lymphocytes were observed in kidneys of SS rats fed the high-protein diet...

  9. Salt Sensitivity Determined From Capillary Blood

    Directory of Open Access Journals (Sweden)

    Hans Oberleithner

    2016-06-01

    Full Text Available Background/Aims: A significant rise of blood pressure in response to a given salt load is a weak indication of high salt sensitivity, supposed to foster the development of arterial hypertension and related diseases in later life. In search of an alternative method we recently developed the salt blood test (SBT, a new concept for quantifying salt sensitivity (SS. Based on this concept, namely that red blood cells (RBC report on salt sensitivity, the SBT-mini was developed. Methods: The SBT-mini utilizes a droplet of capillary blood mixed with a ‘smart' Na+ cocktail. Red blood cells (RBC of this mixture are allowed to sediment by gravity in a glass tube. SS is quantified by measuring RBC sedimentation rate. 90 healthy volunteers (39 males, 51 females; mean age: 23±0.5 years were evaluated and ‘standard values' for males and females were derived. Results: Sodium buffer capacity of female blood is about 20 % smaller as compared to male blood due to the lower hematocrit of females. SS of an individual is related to the mean standard value (set to 100 % of the respective male/female cohort. High SS (> 120 % has been found in 31 % of males and 28 % of females. Conclusions: SS can be estimated derived from the individual RBC sodium buffer capacity as measured by the SBT-mini. About one third of a healthy test cohort exhibits a high sensitivity to salt. Reduction of sodium consumption to at least two grams per day (equals five grams of NaCl per day as suggested by the WHO is recommended, particularly for individuals with high salt sensitivity.

  10. Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

    Science.gov (United States)

    Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

    2014-12-02

    Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  11. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the

  12. Sustained pharmacological inhibition of δPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats

    OpenAIRE

    Qi, Xin; Inagaki, Koichi; Sobel, Raymond A.; Mochly-Rosen, Daria

    2007-01-01

    Hypertensive encephalopathy is a potentially fatal condition associated with cerebral edema and the breakdown of the blood-brain barrier (BBB). The molecular pathways leading to this condition, however, are unknown. We determined the role of δPKC, which is thought to regulate microvascular permeability, in the development of hypertensive encephalopathy using δV1-1 — a selective peptide inhibitor of δPKC. As a model of hypertensive encephalopathy, Dahl salt-sensitive rats were fed an 8% high-s...

  13. 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

    were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated. RESULTS: All hydronephrotic animals developed...... 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......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...

  14. Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Nana Takenaka-Ninagawa

    Full Text Available We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese rats, derived from a cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of metabolic syndrome (MetS. Although the phenotype of DS/obese rats is similar to that of humans with MetS, the pathophysiological and metabolic characteristics in each cell type remain to be clarified. Hence, the establishment of induced pluripotent stem cells (iPSCs derived from MetS rats is essential for investigations of MetS in vitro. Reports of rat iPSCs (riPSCs, however, are few because of the difficulty of comparing to other rodents such as mouse. Recently, the advantage of using mesenchymal stromal cells (MSCs as a cell source for generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr+/Lepr+ (DS/lean rats using lentivirus vectors with only three factors Oct4, Klf4, and Sox2 without c-Myc. The morphology, gene expression profiles, and protein expression of established colonies showed embryonic stem cell (ESCs-like properties, and the differentiation potential into cells from all three germ layers both in vitro and in vivo (teratomas. Both riPSCs became adipocytes after induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR analysis also revealed that both riPSCs and the adipose tissue from DS/obese and DS/lean rats possess similar expression patterns of adipocyte differentiation-related genes. We succeeded in generating riPSCs effectively from MSCs of both DS/obese and DS/lean rats. These riPSCs may well serve as highly effective tools for the investigation of MetS pathophysiology in vitro.

  15. Stylistic Analysis of Roald Dahl's Cinderella

    National Research Council Canada - National Science Library

    Henni

    2010-01-01

    .... Roald Dahl is famous for his ability in creating extraordinary stories, in which linguistic elements, such as sounds and words, are manipulated to create an amusing story that has an unpredictable plot...

  16. Optical cryoimaging of rat kidney and the effective role of chromosome 13 in salt-induced hypertension

    Science.gov (United States)

    Salehpour, F.; Yang, C.; Kurth, T.; Cowley, A. W.; Ranji, M.

    2015-03-01

    The objective of this work is to assess oxidative stress levels in salt-sensitive hypertension animal model using 3D optical cryoimager to image mitochondrial redox ratio. We studied Dahl salt-induced (SS) rats, and compared the results with a consomic SS rat strain (SSBN13). The SSBN13 strain was developed by the introgression of chromosome from the Brown Norway (BN) rat into the salt-sensitive (SS) genetic background and exhibits significant protection from salt induced hypertension1 . These two groups were fed on a high salt diet of 8.0% NaCl for one week. Mitochondrial redox ratio (NADH/FAD=NADH RR), was used as a quantitative marker of the oxidative stress in kidney tissue. Maximum intensity projected images and their corresponding histograms in each group were acquired from each kidney group. The result showed a 49% decrease in mitochondrial redox ratio of SS compared to SSBN13 translated to an increase in the level of oxidative stress of the tissue. Therefore, the results quantify oxidative stress levels and its effect on mitochondrial redox in salt sensitive hypertension.

  17. Wish-Fulfillment and Subversion: Roald Dahl's Dickensian Fantasy "Matilda."

    Science.gov (United States)

    Petzold, Dieter

    1992-01-01

    Demonstrates how an understanding of Roald Dahl's novel, "Matilda," can be enhanced by recognition of the influences of Victorian novels upon the author. Discusses particularly Dahl's affinities with Charles Dickens. (HB)

  18. Salt-Sensitivity in Normotensive and Hypertensive Nigerians | Elias ...

    African Journals Online (AJOL)

    Background: Salt-sensitivity increases the risk for the development of high blood pressure in susceptible persons and also increases the risk for cardiovascular events and mortality. Objective: The study is to determine the pattern of saltsensitivity among normotensive and hypertensive Nigerians. Methods: Twenty-eight (28) ...

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

    African Journals Online (AJOL)

    like endogenous regulator, and there is a great interest to clarify its role in the defence mechanisms against biotic and abiotic stressors. In this study, investigations on the effects of foliar-applied SA on salt sensitivity, hydrogen peroxide (H2O2) ...

  20. Vascular Reactivity and Salt Sensitivity in Normotensive and ...

    African Journals Online (AJOL)

    There are not many studies designed to study the relationship between vascular reactivity and salt sensitivity in a black population. Fifty-two hypertensive (HT) and forty-seven age-matched normotensive (NT) Nigerian subjects took part in the study after informed consent was obtained from them. Ethical clearance was ...

  1. 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

  2. Free radical scavenging reverses fructose-induced salt-sensitive hypertension

    Directory of Open Access Journals (Sweden)

    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

  3. Dahl: Time ripe for DHS net assessment

    OpenAIRE

    2016-01-01

    Article review Center for Homeland Defense and Security instructor Erik Dahl urges the Department of Homeland Security to follow a practice of its military counterparts and establish an Office of Net Assessment that would gauge future threats and the nation's ability to mitigate them.

  4. Development of salt-sensitive hypertension in a sensory denervated model: the underlying mechanisms

    Directory of Open Access Journals (Sweden)

    Donna H Wang

    2001-03-01

    Full Text Available We use a novel salt-sensitive hypertensive model recently developed in our laboratory. This model shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with a significant rise in blood pressure (BP. To test the hypothesis that development of salt-sensitive hypertension in sensory denervated rats is mediated by abnormal regulation of both circulating and tissue renin-angiotensin systems (RAS, neonatal Wistar rats were given capsaicin, 50 mg/kg s.c., on the first and second days of life. Control rats were treated with vehicle solution. After the weaning period, male rats were divided into four groups and subjected to the following treatments for three weeks: control + high sodium diet (4%, CON-HS, capsaicin pretreatment + normal sodium diet (0.5%, CAP-NS, capsaicin pretreatment + high sodium diet (CAP-HS, and capsaicin pretreatment + high sodium diet + candesartan cilexetil (10 mg/kg/per day, CAP-HS-CAN. Radioimmunoassay shows that plasma renin activity (ng/ml/hr, PRA was higher in CAP-NS (2.58±0.17 than in CON-HS (0.14±0.03 and CAP-HS (0.74±0.15, and it was higher in CAP-HS than in CON-HS (p<0.05. Western blot analysis shows that expression of the angiotensin II (Ang II type 1 (AT1 receptor in both the renal cortex and outer medulla was higher in CAP-HS than in CON-HS and CAP-NS rats (p<0.05. Expression of the Ang II type 2 (AT2 receptor in the renal cortex was higher in both CAP-HS and CAP-NS than in CON-HS rats (p<0.05, but there was no difference in AT2-receptor expression in the renal medulla between CAP-HS, CAP-NS, and CON-HS rats. Likewise, there was no difference in AT1-receptor expression in mesenteric resistance arteries between CAP-HS, CAP-NS, and CON-HS rats. In contrast, mesenteric AT2-receptor expression was lower in CAP-HS than in CAP-NS and CON-HS rats (p<0.05. Tail-cuff systolic BP (mmHg shows that blockade of the AT1-receptor with candesartan prevents the development of

  5. Children's Responses to Heroism in Roald Dahl's "Matilda"

    Science.gov (United States)

    Pope, James; Round, Julia

    2015-01-01

    The paper presents findings from a reader response study conducted in February 2013 with 150 children aged 7-11 in which they discussed extracts and clips from Roald Dahl's "Matilda" (1988) and its cinematic adaptation (1996). Dahl and "Matilda" were chosen because they provoke emphatic responses from adults, often commenting…

  6. Matilda: realismo y satira en la obra de Dahl

    National Research Council Canada - National Science Library

    Del Fresno Fernandez, Mercedes

    2009-01-01

    .... Todos estos ingredientes son los que dan como resultado final ese humor corrosivo y universal tan caracteristico de Roald Dahl que ha escandalizado a algunos adultos. Las exageraciones portentosas que Dahl utiliza en sus obras sirven como distanciamiento comico que resta fuerza tanto al miedo como a la fantasia.

  7. Effect of Low Salt Diet on Insulin Resistance in Salt Sensitive versus Salt Resistant Hypertension

    OpenAIRE

    Garg, Rajesh; Sun, Bei; Williams, Jonathan

    2014-01-01

    Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt sensitive versus salt resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after one week of high salt (200 mmol/day Na) and one week of low salt (10 mmol/day Na) diet. Salt sensitivit...

  8. Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models.

    Science.gov (United States)

    Funk, J; Ott, V; Herrmann, A; Rapp, W; Raab, S; Riboulet, W; Vandjour, A; Hainaut, E; Benardeau, A; Singer, T; Jacobsen, B

    2016-03-01

    Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Matilda: realismo y satira en la obra de Dahl

    National Research Council Canada - National Science Library

    Del Fresno Fernandez, Mercedes

    2009-01-01

    .... Tal y como afirma Dieter Petzold, no es una obra realista, sino que, como todas las otras historias de Dahl, es un cuento de hadas tradicional combinado con cierta dosis de realismo, bastante satira y mucha exageracion...

  11. 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.

  12. Roald Dahl--"It's about Children and It's for Children"--But Is It Suitable?

    Science.gov (United States)

    Culley, Jonathon

    1991-01-01

    Explains some of the fascination of Roald Dahl's work and sheds some light on its nature. Discusses that what possibly worries the more anxious teacher or parent are Dahl's additions to the conventional folklore scheme of reference. (MG)

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

    Science.gov (United States)

    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 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 salt group compared to high salt only: 5.33 ± 0.21 versus 7.67 ± 0.31 mmol/24 h; P salt-fed rats, but reduced by 40% in the 20% fructose + high salt group (2139 ± 178 μmol /24 hrs P 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.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Effect of Low Salt Diet on Insulin Resistance in Salt Sensitive versus Salt Resistant Hypertension

    Science.gov (United States)

    Garg, Rajesh; Sun, Bei; Williams, Jonathan

    2014-01-01

    Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt sensitive versus salt resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after one week of high salt (200 mmol/day Na) and one week of low salt (10 mmol/day Na) diet. Salt sensitivity was defined as the fall in systolic blood pressure >15mmHg on low salt diet. The study includes 389 subjects (44% Females, 16% Blacks, BMI 28.5±4.2 Kg/m2). As expected, blood pressure was lower on low salt (129±16/78±9 mmHg) as compared to high salt diet (145±18/86±10 mmHg). Fasting plasma glucose, insulin and HOMA were higher on low salt diet (95.4±19.4 mg/dl, 10.8±7.3 mIU/L and 2.6±1.9) as compared to high salt diet (90.6±10.8 mg/dl, 9.4±5.8 mIU/L and 2.1±1.4) (p salt sensitive (N=193) versus salt resistant (N=196) subjects on either diet. Increase in HOMA on low salt diet was 0.5±1.4 in salt sensitive and 0.4±1.5 in salt resistant subjects (p=NS). On multivariate regression analysis, change in systolic blood pressure was not associated with change in HOMA after including age, BMI, sex, change in serum and urine aldosterone and cortisol into the model. We conclude that the increase in insulin resistance on low salt diet is not affected by salt sensitivity of blood pressure. PMID:25185125

  16. Mechanisms of blood pressure salt sensitivity: new insights from mathematical modeling.

    Science.gov (United States)

    Clemmer, John S; Pruett, W Andrew; Coleman, Thomas G; Hall, John E; Hester, Robert L

    2017-04-01

    Mathematical modeling is an important tool for understanding quantitative relationships among components of complex physiological systems and for testing competing hypotheses. We used HumMod, a large physiological model, to test hypotheses of blood pressure (BP) salt sensitivity. Systemic hemodynamics, renal, and neurohormonal responses to chronic changes in salt intake were examined during normal renal function, fixed low or high plasma angiotensin II (ANG II) levels, bilateral renal artery stenosis, increased renal sympathetic nerve activity (RSNA), and decreased nephron numbers. Simulations were run for 4 wk at salt intakes ranging from 30 to 1,000 mmol/day. Reducing functional kidney mass or fixing ANG II increased salt sensitivity. Salt sensitivity, associated with inability of ANG II to respond to changes in salt intake, occurred with smaller changes in renal blood flow but greater changes in glomerular filtration rate, renal sodium reabsorption, and total peripheral resistance (TPR). However, clamping TPR at normal or high levels had no major effect on salt sensitivity. There were no clear relationships between BP salt sensitivity and renal vascular resistance or extracellular fluid volume. Our robust mathematical model of cardiovascular, renal, endocrine, and sympathetic nervous system physiology supports the hypothesis that specific types of kidney dysfunction, associated with impaired regulation of ANG II or increased tubular sodium reabsorption, contribute to BP salt sensitivity. However, increased preglomerular resistance, increased RSNA, or inability to decrease TPR does not appear to influence salt sensitivity. This model provides a platform for testing competing concepts of long-term BP control during changes in salt intake. Copyright © 2017 the American Physiological Society.

  17. Role of angiotensin II-mediated AMPK inactivation on obesity-related salt-sensitive hypertension.

    Science.gov (United States)

    Deji, Naoko; Kume, Shinji; Araki, Shin-ichi; Isshiki, Keiji; Araki, Hisazumi; Chin-Kanasaki, Masami; Tanaka, Yuki; Nishiyama, Akira; Koya, Daisuke; Haneda, Masakazu; Kashiwagi, Atsunori; Maegawa, Hiroshi; Uzu, Takashi

    2012-02-17

    Salt-sensitive hypertension is a characteristic of the metabolic syndrome. Given the links to cardiovascular events, the mechanisms underlying sodium metabolism may represent an important therapeutic target for this disorder. Angiotensin II (AII) is a key peptide underlying sodium retention. However, 5'AMP-activated protein kinase (AMPK) has also been reported to participate in the regulation of ion transport. In this study we examined the relationship between AII and AMPK on the development of hypertension in two salt-sensitive mouse models. In the first model, the mice were maintained on a high-fat diet (HFD) for 12 weeks, in order to develop features similar to the metabolic syndrome, including salt-sensitive hypertension. HFD-induced obese mice showed elevated systolic blood pressure and lower sodium excretion in response to salt loading, along with an increase in AII contents and inactivation of AMPK in the kidney, which were significantly improved by the treatment of an angiotensin II antagonist, losartan, for 2 weeks. To clarify the effects of AII, a second group of mice was infused with AII via an osmotic pump, which led to higher systolic blood pressure, and decreases in urinary sodium excretion and the expression of AMPK, in a manner similar to those observed in the HFD mice. However, treatment with an AMPK activator, metformin, improved the changes induced by the AII, suggesting that AII induced sodium retention works by acting on AMPK activity. Finally, we evaluated the changes in salt-sensitivity by performing 2-week salt loading experiments with or without metformin. AII infusion elevated blood pressure by salt loading but metformin prevented it. These findings indicate that AII suppresses AMPK activity in the kidney, leading to sodium retention and enhanced salt-sensitivity, and that AMPK activation may represent a new therapeutic target for obesity-related salt-sensitive hypertension. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.

    Science.gov (United States)

    Schachter, Asher D; Ichimura, Takaharu; Kohane, Isaac S

    2005-12-01

    Numerous cellular and molecular perturbations have been studied to elucidate the pathogenic mechanisms underlying nephrotic-range proteinuria, which may in turn shed light on disease-specific mechanisms. We have analyzed the publicly available data from the PhysGen partial panel of consomic rats to determine whether there are quantitative trait loci that associate with nephrotic-range proteinuria. As of this writing, consomic rat strains subjected to the renal protocol have been bred by the Program for Genomic Applications for 15 of the 22 rat chromosomes for both genders, predominantly with the Brown-Norway (BN) and Dahl salt-sensitive (SS) strains as parents. We defined chromosomes of interest as consomic SS-xBN strains whose phenotype measurements differed significantly from SS but not BN strains, stratified by gender. We filtered and clustered differentially expressed genes by function in renal tissue from relevant strains. Proteinuria was significantly higher in male SS vs. male SS-18BN, and it was significantly higher in male SS vs. female SS. Functional clustering of differentially expressed genes yielded two specific functional clusters: apoptosis (p=0.022) and angiogenesis (p=0.046). Gene expression profiles demonstrated differential expression of apoptotic and angiogenic genes. However, TUNEL stains of renal tissue showed no significant difference in the number of apoptotic nuclei. We conclude that chromosomes 18 and X are quantitative trait loci for nephrotic-range proteinuria in rats.

  19. In Silico Analysis of Differential Gene Expression in Three Common Rat Models of Diastolic Dysfunction

    Directory of Open Access Journals (Sweden)

    Raffaele Altara

    2018-02-01

    Full Text Available Standard therapies for heart failure with preserved ejection fraction (HFpEF have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences. The top differentially expressed genes in the left ventricle of Dahl salt sensitive (Dahl/SS, spontaneous hypertensive heart failure (SHHF, and diabetes 1 induced HFpEF models were derived from published data in Gene Expression Omnibus and used for a comprehensive interpretation of the underlying pathophysiological context of each model. The diversity of the underlying transcriptomic of the heart of each model is clearly observed by the different panel of top regulated genes: the diabetic model has 20 genes in common with the Dahl/SS and 15 with the SHHF models. Advanced analytics performed in Ingenuity Pathway Analysis (IPA® revealed that Dahl/SS heart tissue transcripts triggered by upstream regulators lead to dilated cardiomyopathy, hypertrophy of heart, arrhythmia, and failure of heart. In the heart of SHHF, a total of 26 genes were closely linked to cardiovascular disease including cardiotoxicity, pericarditis, ST-elevated myocardial infarction, and dilated cardiomyopathy. IPA Upstream Regulator analyses revealed that protection of cardiomyocytes is hampered by inhibition of the ERBB2 plasma membrane-bound receptor tyrosine kinases. Cardioprotective markers such as natriuretic peptide A (NPPA, heat shock 27 kDa protein 1 (HSPB1, and angiogenin (ANG were upregulated in the diabetes 1 induced model; however, the model showed a different underlying mechanism with a majority of the

  20. Salt loading affects cortisol metabolism in normotensive subjects : Relationships with salt sensitivity

    NARCIS (Netherlands)

    Kerstens, MN; van der Kleij, FGH; Boonstra, AH; Sluiter, WJ; Koerts, J; Navis, G; Dullaart, RPF

    We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive ( ss) normotensive subjects after a low-and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary

  1. Renal sodium handling and haemodynamics are equally affected by hyperinsulinaemia in salt-sensitive and salt-resistant hypertensives

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Donker, AJM; Gans, ROB

    Objective It is well-known that insulin induces renal sodium retention. It is not yet known whether insulin's renal effects are involved in the development of salt-sensitive hypertension. We assessed the effects of insulin on renal sodium handling and haemodynamics in 10 salt-sensitive (SS) and 10

  2. The Role of Uric Acid in Hypertension of Adolescents, Prehypertension and Salt Sensitivity of Blood Pressure.

    Science.gov (United States)

    Wang, Yang; Hu, Jia-Wen; Lv, Yong-Bo; Chu, Chao; Wang, Ke-Ke; Zheng, Wen-Ling; Cao, Yu-Meng; Yuan, Zu-Yi; Mu, Jian-Jun

    2017-02-13

    Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension.

  3. Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways.

    Science.gov (United States)

    Nishimoto, Mitsuhiro; Fujita, Toshiro

    2015-03-01

    Although salt is a major environmental factor in the development of hypertension, the degree of salt sensitivity varies widely among individuals. The mechanisms responsible for this variation remain to be elucidated. Recent studies have revealed the involvement of two important signaling pathways in renal tubules that play key roles in electrolyte balance and the maintenance of normal blood pressure: the β2-adrenergic stimulant-glucocorticoid receptor (GR)-with-no-lysine kinase (WNK)4-Na(+)-Cl(-) cotransporter pathway, which is active in distal convoluted tubule (DCT)1, and the Ras-related C3 botulinum toxin substrate (Rac)1-mineralocorticoid receptor (MR) pathway, which is active in DCT2, connecting tubules, and collecting ducts. β2-Adrenergic stimulation due to increased renal sympathetic activity in obesity- and salt-induced hypertension suppresses histone deacetylase 8 activity via cAMP/PKA signaling, increasing the accessibility of GRs to the negative GR response element in the WNK4 promoter. This results in the suppression of WNK4 transcription followed by the activation of Na(+)-Cl(-) cotransporters in the DCT and elevated Na(+) retention and blood pressure upon salt loading. Rac1 activates MRs, even in the absence of ligand binding, with this activity increased in the presence of ligand. In salt-sensitive animals, Rac1 activation due to salt loading activates MRs in DCT2, connecting tubules, and collecting ducts. Thus, GRs and MRs are independently involved in two pathways responsible for renal Na(+) handling and salt-sensitive hypertension. These findings suggest novel therapeutic targets and may lead to the development of diagnostic tools to determine salt sensitivity in hypertensive patients. Copyright © 2015 the American Physiological Society.

  4. Dahl's chickens: How do they roost in the 21st century? | van Renen ...

    African Journals Online (AJOL)

    Close on two decades after the death of Roald Dahl on 23 November 1990, his legacy as a writer of children's books is apparent in the continuing popularity of his work and in the establishment, in 2001, of the Roald Dahl Museum and Story Centre in Great Missenden. The Story Centre itself promotes a love of creative ...

  5. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Science.gov (United States)

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, phypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  6. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Directory of Open Access Journals (Sweden)

    Stéphanie Rimbaud

    Full Text Available Heart failure (HF is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT. Resveratrol (18 mg/kg/day; HS-RSV was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition. Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001, and prevented the 25% reduction in body weight in HS-NT (P<0.001. Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  7. Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

    Science.gov (United States)

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening −34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  8. Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure.

    Directory of Open Access Journals (Sweden)

    Akira Kawamoto

    Full Text Available BACKGROUND: Many methods have been used to assess mitochondrial function. Technetium-99m sestamibi ((99mTc-MIBI, a lipophilic cation, is rapidly incorporated into myocardial cells by diffusion and mainly localizes to the mitochondria. The purpose of this study was to investigate whether measurement of (99mTc-MIBI signals in animal models could be used as a tool to quantify mitochondrial membrane potential at the organ level. METHODS AND RESULTS: We analyzed (99mTc-MIBI signals in Sprague-Dawley (SD rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP, a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. (99mTc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE. We also measured (99mTc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally or vehicle. (99mTc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by (31P magnetic resonance spectroscopy, decreased simultaneously. Next, we administered (99mTc-MIBI to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The (99mTc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The (99mTc-MIBI signal per liver tissue weight was lower than that per heart tissue weight. CONCLUSION: Measurement of (99mTc-MIBI signals can be an effective tool for semiquantitative investigation of cardiac mitochondrial membrane potential in the SD rat model by using a chemical to decrease the mitochondrial membrane potential. The (99mTc-MIBI signal per heart tissue weight was inversely correlated with the

  9. Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure.

    Science.gov (United States)

    Kawamoto, Akira; Kato, Takao; Shioi, Tetsuo; Okuda, Junji; Kawashima, Tsuneaki; Tamaki, Yodo; Niizuma, Shinichiro; Tanada, Yohei; Takemura, Genzou; Narazaki, Michiko; Matsuda, Tetsuya; Kimura, Takeshi

    2015-01-01

    Many methods have been used to assess mitochondrial function. Technetium-99m sestamibi ((99m)Tc-MIBI), a lipophilic cation, is rapidly incorporated into myocardial cells by diffusion and mainly localizes to the mitochondria. The purpose of this study was to investigate whether measurement of (99m)Tc-MIBI signals in animal models could be used as a tool to quantify mitochondrial membrane potential at the organ level. We analyzed (99m)Tc-MIBI signals in Sprague-Dawley (SD) rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. (99m)Tc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE). We also measured (99m)Tc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle. (99m)Tc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by (31)P magnetic resonance spectroscopy, decreased simultaneously. Next, we administered (99m)Tc-MIBI to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The (99m)Tc-MIBI signal per liver tissue weight was lower than that per heart tissue weight. Measurement of (99m)Tc-MIBI signals can be an effective tool for semiquantitative investigation of cardiac mitochondrial membrane potential in the SD rat model by using a chemical to decrease the mitochondrial membrane potential. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with the severity of heart failure in the Dahl rat model.

  10. Primary care patient willingness for genetic testing for salt-sensitive hypertension: a cross sectional study.

    Science.gov (United States)

    Okayama, Masanobu; Takeshima, Taro; Ae, Ryusuke; Harada, Masanori; Kajii, Eiji

    2013-10-09

    The current research into single nucleotide polymorphisms has extended the role of genetic testing to the identification of increased risk for common medical conditions. Advances in genetic research may soon necessitate preparation for the role of genetic testing in primary care medicine. This study attempts to determine what proportion of patients would be willing to undergo genetic testing for salt-sensitive hypertension in a primary care setting, and what factors are related to this willingness. A cross-sectional study using a self-report questionnaire was conducted among outpatients in primary care clinics and hospitals in Japan. The main characteristics measured were education level, family medical history, personal medical history, concern about hypertension, salt preference, reducing salt intake, and willingness to undergo genetic testing for salt-sensitive hypertension. Of 1,932 potential participants, 1,457 (75%) responded to the survey. Of the respondents, 726 (50%) indicated a willingness to undergo genetic testing. Factors related to this willingness were being over 50 years old (adjusted odds ratio [ad-OR] = 1.42, 95% Confidence interval = 1.09 - 1.85), having a high level of education (ad-OR: 1.83, 1.38 - 2.42), having a family history of hypertension (ad-OR: 1.36, 1.09 - 1.71), and worrying about hypertension (ad-OR: 2.06, 1.59 - 2.68). Half of the primary care outpatients surveyed in this study wanted to know their genetic risk for salt-sensitive hypertension. Those who were worried about hypertension or had a family history of hypertension were more likely to be interested in getting tested. These findings suggest that primary care physicians should provide patients with advice on genetic testing, as well as address their anxieties and concerns related to developing hypertension.

  11. Comparative efficacy of antihypertensive agents in salt-sensitive hypertensive patients: a network meta-analysis.

    Science.gov (United States)

    Qi, Han; Liu, Zheng; Cao, Han; Sun, Wei-Ping; Peng, Wen-Juan; Liu, Bin; Dong, Sheng-Jie; Xiang, Yu-Tao; Zhang, Ling

    2018-02-09

    Salt-sensitive hypertension (SSH) is an intermediate inherited phenotype of essential hypertension as well as being an independent risk factor for cardiovascular disease. However, effective medications for the treatment of SSH have not been clarified. This study was to compare the efficacious of different classes of antihypertensive agents combined with salt intake on the reduction of blood pressure in patients with salt-sensitive hypertension (SSH). We used sources as PubMed, EMBASE, Cochrane Library, CENTRAL, ClinicalTrials.gov, ICTRP, CNKI and WANFANG database from inception to November 2016. Studies that compared the efficacy of two or more antihypertensive agents or placebos in adult salt-sensitive hypertensive patients were included. The outcomes included variations in mean arterial blood pressure, systolic and diastolic blood pressure. Twenty-five studies were involved in this meta-analysis. A CCB with hydrochlorothiazide and moderate salt intake was significantly the most efficacious in comparison with placebo [standardized mean differences (SMD), 95% credibility intervals (CI): 26.66, 12.60-40.16], ARBs [SMD, 95% CI: 22.94, 5.26-40.51] and the other interventions for patients with SSH and no concomitant diseases. For SSH patients who were obese, the effect size of CCB with metformin and moderate salt intake was [SMD, 95% CI: 17.90, 6.26 -29.33]. For SSH patients with no concomitant diseases, CCB combined with hydrochlorothiazide and moderate salt intake were optimal in reducing blood pressure, while CCB combined with metformin and moderate salt intake were the most efficacious at reducing blood pressure in SSH patients with coexisting obesity.

  12. Increased Salt-Sensitivity in Endothelial Nitric Oxide Synthase-Knockout Mice

    OpenAIRE

    Leonard, Allison M.; Chafe, Linda L.; Montani, Jean-Pierre; Vliet, Bruce N Van

    2017-01-01

    Background: Although impaired nitric oxide production contributes importantly to salt-sensitivity, the role of the endothelial isoform of nitric oxide synthase (eNOS) has received little attention. In the present study we compared the effects of a high-salt diet on the blood pressure response of eNOS knockout (eNOS−/−) and control (eNOS+/+) mice. Methods: Mean arterial pressure (MAP), heart rate, pulse pressure, and activity levels were recorded by telemetry in mice fed a regular-salt diet (0...

  13. Short Term Effect of Salt Shock on Ethylene and Polyamines Depends on Plant Salt Sensitivity

    OpenAIRE

    Zapata, Pedro J.; María Serrano; Manuel F. García-Legaz; Pretel, M. T.; Botella, M. A.

    2017-01-01

    In the present manuscript the short term effect (3–24 h) of a saline shock (NaCl 100 mM) on fresh weight, water content, respiration rate, ethylene production and Na+, Cl-, ACC and polyamine concentration was studied in four plant species with different salt sensitivity, pepper, lettuce, spinach, and beetroot. Higher reduction in fresh weight and water content as a consequence of saline shock was found in pepper and lettuce plants than in spinach and beetroot, the latter behaving as more sali...

  14. Differences in genotype frequencies of salt-sensitive genes between fishing and nonfishing communities in Japan

    Directory of Open Access Journals (Sweden)

    Harada M

    2016-04-01

    Full Text Available Masanori Harada,1 Taro Takeshima,2 Masanobu Okayama,2,3 Eiji Kajii,21Department for Support of Rural Health Care, Yamaguchi Grand Medical Center, Hofu, Yamaguchi, 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke, 3Division of Community Medicine and Medical Education, Kobe University Graduate School of Medicine, Kobe, Japan Purpose: To identify the differences in genotype frequencies of salt-sensitive genes between residents of fishing communities (FCs and nonfishing communities (NFCs. Methods: The subjects included 18,156 individuals (8,043 males [44%] and 10,113 females [56%]; average age: 57.2±16.1 years from the general population who were registered with large-scale genome banks and resided in 30 prefectures and 78 different regions in Japan. The measurement items were age, sex, blood pressure, presence or absence of hypertension, body mass index, alcohol consumption, and smoking habit. Furthermore, to analyze the genotype frequencies of salt-sensitive genes, α-adducin 1 (ADD1, angiotensinogen (AGT, angiotensin II receptor type 1 (AT1, and guanine nucleotide-binding protein β  peptide 3 (GNB3 were measured. According to the 2004 government classification of municipalities (cities, towns, and villages, communities existing in areas bordering an ocean and with an ocean port were defined as FCs (28 areas. The others were defined as NFCs (50 areas. A logistic regression model was used for comparison of genotype frequencies between subjects residing in FCs and NFCs. Results: Of the included subjects, 4,916 (27.0% and 13,240 (73.0% resided in FCs and NFCs, respectively. In FCs, the mean age was 59.4±16.7 years and men accounted for 41.0% of the cohort (n=2,015. In NFCs, the mean age was 56.4±15.8 years and men accounted for 45.5% of the cohort (n=6,028. The adjusted odds ratios of the AA and AG genotypes compared with the GG genotype for AGT were 0.80 (95% confidence interval [CI

  15. Marvelous medicine: the untold story of the Wade-Dahl-Till valve.

    Science.gov (United States)

    Sandler, Adam L; Sturrock, Donald; Branfield, Jane; Abbott, Rick; Goodrich, James T; Biswas, Arundhati; Daniels, Lawrence B; Flamm, Eugene S

    2012-05-01

    On December 5, 1960, 4-month-old Theo Dahl, the only son of best-selling author Roald Dahl (1916-1990), had his skull shattered in a horrific traffic accident. What began as a personal tragedy for the Dahl family would soon evolve into a dogged crusade by Dahl to expand upon preexisting valve technology with the goal of developing a shunt that would not become obstructed. Based upon exclusive access to private archives of the Dahl estate, as well as interviews with those involved, this article tells the intricate tale of one famous father's drive to significantly alter the natural history of pediatric hydrocephalus. Dahl's collaboration with British toymaker Stanley Wade and pioneering pediatric neurosurgeons Joseph Ransohoff, Kenneth Shulman, and Kenneth Till to create the Wade-Dahl-Till (WDT) valve is examined in detail. The ensuing rift between the American and British contingents, the valve's multiple design revisions, and the goal of creating an affordable shunt for children in developing countries are among the issues addressed. The development of the WDT valve marked a significant turning point in the surgical management of pediatric hydrocephalus in general and in shunt valve technology in particular.

  16. 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.

  17. Intrarenal ghrelin receptor antagonism prevents high-fat diet-induced hypertension in male rats.

    Science.gov (United States)

    Kemp, Brandon A; Howell, Nancy L; Gildea, John J; Padia, Shetal H

    2014-07-01

    Excess weight gain contributes up to 65% of the risk of primary hypertension, and the increase in blood pressure in response to high-fat diet (HFD) is preceded by significant increases in renal tubular sodium (Na(+)) reabsorption. In normal rats, intrarenal ghrelin infusion increases distal nephron-dependent Na(+) reabsorption via activation of the intrarenal ghrelin receptor (GHSR). This study focusses on the role of intrarenal GHSR-mediated Na(+) reabsorption in HFD-induced hypertension. Dahl salt-sensitive rats received standard diet or HFD for 6 weeks. Rats underwent uninephrectomy and osmotic minipump implantation for chronic intrarenal delivery of vehicle (0.25 μL/h × 28 d), selective GHSR antagonist [D-Lys-3]-growth hormone releasing peptide-6 (0.2μM/d), or GHSR inverse agonist [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P (SUB-P) (3.6μM/d). HFD rats with vehicle pumps had significantly increased renal GHSR expression compared with standard diet (0.092 ± 0.005 vs 0.065 ± 0.004 arbitrary units; P ghrelin levels were similar (16.3±6.2 vs 15.7±8.7 pg/g tissue). HFD rats with vehicle pumps became hypertensive after 2 weeks (P ghrelin-dependent, activity of the GHSR, and HFD-induced α-epithelial Na(+) channel up-regulation was abolished during GHSR antagonism, these data suggest that HFD increases the constitutive activity of renal GHSR to increase Na(+) reabsorption and induce hypertension in rats.

  18. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice.

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    Masaki Hatanaka

    Full Text Available A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day, candesartan (0.3 mg/kg/day, or vehicle via the oral route in conjunction with a normal- (0.3% or high-salt (8.0% diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle. The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle. A pressure-natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3 protein (the major sodium transporter in renal proximal tubules in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3

  19. The metabolic profile of a rat model of chronic kidney disease

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    Yohei Tanada

    2017-05-01

    Full Text Available Background The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD with cardiorenal syndrome (CRS induced by prolonged hypertension. Methods We used inbred male Dahl salt-sensitive (DS rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group or a 0.3% NaCl diet as controls (low-salt; LS group. We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. Results DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA cycle, decreased. Conclusions DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

  20. micro-RNA screening and prediction model construction for diagnosis of salt-sensitive essential hypertension.

    Science.gov (United States)

    Qi, Han; Liu, Zheng; Liu, Bin; Cao, Han; Sun, Weiping; Yan, Yuxiang; Zhang, Ling

    2017-04-01

    Commonly used tests for diagnosis of salt-sensitive hypertension (SSH) are complex and time-consuming, so new methods are required. Many studies have demonstrated roles for miRNAs in hypertension; however, the diagnostic value of miRNAs has yet to be determined for human SSH. In this study, we examined miRNA expression profiles by initial high-throughput miRNA sequencing of samples from patients with salt-sensitive and salt-resistant hypertension (SSH and SRH, respectively; n = 6, both groups), followed by validation by quantitative real-time polymerase chain reaction (qRT-PCR) in a larger cohort (n = 91). We also evaluated differences in baseline characteristics (e.g., age, sex, body mass index, consumption of specific foods) between the SSH and SRH groups. Of 36 miRNAs identified as differentially expressed between SSH and SRH groups by RNA-Seq, 8 were analyzed by qRT-PCR. There were significant differences in the expression levels of hsa-miR-361-5p and hsa-miR-362-5p between the 2 groups (P = .023 and.049, respectively). In addition, there were significant differences in sauce and poultry consumption between the 2 groups (P = .004 and.001, respectively). The areas under the curve (AUC) determined by receptor operating characteristic (ROC) analysis for hsa-miR-361-5p and all 8 miRNAs were 0.793 (95% CI, 0.698-0.888; sensitivity = 73.9%, specificity = 74.4%; P SSH.

  1. Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives.

    Science.gov (United States)

    Anderson, David E; Fedorova, Olga V; Morrell, Christopher H; Longo, Dan L; Kashkin, Vladimir A; Metzler, Jessica D; Bagrov, Alexei Y; Lakatta, Edward G

    2008-04-01

    Factors that mediate increases in salt sensitivity of blood pressure with age remain to be clarified. The present study investigated 1) the effects of high-NaCl intake on two Na pump inhibitors, endogenous ouabain (EO) and marinobufagenin (MBG), in middle-aged and older normotensive Caucasian women; and 2) whether individual differences in EO and MBG are linked to variations in sodium excretion or salt sensitivity. A change from 6 days of a lower (0.7 mmol.kg(-1).day(-1))- to 6 days of a higher (4 mmol.kg(-1).day(-1))-NaCl diet elicited a sustained increase in MBG excretion that directly correlated with an increase in the fractional Na excretion and was inversely related to age and to an age-dependent increase in salt sensitivity. In contrast, EO excretion increased only transiently in response to NaCl loading and did not vary with age or correlate with fractional Na excretion or salt sensitivity. A positive correlation of both plasma and urine levels of EO and MBG during salt loading may indicate a casual link between two Na pump inhibitors in response to NaCl loading, as observed in animal models. A linear mixed-effects model demonstrated that age, dietary NaCl, renal MBG excretion, and body mass index were each independently associated with systolic blood pressure. Thus, a sustained increase in MBG in response to acutely elevated dietary NaCl is inversely linked to salt sensitivity in normotensive middle-aged and older women, and a relative failure of MBG elaboration by these older persons may be involved in the increased salt sensitivity with advancing age.

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

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    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.

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

    Science.gov (United States)

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    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.

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

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    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.

  5. Early-life Sodium-exposure Unmasks Susceptibility to Stroke in hyperlipidemic-hypertensive Tg[hCETP]25-Rats

    Science.gov (United States)

    Decano, Julius L.; Viereck, Jason C.; McKee, Ann C.; Hamilton, James A.; Ruiz-Opazo, Nelson; Herrera, Victoria L.M.

    2009-01-01

    Background Early-life risk factor exposure increases aortic atherosclerosis and blood pressure in humans and animal models, however, limited insight has been made into end-organ complications. Methods and Results We investigated the effects of early-life Na-exposure (0.23% vs 0.4%NaCl regular-rat chow) on vascular disease outcomes using the inbred, transgenic[hCETP]25 Dahl salt-sensitive hypertensive rat model of male-predominant coronary atherosclerosis, Tg25. Rather than the expected increased coronary heart disease, fetal 0.4%Na-exposure (≤2g-Na/2000cal/diet/day) induced adult-onset stroke in both sexes (ANOVA Pcerebral cortical hemorrhagic infarctions, microhemorrhages, neuronal ischemia, microvascular injury. Ex-vivo MRI of stroke+ rat brains detected cerebral hemorrhages, microhemorrhages and ischemia with middle cerebral artery-distribution, and cerebellar non-involvement. Ultrasound micro-imaging detected carotid artery disease. Pre-stroke analysis detected neuronal ischemia, and decreased mass of isolated cerebral, but not cerebellar, microvessels. Conclusions Early-life Na-exposure exacerbated hypertension and unmasked stroke susceptibility with greater female vulnerability in hypertensive-hyperlipidemic Tg25-rats. The reproducible modeling in Tg25sp rats of carotid artery disease, cerebral hemorrhagic-infarctions, neuronal ischemia, microhemorrhages, and microvascular alterations suggests a pathogenic spectrum with causal interrelationships. This “mixed-stroke” spectrum could represent paradigms of ischemic-hemorrhagic transformation, and/or a microangiopathic basis for the association of ischemic-lesions, microhemorrhages, and strokes in humans. Altogether, the data reveal early-life Na-exposure as a significant modifier of hypertension and stroke disease-course, hence a potential modifiable prevention target deserving systematic study. PMID:19273719

  6. 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.

  7. High Salt Intake Increases Copeptin but Salt Sensitivity Is Associated with Fluid Induced Reduction of Copeptin in Women

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    Irina Tasevska

    2014-01-01

    Full Text Available This study investigated if copeptin is affected by high salt intake and whether any salt-induced changes in copeptin are related to the degree of salt sensitivity. The study was performed on 20 men and 19 women. In addition to meals containing 50 mmol NaCl daily, capsules containing 100 mmol NaCl and corresponding placebo capsules were administered during 4 weeks each, in random order. Measurements of 24 h blood pressure, body weight, 24 h urinary volume, and fasting plasma copeptin were performed at high and low salt consumption. Copeptin increased after a high compared to low dietary salt consumption in all subjects 3,59 ± 2,28 versus 3,12 ± 1,95 (P = 0,02. Copeptin correlated inversely with urinary volume, at both low (r = −0,42; P = 0,001 and high (r = −0,60; P < 0,001 salt consumption, as well as with the change in body weight (r = −0,53; P < 0,001. Systolic salt sensitivity was inversely correlated with salt-induced changes of copeptin, only in females (r = −0,58; P = 0,017. As suppression of copeptin on high versus low salt intake was associated with systolic salt sensitivity in women, our data suggest that high fluid intake and fluid retention may contribute to salt sensitivity.

  8. Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension.

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    Lorena Citterio

    Full Text Available The importance of excess salt intake in the pathogenesis of hypertension is widely recognized. Blood pressure is controlled primarily by salt and water balance because of the infinite gain property of the kidney to rapidly eliminate excess fluid and salt. Up to fifty percent of patients with essential hypertension are salt-sensitive, as manifested by a rise in blood pressure with salt loading. We conducted a two-stage genetic analysis in hypertensive patients very accurately phenotyped for their salt-sensitivity. All newly discovered never treated before, essential hypertensives underwent an acute salt load to monitor the simultaneous changes in blood pressure and renal sodium excretion. The first stage consisted in an association analysis of genotyping data derived from genome-wide array on 329 subjects. Principal Component Analysis demonstrated that this population was homogenous. Among the strongest results, we detected a cluster of SNPs located in the first introns of PRKG1 gene (rs7897633, p = 2.34E-05 associated with variation in diastolic blood pressure after acute salt load. We further focused on two genetic loci, SLC24A3 and SLC8A1 (plasma membrane sodium/calcium exchange proteins, NCKX3 and NCX1, respectively with a functional relationship with the previous gene and associated to variations in systolic blood pressure (the imputed rs3790261, p = 4.55E-06; and rs434082, p = 4.7E-03. In stage 2, we characterized 159 more patients for the SNPs in PRKG1, SLC24A3 and SLC8A1. Combined analysis showed an epistatic interaction of SNPs in SLC24A3 and SLC8A1 on the pressure-natriuresis (p interaction = 1.55E-04, p model = 3.35E-05, supporting their pathophysiological link in cellular calcium homeostasis. In conclusions, these findings point to a clear association between body sodium-blood pressure relations and molecules modulating the contractile state of vascular cells through an increase in cytoplasmic calcium concentration.

  9. Arabidopsis histidine kinase 5 regulates salt sensitivity and resistance against bacterial and fungal infection.

    Science.gov (United States)

    Pham, Jasmine; Liu, Jasmine; Bennett, Mark H; Mansfield, John W; Desikan, Radhika

    2012-04-01

    • The ability of plants to adapt to multiple stresses imposed by the natural environment requires cross-talk and fine-tuning of stress signalling pathways. The hybrid histidine kinase Arabidopsis histidine kinase 5 (AHK5) is known to mediate stomatal responses to exogenous and endogenous signals in Arabidopsis thaliana. The purpose of this study was to determine whether the function of AHK5 in stress signalling extends beyond stomatal responses. • Plant growth responses to abiotic stresses, tissue susceptibility to bacterial and fungal pathogens, and hormone production and metabolism of reactive oxygen species were monitored in a T-DNA insertion mutant of AHK5. • The findings of this study indicate that AHK5 positively regulates salt sensitivity and contributes to resistance to the bacterium Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea. • This is the first report of a role for AHK5 in the regulation of survival following challenge by a hemi-biotrophic bacterium and a necrotrophic fungus, as well as in the growth response to salt stress. The function of AHK5 in regulating the production of hormones and redox homeostasis is discussed. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  10. Sustained pharmacological inhibition of deltaPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats.

    Science.gov (United States)

    Qi, Xin; Inagaki, Koichi; Sobel, Raymond A; Mochly-Rosen, Daria

    2008-01-01

    Hypertensive encephalopathy is a potentially fatal condition associated with cerebral edema and the breakdown of the blood-brain barrier (BBB). The molecular pathways leading to this condition, however, are unknown. We determined the role of deltaPKC, which is thought to regulate microvascular permeability, in the development of hypertensive encephalopathy using deltaV1-1 - a selective peptide inhibitor of deltaPKC. As a model of hypertensive encephalopathy, Dahl salt-sensitive rats were fed an 8% high-salt diet from 6 weeks of age and then were infused s.c. with saline, control TAT peptide, or deltaV1-1 using osmotic minipumps. The mortality rate and the behavioral symptoms of hypertensive encephalopathy decreased significantly in the deltaV1-1-treated group relative to the control-treated group, and BBB permeability was reduced by more than 60%. Treatment with deltaV1-1 was also associated with decreased deltaPKC accumulation in capillary endothelial cells and in the endfeet of capillary astrocytes, which suggests decreased microvasculature disruption. Treatment with deltaV1-1 prevented hypertension-induced tight junction disruption associated with BBB breakdown, which suggests that deltaPKC may specifically act to dysregulate tight junction components. Together, these results suggest that deltaPKC plays a role in the development of hypertension-induced encephalopathy and may be a therapeutic target for the prevention of BBB disruption.

  11. Genetic background specific hypoxia resistance in rat is correlated with balanced activation of a cross-chromosomal genetic network centering on physiological homeostasis

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    Lei eMao

    2012-10-01

    Full Text Available Genetic background of an individual can drastically influence an organism’s response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN, Dahl salt-sensitive (SS rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availability of PhysGen SS-BN consomic rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 consomic rat strains under normoxia and two-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9BN and SS-18BN represent the most hypoxia resistant CS strains with phenotype similar to BN, whereas SS-6BN and SS-YBN segregated to the direction of SS. A meta-analysis on the transcriptomic profiles of these consomic rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromosomes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia-relevant core genetic network was reverse-engineered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential network activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward

  12. Early-life sodium exposure unmasks susceptibility to stroke in hyperlipidemic, hypertensive heterozygous Tg25 rats transgenic for human cholesteryl ester transfer protein.

    Science.gov (United States)

    Decano, Julius L; Viereck, Jason C; McKee, Ann C; Hamilton, James A; Ruiz-Opazo, Nelson; Herrera, Victoria L M

    2009-03-24

    Early-life risk factor exposure increases aortic atherosclerosis and blood pressure in humans and animal models; however, limited insight has been gained as to end-organ complications. We investigated the effects of early-life Na exposure (0.23% versus 0.4% NaCl regular rat chow) on vascular disease outcomes using the inbred, transgenic [hCETP](25) Dahl salt-sensitive hypertensive rat model of male-predominant coronary atherosclerosis, Tg25. Rather than the expected increase in coronary heart disease, fetal 0.4% Na exposure (cerebral cortical hemorrhagic infarctions, microhemorrhages, neuronal ischemia, and microvascular injury. Ex vivo MRI of stroke-positive rat brains detected cerebral hemorrhages, microhemorrhages, and ischemia with middle cerebral artery distribution and cerebellar noninvolvement. Ultrasound microimaging detected carotid artery disease. Prestroke analysis detected neuronal ischemia and decreased mass of isolated cerebral but not cerebellar microvessels. Early-life Na exposure exacerbated hypertension and unmasked stroke susceptibility, with greater female vulnerability in hypertensive, hyperlipidemic Tg25 rats. The reproducible modeling in stroke-prone Tg25 rats of carotid artery disease, cerebral hemorrhagic infarctions, neuronal ischemia, microhemorrhages, and microvascular alterations suggests a pathogenic spectrum with causal interrelationships. This "mixed-stroke" spectrum could represent paradigms of ischemic-hemorrhagic transformation and/or a microangiopathic basis for the association of ischemic lesions, microhemorrhages, and strokes in humans. Together, the data reveal early-life Na exposure to be a significant modifier of hypertension and stroke disease course and hence a potentially modifiable prevention target that deserves systematic study.

  13. A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept.

    Science.gov (United States)

    Katori, Makoto; Majima, Masataka

    2010-01-07

    Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is secreted from the distal connecting tubule cells of the kidney, and its substrates, low molecular kininogen, from the principal cells of the cortical collecting ducts (CD). Formed kinins inhibit reabsorption of NaCl through bradykinin (BK)-B₂ receptors, localized along the CD. Degradation pathway of BK by kinin-destroying enzymes in urine differs completely from that in plasma, so that ACE inhibitors are ineffective. Urinary BK is destroyed mainly by a carboxypeptidase-Y-like exopeptidase (CPY) and partly by a neutral endopeptidase (NEP). Inhibitors of CPY and NEP, ebelactone B and poststatin, respectively, were found. Renal kallikrein secretion is accelerated by potassium and ATP-sensitive potassium (KATP) channel blockers, such as PNU-37883A. Ebelactone B prevents DOCA-salt hypertension in rats. Only high salt intake causes hypertension in animals deficient in BK-B2 receptors, tissue kallikrein, or kininogen. Hypertensive patients, and spontaneously hypertensive rats, excrete less kallikrein than normal subjects, irrespective of races, and become salt-sensitive. Ebelactone B, poststatin, and KATP channel blockers could become novel antihypertensive drugs by increase in urinary kinin levels. Roles of kinin in cardiovascular diseases were discussed.

  14. A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept

    Directory of Open Access Journals (Sweden)

    Masataka Majima

    2010-01-01

    Full Text Available Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is secreted from the distal connecting tubule cells of the kidney, and its substrates, low molecular kininogen, from the principal cells of the cortical collecting ducts (CD. Formed kinins inhibit reabsorption of NaCl through bradykinin (BK-B2 receptors, localized along the CD. Degradation pathway of BK by kinin-destroying enzymes in urine differs completely from that in plasma, so that ACE inhibitors are ineffective. Urinary BK is destroyed mainly by a carboxypeptidase-Y-like exopeptidase (CPY and partly by a neutral endopeptidase (NEP. Inhibitors of CPY and NEP, ebelactone B and poststatin, respectively, were found. Renal kallikrein secretion is accelerated by potassium and ATP-sensitive potassium (KATP channel blockers, such as PNU-37883A. Ebelactone B prevents DOCA-salt hypertension in rats. Only high salt intake causes hypertension in animals deficient in BK-B2 receptors, tissue kallikrein, or kininogen. Hypertensive patients, and spontaneously hypertensive rats, excrete less kallikrein than normal subjects, irrespective of races, and become salt-sensitive. Ebelactone B, poststatin, and KATP channel blockers could become novel antihypertensive drugs by increase in urinary kinin levels. Roles of kinin in cardiovascular diseases were discussed.

  15. Effect of low salt diet on insulin resistance in salt-sensitive versus salt-resistant hypertension.

    Science.gov (United States)

    Garg, Rajesh; Sun, Bei; Williams, Jonathan

    2014-12-01

    Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt-sensitive versus salt-resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after 1 week of high salt (200 mmol per day sodium) and 1 week of low salt (10 mmol per day sodium) diet. Salt sensitivity was defined as the fall in systolic blood pressure>15 mm Hg on low salt diet. The study includes 389 subjects (44% women; 16% blacks; body mass index, 28.5±4.2 kg/m2). As expected, blood pressure was lower on low salt (129±16/78±9 mm Hg) as compared with high salt diet (145±18/86±10 mm Hg). Fasting plasma glucose, insulin, and homeostasis model assessment were higher on low salt diet (95.4±19.4 mg/dL; 10.8±7.3 mIU/L; 2.6±1.9) as compared with high salt diet (90.6±10.8 mg/dL; 9.4±5.8 mIU/L; 2.1±1.4; Psalt-sensitive (n=193) versus salt-resistant (n=196) subjects on either diet. Increase in homeostasis model assessment on low salt diet was 0.5±1.4 in salt-sensitive and 0.4±1.5 in salt-resistant subjects (P=NS). On multivariate regression analysis, change in systolic blood pressure was not associated with change in homeostasis model assessment after including age, body mass index, sex, change in serum and urine aldosterone, and cortisol into the model. We conclude that the increase in insulin resistance on low salt diet is not affected by salt sensitivity of blood pressure. © 2014 American Heart Association, Inc.

  16. Short Term Effect of Salt Shock on Ethylene and Polyamines Depends on Plant Salt Sensitivity

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    Pedro J. Zapata

    2017-05-01

    Full Text Available In the present manuscript the short term effect (3–24 h of a saline shock (NaCl 100 mM on fresh weight, water content, respiration rate, ethylene production and Na+, Cl-, ACC and polyamine concentration was studied in four plant species with different salt sensitivity, pepper, lettuce, spinach, and beetroot. Higher reduction in fresh weight and water content as a consequence of saline shock was found in pepper and lettuce plants than in spinach and beetroot, the latter behaving as more salinity tolerant. In general, salinity led to rapid increases in respiration rate, ethylene production and ACC and polyamine (putrescine, spermidine, and spermine concentrations in shoot and root. These increases were related to plant salinity sensitivity, since they were higher in the most sensitive species and vice versa. However, ethylene and respiration rates in salt stressed plants recovered similar values to controls after 24 h of treatment in salt tolerant plants, while still remaining high in the most sensitive. On the other hand, sudden increases in putrescine, spermidine, and spermine concentration were higher and occurred earlier in pepper and lettuce, the most sensitive species, than in spinach and beetroot, the less sensitive ones. These increases tended to disappear after 24 h, except in lettuce. These changes would support the conclusion that ethylene and polyamine increases could be considered as a plant response to saline shock and related to the plant species sensitivity to this stress. In addition, no competition between polyamines and ethylene biosynthesis for their common precursor was observed.

  17. Common variants in epithelial sodium channel genes contribute to salt sensitivity of blood pressure: The GenSalt study.

    Science.gov (United States)

    Zhao, Qi; Gu, Dongfeng; Hixson, James E; Liu, De-Pei; Rao, Dabeeru C; Jaquish, Cashell E; Kelly, Tanika N; Lu, Fanghong; Ma, Jixiang; Mu, Jianjun; Shimmin, Lawrence C; Chen, Jichun; Mei, Hao; Hamm, L Lee; He, Jiang

    2011-08-01

    Rare mutations of the epithelial sodium channel (ENaC) lead to mendelian forms of salt-sensitive hypertension or salt-wasting hypotension. We aimed to examine the association between common variants in the ENaC genes and salt sensitivity of blood pressure (BP). A total of 1906 Han Chinese participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, which includes a 7-day low-sodium intake (51.3 mmol sodium/d) followed by a 7-day high-sodium intake (307.8 mmol sodium/d). Nine BP measurements were obtained at baseline and each intervention period using a random-zero sphygmomanometer. Single-nucleotide polymorphisms, both tagging and functional, from the 3 ENaC subunits, α, β, and γ (SCNN1A, SCNN1B, and SCNN1G), were genotyped. Multiple common single-nucleotide polymorphisms in SCNN1G were significantly associated with BP response to low-sodium intervention (rs4073930, P=1.7×10(-5); rs4073291, P=1.1×10(-5); rs7404408, P=1.9×10(-5); rs5735, P=3.0×10(-4); rs4299163, P=0.004; and rs4499238, P=0.002) even after correcting for multiple testing. For example, under an additive model, the minor allele G of SNP rs4073291 was associated with 1.33 mm Hg lower systolic BP reduction during low-sodium intervention. This large dietary sodium intervention study indicates that common variants of ENaC subunits may contribute to the variation of BP response to dietary sodium intake. Future studies are warranted to confirm these findings in an independent population and to identify functional variants for salt sensitivity. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00721721.

  18. Effect of Salt Intake on Serum Glucagon-Like Peptide-1 Levels in Normotensive Salt-Sensitive Subjects

    Directory of Open Access Journals (Sweden)

    Wen-Ling Zheng

    2017-10-01

    Full Text Available Background/Aims: Excess dietary salt is a critical risk factor of salt-sensitive hypertension. Glucagon-like peptide-1 (GLP-1 , a gut incretin hormone, conferring benefits for blood pressure by natriuresis and diuresis. We implemented a randomized trial to verify the effect of altered salt intake on serum GLP-1 level in human beings. Methods: The 38 subjects were recruited from a rural community of Northern China. All subjects were sequentially maintained a baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of NaCl , and a high-salt diet period for additional 7 days (18.0g/day of NaCl. Results: Serum GLP-1 level increased significantly with the change from the baseline period to the low-salt diet period and decreased with the change from the low-salt to high-salt diet in normotensive salt-sensitive (SS but not salt-resistant (SR individuals. There was a significant inverse correlation between the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the serum GLP-1 level and 24-h urinary sodium excretion was also found among different dietary interventions in SS subjects. Conclusions: Our study indicates that variations in dietary salt intake affect the serum GLP-1 level in normotensive salt-sensitive Chinese adults.

  19. 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

  20. Women Behaving Badly: Dahl's Witches Meet the Women of the Eighties.

    Science.gov (United States)

    Bird, Anne-Marie

    1998-01-01

    Investigates the issue of misogyny in Roald Dahl's 1983 book and Nicolas Roeg's 1989 film, "The Witches." Looks at the general differences in the two texts--the most explicit difference is in the film's ending. Explores the significance of the witch in the book and to what extent Roeg's film uses the implied connection between evil and gender. (PA)

  1. Using Roald Dahl's "Charlie and the Chocolate Factory" to Teach Different Recruitment and Selection Paradigms

    Science.gov (United States)

    Billsberry, Jon; Gilbert, Louise H.

    2008-01-01

    This article makes a case for using Roald Dahl's children's fantasy and morality tale "Charlie and the Chocolate Factory" to teach recruitment and selection. It draws attention to its relevance in illustrating and explaining three different recruitment and selection paradigms: psychometric, social process, and fit. It argues that the use of this…

  2. 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

  3. Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks.

    Science.gov (United States)

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

    2012-11-01

    Blacks 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 blacks with hypertension and cardiac hypertrophy. In this study, we tested the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type (WT) 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 (KO) 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 proatrial 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 to 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 blacks who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in blacks.

  4. Two Languages, Number One Authors: The Influence of Bilingual Upbringing on the Literary Accomplishments of Roald Dahl and Dr. Seuss

    OpenAIRE

    Ivana Marinić; Željka Nemet

    2008-01-01

    This paper focuses on the nature and impact of bilingual upbringing on cognitive development, thought and cultural experience of two bestselling authors, Roald Dahl and Theodor Seuss Geisel (Dr. Seuss). It argues that this bilingual upbringing resulted in a specific use of language in their literary accomplishments. Several segments from representative works by Dahl and Dr. Seuss are examined in order to reveal the stylistic particularities of the two authors, such as their original argot, wo...

  5. PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Koji Isodono

    Full Text Available To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1. While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER. In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease.

  6. Roald Dahl - odraz jeho životních zkušeností v jeho povídkách

    OpenAIRE

    Vladyková, Dagmar

    2006-01-01

    The main goal of this thesis is to point out the many similar features of Roald Dahl's work and life. The short stories, in the thesis briefly characterised, are put into chronological order according to Roald Dahl's life periods. The analysis of the short stories suggests to which extent they are autobiographical. The author's autobiographies, Boy- Tales of Childhood, Going Solo and the biography Roald Dahl by Jeremy Treglown, are used as the basis of this parallelism. Powered by TCPDF (www....

  7. An analysis of the modified Dahl and Masing models: application to a belt tensioner

    OpenAIRE

    Bastien, Jérome; Michon, Guilhem; Manin, Lionel; Dufour, Regis

    2007-01-01

    The objective of this paper is to describe the modified Dahl and Masing models used for predicting hysteretic behavior, and tested on a belt tensioner for automotive engines. An experimental study with deflection imposed on the tensioner is first carried out to identify hysteresis loop parameters for the two models. The models are implemented in the general motion equations which govern the behavior of a belt–tensioner–mass system. Particular attention is paid to the use of numerical schemes....

  8. ROALD DAHL E A FANTÁSTICA FÁBRICA DE LITERATURA

    Directory of Open Access Journals (Sweden)

    Adriane Ferreira Veras

    2011-08-01

    Full Text Available Este artigo faz um comentário crítico e informado da vida e obra do escritor galês Roald Dahl. Justifica-se por ser inédito no Brasil, visto que não há análises acadêmico-científicas publicadas a respeito deste importante autor até o momento neste país. Dahl é responsável por obras aclamadas principalmente, porém não exclusivamente, pelo público infantil. Grande parte de seus livros foram transformados em célebres adaptações cinematográficas, com especial destaque para A Fantástica Fábrica de Chocolate, nas versões de 1971 e 2005. O presente texto percorre os eventos mais importantes na trajetória do autor sempre os correlacionando com elementos que, direta ou indiretamente, influenciaram significativamente em suas criações literárias. Concluímos interpretando os motivos que levam as crianças a adorarem e a se identificarem psicologicamente em nível profundo com as obras de Dahl e os adultos a demonstrarem atitude ideologicamente inversa.

  9. Synthesis, characterization, and swelling behaviors of salt-sensitive maize bran-poly(acrylic acid) superabsorbent hydrogel.

    Science.gov (United States)

    Zhang, Mingyue; Cheng, Zhiqiang; Zhao, Tianqi; Liu, Mengzhu; Hu, Meijuan; Li, Junfeng

    2014-09-03

    A novel composite hydrogel was prepared via UV irradiation copolymerization of acrylic acid and maize bran (MB) in the presence of composite initiator (2,2-dimethoxy-2-phenylacetophenone and ammonium persulfate) and cross-linker (N,N'-methylenebis(acrylamide)). Under the optimized conditions, maize bran-poly(acrylic acid) was obtained (2507 g g(-1) in distilled water and 658 g g(-1) in 0.9 wt % NaCl solution). Effects of granularity, salt concentration, and various cations and anions on water absorbency were investigated. It was found that swelling was extremely sensitive to the ionic strength and cation and anion type. Swelling kinetics and water diffusion mechanism in distilled water were also discussed. Moreover, the product showed excellent water retention capability under the condition of high temperature or high pressure. The salt sensitivity, good water absorbency, and excellent water retention capability of the hydrogels give this intelligentized polymer wide potential applications.

  10. Roald Dahl and the complete locked-in syndrome: "Cold dead body, living brain"

    DEFF Research Database (Denmark)

    Kondziella, Daniel

    2017-01-01

    The classical locked-in syndrome in which partially preserved eye movements allow for communication is well-recognized by most neurologists. Yet, it is much less well-known that patients exist who are clearly conscious but have lost all means of communicating it to the outside world because...... they no longer have any motor output at all. Of note, Roald Dahl, the internationally acclaimed children book author, described this complete locked-in syndrome in one of his short stories, William and Mary (1959), almost half a century before the medical community became aware of this devastating condition...

  11. 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.

  12. 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

  13. The Pilgaard-Dahl syndrome: laughter-induced pneumothorax - one of the many potentially detrimental consequences of laughter

    DEFF Research Database (Denmark)

    Andreasen, Dorthe Bach; El Fassi, Daniel

    2010-01-01

    In this article we propose the eponym Pilgaard-Dahl syndrome (named after two Danish revue actors). The syndrome consists of laughter-induced pneumothorax in smoking middle-aged men when exposed to hearty humour. The epidemiology and pathophysiology of spontaneous pneumothorax - in particular...

  14. A Fucking Tragedy - Krimien som vor tids tragedie? Arne Dahls Europa Blues og Jan Arnalds Övervåld

    DEFF Research Database (Denmark)

    Kirkegaard, Peter

    2010-01-01

    Artiklen indkredser historisk det halvt opløste genrebegreb 'tragedie' og diskuterer det i forhold til det mere modstandsdygtige og åbne begreb om det tragiske' som en særskilt modalitet. Det sker i sidste ende for at godtgøre, at også den moderne, avancerede krimi - in casu svenske Arne Dahls Eu...

  15. "We Have a Great Task Ahead of Us!": Child-Hate in Roald Dahl's "The Witches"

    Science.gov (United States)

    Curtis, James M.

    2014-01-01

    The depictions of cruel witches in Roald Dahl's novel "The Witches" echo the cruel, abusive measures taken by adults in the historical treatment of children. The concept of child-hatred, described by Lloyd Demause and other critics, is an effective lens through which to view the hyperbolized hatred of children described in "The…

  16. Signaling with the Eyebrows – Commentary on Huron, Dahl, and Johnson

    Directory of Open Access Journals (Sweden)

    John Ohala

    2009-11-01

    Full Text Available Huron, Dahl, and Johnson, in their paper “Facial Expression and Vocal Pitch Height: Evidence of an Intermodal Association”, demonstrated a positive correlation between the pitch of a sung note and the vertical position of the singer’s eyebrows. Moreover, other subjects viewing photographs of the faces of the singers, with the lower part of the face and neck of the singers blocked out, could accurately judge whether a high note or low note had been sung. The authors offer a number of hypothetical explanations for their findings. I propose a speculative, ethologically-based, explanation for these correlations: namely, how both pitch of voice and eyebrow position would be correlated in this way to convey to the viewer the degree of potential threat – or lack of threat – posed by the signaler.

  17. Roald Dahl and the complete locked-in syndrome: "Cold dead body, living brain".

    Science.gov (United States)

    Kondziella, Daniel

    2017-08-15

    The classical locked-in syndrome in which partially preserved eye movements allow for communication is well-recognized by most neurologists. Yet, it is much less well-known that patients exist who are clearly conscious but have lost all means of communicating it to the outside world because they no longer have any motor output at all. Of note, Roald Dahl, the internationally acclaimed children book author, described this complete locked-in syndrome in one of his short stories, William and Mary (1959), almost half a century before the medical community became aware of this devastating condition. The present clinical commentary highlights an under-recognized and clinically highly relevant topic, exemplified by a lesser-known but stunning piece of literature from one of the most beloved contemporary novelist. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Application of the Dahl friction model in the dynamics analysis of grab cranes

    Directory of Open Access Journals (Sweden)

    Urbaś A.

    2016-01-01

    Full Text Available The paper presents dynamics analysis of grab cranes. The cranes can be built out of any number of links, however, only selected links have their own drive that is considered in the flexible form. The cranes are mounted to the ground by means of any number of flexible supports. Joint coordinates and homogeneous transformation matrices are used to describe the cranes’ geometry. Equations of motion are derived using Lagrange equations. Friction phenomenon is taken into account in all joints. The joint forces and torques used to calculate friction torques in the revolute joints and friction forces in the prismatic joints are determined using the recursive Newton-Euler algorithm. Models of revolute and prismatic joints are worked out. Friction coefficients are defined using the Dahl friction model. The results of numerical calculations present the influence of friction on the driving torques, force and behaviour of the load.

  19. Two Languages, Number One Authors: The Influence of Bilingual Upbringing on the Literary Accomplishments of Roald Dahl and Dr. Seuss

    Directory of Open Access Journals (Sweden)

    Ivana Marinić

    2008-06-01

    Full Text Available This paper focuses on the nature and impact of bilingual upbringing on cognitive development, thought and cultural experience of two bestselling authors, Roald Dahl and Theodor Seuss Geisel (Dr. Seuss. It argues that this bilingual upbringing resulted in a specific use of language in their literary accomplishments. Several segments from representative works by Dahl and Dr. Seuss are examined in order to reveal the stylistic particularities of the two authors, such as their original argot, word play, neologisms, the art of exaggeration and nonsense, as well as various aspects of metaphor. This is to show that bilingualism may be a decisive factor in creating a fruitful environment for the development of original and recognizable mode of written expression, which not only transcends cognitive and linguistic boundaries, but also cultural borderlines, resulting in the emergence of a new cultural artistic identity.

  20. Effect of Genetic Information Regarding Salt-Sensitive Hypertension on the Intent to Maintain a Reduced Salt Diet: Implications for Health Communication in Japan.

    Science.gov (United States)

    Miyamoto, Keiko; Iwakuma, Miho; Nakayama, Takeo

    2017-03-01

    The authors investigated the relationship between the awareness of dietary salt and genetics and the intent to maintain a low-salt diet. In particular, they assessed whether hypothetical genetic information regarding salt-sensitive hypertension motivates the intent to reduce dietary salt for communicating the health benefits of lower salt consumption to citizens. A self-administered questionnaire survey was conducted with 2500 randomly sampled residents aged 30 to 69 years living in Nagahama, Japan. Genetic information regarding higher salt sensitivity increased motivation to reduce salt intake for both those who agreed that genes cause hypertension and those who did not. Less than 50% of those who agreed that genes cause hypertension lost their intention to lower their salt consumption when they found they did not possess the susceptibility gene. Communicating genetic information positively affected motivation to reduce salt intake. The present study clarifies the difficulty in changing the behavioral intent of those who have significantly less incentive to reduce salt intake. Therefore, a multidimensional approach is crucial to reduce salt consumption. ©2016 Wiley Periodicals, Inc.

  1. Overexpression of a tobacco small G protein gene NtRop1 causes salt sensitivity and hydrogen peroxide production in transgenic plants.

    Science.gov (United States)

    Cao, YangRong; Li, ZhiGang; Chen, Tao; Zhang, ZhiGang; Zhang, JinSong; Chen, ShouYi

    2008-05-01

    The small GTPases of Rop/Rho family is central regulators of important cellular processes in plants. Tobacco small G protein gene NtRop1 has been isolated; however, its roles in stress responses were unknown. In the present study, the genomic sequence of NtRop1 was cloned, which has seven exons and six introns, similar to the Rop gene structure from Arabidopsis. The NtRop1 gene was constitutively expressed in the different organs whereas the other six Rop genes from tobacco had differential expression patterns. The expression of the NtRop1 gene was moderately induced by methyl viologen, NaCl, and ACC treatments, but slightly inhibited by ABA treatment, with no significant induction by NAA treatment. The transgenic Arabidopsis plants overexpressing the NtRop1 showed increased salt sensitivity as can be seen from the reduced root growth and elevated relative electrolyte leakage. The hydrogen peroxide production was also promoted in the NtRop1-trangenic plants in comparison with wild type plants. These results imply that the NtRop1 may confer salt sensitivity through activation of H2O2 production during plant response to salt stress.

  2. Myocardial {sup 99m}Tc-sestamibi extraction and washout in hypertensive heart failure using an isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Fukushima, Kenji [Department of Cardiology, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Department of Radiology, Johns Hopkins University, Baltimore, MD (United States); Momose, Mitsuru, E-mail: mmomose@rad.twmu.ac.j [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Kondo, Chisato [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Higuchi, Takahiro [Department of Radiology, Johns Hopkins University, Baltimore, MD (United States); Kusakabe, Kiyoko [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Hagiwara, Nobuhisa [Department of Cardiology, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan)

    2010-11-15

    Purpose: Myocardial mitochondria are the primary part of energy production for healthy cardiac contraction. And mitochondrial dysfunction would play an important role in progressive heart failure. In the recent years, myocardial washout of {sup 99m}Tc-sestamibi [({sup 99m}Tc-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI)] has been introduced to be a potential marker in patients with heart failure. The objective of this study was to clarify MIBI extraction and washout kinetics using isolated perfusion system in hypertension induced model of myocardial dysfunction. Methods: Six-week-old Dahl-salt sensitive rats, allotted to 4 groups; a 5-week high-salt group (5wk-HS), 12-week high-salt group (12wk-HS) and two age-matched, low-salt diet control groups (5wk-LS and 12wk-LS). The rats in 5wk-HS and 12wk-HS groups were fed a high-salt diet (containing 8% NaCl). Cardiac function was examined by echocardiography before removing heart. Hearts were perfused according to the Langendorff method at a constant flow rate, in which 20-min MIBI washin was conducted followed by 25-min MIBI washout. Whole heart radioactivity was collected every sec by an external gamma detector. The myocardial extraction, K{sub 1} (ml/min) and washout rate, k{sub 2} (min{sup -1}) were generated. Results: High-salt diet groups showed significant high-blood pressure. Echocardiography revealed thickened LV walls in 5wk-HS, and reduced cardiac function in 12wk-HS, compared to each age-matched control group. K{sub 1} showed no significant difference among all groups (5wk-HS: 2.36{+-}1.07, 5wk-control: 2.59{+-}0.28, 12wk-HS: 1.91{+-}0.90, and 12wk-control: 2.84{+-}0.57). k{sub 2} in 5wk-HS was comparable to that in the age matched control group (0.00030{+-}0.00039 vs -0.000010{+-}0.00044), but it was increased remarkably in 18wk-HS compared to the age matched control group (0.0025{+-}0.0011 vs 0.000025{+-}0.000041, P<.01), and 5wk-HS (P<.01). Conclusion: In the course of hypertensive heart disease, MIBI

  3. An ABRE-binding factor, OSBZ8, is highly expressed in salt tolerant cultivars than in salt sensitive cultivars of indica rice

    Directory of Open Access Journals (Sweden)

    Gupta Sudhiranjan

    2006-08-01

    Full Text Available Abstract Background The bZIP class Abscisic acid Responsive Element (ABRE-binding factor, OSBZ8 (38.5 kD has been considered to regulate ABA-mediated transcription in the suspension cultured cells of japonica rice. Still, nothing is known about the expression of OSBZ8 at protein level in vegetative tissue of salt sensitive and salt tolerant rice plants. In our previous study, Electrophoretic Mobility Shift Assay (EMSA of [32P]ABRE-DNA and nuclear extracts prepared from the lamina of Pokkali rice plants has detected the presence of an ABRE-binding factor. Northern analysis has also detected salinity stress induced accumulation of transcripts for bZIP class of factor. Therefore, OSBZ8 was considered to play an important role in the regulation of transcription in the vegetative tissue of rice. The aim of this study is to find out whether OSBZ8 has any role in regulating the NaCl-stress induced gene expression in vegetative tissue and whether the expression of OSBZ8 factor directly correlates with the stress tolerance of different varieties of indica type rice. Results Northern analysis of total RNA from roots and lamina of salt-sensitive M-I-48 and salt-tolerant Nonabokra, when probed with the N-terminal unique region of OSBZ8 (OSBZ8p, without the highly conserved basic region, a transcript of 1.3 kb hybridized and its level was much higher in tolerant cultivar. EMSA with Em1a, the strongest ABA Responsive Element till reported from the upstream of EmBP1, and the nuclear extracts from laminar tissue of untreated and salt-treated seedlings of three salt sensitive, one moderately sensitive and two salt tolerant indica rice cultivars showed specific binding of nuclear factor to ABRE element. Intensity of binding was low and inducible in salt sensitive rice cultivars while high and constitutive in salt tolerant cultivars. EMSA with 300 bp 5'upstream region of Rab16A gene, a well known salt stress and ABA-inducible gene of rice, showed formation of two

  4. An ABRE-binding factor, OSBZ8, is highly expressed in salt tolerant cultivars than in salt sensitive cultivars of indica rice

    Science.gov (United States)

    Mukherjee, Kakali; Choudhury, Aryadeep Roy; Gupta, Bhaskar; Gupta, Sudhiranjan; Sengupta, Dibyendu N

    2006-01-01

    Background The bZIP class Abscisic acid Responsive Element (ABRE)-binding factor, OSBZ8 (38.5 kD) has been considered to regulate ABA-mediated transcription in the suspension cultured cells of japonica rice. Still, nothing is known about the expression of OSBZ8 at protein level in vegetative tissue of salt sensitive and salt tolerant rice plants. In our previous study, Electrophoretic Mobility Shift Assay (EMSA) of [32P]ABRE-DNA and nuclear extracts prepared from the lamina of Pokkali rice plants has detected the presence of an ABRE-binding factor. Northern analysis has also detected salinity stress induced accumulation of transcripts for bZIP class of factor. Therefore, OSBZ8 was considered to play an important role in the regulation of transcription in the vegetative tissue of rice. The aim of this study is to find out whether OSBZ8 has any role in regulating the NaCl-stress induced gene expression in vegetative tissue and whether the expression of OSBZ8 factor directly correlates with the stress tolerance of different varieties of indica type rice. Results Northern analysis of total RNA from roots and lamina of salt-sensitive M-I-48 and salt-tolerant Nonabokra, when probed with the N-terminal unique region of OSBZ8 (OSBZ8p, without the highly conserved basic region), a transcript of 1.3 kb hybridized and its level was much higher in tolerant cultivar. EMSA with Em1a, the strongest ABA Responsive Element till reported from the upstream of EmBP1, and the nuclear extracts from laminar tissue of untreated and salt-treated seedlings of three salt sensitive, one moderately sensitive and two salt tolerant indica rice cultivars showed specific binding of nuclear factor to ABRE element. Intensity of binding was low and inducible in salt sensitive rice cultivars while high and constitutive in salt tolerant cultivars. EMSA with 300 bp 5'upstream region of Rab16A gene, a well known salt stress and ABA-inducible gene of rice, showed formation of two complexes, again very

  5. Gender-based differences on the association between salt-sensitive genes and obesity in Korean children aged between 8 and 9 years.

    Science.gov (United States)

    Lee, Myoungsook; Kim, Mi Kyung; Kim, Seon-Mee; Park, Hyesoon; Park, Chang Gyu; Park, Hye Kyung

    2015-01-01

    High sodium intake is associated with the development of chronic diseases such as obesity. Although its role in obesity remains controversial, there may be a correlation between salt sensitivity and the early onset of chronic diseases in obese children. In all, 2,163 Korean children (1,106 boys and 1,057 girls) aged 8-9 years were recruited from seven elementary schools in Seoul. To evaluate whether obesity risk was modulated by the salt sensitivity, 11 SNPs related to salt sensitive genes (SSG) became the target of sodium intakes in obese children. BP, HOMA-IR, LDLc, TG, and the girls' sodium intake significantly increased, but HDLc significantly decreased with increase in BMI. Regardless of sex, the obesity risk was 5.27-fold (CI; 1.320-27.560) higher in the Q2 to Q5 of sodium intake adjusted by energy (4044.9-5058.9 mg/day) than in the lowest Q1 level (2287.6 mg/day) in obese children. BP was sensitively dependent on insulin resistance and lipid accumulation in all subjects; however, sodium intake may be an independent risk factor of obesity without increasing BP in girls. GRK4 A486V mutant homozygote was highly distributed in the obese group, but other SNPs had no impact. The obesity risk increased 7.06, 16.8, and 46.09-fold more in boys with GRK4 A486V, ACE, and SLC12A3 mutants as sodium intake increased. Among girls, the obesity risk increased in GRK4 A486V heterozygote and CYP11β-2 mutant homozygote although sodium intake was relatively lower, implying that ACE, SLC12A, CYP11β-2, and GRK4 A486V polymorphisms showed gender-based differences with regard to interaction between sodium intake and obesity. A high sodium intake markedly increased the obesity risk in variants of GRK4 A486V regardless of sex. The obesity risk increased with GRK4 A486V, ACE, and SLC12A3 variants in boys, whereas it increased with GRK4 A486V and CYP11B2 variants in girls as sodium intake increased. Obese children with the specific gene variants are recommended to reduce their sodium

  6. Gender-Based Differences on the Association between Salt-Sensitive Genes and Obesity in Korean Children Aged between 8 and 9 Years

    Science.gov (United States)

    Kim, Seon-Mee; Park, Hyesoon; Park, Chang gyu; Park, Hye Kyung

    2015-01-01

    Background High sodium intake is associated with the development of chronic diseases such as obesity. Although its role in obesity remains controversial, there may be a correlation between salt sensitivity and the early onset of chronic diseases in obese children. Methods In all, 2,163 Korean children (1,106 boys and 1,057 girls) aged 8–9 years were recruited from seven elementary schools in Seoul. To evaluate whether obesity risk was modulated by the salt sensitivity, 11 SNPs related to salt sensitive genes (SSG) became the target of sodium intakes in obese children. Results BP, HOMA-IR, LDLc, TG, and the girls’ sodium intake significantly increased, but HDLc significantly decreased with increase in BMI. Regardless of sex, the obesity risk was 5.27-fold (CI; 1.320–27.560) higher in the Q2 to Q5 of sodium intake adjusted by energy (4044.9–5058.9 mg/day) than in the lowest Q1 level (2287.6 mg/day) in obese children. BP was sensitively dependent on insulin resistance and lipid accumulation in all subjects; however, sodium intake may be an independent risk factor of obesity without increasing BP in girls. GRK4 A486V mutant homozygote was highly distributed in the obese group, but other SNPs had no impact. The obesity risk increased 7.06, 16.8, and 46.09-fold more in boys with GRK4 A486V, ACE, and SLC12A3 mutants as sodium intake increased. Among girls, the obesity risk increased in GRK4 A486V heterozygote and CYP11β-2 mutant homozygote although sodium intake was relatively lower, implying that ACE, SLC12A, CYP11β-2, and GRK4 A486V polymorphisms showed gender-based differences with regard to interaction between sodium intake and obesity. Conclusion A high sodium intake markedly increased the obesity risk in variants of GRK4 A486V regardless of sex. The obesity risk increased with GRK4 A486V, ACE, and SLC12A3 variants in boys, whereas it increased with GRK4 A486V and CYP11B2 variants in girls as sodium intake increased. Obese children with the specific gene

  7. Transcriptome analysis reveals that distinct metabolic pathways operate in salt-tolerant and salt-sensitive upland cotton varieties subjected to salinity stress.

    Science.gov (United States)

    Guo, Jinyan; Shi, Gongyao; Guo, Xiaoyan; Zhang, Liwei; Xu, Wenying; Wang, Yumei; Su, Zhen; Hua, Jinping

    2015-09-01

    Salinity stress is one of the most devastating abiotic stresses in crop plants. As a moderately salt-tolerant crop, upland cotton (Gossypium hirsutum L.) is a major cash crop in saline areas and a suitable model for salt stress tolerance research. In this study, we compared the transcriptome changes between the salt-tolerant upland cotton cultivar Zhong 07 and salt-sensitive cultivar Zhong G5 in response to NaCl treatments. Transcriptional regulation, signal transduction and secondary metabolism in two varieties showed significant differences, all of which might be related to mechanisms underlying salt stress tolerance. The transcriptional profiles presented here provide a foundation for deciphering the mechanism underlying salt tolerance. Based on our findings, we proposed several candidate genes that might be used to improve salt tolerance in upland cotton. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Pathway analysis of the transcriptome and metabolome of salt sensitive and tolerant poplar species reveals evolutionary adaption of stress tolerance mechanisms

    Directory of Open Access Journals (Sweden)

    Schmitt-Kopplin Philippe

    2010-07-01

    Full Text Available Abstract Background Populus euphratica is a salt tolerant and Populus × canescens a salt sensitive poplar species. Because of low transcriptional responsiveness of P. euphratica to salinity we hypothesized that this species exhibits an innate activation of stress protective genes compared with salt sensitive poplars. To test this hypothesis, the transcriptome and metabolome of mature unstressed leaves of P. euphratica and P. × canescens were compared by whole genome microarray analyses and FT-ICR-MS metabolite profiling. Results Direct cross-species comparison of the transcriptomes of the two poplar species from phylogenetically different sections required filtering of the data set. Genes assigned to the GO slim categories 'mitochondria', 'cell wall', 'transport', 'energy metabolism' and 'secondary metabolism' were significantly enriched, whereas genes in the categories 'nucleus', 'RNA or DNA binding', 'kinase activity' and 'transcription factor activity' were significantly depleted in P. euphratica compared with P. × canescens. Evidence for a general activation of stress relevant genes in P. euphratica was not detected. Pathway analyses of metabolome and transcriptome data indicated stronger accumulation of primary sugars, activation of pathways for sugar alcohol production, and faster consumption of secondary metabolites in P. euphratica compared to P. × canescens. Physiological measurements showing higher respiration, higher tannin and soluble phenolic contents as well as enrichment of glucose and fructose in P. euphratica compared to P. × canescens corroborated the results of pathway analyses. Conclusion P. euphratica does not rely on general over-expression of stress pathways to tolerate salt stress. Instead, it exhibits permanent activation of control mechanisms for osmotic adjustment (sugar and sugar alcohols, ion compartmentalization (sodium, potassium and other metabolite transporters and detoxification of reactive oxygen species

  9. Does a medical history of hypertension influence disclosing genetic testing results of the risk for salt-sensitive hypertension, in primary care?

    Directory of Open Access Journals (Sweden)

    Okayama M

    2016-07-01

    Full Text Available Masanobu Okayama,1,2 Taro Takeshima,2 Masanori Harada,3 Ryusuke Ae,4 Eiji Kajii2 1Division of Community Medicine and Medical Education, Kobe University Graduate School of Medicine, Kobe, Hyogo, 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke, Tochigi, 3Department of Support of Rural Medicine, Yamaguchi Grand Medical Center, Hofu, Yamaguchi, 4Division of Public Health, Center for Community Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan Objective: Disclosing genetic testing results may contribute to the prevention and management of many common diseases. However, whether the presence of a disease influences these effects is unclear. This study aimed to clarify the difference in the effects of disclosing genetic testing results of the risk for developing salt-sensitive hypertension on the behavioral modifications with respect to salt intake in hypertensive and nonhypertensive patients.Methods: A cross-sectional study using a self-administered questionnaire was conducted for outpatients aged >20 years (N=2,237 at six primary care clinics and hospitals in Japan. The main factors assessed were medical histories of hypertension, salt preferences, reduced salt intakes, and behavior modifications for reducing salt intake. Behavioral modifications of participants were assessed using their behavior stages before and after disclosure of the hypothetical genetic testing results. Results: Of the 2,237 participants, 1,644 (73.5% responded to the survey. Of these respondents, 558 (33.9% patients were hypertensive and 1,086 (66.1% were nonhypertensive. After being notified of the result “If with genetic risk”, the nonhypertensive participants were more likely to make positive behavioral modifications compared to the hypertensive patients among all participants and in those aged <65 years (adjusted relative ratio [ad-RR], 1.76; 95% confidence interval, 1.12−2.76 and ad-RR, 1

  10. Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).

    Science.gov (United States)

    Nierenberg, Jovia L; Li, Changwei; He, Jiang; Gu, Dongfeng; Chen, Jichun; Lu, Xiangfeng; Li, Jianxin; Wu, Xigui; Gu, C Charles; Hixson, James E; Rao, Dabeeru C; Kelly, Tanika N

    2017-12-01

    We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS (P=2.7×10-8, 9.8×10-8, and 6.4×10-6, respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention (P=1.4×10-3, 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions (P=0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension. © 2017 American Heart Association, Inc.

  11. Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension.

    Science.gov (United States)

    Wang, Tzung-Dau; Tan, Ru-San; Lee, Hae-Young; Ihm, Sang-Hyun; Rhee, Moo-Yong; Tomlinson, Brian; Pal, Parasar; Yang, Fan; Hirschhorn, Elizabeth; Prescott, Margaret F; Hinder, Markus; Langenickel, Thomas H

    2017-01-01

    Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both Pblood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576. © 2016 American Heart Association, Inc.

  12. Milline on olnud Teie seos noorteorganisatsioonidega ja millist rolli näed neil tänapäeval? / Dahl, Maarja; Nael, Jüri; Niiler, Kristiina; Paet, Urmas; Tõniste, Toomas

    Index Scriptorium Estoniae

    2007-01-01

    Küsimusele vastavad Eesti Noorteühenduste Liidu juhatuse esimees Maarja Dahl, Tallinna Ülikooli kunstide teaduskonna koreograafiaosakonna juhataja Jüri Nael, "Aasta vabatahtlik 2006" Kristiina Niiler, välisminister Urmas Paet ja Riigikogu liige, Riigikogu Skautide Ühenduse esimees Toomas Tõniste

  13. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  14. Global Democracy Arising from the modern state Transnationalization : The ( Im possibility of System Building International Democratic According to Robert Dahl , David Held and Anne Peters

    Directory of Open Access Journals (Sweden)

    Alvaro de Oliveira Azevedo Neto

    2016-06-01

    Full Text Available The present paper has as its main goal to analyze the possibility of the transition of democratic institutes present in the domestic system towards the global arena. The idea of an international democracy is evaluated as a potential formal solution to the democratic deficit resulting in the low citizen participation in the global sphere. In this sense, using a comparative model, three theories represented by DAHL, HELD and PETERS are proposed and analyzed together before proposing a final composition. First, a description of the modern State and its transnationalization is proposed, where democracy is adja- cent to this creation and development. Next, the potential of the transnationalization of democracy is studied, and its result is that even though it is seen as possible and desirable, the system still needs to evolve so that it can be attainable.

  15. A complex network analysis of hypertension-related genes

    Science.gov (United States)

    Wang, Huan; Xu, Chuan-Yun; Hu, Jing-Bo; Cao, Ke-Fei

    2014-01-01

    In this paper, a network of hypertension-related genes is constructed by analyzing the correlations of gene expression data among the Dahl salt-sensitive rat and two consomic rat strains. The numerical calculations show that this sparse and assortative network has small-world and scale-free properties. Further, 16 key hub genes (Col4a1, Lcn2, Cdk4, etc.) are determined by introducing an integrated centrality and have been confirmed by biological/medical research to play important roles in hypertension.

  16. Effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism in rats with metabolic syndrome.

    Science.gov (United States)

    Uchinaka, Ayako; Yoneda, Mamoru; Yamada, Yuichiro; Murohara, Toyoaki; Nagata, Kohzo

    2017-08-01

    The mammalian target of rapamycin (mTOR) is a regulator of metabolism and is implicated in pathological conditions such as obesity and diabetes. We aimed to investigate the role of mTOR in obesity. A new animal model of metabolic syndrome (MetS), named DahlS.Z-Lepr(fa) /Lepr(fa) (DS/obese) rats was established previously in our laboratory. In this study, we used this model to evaluate the effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism. DS/obese rats were treated with the mTOR inhibitor, everolimus, (0.83 mg/kg per day, per os) for 4 weeks at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr(+) /Lepr(+) or DS/lean) littermates of DS/obese rats were used as controls. Treatment with everolimus ameliorated hypertension, left ventricular (LV) hypertrophy and fibrosis, and LV diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats, but had no effect on these parameters in DS/lean rats. Treatment with everolimus reduced Akt Thr308 phosphorylation in the heart of DS/obese rats. It also alleviated obesity, hyperphagia, adipocyte hypertrophy, and adipose tissue inflammation in DS/obese rats. Everolimus treatment exacerbated glucose intolerance, but did not affect Akt phosphorylation levels in the fat or liver in these rats. Pancreatic β-cell mass was increased in DS/obese rats compared with that in DS/lean rats and this effect was attenuated by everolimus. Activation of mTOR signaling contributes to the pathophysiology of MetS and its associated complications. And mTOR inhibition with everolimus ameliorated obesity as well as cardiac and adipose tissue pathology, but exacerbated glucose metabolism in rats with MetS. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

  17. Henrik Dahl, du tager fejl

    DEFF Research Database (Denmark)

    Clark, Daniel Aasdal; Serritzlev, Mark Guldholm; Djørup, Emil

    2014-01-01

    Akkrediteringsrådet, som skal beslutte, hvorvidt danske universitetsuddannelser lever op til kravene om kvalitet og kvalificering, meddelte for nyligt, at uddannelsen Humanistisk Informatik på Aalborg Universitet skulle lukkes, skriver studievejleder Daniel Aasdal Clark sammen med Mark Guldholm...... Serritzlev og Emil Djørup, begge studerende. Senere har rådet udskudt beslutningen på grund af en "teknikalitet". Dette er uprofessionelt, men hvad mere er, beslutningen var forkert til at starte med. Blandt andet har forskellige aktører i erhvervslivet således en positiv holdning til uddannelsen. Dette må...

  18. High Salt Diet Affects Renal Sodium Excretion and ERRα Expression.

    Science.gov (United States)

    Wang, Dan; Wang, Yang; Liu, Fu-Qiang; Yuan, Zu-Yi; Mu, Jian-Jun

    2016-04-01

    Kidneys regulate the balance of water and sodium and therefore are related to blood pressure. It is unclear whether estrogen-related receptor α (ERRα), an orphan nuclear receptor and transcription factor highly expressed in kidneys, affects the reabsorption of water and sodium. The aim of this study was to determine whether changes in the expressions of ERRα, Na⁺/K⁺-ATPase and epithelial sodium channel (ENaC) proteins affected the reabsorption of water and sodium in kidneys of Dahl salt-sensitive (DS) rats. SS.13BN rats, 98% homologous to the DS rats, were used as a normotensive control group. The 24 h urinary sodium excretion of the DS and SS.13BN rats increased after the 6-week high salt diet intervention, while sodium excretion was increased in DS rats with daidzein (agonist of ERRα) treatment. ERRα expression was decreased, while β- and γ-ENaC mRNA expressions were increased upon high sodium diet treatment in the DS rats. In the chromatin immunoprecipitation (CHIP) assay, positive PCR signals were obtained in samples treated with anti-ERRα antibody. The transcriptional activity of ERRα was decreased upon high salt diet intervention. ERRα reduced the expressions of β- and γ-ENaC by binding to the ENaC promoter, thereby increased Na+ reabsorption. Therefore, ERRα might be one of the factors causing salt-sensitive hypertension.

  19. Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals.

    Science.gov (United States)

    Ojewole, J A O; Kamadyaapa, D R; Gondwe, M M; Moodley, K; Musabayane, C T

    2007-01-01

    The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.

  20. Effects of high-sodium intake on systemic blood pressure and vascular responses in spontaneously diabetic WBN/Kob-Lepr(fa/fa) rats.

    Science.gov (United States)

    Takagi, Yoshiichi; Kadowaki, Haruno; Kobayashi, Ikumi; Ito, Kaoru; Ito, Katsuaki; Shirai, Mitsuyuki; Asai, Fumitoshi

    2017-02-01

    The prevalence of type 2 diabetes mellitus (T2DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high-salt intake on the systolic blood pressure (SBP) and vascular responses in WBN/Kob-Lepr(fa/fa) (WBKDF) rats, a new spontaneous animal model of T2DM. 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 14 weeks: (i) Wistar rats on NS diet (Wistar-NS); (ii) Wistar rats on HS diet (Wistar-HS); (iii) WBKDF rats on NS diet (WBKDF-NS); (iv) WBKDF rats on HS diets (WBKDF-HS). Neither WBKDF-NS nor Wistar-NS rats showed significant changes in SBP throughout the experiment, but both WBKDF-HS and Wistar-HS exhibited significant elevation of SBP, which was more prominent (Psodium ions were observed in WBKDF-HS than in Wistar-HS. The current study demonstrated that WBKDF-HS rats developed salt-sensitive hypertension associated with vascular dysfunction. The WBKDF rat may be a useful model for investigating the etiology of hypertension with T2DM. © 2016 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

  1. Vascular Reactivity and Salt Sensitivity in Normotensive and ...

    African Journals Online (AJOL)

    Department of Physiology, 1Lagos State University College of Medicine, Ikeja, Nigeria and 2College of Medicine,. University of Lagos, (CMUL), .... were excluded from the study if they were pregnant or breast feeding or if they had history of poor ..... The present results show higher SBP reactivity in the normotensive subjects ...

  2. Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression.

    Science.gov (United States)

    Raff, Hershel; Gehrand, Ashley; Bruder, Eric D; Hoffman, Matthew J; Engeland, William C; Moreno, Carol

    2015-01-01

    The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. Copyright © 2015 the American Physiological Society.

  3. Gender and obesity influence sodium intake and fluid regulation in Zucker rats following repeated sodium depletions.

    Science.gov (United States)

    Omouessi, S T; Chapleur, M; Leshem, M; Thornton, S N

    2006-11-30

    The Zucker obese rat is an important model for the metabolic syndrome, which includes renal disease and salt-sensitive hypertension, suggesting abnormalities of body fluid regulation. Here, in Zucker rats, lean and obese, and of both sexes, we compared 48 h of sodium intake and fluid regulation responses with repeated depletions with furosemide to repeated control saline injections. Increased urine volume excretion was observed after each furosemide administration for the 4 groups and obese rats excreted more than the leans on the control days. Male obese rats did not excrete sodium nor increase intake of 2% NaCl following the first furosemide administration, whereas the other 3 groups did. Subsequent depletions increased 2% NaCl consumption and urinary sodium excretion in all groups. Males excreted more sodium in their urine than the females on the control days. Females showed an increase in 2% NaCl intake on control days. Water intake increased in the female leans after each depletion, increased in the males after the 2nd and 3rd depletion and increased in the obese females only after the 2nd depletion. These findings show clearly that there are gender- and weight-related differences in the response of Zucker rats to furosemide-induced depletion. However, the main differences occurred with the first depletion. With repeated depletions the rats adjusted sodium and fluid intake and excretion so that differences due to gender and body weight tended to disappear. Our findings caution against drawing conclusions about differences due to gender and body weight based on single treatments.

  4. Defective renal dopamine function and sodium-sensitive hypertension in adult ovariectomized Wistar rats: role of the cytochrome P-450 pathway.

    Science.gov (United States)

    Di Ciano, Luis A; Azurmendi, Pablo J; Colombero, Cecilia; Levin, Gloria; Oddo, Elisabet M; Arrizurieta, Elvira E; Nowicki, Susana; Ibarra, Fernando R

    2015-06-15

    We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of the total Na(+)-K(+)-ATPase (NKA) α1-subunit (Di Ciano LA, Azurmendi PJ, Toledo JE, Oddo EM, Zotta E, Ochoa F, Arrizurieta EE, Ibarra FR. Clin Exp Hypertens 35: 475-483, 2013). Upon high sodium (HS) intake, ovariectomized (oVx) rats developed defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats, HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in cytochrome P-4504A (CYP4A) expression, and in 20-HETE production, while MBP kept normal. Blockade of the D1 receptor (D1R) with the D1-like receptor antagonist SCH 23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50%, and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both P < 0.05), NKA was more dephosphorylated than in IFHS, and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal DA system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load, and the development of salt-sensitive hypertension. Copyright © 2015 the American Physiological Society.

  5. Long term salinity stress in relation to lipid peroxidation, super oxide dismutase activity and proline content of salt-sensitive and salt-tolerant wheat cultivars Estrés salino a largo plazo en relación con peroxidación lipídica, actividad superóxido dismutasa y contenido de prolina de cultivares de trigo sensibles y tolerantes a la salinidad

    Directory of Open Access Journals (Sweden)

    Azam Borzouei

    2012-12-01

    Full Text Available Salinity is a widespread root medium problem limiting productivity of cereal crops worldwide. The ability of plants to tolerate salt is determined by multiple biochemical pathways that facilitate retention and/or acquisition of water, protect chloroplast functions, and maintain ion homeostasis. Therefore, the ability of salt-sensitive ('Tajan' and salt-tolerant cultivar ('Bam' of Triticum aestivum L. to adapt to a saline environment were evaluated in a set of greenhouse experiments under salt stress during three growth stages (tillering, 50% anthesis, and 10 d after anthesis. Plants were irrigated by different saline waters with electrical conductivities of 1.3, 6, 8, 10, and 12 dS m-1, which were obtained by adding NaCl:CaCl2 in 10:1 molar ratio to fresh water. Differences in growth parameters, lipid peroxidation, superoxide dismutase (SOD activity, and proline accumulation were tested in order to put forward the relative tolerance or sensitivity of cultivars. Results indicated that both parameters differ according to the cultivar's ability in coping oxidative stress caused by salinity. We observed a greater decline in the growth parameters and grain yield under salt stress in 'Tajan' than in 'Bam'. Malondialdehyde content was also higher in 'Tajan'. The improved performance of the 'Bam' under high salinity was accompanied by an increase in SOD (EC 1.15.1.1 activity and proline content at all growth stages. Growth parameters, lipid peroxidation and proline accumulation results are also in good correlation with supporting this cultivar is being relatively tolerant.La salinidad es un problema del medio radical ampliamente distribuido que limita la productividad de los cultivos de cereal en todo el mundo. La capacidad de las plantas para tolerar la sal está determinada por multiples vías bioquímicas que facilitan la retención y/o adquisición de agua, protegen las funciones del cloroplasto, y mantienen la homeostasis iónica. Por lo tanto, se

  6. Antihypertensive effect of peptide-enriched soy sauce-like seasoning and identification of its angiotensin I-converting enzyme inhibitory substances.

    Science.gov (United States)

    Nakahara, Takeharu; Sano, Atsushi; Yamaguchi, Hitomi; Sugimoto, Katsutoshi; Chikata, Hiroyuki; Kinoshita, Emiko; Uchida, Riichiro

    2010-01-27

    We have developed a peptide-enriched soy sauce-like seasoning termed Fermented Soybean Seasoning (FSS), by modifying the process of soy sauce brewing. The FSS has a 2.7-fold higher concentration of total peptides than regular soy sauce. The angiotensin I-converting enzyme (ACE) inhibitory activity of FSS (IC(50) = 454 microg/mL) was greater than that of regular soy sauce (IC(50) = 1620 microg/mL). The FSS demonstrated antihypertensive effects both in spontaneously hypertensive rats and in Dahl salt-sensitive rats during continuous feeding. The ACE inhibitory substances were purified from FSS by reversed-phase chromatography. Ala-Trp IC(50) = 10 microM; Gly-Trp IC(50) = 30 microM; Ala-Tyr IC(50) = 48 microM; Ser-Tyr, IC(50) = (67 microM; Gly-Tyr, IC(50) = 97 microM; Ala-Phe, IC(50) = 190 microM; Val-Pro, IC(50) = (480 microM; Ala-Ile, IC(50) = 690 microM; Val-Gly, IC(50) = 1100 microM; and a nicotianamine, IC(50) = 0.26 microM. [corrected] The concentrations of these substances in the FSS were revealed to be higher than that of regular soy sauce through quantitative LC-MS/MS analysis.

  7. Transcriptome analysis of salt-stressed Deinococcus radiodurans and characterization of salt-sensitive mutants.

    Science.gov (United States)

    Im, Seonghun; Joe, Minho; Kim, Dongho; Park, Don-Hee; Lim, Sangyong

    2013-11-01

    Deinococcus radiodurans is a bacterium best known for its extreme resistance to high levels of ionizing radiation. Gene expression profiles of D. radiodurans exposed to 0.3 M NaCl revealed that at least 389 genes were induced and 415 were repressed by twofold or more. A general down-regulation of the central metabolic pathways and a strong decrease of nrd gene expression, which encodes proteins necessary for DNA synthesis, likely reflect the growth retardation induced by NaCl stress. The expression of rsbRSTX, which encodes sigma B (σ(B)) activity regulators, was also reduced by NaCl stress even though D. radiodurans does not have σ(B). The mutation of rsbX (drB0027) decreased the tolerance of D. radiodurans to NaCl, suggesting the possible role of the Rsb module in NaCl response. On the other hand, NaCl stress activated genes associated with osmoprotectant accumulation: the pstSCAB operon, which encodes a high affinity phosphate transporter, and DRA0135 and DR1438, which are components of transporters of glycine betaine and trehalose. Survival analysis of mutant strains lacking DR0392 (membrane-binding protein) and DR1115 (S-layer protein), whose expressions were highly activated by NaCl, showed a reduction in NaCl tolerance. In addition, the Δdr0392 strain showed sensitivity to γ-irradiation compared to the wild type. These results suggest that DR0392 plays a role in the resistance of D. radiodurans to NaCl and γ-irradiation. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Correlation of Salt Sensitivity, Plasma Renin Activity and Aldosterone in Hypertensive Patients

    Directory of Open Access Journals (Sweden)

    Tasic Nebojsa

    2017-09-01

    Full Text Available Plasma-renin values vary in normotensive and hypertensive populations. Some studies consider renin to be a key factor in the aetiology of hypertension, but other studies note that renin is an important factor in cardiovascular homeostasis and functions more as a growth factor than as a pressor hormone. The aim of this study was to assess the PRA and aldosterone values under different salt intake regimes in patients with essential hypertension. The study group consisted of 50 untreated patients (27 women and 23 men; average age 42±9,2 yrs.; average BMI 27,91±4,6 kg/m2 with essential hypertension. All patients were put on a high-sodium diet (200 mmol NaCl per day for one week after a week on a low-sodium diet (20 mmol NaCl per day. Sodium sensitivity (SS was defined as a 10-mmHg increase in the mean blood pressure at the end of the high- vs. the low-sodium diet. The SS group consisted of 26 patients, and the sodiuminsensitive group consisted of 24 patients. The PRA and aldosterone levels were determined in 12 patients. PRA values in the SS group during rest were significantly lower compared with the salt-resistant group during all regimes of salt intake (F=10,56, p=0,0012. Salt loading in SS patients causes a significant decrease in PRA (in rest and effort values in comparison to values during a low salt intake regime (rest: t=4,49, p<0,001; effort: t=3,45, p<0,01. The PRA values in the salt-resistant group did not vary significantly under the different salt intake regimes. The aldosterone values followed the pattern of the PRA values. It is necessary to distinguish investigations on salt intake effects based on incidence and value of blood pressure and investigations on salt restriction’s effects on of blood pressure levels (i.e., non-pharmacological hypertension therapy.

  9. Rat-bite fever

    Science.gov (United States)

    ... dwellings may help prevent rat-bite fever. Taking antibiotics by mouth after a rat bite may also help prevent this illness. Alternative Names Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic ...

  10. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  11. Cardioprotection and lifespan extension by the natural polyamine spermidine

    Science.gov (United States)

    Eisenberg, Tobias; Abdellatif, Mahmoud; Schroeder, Sabrina; Primessnig, Uwe; Stekovic, Slaven; Pendl, Tobias; Harger, Alexandra; Schipke, Julia; Zimmermann, Andreas; Schmidt, Albrecht; Tong, Mingming; Ruckenstuhl, Christoph; Dammbrueck, Christopher; Gross, Angelina S.; Herbst, Viktoria; Magnes, Christoph; Trausinger, Gert; Narath, Sophie; Meinitzer, Andreas; Hu, Zehan; Kirsch, Alexander; Eller, Kathrin; Gutierrez, Didac-Carmona; Büttner, Sabrina; Pietrocola, Federico; Knittelfelder, Oskar; Schrepfer, Emilie; Rockenfeller, Patrick; Simonini, Corinna; Rahn, Alexandros; Horsch, Marion; Moreth, Kristin; Beckers, Johannes; Fuchs, Helmut; Gailus-Durner, Valerie; Neff, Frauke; Janik, Dirk; Rathkolb, Birgit; Rozman, Jan; de Angelis, Martin Hrabe; Moustafa, Tarek; Haemmerle, Guenter; Mayr, Manuel; Willeit, Peter; von Frieling-Salewsky, Marion; Pieske, Burkert; Scorrano, Luca; Pieber, Thomas; Pechlaner, Raimund; Willeit, Johann; Sigrist, Stephan J.; Linke, Wolfgang A.; Mühlfeld, Christian; Sadoshima, Junichi; Dengjel, Joern; Kiechl, Stefan; Kroemer, Guido; Sedej, Simon; Madeo, Frank

    2018-01-01

    Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for the protection from cardiovascular disease. PMID:27841876

  12. Cardioprotection and lifespan extension by the natural polyamine spermidine.

    Science.gov (United States)

    Eisenberg, Tobias; Abdellatif, Mahmoud; Schroeder, Sabrina; Primessnig, Uwe; Stekovic, Slaven; Pendl, Tobias; Harger, Alexandra; Schipke, Julia; Zimmermann, Andreas; Schmidt, Albrecht; Tong, Mingming; Ruckenstuhl, Christoph; Dammbrueck, Christopher; Gross, Angelina S; Herbst, Viktoria; Magnes, Christoph; Trausinger, Gert; Narath, Sophie; Meinitzer, Andreas; Hu, Zehan; Kirsch, Alexander; Eller, Kathrin; Carmona-Gutierrez, Didac; Büttner, Sabrina; Pietrocola, Federico; Knittelfelder, Oskar; Schrepfer, Emilie; Rockenfeller, Patrick; Simonini, Corinna; Rahn, Alexandros; Horsch, Marion; Moreth, Kristin; Beckers, Johannes; Fuchs, Helmut; Gailus-Durner, Valerie; Neff, Frauke; Janik, Dirk; Rathkolb, Birgit; Rozman, Jan; de Angelis, Martin Hrabe; Moustafa, Tarek; Haemmerle, Guenter; Mayr, Manuel; Willeit, Peter; von Frieling-Salewsky, Marion; Pieske, Burkert; Scorrano, Luca; Pieber, Thomas; Pechlaner, Raimund; Willeit, Johann; Sigrist, Stephan J; Linke, Wolfgang A; Mühlfeld, Christian; Sadoshima, Junichi; Dengjel, Joern; Kiechl, Stefan; Kroemer, Guido; Sedej, Simon; Madeo, Frank

    2016-12-01

    Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.

  13. Endogenous ligand of alpha(1) sodium pump, marinobufagenin, is a novel mediator of sodium chloride--dependent hypertension.

    Science.gov (United States)

    Fedorova, Olga V; Talan, Mark I; Agalakova, Natalia I; Lakatta, Edward G; Bagrov, Alexei Y

    2002-03-05

    Digitalis-like sodium pump ligands (SPLs) effect natriuresis via inhibition of renal tubular Na(+),K(+)-ATPase but may induce vasoconstriction. The present study investigated the potential roles of 2 putative endogenous SPLs, an ouabain-like compound (OLC) and an alpha(1) Na(+),K(+)-ATPase inhibitor, marinobufagenin (MBG), in regulating natriuresis and blood pressure (BP) responses to sustained and acute NaCl loading in Dahl salt-sensitive rats (DS). During 4 weeks of an 8% NaCl diet, DS exhibited a progressive increase in MBG renal excretion (66 +/-13 pmol/24 hours at week 4 versus 11 +/- 1 pmol/24 hours at baseline, n=48), which paralleled an increase in systolic BP (174 +/- 10 mm Hg at week 4 versus 110 +/- 2 mm Hg at baseline). By contrast, OLC excretion peaked at week 1 and returned to baseline levels. Administration of an anti-MBG, but not anti-ouabain antibody, to DS after 3 weeks of a high NaCl diet lowered BP (139 +/- 7 versus 175 +/- 5 mm Hg, Psodium and MBG but not that of OLC. An anti-ouabain antibody (n=5) reduced sodium excretion and both OLC and MBG. An initial transient stimulation of OLC induced by NaCl loading of DS precedes an MBG response. A sustained increase in MBG production in DS contributes to the chronic BP elevation induced by a sustained high NaCl intake.

  14. Rat Bite Fever

    Science.gov (United States)

    ... Issues Listen Español Text Size Email Print Share Rat Bite Fever Page Content Article Body Rat-bite fever is a disease that occurs in humans who have been bitten by an infected rat or, in some cases, squirrels, mice, cats, and ...

  15. "Mida jutustaksin tulest..." : [luuletused] / Rita Dahl ; tlk. Elo Viiding

    Index Scriptorium Estoniae

    Dahl, Rita, 1971-

    2008-01-01

    Sisu: "Mida jutustaksin tulest..." ; "Seda tuld ei saa kustutada..." ; "Kevade udu silmis..." ; "Öösel, kui arvad, et oled üksi..." ; "Minu oma on see..." ; Probleemiks koerasitt ; Inimesel ei ole hea olla üksi ; I Pank magab tänaval ; II Kustutatud tuledega buss roomab ; 9. Ootasin, et mu hing muutub koeraks ; Surmamõistetu on ära karanud. Andmed autori kohta lk. 1689

  16. High Salt Intake Increases Blood Pressure in Normal Rats: Putative Role of 20-HETE and No Evidence on Changes in Renal Vascular Reactivity

    Directory of Open Access Journals (Sweden)

    A. Walkowska

    2015-05-01

    Full Text Available Background/Aims. High salt (HS intake may elevate blood pressure (BP, also in animals without genetic salt sensitivity. The development of salt-dependent hypertension could be mediated by endogenous vasoactive agents; here we examined the role of vasodilator epoxyeicosatrienoic acids (EETs and vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE. Methods. In conscious Wistar rats on HS diet systolic BP (SBP was examined after chronic elevation of EETs using 4-[4-(3-adamantan-1-yl-ureido-cyclohexyloxy]-benzoic acid (c-AUCB, a blocker of soluble epoxide hydrolase, or after inhibition of 20-HETE with 1-aminobenzotriazole (ABT. Thereafter, in acute experiments the responses of renal artery blood flow (Transonic probe and renal regional perfusion (laser-Doppler to intrarenal acetylcholine (ACh or norepinephrine were determined. Results. HS diet increased urinary 20-HETE excretion. The SBP increase was not reduced by c-AUCB but prevented by ABT until day 5 of HS exposure. Renal vasomotor responses to ACh or norepinephrine were similar on standard and HS diet. ABT but not c-AUCB abolished the responses to ACh. Conclusions. 20-HETE seems to mediate the early-phase HS diet-induced BP increase while EETs are not engaged in the process. Since HS exposure did not alter renal vasodilator responses to Ach, endothelial dysfunction is not a critical factor in the mechanism of salt-induced blood pressure elevation.

  17. Hippocampal neurogenesis response: What can we expect from two different models of hypertension?

    Science.gov (United States)

    Pedroso, Daniela; Nunes, Ana R; Diogo, Lucília N; Oudot, Carole; Monteiro, Emília C; Brenner, Catherine; Vieira, Helena L A

    2016-09-01

    Hypertension is associated with cerebrovascular disease, white matter lesion and cognitive deficit, both in experimental models and clinical observations. Furthermore, in non-clinical models it is shown that hippocampus is affected by hypertension and hypoxia. Herein, two distinct hypertension models were used to study neurogenic response in hippocampus. Dahl salt sensitive (DSS) rat model is a genetic based idiopathic model, while chronic intermittent hypoxia (CIH) mimics the hypertension observed in patients with obstructive sleep apnea (OSA). Both models are chronic and trigger hypertension. No macroscopic alterations based on histological analysis were found in hippocampus derived from DSS and CIH exposure rats. Nevertheless, in hippocampus derived from CIH-induced hypertensive rats, there was a decrease on neuronal population (MAP2 and NeuN positive cells) and an increase on astrocytic marker GFAP. Accordingly, a higher increase on Ki67 expressing cells was found in dentate gyrus (DG) region, suggesting an enhancement of cell proliferation, concomitantly with an increase of Nestin staining, which indicates the presence of immature neurons under differentiation. While, in hippocampus of DSS rats with or without high salt diet, there was no remarkable difference indicating potential neuronal loss, astrocytic activation or neurogenesis. Furthermore, in both models hypertension did not alter the levels of expression of the stress response enzyme heme oxygenase-1 in DG. These data indicate that intermittent hypoxia might be the key factor involved in neurogenesis modulation in hippocampus. Furthermore, two hypotheses can be explored: (i) activation of neurogenesis is a response against neuronal loss induced by hypertension and/or hypoxia or (ii) neurogenesis can be directly stimulated by hypoxia as a neuroprotective mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. SWEEP Project RAT

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Madsen, Søren; Petersen, L. B.

    This report presents the results from the design analyses made for the clustered suction caisson used as foundation for a Riser Access Tower (RAT). The RAT is intended built next to the K15-FA-1 Platform in the Dutch Sector of the North Sea....

  19. No Evidence of Rat Hepatitis E Virus Excretion in Urine Samples of Rats.

    Science.gov (United States)

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Johne, Reimar; Wakita, Takaji

    2017-05-24

    To investigate whether rat hepatitis E virus (rat HEV) is excreted in the urine of HEV-infected rats, we infected 3 Wistar and 6 nude rats with rat HEV and examined the rat-HEV RNA in serum, fecal, and urine samples. We detected rat-HEV RNA in the serum and fecal samples of all 9 rats but not in any of the urine samples. Our results suggest that in rats, rat HEV is not transmitted via urine.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Longtransplantatie bij de rat

    NARCIS (Netherlands)

    Marck, Klaas Willem

    1983-01-01

    Op grond van de resultaten van het hierboven beschreven onderzoek en de eraan gewijde beschouwingen zijn de volgende conclasies getrokken: 1. Orthotope linkszijdige longtransplantatie bij de rat is operatietechnisch mogelijk. 2. Longpercusiescintigrafie met radioactief ,,gelabelde" microbolletjes is

  2. 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...

  3. Dysglycemia induces abnormal circadian blood pressure variability

    Directory of Open Access Journals (Sweden)

    Kumarasamy Sivarajan

    2011-11-01

    Full Text Available Abstract Background Prediabetes (PreDM in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV. Hypothesis Systemic inflammation and glycemia influence circadian blood pressure variability. Methods Dahl salt-sensitive (S rats (n = 19 after weaning were fed either an American (AD or a standard (SD diet. The AD (high-glycemic-index, high-fat simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG, adipokines (leptin and adiponectin, and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1 and tumor necrosis factor-α (TNF-α] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP and heart rate (HR were recorded by telemetry every 5 minutes during both sleep (day and active (night periods. Pulse pressure (PP was calculated (PP = SBP-DBP. Results [mean(SEM]: The AD fed group displayed significant increase in body weight (after 90 days; p Conclusion These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system which generate abnormal CBPV.

  4. Transient Receptor Potential Melastatin 4 (TRPM4) Contributes to High Salt Diet-Mediated Early-Stage Endothelial Injury.

    Science.gov (United States)

    Ding, Xiao-Qing; Ban, Tao; Liu, Zeng-Yan; Lou, Jie; Tang, Liang-Liang; Wang, Jia-Xin; Chu, Wen-Feng; Zhao, Dan; Song, Bin-Lin; Zhang, Zhi-Ren

    2017-01-01

    The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused

  5. The immune system: role in hypertension.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2013-05-01

    Over the past 20 years it has become recognized that low-grade inflammation plays a role in cardiovascular disease. More recently, participation of the innate and the adaptive immune response in mechanisms that contribute to inflammation in cardiovascular disease has been reported in atherosclerosis and hypertension. Different subsets of lymphocytes and their cytokines are involved in vascular remodelling and hypertensive renal disease as well as heart disease. Effector T cells including T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (interleukin-4 producing), as well as Th17 (which produce interleukin-17), and T suppressor lymphocytes such as T regulatory cells, which express the transcription factor forkhead box P3, participate respectively as pro- and anti-inflammatory cells, and mediate effects of angiotensin II and mineralocorticoids. Involvement of immune mechanisms in cardiac, vascular, and renal changes in hypertension has been demonstrated in many experimental models, an example being the Dahl-salt sensitive rat and the spontaneously hypertensive rat. How activation of immunity is triggered remains unknown, but neoantigens could be generated by elevated blood pressure through damage-associated molecular pattern receptors or other mechanisms. When activated, Th1 may contribute to blood pressure elevation by affecting the kidney, vascular remodelling of blood vessels directly via effects of the cytokines produced, or through their effects on perivascular fat. T regulatory cells protect from blood pressure elevation acting on similar targets. These novel findings may open the way for new therapeutic approaches to improve outcomes in hypertension and cardiovascular disease in humans. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  6. Transient Receptor Potential Melastatin 4 (TRPM4 Contributes to High Salt Diet-Mediated Early-Stage Endothelial Injury

    Directory of Open Access Journals (Sweden)

    Xiao-Qing Ding

    2017-02-01

    Full Text Available Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4 channel plays a role in high salt diet (HSD-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs. Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1, vascular cell adhesion protein 1 (VCAM-1, and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2 and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular

  7. Acetic acid modulates spike rate and spike latency to salt in peripheral gustatory neurons of rats

    Science.gov (United States)

    Breza, Joseph M.

    2012-01-01

    Sour and salt taste interactions are not well understood in the peripheral gustatory system. Therefore, we investigated the interaction of acetic acid and NaCl on taste processing by rat chorda tympani neurons. We recorded multi-unit responses from the severed chorda tympani nerve (CT) and single-cell responses from intact narrowly tuned and broadly tuned salt-sensitive neurons in the geniculate ganglion simultaneously with stimulus-evoked summated potentials to signal when the stimulus contacted the lingual epithelium. Artificial saliva served as the rinse and solvent for all stimuli [0.3 M NH4Cl, 0.5 M sucrose, 0.1 M NaCl, 0.01 M citric acid, 0.02 M quinine hydrochloride (QHCl), 0.1 M KCl, 0.003–0.1 M acetic acid, and 0.003–0.1 M acetic acid mixed with 0.1 M NaCl]. We used benzamil to assess NaCl responses mediated by the epithelial sodium channel (ENaC). The CT nerve responses to acetic acid/NaCl mixtures were less than those predicted by summing the component responses. Single-unit analyses revealed that acetic acid activated acid-generalist neurons exclusively in a concentration-dependent manner: increasing acid concentration increased response frequency and decreased response latency in a parallel fashion. Acetic acid suppressed NaCl responses in ENaC-dependent NaCl-specialist neurons, whereas acetic acid-NaCl mixtures were additive in acid-generalist neurons. These data suggest that acetic acid attenuates sodium responses in ENaC-expressing-taste cells in contact with NaCl-specialist neurons, whereas acetic acid-NaCl mixtures activate distinct receptor/cellular mechanisms on taste cells in contact with acid-generalist neurons. We speculate that NaCl-specialist neurons are in contact with type I cells, whereas acid-generalist neurons are in contact with type III cells in fungiform taste buds. PMID:22896718

  8. in albino rats

    African Journals Online (AJOL)

    hope&shola

    2010-09-23

    Sep 23, 2010 ... cell carcinoma, malignant fibrous histiocytoma, atrophy, fibro- sarcoma, chronic inflammation, squamous cell carcinoma in situ and osteoma at the end of the experiment. The lesions were then diagnosed according to the histopathological changes by using ether to anesthetize the rats. All the animals were ...

  9. CAMALDULENSIS IN RATS

    African Journals Online (AJOL)

    DR. AMIN

    ABSTRACT. Sub – acute toxicity study of the aqueous leaf extract of Eucalyptus camaldulensis was carried out on albino rats. Doses of 250mg, 500mg, 750mg and 1000mg per kilogram body weight of the extract were administered orally for 21 days. The activities of Alanine Aminotransferase (ALT),. Aspartate ...

  10. The academic rat race

    DEFF Research Database (Denmark)

    Landes, Xavier; Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2012-01-01

    : an increased pressure to produce articles (in peer-reviewed journals) has created an unbalanced emphasis on the research criterion at the expense of the latter two. More fatally, this pressure has turned academia into a rat race, leading to a deep change in the fundamental structure of academic behaviour...

  11. Running the rat race

    African Journals Online (AJOL)

    SASA Refresher Course Texts: Running the rat race. 74. 2014;20(1) ... and feelings of existential despair which characterise the human condition, to emerge as they are today: whole, satisfied, well .... Pure efficiency only exists on paper. In the ...

  12. Rat on Mars

    Science.gov (United States)

    2004-01-01

    This image taken on Mars by the panoramic camera on the Mars Exploration Rover Opportunity shows the rover's rock abrasion tool, also known as 'rat' (circular device in center), located on its instrument deployment device, or 'arm.' The image was acquired on the ninth martian day or sol of the rover's mission.

  13. Behavior modulation of rats to a robotic rat in multi-rat interaction.

    Science.gov (United States)

    Shi, Qing; Ishii, Hiroyuki; Tanaka, Katsuaki; Sugahara, Yusuke; Takanishi, Atsuo; Okabayashi, Satoshi; Huang, Qiang; Fukuda, Toshio

    2015-09-28

    In this paper, we study the behavioral response of rats to a robotic rat during multi-rat interaction. Experiments are conducted in an open-field where a robotic rat called WR-5 is put together with three laboratory rats. WR-5 is following one rat (target), while avoiding the other two rats (outside observers) during interaction. The behavioral characteristics of each target rat is evaluated by scoring its locomotor activity and frequencies of performing rearing, body grooming and mounting actions. Additionally, the frequency of being mounted by other rats is also measured. Experimental results show that the target becomes more active after interaction. The rat species, with more active behavioral characteristics, is more susceptible to being adjusted by the robot. The increased time spent by the outside observers in the vicinity of the robot indicates that a biomimetic robot has the promise for modulating rat behavior even without direct interaction. Thus, this study provide a novel approach to shaping the sociality of animals living in groups.

  14. Modified carrageenan. 2. Hydrolyzed crosslinked kappa-carrageenan-g-PAAm as a novel smart superabsorbent hydrogel with low salt sensitivity.

    Science.gov (United States)

    Hosseinzadeh, H; Pourjavavdi, A; Zohuriaan-Mehr, M J

    2004-01-01

    A novel pH-responsive superabsorbing hydrogel based on K-carrageenan (kappaC) was prepared through polyacrylamide crosslinking grafting followed by alkaline hydrolysis. The hydrogel structure was confirmed using FT-IR spectroscopy. The hydrolysis conditions were systematically optimized to obtain a hydrogel with maximum swelling capacity. Thus, the reaction variables, including the hydrolysis time and temperature, concentration of sodium hydroxide, amount of hydrogel hydrolyzed and post-neutralization pH, were optimized. The swelling measurements of the hydrogels were conducted in 0.15 M aqueous solutions of LiCl, NaCl, KCI, CaCl2 and AlCl3. As observed for the hydrolyzed hydrogel (H-carragPAM), it was found that a 'charge screening' action of small cations and carboxylate anions affected the swelling in univalent salt solutions. In the case of the non-hydrolyzed hydrogel (carragPAM), however, a converse trend was observed. As a result, carragPAM and H-carragPAM superabsorbent hydrogels showed a maximum swelling of 45 and 135 g/g in LiCl and KCl solutions, respectively. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as anti-salt superabsrbents. The swelling of superabsorbing hydrogels was examined in buffer solutions with pH values ranging between 1 and 13. The H-carragPAM hydrogel exhibited a pH-responsie character so that a swelling-deswelling pulsatile behavior was recorded at pH 4 and 9. The swelling kinetics of H-carragPAM were preliminary investigated.

  15. The proteome response of salt-resistant and salt-sensitive barley genotypes to long-term salinity stress

    NARCIS (Netherlands)

    Fatehi, F.; Hosseinzadeh, A.; Alizadeh, H.; Brimavandi, T.; Struik, P.C.

    2012-01-01

    Responses of plants to salinity stress and the development of salt tolerance are extremely complex. Proteomics is a powerful technique to identify proteins associated with a particular environmental or developmental signal. We employed a proteomic approach to further understand the mechanism of

  16. Salt sensitivity of the morphometry of Artemia franciscana during development: a demonstration of 3D critical windows.

    Science.gov (United States)

    Mueller, Casey A; Willis, Eric; Burggren, Warren W

    2016-02-01

    A 3D conceptual framework of 'critical windows' was used to examine whether the morphometry of Artemia franciscana is altered by salinity exposure during certain key periods of development. Artemia franciscana were hatched at 20 ppt (designated control salinity) and were then exposed to 10, 30, 40 or 50 ppt either chronically (days 1-15) or only on days 1-6, 7-9, 10-12 or 13-15. On day 15, maturity was assessed and morphometric characteristics, including mass, total body length, tail length and width, length of the third swimming appendage and eye diameter, were measured. Maturation and morphometry on day 15 were influenced by the exposure window and salinity dose. Artemia franciscana were generally larger following exposure to 10 and 40 ppt during days 1-6 and 7-9 when compared with days 10-12 and 13-15, in part due to a higher percentage of mature individuals. Exposure to different salinities on days 1-6 produced the greatest differences in morphometry, and thus this appears to be a period in development when A. franciscana is particularly sensitive to salinity. Viewing the developmental window as three-dimensional allowed more effective visualization of the complex interactions between exposure window, stressor dose and the magnitude of morphometric changes in A. franciscana. © 2016. Published by The Company of Biologists Ltd.

  17. Laughing rats are optimistic.

    Directory of Open Access Journals (Sweden)

    Rafal Rygula

    Full Text Available Emotions can bias human decisions- for example depressed or anxious people tend to make pessimistic judgements while those in positive affective states are often more optimistic. Several studies have reported that affect contingent judgement biases can also be produced in animals. The animals, however, cannot self-report; therefore, the valence of their emotions, to date, could only be assumed. Here we present the results of an experiment where the affect-contingent judgement bias has been produced by objectively measured positive emotions. We trained rats in operant Skinner boxes to press one lever in response to one tone to receive a food reward and to press another lever in response to a different tone to avoid punishment by electric foot shock. After attaining a stable level of discrimination performance, the animals were subjected to either handling or playful, experimenter-administered manual stimulation - tickling. This procedure has been confirmed to induce a positive affective state in rats, and the 50-kHz ultrasonic vocalisations (rat laughter emitted by animals in response to tickling have been postulated to index positive emotions akin to human joy. During the tickling and handling sessions, the numbers of emitted high-frequency 50-kHz calls were scored. Immediately after tickling or handling, the animals were tested for their responses to a tone of intermediate frequency, and the pattern of their responses to this ambiguous cue was taken as an indicator of the animals' optimism. Our findings indicate that tickling induced positive emotions which are directly indexed in rats by laughter, can make animals more optimistic. We demonstrate for the first time a link between the directly measured positive affective state and decision making under uncertainty in an animal model. We also introduce innovative tandem-approach for studying emotional-cognitive interplay in animals, which may be of great value for understanding the emotional

  18. Electroejaculation of chimeric rats

    OpenAIRE

    McCoy, Marina R.; Montonye, Daniel; Bryda, Elizabeth C.

    2013-01-01

    With the advent of genetic engineering of rodents came the need to assess fertility and germline competency, especially in chimeric rodents generated using embryonic stem cells. Traditional methods rely on natural mating and progeny testing, which is time- and cost-intensive. Electroejaculation is a faster method of collecting sperm for genetic analysis and offers the additional benefit of using fewer animals. This column describes a refined electroejaculation technique for chimeric rats usin...

  19. Gravitational Biology: The Rat Model

    Science.gov (United States)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  20. Generation of Hprt-disrupted rat through mouse←rat ES chimeras

    OpenAIRE

    Ayako Isotani; Kazuo Yamagata; Masaru Okabe; Masahito Ikawa

    2016-01-01

    We established rat embryonic stem (ES) cell lines from a double transgenic rat line which harbours CAG-GFP for ubiquitous expression of GFP in somatic cells and Acr3-EGFP for expression in sperm (green body and green sperm: GBGS rat). By injecting the GBGS rat ES cells into mouse blastocysts and transplanting them into pseudopregnant mice, rat spermatozoa were produced in mouse?rat ES chimeras. Rat spermatozoa from the chimeric testis were able to fertilize eggs by testicular sperm extraction...

  1. model in female wistar rats

    African Journals Online (AJOL)

    2013-12-31

    Dec 31, 2013 ... cyclodextrin on wister rats : histopathologic analoges. Fundan Clin. Pharmacol.; 23(6) :747-755. Sandor, V., Cuparencu, B., Dumitrascu, L.D., Birt, A.M. and Krausz, L.T. (2006). Protective effects of amphetamine on gastric ulcerations induced by indomethacin in rats. World J. Gastroenterol.; 12(44): ...

  2. Do rats have orgasms?

    Directory of Open Access Journals (Sweden)

    James G. Pfaus

    2016-10-01

    Full Text Available Background: Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method: Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs in other species: 1 physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2 short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3 long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results: Both male and female rats display behavioral patterns consistent with OLRs. Conclusions: The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research.

  3. Do rats have orgasms?

    Science.gov (United States)

    Pfaus, James G; Scardochio, Tina; Parada, Mayte; Gerson, Christine; Quintana, Gonzalo R; Coria-Avila, Genaro A

    2016-01-01

    Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs) in other species: 1) physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2) short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3) long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Both male and female rats display behavioral patterns consistent with OLRs. The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research.

  4. Do rats have orgasms?

    Science.gov (United States)

    Pfaus, James G.; Scardochio, Tina; Parada, Mayte; Gerson, Christine; Quintana, Gonzalo R.; Coria-Avila, Genaro A.

    2016-01-01

    Background Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs) in other species: 1) physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2) short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3) long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results Both male and female rats display behavioral patterns consistent with OLRs. Conclusions The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research. PMID:27799081

  5. Electroejaculation of chimeric rats.

    Science.gov (United States)

    McCoy, Marina R; Montonye, Daniel; Bryda, Elizabeth C

    2013-06-01

    With the advent of genetic engineering of rodents came the need to assess fertility and germline competency, especially in chimeric rodents generated using embryonic stem cells. Traditional methods rely on natural mating and progeny testing, which is time- and cost-intensive. Electroejaculation is a faster method of collecting sperm for genetic analysis and offers the additional benefit of using fewer animals. This column describes a refined electroejaculation technique for chimeric rats using light gas anesthesia and a custom-made platform for sperm collection.

  6. Serum testosterone concentration in chloroquine- treated rats ...

    African Journals Online (AJOL)

    ONOS

    2010-07-05

    Jul 5, 2010 ... The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2.

  7. Serum testosterone concentration in chloroquinetreated rats: effects ...

    African Journals Online (AJOL)

    The effects of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) were studied on serum testosterone concentration in chloroquine-treated rats. Thirty five (35) adult male rats weighing 160 - 200 g were divided into seven groups of five (5) rats each. Group I rats served as the control and received 2 ml/kg of normal ...

  8. PENICILLIN EPILEPSY IN RATS

    Directory of Open Access Journals (Sweden)

    Voja Pavlović

    2004-12-01

    Full Text Available The purpose of this study is to test, in a model of experimental penicillin epilepsy, a hypothesis of primary and dominant role of cortex in genesis of epileptic discharges, by using recordings of electrocorticograms (EcoG. The experiments were made with around two and a half old male rats. The rats were divided into four groups of five animals each. In the case of the first group, antibiotics were applied intraperitoneally (i.p.. Epileptic generalized discharges of this group were not registered until administering a dosage of antibiotics higher than 1.8 x 106 IU/kg. In the second group, application of a dosage of 1.2 x 106 IU/kg resulted in individual discharges. In the third group, antibiotics were applied intracortically (i.c. in a dosage of 50 IU and caused individual discharges without big seizures. The fourth group needed a dosage of 100 IU/kg of penicillin applied i.c. to develop a big seizure. Discharges in the first three groups were registered first as unilateral with a subsequent development of bilateral synchrony. In the case of the fourth group, immediately and abruptly after the application of penicillin big seizures developed violently and repeated several times. We consider that the very implantation of electrodes provokes occurrence of discharging.

  9. The Rat Race

    CERN Multimedia

    Stephen Haywood

    Dear Muriel, Being an animal, you are probably more familiar with rats than most of us. Yet it seems to me that our Community (not just ATLAS) is stuck in a huge "rat race". I am somewhat mystified as to how we have got ourselves into this and I wonder whether you or your readers could explain this - I give my own observations below. In HEP and ATLAS specifically, we are all working long hours and we are all becoming exhausted. There are people at Point 1 who are working day and night, every day of the week; there are people writing software who send emails round the clock, including weekends. It is one thing to have bursts of activity which require us to put in some longer hours, but in ATLAS, the bursts last months or years. I have been on ATLAS 14 years and it has felt like one endless rush. Why do we do this? We are all highly motivated, we love our work and want to succeed individually and collectively. We are parts of various teams, and we do not want to let the side down. We worked hard at school an...

  10. Postural development in rats.

    Science.gov (United States)

    Lelard, T; Jamon, M; Gasc, J-P; Vidal, P-P

    2006-11-01

    Mammals adopt a limited number of postures during their day-to-day activities. These stereotyped skeletal configurations are functionally adequate and limit the number of degrees of freedom to be controlled by the central nervous system. The temporal pattern of emergence of these configurations in altricial mammals is unknown. We therefore carried out an X-ray study in unrestrained rats from birth (P0) until postnatal day 23 (P23). The X-rays showed that many of the skeletal configurations described in adult rodents were already present at birth. By contrast, limb placement changed abruptly at around P10. These skeletal configurations, observed in anesthetized pups, required the maintenance of precise motor control. On the other hand, motor control continued to mature, as shown by progressive changes in resting posture and head movements from P0 to P23. We suggest that a few innate skeletal configurations provide the necessary frames of reference for the gradual construction of an adult motor repertoire in altricial mammals, such as the rat. The apparent absence of a requirement for external sensorial cues in the maturation of this repertoire may account for the maturation of postural and motor control in utero in precocial mammals (Muir et al., 2000 for a review on the locomotor behavior of altricial and precocial animals).

  11. Oxidative Stress in Aged Rats

    Directory of Open Access Journals (Sweden)

    Damisela Ramírez Ramírez

    2013-12-01

    Full Text Available Background: aging is one of the major problems that the world is facing today due to its impact on all areas of society. Objective: to determine the concentrations of advanced oxidation protein products and malondialdehyde as indicators of oxidative damage and to determine the antioxidant defense capacity of the enzymes superoxide dismutase, catalase and the reduced glutathione concentration in aged rats. Methods: a total of 20 male Wistar rats with a body weight of approximately 200 to 250 grams were selected to form two groups with 10 young adult rats and 10 old rats. 2 ml of blood was drawn from the paranasal sinus. The sample was collected in 5 ml vials and after being homogenized, it was sent to the Biomedical Research Center, where it was used to assess the following oxidative stress variables: degree of oxidative damage and antioxidant defense level. An analysis of variance was performed to study the behavior of the different groups. Differences were considered significant when P value was less than 0.05. Results: no significant changes were found in the concentrations of malondialdehyde and glutathione, as well as in the superoxide dismutase and catalase activity in aged rats compared to young. Concentration of advanced oxidation protein products increased significantly in aged rats. Conclusions: aged rats showed an increase in oxidative damage to proteins. Antioxidant defense capacity of the enzymes superoxide dismutase and catalase and reduced glutathione concentration showed no changes.

  12. Rat traps: filling the toolbox for manipulating the rat genome

    NARCIS (Netherlands)

    van Boxtel, R.; Cuppen, E.

    2010-01-01

    The laboratory rat is rapidly gaining momentum as a mammalian genetic model organism. Although traditional forward genetic approaches are well established, recent technological developments have enabled efficient gene targeting and mutant generation. Here we outline the current status, possibilities

  13. Population Structure of Rat-Derived Pneumocystis carinii in Danish Wild Rats

    DEFF Research Database (Denmark)

    Palmer, Robert J.; Settnes, Osvald P.; Lodal, Jens

    2000-01-01

    The rat model of Pneumocystis carinii pneumonia is frequently used to study human P. carinii infection, but there are many differences between the rat and human infections. We studied naturally acquired P. carinii in wild rats to examine the relevance of the rat model for human infection. P. cari...

  14. TRANSFER OF A RESPONSE TO NAIVE RATS BY INJECTION OF RIBONUCLEIC ACID EXTRACTED FROM TRAINED RATS.

    Science.gov (United States)

    BABICH, F R; JACOBSON, A L; BUBASH, S; JACOBSON, A

    1965-08-06

    Rats were trained in a Skinner box to approach the food cup when a distinct click was sounded. Ribonucleic acid was extracted from the brains of these rats and injected into untrained rats. The untrained rats then manifested a significant tendency (as compared with controls) to approach the food cup when the click, unaccompanied by food, was presented.

  15. Whey Protein Concentrate and Dexamethasone Protected Rat ...

    African Journals Online (AJOL)

    Dr Olaleye

    ABSTRACT. The possible radioprotective effect of Immunocal® (whey protein]) supplement and dexamethasone on gamma-irradiated cerebellar tissue of Wistar rat was investigated in this study. Forty male albino rats were acclimatized and randomized into four groups of 10 animals each. Group I rats served as control; ...

  16. seed on haematological parameters of albino rats

    African Journals Online (AJOL)

    Dr Ejere

    2015-06-23

    Jun 23, 2015 ... albino rats (Rattus novergicus). Ejere, Vincent C.*, Ugwu, Godwin C., Chukwuka, Christian O. and Nnamonu, Emmanuel I. ... Similarly, lectin from M. sloanei has been reported as an effective and suitable cell ... male albino rats were then assigned into four groups (A, B, C, and. D) of 12 rats per group.

  17. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  18. Tuberculosis Detection by Giant African Pouched Rats

    Science.gov (United States)

    Poling, Alan; Weetjens, Bart; Cox, Christophe; Beyene, Negussie; Durgin, Amy; Mahoney, Amanda

    2011-01-01

    In recent years, operant discrimination training procedures have been used to teach giant African pouched rats to detect tuberculosis (TB) in human sputum samples. This article summarizes how the rats are trained and used operationally, as well as their performance in studies published to date. Available data suggest that pouched rats, which can…

  19. Whey protein concentrate and dexamethasone protected rat ...

    African Journals Online (AJOL)

    The possible radioprotective effect of Immunocal® (whey protein]) supplement and dexamethasone on gamma-irradiated cerebellar tissue of Wistar rat was investigated in this study. Forty male albino rats were acclimatized and randomized into four groups of 10 animals each. Group I rats served as control; Group II: ...

  20. Chronic study on BHT in rats

    DEFF Research Database (Denmark)

    Würtzen, G.; Olsen, P.

    1986-01-01

    Groups of 40, 29, 39 and 44 F0 rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated, and groups of 100, 80, 80 and 100 F1 rats of each sex wer...

  1. Rat penis as a replantation model.

    Science.gov (United States)

    Karamürsel, Sebat; Karamürsel, Tamer; Celebioğlu, Selim

    2005-11-01

    The aim of this study is to assess the feasibility of rat penile replantation as a new microsurgical training model. The study was performed in 2 parts. ANATOMIC STUDIES: Fifteen Wistar albino rats were used to study and document the penile vascular anatomy. In 5 rats, dissections were performed after colored silicone injections, while 5 rats were operated under anesthesia to develop the strategy of flap elevation. In the remaining 5 rats, microangiographic study was performed with silicone-lead oxide mixture. FLAP STUDIES: As flap studies in 5 rats, penis were elevated based on right-side internal pudendal artery and internal pudendal vein and resutured. In 6 rats, penis were elevated as free flaps, and in 3 rats the penis were implanted in right thigh of the rats being the femoral artery and vein recipient. In the remaining 3 rats, penis were resutured in their original place, with saphenous artery and vein being the recipient and rerouted to the pubic region. At postoperative fifth day, the penis were examined for viability, and selected ones were histologically examined. Rat penis has a dual blood supply from bilateral internal pudendal arteries. Venous drainage is via both crural veins and dorsal vein. One side of the internal pudendal artery and anastomotic vein (branch of pudendal plexus) may be used as the vascular pedicle of the flap. Rat penis may be successfully elevated as a free flap and also may be replanted in its original place.

  2. Sleep in spontaneous dwarf rats.

    Science.gov (United States)

    Peterfi, Zoltan; Obal, Ferenc; Taishi, Ping; Gardi, Janos; Kacsoh, Balint; Unterman, Terry; Krueger, James M

    2006-09-07

    Spontaneous dwarf rats (SDRs) display growth hormone (GH) deficiency due to a mutation in the GH gene. This study investigated sleep in SDRs and their somatotropic axis and compared to Sprague-Dawley rats. SDRs had almost undetectable levels of plasma GH. Hypothalamic GH-releasing hormone (GHRH) mRNA was increased, whereas GHRH-receptor (GHRH-R) and somatostatin mRNAs were decreased in SDRs. Hypothalamic GHRH and somatostatin peptide content decreased in SDRs. Quantitative immunohistochemistry for GHRH and GHRH-R corroborated and extended these findings. In the arcuate nucleus, the number of GHRH-positive cells was significantly higher, whereas GHRH-R-positive perikarya were diminished in SDRs. Cortical GHRH and GHRH-R measurements showed similar expression characteristics as those found in the hypothalamus. SDRs had less rapid eye movement sleep (REMS) and more non-REMS (NREMS) than the control rats during the light period. The electroencephalogram (EEG) delta and theta power decreased during NREMS in the SDRs. After 4-h of sleep deprivation, SDRs had a significantly reduced REMS rebound compared to the controls, whereas NREMS rebound was normal in SDRs. The enhancement in delta power was significantly less than in the control group during recovery sleep. Intracerebroventricular (icv) administration of GHRH promoted NREMS in both strains of rats; however, increased REMS and EEG delta activity was observed only in control rats. Icv injection of insulin-like growth factor 1 increased NREMS in control rats, but not in the SDRs. These results support the ideas that GHRH is involved in NREMS regulation and that GH is involved in the regulation of REMS and in EEG slow wave activity regulation during NREMS.

  3. Voluntary Sleep Loss in Rats

    Science.gov (United States)

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  4. A Focused Microarray for Screening Rat Embryonic Stem Cell Lines

    OpenAIRE

    Hong, James; He, Hong; Bui, Phuoc; Ryba-White, Ben; Rumi, Mohammad A.K.; Soares, Michael J.; Dutta, Debasree; Paul, Soumen; Kawamata, Masaki; Ochiya, Takahiro; Ying, Qi-Long; Rajanahalli, Pavan; Mark L. Weiss

    2012-01-01

    Here, we describe a focused microarray for screening rat embryonic stem cells (ESCs) and provide validation data that this array can distinguish undifferentiated rat ESCs from rat trophoblast stem (TS) cells, rat extraembryonic endoderm cells, mouse embryonic fibroblast feeder cells, and differentiated rat ESCs. Using this tool, genuine rat ESC lines, which have been expanded in a conventional rat ESC medium containing two inhibitors (2i), for example, glycogen synthase kinase 3 (GSK3) and mi...

  5. Swimming-based pica in rats.

    Science.gov (United States)

    Nakajima, Sadahiko

    2016-09-01

    We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats. Copyright © 2016. Published by Elsevier B.V.

  6. Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses.

    Science.gov (United States)

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Yasuda, Shumpei P; Yoshimatsu, Kumiko; Arikawa, Jiro; Takeda, Naokazu; Wakita, Takaji

    2013-04-12

    To determine whether or not rats are susceptible to hepatitis E virus (HEV) infection, each of group containing three laboratory rats (Wistar) were experimentally inoculated with genotypes 1, 3, 4 and rat HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA, respectively. The virus infection was monitored up to 3 months after inoculation. None of the serum or stool samples collected from the rats inoculated with G1, G3, or G4 HEV indicated positive sign for virus replication. Although no alteration was observed in ALT level, rat HEV RNA was detected in stools from both of the rats inoculated with rat HEV, and both rats were positive for anti-rat HEV IgG and IgM from 3 weeks after inoculation. These results demonstrated that rats are susceptible to rat HEV but not to G1, G3, and G4 HEV. We also confirm that the nude rats were useful for obtaining a large amount of rat HEV and that the rat HEV was transmitted by the fecal-oral route. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Immunochemistry of Rat Lung Tumorigenesis

    Science.gov (United States)

    1983-01-01

    3 * f.*. b; 3 - .’ • ~ -•. -. 3 *. 3 . , . 3• • . .• . • used in this set of experiments. Animals were anesthetized with methoxyflurane and...by supplying methoxyflurane to the rats’ noses in a small plastic funnel. The surgery consisted of making a small slit in the neck and injecting the

  8. wheat flour (dubbie) in rats

    African Journals Online (AJOL)

    2 Central Food Technological Research Institute. Mysore 570013, Mysore, India. ABSTRACT: Anaemic rats were fed on diets containing sour dough bread. (Di/'0 dabbo) or porridge prepared from soy-fortified wheat flour (Dubbie) as the source of nonheme iron. The criteria used to determine the relative biological.

  9. CCl4 cirrhosis in rats

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1991-01-01

    Cirrhosis of the rat liver was induced by a 12 week individualized CCl4/phenobarbital treatment. After treatment, all surviving animals (81%) showed cirrhosis of the liver. The cirrhosis induced was irreversible when evaluated 24 weeks after cessation of treatment. Quantitative liver function...

  10. The rat GPRC6A

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Burhenne, Nicole; Christiansen, Bolette

    2007-01-01

    GPRC6A is a novel member of family C of G protein-coupled receptors with so far elusive biological function. GPRC6A has been described in human and mouse as a promiscuous l-alpha-amino acid receptor. We now report the cloning, expression analysis and, functional characterization of the rat orthol...

  11. induced hepatic injury in rats

    African Journals Online (AJOL)

    Toxicological evaluation of Thymelaea hirsuta and protective effect against CCl 4 -induced hepatic injury in rats. ... There were no significant differences in red blood cells count (p<0.05), in Hemoglobin and Hematocrit serum levels but a significant increase in white blood cells count (p<0.001) and in platelets (p< 0.05) for all ...

  12. ideal hepatotoxicity model in rats using carbon tetrachloride (ccl4)

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. A study to produce ideal Hepatotoxicity rats' models using varying concentrations of carbon tetrachloride (CCl4) was carried out. A total of seventy five rats were divided into five (5) groups of twenty five (25) rats each; rats in group I are negative control, were not induced with lipid peroxidation. Rats in groups II, ...

  13. Voluntary Sleep Loss in Rats.

    Science.gov (United States)

    Oonk, Marcella; Krueger, James M; Davis, Christopher J

    2016-07-01

    Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. © 2016 Associated Professional Sleep Societies, LLC.

  14. Kangaroo rat bone compared to white rat bone after short-term disuse and exercise

    Science.gov (United States)

    Muths, E.; Reichman, O. J.

    1996-01-01

    Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly “stronger” bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.

  15. Advances on genetic rat models of epilepsy

    Science.gov (United States)

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  16. Advances on genetic rat models of epilepsy.

    Science.gov (United States)

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  17. Sevoflurane-induced pica in female rats.

    Science.gov (United States)

    Yamamoto, Kouichi; Yamamoto, Emiri; Sugimoto, Toru; Sagakami, Takuya; Yamatodani, Atsushi

    2016-05-01

    We examined the effects of volatile anesthetics on pica, which can be used to assess nausea and vomiting in rats. We found that inhalation anesthesia with sevoflurane significantly induced pica in female but not male rats. Among the female rats, young rats (8 weeks old) were more susceptible to its induction than adult rats (20 weeks old) with ovariectomy or sham-surgery. Anti-emetic drugs that are used to prevent postoperative nausea and vomiting (PONV) inhibited the pica. These results suggest that sevoflurane-induced pica in young female rats has the potential to be an animal model of PONV in humans. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  18. Cardiovascular end-organ damage in Ren-2 transgenic rats compared to spontaneously hypertensive rats

    NARCIS (Netherlands)

    Pinto, YM; Buikema, H; vanGilst, WH; vanGeel, PP; deGraeff, PA; Wagner, J; Paul, M

    To compare hypertensive end-organ damage in two genetic forms of hypertension we assessed cardiovascular function in two rat strains of generic hypertension: transgenic rats overexpressing the mouse Ren-2 gene [(TGR(mREN2)27]) and blood pressure matched spontaneously hypertensive rats (SHR). Despite

  19. Unraveling the Obesity of OLETF Rats

    OpenAIRE

    Moran, Timothy H.

    2007-01-01

    Cholecystokinin (CCK) is a brain gut peptide that plays an important role in satiety. CCK inhibits food intake by reducing meal size. CCK’s satiety actions are mediating through its interaction with CCK1 receptors. Otsuka Long Evans Tokushima Fatty (OLETF) rats are a CCK1 receptor knockout model that allows the study of multiple CCK functions. OLETF rats are hyperphagic with the hyperphagia expressed as a significant increase in the size of meals. OLETF rat obesity is secondary to the hyperph...

  20. The thymus reconstituted nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B

    1987-01-01

    The monoclonal antibodies OX6, OX19, W3/13, OX7, OX8, and W3/25 were used to gain information about the distribution of different lymphocyte subpopulations in peripheral lymphoid organs of neonatally isogeneic and allogeneic thymus reconstituted nude rats. Splenic mitogen responsiveness, xenogeneic...... skin rejection, and antibody titers were also measured in the same groups of animals. The experiments showed that both allogeneic and isogeneic thymus grafting cause a significant amplification of cells in the different T lymphocyte subpopulations. The functional tests, however, indicate that the T...... cell response is far better following isografting. We, therefore, conclude that isogeneic thymus grafting is an easy method of reconstituting the nude rat immunologically....

  1. Isolation of rat adrenocortical mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  2. Phosphodiesterases in the rat ovary

    DEFF Research Database (Denmark)

    Petersen, Tonny Studsgaard; Stahlhut, Martin; Andersen, Claus Yding

    2015-01-01

    Phosphodiesterases (PDEs) are important regulators of the intracellular cAMP concentration, which is a central second messenger that affects a multitude of intracellular functions. In the ovaries, cAMP exerts diverse functions, including regulation of ovulation and it has been suggested...... that augmented cAMP levels stimulate primordial follicle growth. The present study examined the gene expression, enzyme activity and immunolocalization of the different cAMP hydrolysing PDEs families in the rat ovary. Further, the effect of PDE4 inhibition on primordial follicle activation in cultured neonatal...... rat ovaries was also evaluated. We found varied expression of all eight families in the ovary with Pde7b and Pde8a having the highest expression each accounting for more than 20% of the total PDE mRNA. PDE4 accounted for 15-26% of the total PDE activity. Immunoreactive PDE11A was found in the oocytes...

  3. A survey of the East Palaearctic Lycosidae (Araneae. 9. Genus Xerolycosa Dahl, 1908 (Evippinae

    Directory of Open Access Journals (Sweden)

    Yuri Marusik

    2011-07-01

    Full Text Available Three species of Xerolycosa: X. nemoralis (Westring, 1861, X. miniata (C.L. Koch, 1834 and X. mongolica (Schenkel, 1963, occurring in the Palaearctic Region are surveyed, illustrated and redescribed. Arctosa mongolica Schenkel, 1963 is removed from synonymy with X. nemoralis and transferred to Xerolycosa, and the new combination Xerolycosa mongolica (Schenkel, 1963 comb. n. is established. One new synonymy, Xerolycosa undulata Chen, Song et Kim, 1998 syn. n. from Heilongjiang = X. mongolica (Schenkel, 1963, is proposed. In addition, one more new combination is established, Trochosa pelengena (Roewer, 1960 comb. n., ex Xerolycosa.

  4. Roald Dahl's "Charlie and the Chocolate Factory": A Classic That Slipped by the Gatekeepers.

    Science.gov (United States)

    West, Mark I.

    1999-01-01

    Considers how the book "Charlie and the Chocolate Factory"'s achievement of the status of a modern classic provides evidence that children's collective voices can sometimes cause the walls erected by the field's adult gatekeepers to come tumbling down. Discusses reasons for the popularity and controversy surrounding the book. (SC)

  5. Comparison of Pointing Control Systems Utilizing Dahl and Coulomb Friction Model Compensation

    Science.gov (United States)

    1991-12-01

    Himmel Friction Compensator 1-4 1-2 Mathematical Model for the Walrath Friction Compensator 1-4 2-1 Plot of Ideal Friction vs Time 2-1 2-2 Typical...There are two papers that relate closely to this research effort. One was written by Lewis C. Himmel , et. al., of The Aerospace Co. (2:642-643) and the... Himmel and company used a second order difference scheme to estimate the friction acceleration. Walrath, on the other hand, developed an adaptive

  6. LIEER OF WISTAR RAT MODELS

    African Journals Online (AJOL)

    homeostasis synthesised in the liver, has been raised in cases of impaired liver. fimcflun. ... Bil rats served as co:|rtrols, while Eflmts more test animals. The .... between 13D-15tJg were used. These anin1alswe1'edividedlntotwo[2]n1eiJ1 groups: the control group and the test animals. Each group comprised sixty [60].

  7. Renal function in streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Jensen, P K; Christiansen, J S; Steven, K

    1981-01-01

    Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion...... to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mm......-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow...

  8. Automatic Training of Rat Cyborgs for Navigation

    Science.gov (United States)

    Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

    2016-01-01

    A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs. PMID:27436999

  9. Hyperparathyroidism is augmented by ovariectomy in Nagase analbuminemic rats.

    Science.gov (United States)

    Inaba, M; Morii, H; Katsumata, T; Goto, H; Ishimura, E; Kawagishi, T; Kamao, M; Okano, T; Nishizawa, Y

    2000-06-01

    The role of albumin in bone metabolism was studied in Nagase analbuminemic (NA) rats. Serum calcium (Ca), inorganic phosphate (Pi) and magnesium (Mg) concentrations did not differ between female NA and control Sprague-Dawley (SD) rats at the time of ovariectomy (ovx), although serum ionized Ca was significantly lower in NA rats than in SD rats. Serum parathyroid hormone (PTH) and osteocalcin (OC) concentrations and urinary Ca excretion were significantly greater in NA rats than in SD rats, suggesting hyperparathyroidism and the resultant enhanced bone turnover in NA rats. Paradoxically, ovx increased serum PTH and OC in NA rats but not in SD rats. Ovx-induced exacerbation of hyperparathyroidism was confirmed by significantly greater conversion of 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D in ovx NA rats even after normalization to vitamin D-binding protein. Bone mineral density (BMD) in proximal tibia increased similarly in a time-dependent manner in sham-operated NA and SD rats. However, ovx ablated the time-dependent increase of BMD in SD rats and significantly decreased BMD in NA rats by 2 wk after ovx, resulting in a significantly lower BMD in ovx NA rats than in ovx SD rats. In summary, NA rats, which are analbuminemic with compensatory increases in lipid and protein synthesis, developed hyperparathyroidism, possibly due to an increase in serum Pi and a reduction of ionized Ca, and ovx induced a greater BMD reduction in NA rats than in SD rats, probably by exacerbating hyperparathyroidism.

  10. Stevia preferences in Wistar rats.

    Science.gov (United States)

    Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

    2016-11-01

    The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

  11. Pathophysiology of the Belgrade Rat

    Directory of Open Access Journals (Sweden)

    Tania eVeuthey

    2014-04-01

    Full Text Available The Belgrade rat is an animal model of Divalent Metal Transporter-1 (DMT1 deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis.

  12. Costimulation and autoimmune diabetes in BB rats

    NARCIS (Netherlands)

    Beaudette-Zlatanova, BC; Whalen, B; Zipris, D; Yagita, H; Rozing, J; Groen, H; Benjamin, CD; Hunig, T; Drexhage, HA; Ansari, MJ; Leif, J; Mordes, JP; Greiner, DL; Sayegh, MH; Rossini, AA

    Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55-120 days of age. We observed that two anti-CD28

  13. THE GREATER CANE RATS (THRYONOMIS SWINDERIANUS,

    African Journals Online (AJOL)

    2017-01-12

    Jan 12, 2017 ... ABSTRACT. The adrenal glands of domesticated greater cane rats (Thryonomys swinderianus), were studied using histological and ultrastructural techniques. A total of seven (7) adult male greater cane rats, aged from 10-14 months, with an average weight of 1.89 kg (range: 1.6 -2.2 kg) were used in this ...

  14. Same-Different Categorization in Rats

    Science.gov (United States)

    Wasserman, Edward A.; Castro, Leyre; Freeman, John H.

    2012-01-01

    Same-different categorization is a fundamental feat of human cognition. Although birds and nonhuman primates readily learn same-different discriminations and successfully transfer them to novel stimuli, no such demonstration exists for rats. Using a spatial discrimination learning task, we show that rats can both learn to discriminate arrays of…

  15. Experimental Salmonella typhimurium infections in rats. I

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1989-01-01

    The course of experimentally induced Salmonella typhimurium infection was studied in three groups of inbred LEW rats: homozygous +/+, athymic rnu/rnu and isogeneic thymus-grafted rnu/rnu rats. In the first experiment the animals were inoculated intraperitoneally with 10(8) bacteria and all animals...

  16. Bromsulphalein (BSP) clearance in ageing rats

    NARCIS (Netherlands)

    Hollander, C.F.; Leeuw-Israel, F.R. de; Arp-Neefjes, J.M.

    1968-01-01

    Liver function in ageing rats was studied, using the bromsulphalein (BSP) clearance test. The test was done on ultramicro scale. This made it possible to repeat the test several times in the same animal and to start a longitudinal study. In 3-month-old rats the BSP retentions, measured 15, 30 and 45

  17. Attachment in rat pups, an experimental approach

    NARCIS (Netherlands)

    Gispen, W.H.; Sigling, H.; Engeland, H. van; Spruijt, B.M.

    1998-01-01

    John Bowlby's attachment theory states that attachment behavior has been strengthened throughout evolution as a consequence of its adaptive value. We investigated the presence of attachment-like behavior in rat pups, by offering a choice between the home nest and a same aged other nest. Rat pups

  18. in Cardiac Muscles of Hemorrhagic Shocked Rats

    African Journals Online (AJOL)

    Purpose: To investigate the protective effects of various resuscitating fluids on severe hemorrhagic shocked (HS) rats by comparing the expression changes of hsp90α in cardiac muscles and survival of rats. Methods: Western-blot and immunohistochemistry methods were performed to determine hsp90á expressions in ...

  19. growing African giant rats Cricetomys gambianus

    African Journals Online (AJOL)

    Thermoregulation and evaporative water loss in growing African giant rats Cricetomys gambianus. M.H. Knight. Mammal Research Institute, University of Pretoria, Pretoria. With an increase in mass, weaned giant rat pups. Cricetomys gambianus, showed a corresponding decline in mass specific metabolism, conductance ...

  20. Training pouched rats to find people.

    Science.gov (United States)

    La Londe, Kate B; Mahoney, Amanda; Edwards, Timothy L; Cox, Christophe; Weetjens, Bart; Durgin, Amy; Poling, Alan

    2015-01-01

    Giant African pouched rats equipped with video cameras may be a tenable option for locating living humans trapped under debris from collapsed structures. In the present study, 5 pouched rats were trained to contact human targets in a simulated collapsed building and to return to the release point after hearing a signal to do so. During test sessions, each rat located human targets more often than it located similar-sized inanimate targets on which it had not previously been trained and spent more time within 1 m of the human target than within 1 m of the other targets. Overall, the rats found humans, plastic bags containing clothes, and plastic bags without clothes on 83%, 37%, and 11% of trials, respectively. These findings suggest that using pouched rats to search for survivors in collapsed structures merits further attention. © Society for the Experimental Analysis of Behavior.

  1. blood pressure reducing effect of bitter kola in wistar rats

    African Journals Online (AJOL)

    DEAN'S OFFICE

    ABSTRACT: In this study the effect of Garcinia kola (GK) on blood pressure was investigated. Albino wistar rats were divided into three groups. Groups A rats had normal rat chow and water ad-libitum while groups B and C rats had Garcinia kola diet of 10% w/w and 15% w/w respectively, their blood pressures were ...

  2. Liver function of Streptozotocin- Induced Diabetic Rats Orally ...

    African Journals Online (AJOL)

    This study evaluated the liver status of STZ- induced diabetic rats treated with aqueous root-bark extract of T. tetraptera for 35 days. Twenty-four (24) rats in four groups (normal control, diabetic control, T. tetraptera treated STZ induced diabetic rats at 150 mg/kg b. w. and T. tetraptera treated STZ-diabetic rats at 300 mg/kg ...

  3. Comparative bone marrow responses of albino rats experimentally ...

    African Journals Online (AJOL)

    It involved laboratory based experimental infection of albino rats as research models. A total of 32 adult albino rats of mixed sexes were used for this investigation. The rats were randomly grouped into three groups, A, B, C made up of 8 rats each, and infected with T. congolense, T brucei and mixed infection of these species ...

  4. Social exclusion intensifies anxiety-like behavior in adolescent rats.

    Science.gov (United States)

    Lee, Hyunchan; Noh, Jihyun

    2015-05-01

    Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Correlation of histological and histometric changes in rats testes ...

    African Journals Online (AJOL)

    Histological and histometric changes in the testes of albino Wistar rats were correlated. Wistar rats weighing between 180-240g were randomly divided into three groups of ten rats each. One group served as control and the rats were given normal saline. The second and third groups received 2mg/kg and 4mg/kg body ...

  6. Anxiolytic Treatment Impairs Helping Behavior in Rats.

    Science.gov (United States)

    Ben-Ami Bartal, Inbal; Shan, Haozhe; Molasky, Nora M R; Murray, Teresa M; Williams, Jasper Z; Decety, Jean; Mason, Peggy

    2016-01-01

    Despite decades of research with humans, the biological mechanisms that motivate an individual to help others remain poorly understood. In order to investigate the roots of pro-sociality in mammals, we established the helping behavior test, a paradigm in which rats are faced with a conspecific trapped in a restrainer that can only be opened from the outside. Over the course of repeated test sessions, rats exposed to a trapped cagemate learn to open the door to the restrainer, thereby helping the trapped rat to escape (Ben-Ami Bartal et al., 2011). The discovery of this natural behavior provides a unique opportunity to probe the motivation of rodent helping behavior, leading to a deeper understanding of biological influences on human pro-sociality. To determine if an affective response motivates door-opening, rats receiving midazolam, a benzodiazepine anxiolytic, were tested in the helping behavior test. Midazolam-treated rats showed less helping behavior than saline-treated rats or rats receiving no injection. Yet, midazolam-treated rats opened a restrainer containing chocolate, highlighting the socially specific effects of the anxiolytic. To determine if midazolam interferes with helping through a sympatholytic effect, the peripherally restricted beta-adrenergic receptor antagonist nadolol was administered; nadolol did not interfere with helping. The corticosterone response of rats exposed to a trapped cagemate was measured and compared to the rats' subsequent helping behavior. Rats with the greatest corticosterone responses showed the least helping behavior and those with the smallest responses showed the most consistent helping at the shortest latency. These results are discussed in terms of their implications for the interaction between stress and pro-social behavior. Finally, we observed that door-opening appeared to be reinforcing. A novel analytical tool was designed to interrogate the pattern of door-opening for signs that a rat's behavior on one session

  7. How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

    Science.gov (United States)

    Combe, Roy; Mudgett, John; El Fertak, Lahcen; Champy, Marie-France; Ayme-Dietrich, Estelle; Petit-Demoulière, Benoit; Sorg, Tania; Herault, Yann; Madwed, Jeffrey B; Monassier, Laurent

    2016-01-01

    Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies. The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry). In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges. Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

  8. Synthesis and super-swelling behavior of a novel low salt-sensitive protein-based superabsorbent hydrogel: collagen-g-poly(AMPS)

    OpenAIRE

    Sadeghi, Mohammad; Hosseinzadeh, Hossein

    2014-01-01

    Superabsorbent polymers are obtained by the graft copolymerization of 2-acrylamido-2-methylpropanesul- fonic acid (AMPS) monomer onto collagen, using ammonium persulfate as a free radical initiator in the presence of methylene bisacrylamide as a crosslinker. Infrared spectroscopy and TGA thermal analysis were carried out to confirm the chemical structure of the hydrogel. Moreover, morphology of the samples was examined by scanning electron microscopy (SEM). The effect of reaction var...

  9. Characterisation of FUT4 and FUT6 α-(1 → 2-fucosyltransferases reveals that absence of root arabinogalactan fucosylation increases Arabidopsis root growth salt sensitivity.

    Directory of Open Access Journals (Sweden)

    Theodora Tryfona

    Full Text Available Plant type II arabinogalactan (AG polysaccharides are attached to arabinogalactan proteins (AGPs at hydroxyproline residues, and they are very diverse and heterogeneous structures. The AG consists of a β-(1 → 3-linked galactan backbone with β-(1 → 6-galactan side chains that are modified mainly with arabinose, but they may also contain glucuronic acid, rhamnose or other sugars. Here, we studied the positions of fucose substitutions in AGPs, and we investigated the functions of this fucosylation. Monosaccharide analysis of Arabidopsis leaf AGP extracts revealed a significant reduction in L-Fucose content in the fut4 mutant, but not in the fut6 mutant. In addition, Fucose was reduced in the fut4 mutant in root AGP extracts and was absent in the fut4/fut6 mutant. Curiously, in all cases reduction of fucose was accompanied with a reduction in xylose levels. The fucosylated AGP structures in leaves and roots in wild type and fut mutant plants were characterised by sequential digestion with AG specific enzymes, analysis by Polysaccharide Analysis using Carbohydrate gel Electrophoresis, and Matrix Assisted Laser Desorption/Ionisation (MALDI-Time of Flight Mass spectrometry (MS. We found that FUT4 is solely responsible for the fucosylation of AGPs in leaves. The Arabidopsis thaliana FUT4 and FUT6 genes have been previously proposed to be non-redundant AG-specific fucosyltransferases. Unexpectedly, FUT4 and FUT6 enzymes both fucosylate the same AGP structures in roots, suggesting partial redundancy to each other. Detailed structural characterisation of root AGPs with high energy MALDI-Collision Induced Dissociation MS and NMR revealed an abundant unique AG oligosaccharide structure consisting of terminal xylose attached to fucose. The loss of this structure in fut4/fut6 mutants explains the reduction of both fucose and xylose in AGP extracts. Under salt-stress growth conditions the fut4/fut6 mutant lacking AGP fucosylation exhibited a shorter root phenotype than wild type plants, implicating fucosylation of AGPs in maintaining proper cell expansion under these conditions.

  10. How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

    Directory of Open Access Journals (Sweden)

    Roy Combe

    Full Text Available Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies.The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry.In this study, we have shown that, despite a strong blood pressure (BP basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges.Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

  11. Contrasting physiological responses to high salinity between two varieties of corn 'Lluteño' (salt tolerant and 'Jubilee' (salt sensitive

    Directory of Open Access Journals (Sweden)

    Libertad Carrasco-Ríos

    2013-09-01

    Full Text Available 'Lluteño' is the only one corn capable to prosper in the Valley of Lluta under saline conditions (EC = 9.1 dS m-1. This cultivar has been little studied and there is no current information about its growth and about the possible mechanisms involved in its tolerance to salts. The aim of this research was to compare the growth of young plants of corn (Zea mays L. 'Lluteño' to that of the bred 'Jubilee', both grown under different salt concentrations, to characterize the absorption and distribution of Na+ and other nutrients in the plant and to evaluate the effect of the saline conditions in the osmotic adjustment in both cultivars. The plants of 21 d old were subjected for 15 d to two saline treatments: 50 and 100 mM NaCl. The accumulation of DM was reduced from 5.12 to 1.80 g plant-1 in 'Jubilee' and 5.53 to 4.12 g plant-1 in 'Lluteño' (P d" 0.05. 'Lluteño' showed to be more tolerant to salt stress that 'Jubilee' by greatest accumulation of biomass under saline conditions, it was associated with a lower accumulation of Na+, steadiness of K+ and Ca²+ content and accumulation of osmolytes in leaves. The latter affecting positively the maintenance of relative water content and the osmotic adjustment of this cultivar in the leaves.

  12. A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept

    OpenAIRE

    Masataka Majima; Makoto Katori

    2010-01-01

    Terrestrial animals must conserve water and NaCl to survive dry environments. The kidney reabsorbs 95% of the sodium filtered from the glomeruli before sodium reaches the distal connecting tubules. Excess sodium intake requires the renal kallikrein-kinin system for additional excretion. Renal kallikrein is secreted from the distal connecting tubule cells of the kidney, and its substrates, low molecular kininogen, from the principal cells of the cortical collecting ducts (CD). Formed kinins in...

  13. Salt-sensitivity of σH and Spo0A prevents sporulation of Bacillus subtilis at high osmolarity avoiding death during cellular differentiation

    Science.gov (United States)

    Widderich, Nils; Rodrigues, Christopher D.A.; Commichau, Fabian M.; Fischer, Kathleen E.; Ramirez-Guadiana, Fernando H.; Rudner, David Z.; Bremer, Erhard

    2016-01-01

    Summary The spore-forming bacterium Bacillus subtilis frequently experiences high osmolarity as a result of desiccation in the soil. The formation of a highly desiccation-resistant endospore might serve as a logical osmostress escape route when vegetative growth is no longer possible. However, sporulation efficiency drastically decreases concomitant with an increase in the external salinity. Fluorescence microscopy of sporulation-specific promoter fusions to gfp revealed that high salinity blocks entry into the sporulation pathway at a very early stage. Specifically, we show that both Spo0A- and SigH-dependent transcription are impaired. Furthermore, we demonstrate that the association of SigH with core RNA polymerase is reduced under these conditions. Suppressors that modestly increase sporulation efficiency at high salinity map to the coding region of sigH and in the regulatory region of kinA, encoding one the sensor kinases that activates Spo0A. These findings led us to discover that B. subtilis cells that overproduce KinA can bypass the salt-imposed block in sporulation. Importantly, these cells are impaired in the morphological process of engulfment and late forespore gene expression and frequently undergo lysis. Altogether our data indicate that B. subtilis blocks entry into sporulation in high-salinity environments preventing commitment to a developmental program that it cannot complete. PMID:26712348

  14. 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.

  15. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    NARCIS (Netherlands)

    Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as

  16. Lessons From Experiments in Rats

    Directory of Open Access Journals (Sweden)

    Albert Gramsbergen

    2001-01-01

    Full Text Available In this essay a few relevant aspects of the neural and behavioral development of the brain in the human and in the rat are reviewed and related to the consequences of lesions in the central and peripheral nervous system at early and later age. Movements initially are generated by local circuits in the spinal cord and without the involvement of descending projections. After birth, both in humans and in rats it seems that the devlopment of postural control is the limiting factor for several motor behaviors to mature. Strong indications exist that the cerebellum is significantly involved in this control. Lesions in the CNS at early stages interfere with fundamental processes of neural development, such as the establishment of fiber connections and cell death patterns. Consequently, the functional effects are strongly dependent on the stage of development. The young and undisturbed CNS, on the other hand, has a much greater capacity than the adult nervous system for compensating abnormal reinnervation in the peripheral nervous system. Animal experiments indicated that the cerebellar cortex might play an important part in this compensation. This possibility should be investigated further as it might offer important perspectives for treatment in the human.

  17. Analysis of vkorc1 polymorphisms in Norway rats using the roof rat as outgroup.

    Science.gov (United States)

    Díaz, Juan C; Song, Ying; Moore, Anthony; Borchert, Jeff N; Kohn, Michael H

    2010-05-24

    Certain mutations in the vitamin K epoxide reductase subcomponent 1 gene (vkorc1) mediate rodent resistance to warfarin and other anticoagulants. Testing for resistance often involves analysis of the vkorc1. However, a genetic test for the roof rat (Rattus rattus) has yet to be developed. Moreover, an available roof rat vkorc1 sequence would enable species identification based on vkorc1 sequence and the evaluation of natural selection on particular vkorc1 polymorphisms in the Norway rat (R. norvegicus). We report the coding sequence, introns and 5' and 3' termini for the vkorc1 gene of roof rats (R. r. alexandrinus and R. r. frugivorus) from Uganda, Africa. Newly designed PCR primers now enable genetic testing of the roof rat and Norway rat. Only synonymous and noncoding polymorphisms were found in roof rats from Uganda. Both nominal subspecies of roof rats were indistinguishable from each other but were distinct from R. losea and R. flavipectus; however, the roof rat also shares at least three coding sequence polymorphisms with R. losea and R. flavipectus. Many of recently published vkorc1 synonymous and non-synonymous single nucleotide polymorphisms (SNPs) in Norway rats are likely SNPs from roof rats and/or other Rattus species. Tests applied to presumably genuine Norway rat vkorc1 SNPs are consistent with a role for selection in two populations carrying the derived Phe63Cys and Tyr139Cys mutations. Geographic mapping of vkorc1 SNPs in roof rats should be facilitated by our report. Our assay should be applicable to most species of Rattus, which are intermediate in genetic distance from roof and Norway rats. Vkorc1-mediated resistance due to non-synonymous coding SNPs is not segregating in roof rats from Uganda. By using the roof rat sequence as a reference vkorc1, SNPs now can be assigned to the correct rat species with more confidence. Sampling designs and genotyping strategies employed so far have helped detect candidate mutations underlying vkorc1-mediated

  18. Decline of umami preference in aged rats.

    Science.gov (United States)

    Miura, Hirohito; Ooki, Makoto; Kanemaru, Norikazu; Harada, Shuitsu

    2014-08-08

    The effects of aging on the umami sensation were compared between the preference and neural responses from the greater superficial petrosal nerve (GSP innervating the soft palate) and the chorda tympani nerve (CT innervating the fungiform papillae) in the Sprague Dawley rat. A two-bottle preference test revealed that younger rats (5-12 weeks) preferred significantly 0.001 M 5'-inosine monophosphate (IMP), 0.01 M mono sodium glutamate (MSG), and binary mixtures of 0.001 M IMP+0.01 M MSG than deionized water. However, aged rats (21-22 months) showed no significant preference to these umami solutions compared to deionized water. Among the other four basic taste stimuli, there were no significant differences in preference between young and aged rats. Regardless of the age of the rat, neural responses from the GSP and CT produced robust integrated responses to all three umami solutions used in the two-bottle tests. These results indicate that the lack of preference to umami in aged rats is a central nervous system phenomenon and suggests that the loss of preference to umami taste in aged rats is caused by homeostatic changes in the brain incurred by aging. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation

    DEFF Research Database (Denmark)

    Yderstræde, Knud Bonnet; Starklint, Henrik; Steinbrüchel, Daniel Andreas

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets...... to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes....... The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet...

  20. Detection of rat hepatitis E virus in wild Norway rats (Rattus norvegicus) and Black rats (Rattus rattus) from 11 European countries.

    Science.gov (United States)

    Ryll, René; Bernstein, Samuel; Heuser, Elisa; Schlegel, Mathias; Dremsek, Paul; Zumpe, Maxi; Wolf, Sandro; Pépin, Michel; Bajomi, Daniel; Müller, Gabi; Heiberg, Ann-Charlotte; Spahr, Carina; Lang, Johannes; Groschup, Martin H; Ansorge, Hermann; Freise, Jona; Guenther, Sebastian; Baert, Kristof; Ruiz-Fons, Francisco; Pikula, Jiri; Knap, Nataša; Tsakmakidis, Ιoannis; Dovas, Chrysostomos; Zanet, Stefania; Imholt, Christian; Heckel, Gerald; Johne, Reimar; Ulrich, Rainer G

    2017-09-01

    Rat hepatitis E virus (HEV) is genetically only distantly related to hepeviruses found in other mammalian reservoirs and in humans. It was initially detected in Norway rats (Rattus norvegicus) from Germany, and subsequently in rats from Vietnam, the USA, Indonesia, China, Denmark and France. Here, we report on a molecular survey of Norway rats and Black rats (Rattus rattus) from 12 European countries for ratHEV and human pathogenic hepeviruses. RatHEV-specific real-time and conventional RT-PCR investigations revealed the presence of ratHEV in 63 of 508 (12.4%) rats at the majority of sites in 11 of 12 countries. In contrast, a real-time RT-PCR specific for human pathogenic HEV genotypes 1-4 and a nested broad-spectrum (NBS) RT-PCR with subsequent sequence determination did not detect any infections with these genotypes. Only in a single Norway rat from Belgium a rabbit HEV-like genotype 3 sequence was detected. Phylogenetic analysis indicated a clustering of all other novel Norway and Black rat-derived sequences with ratHEV sequences from Europe, the USA and a Black rat-derived sequence from Indonesia within the proposed ratHEV genotype 1. No difference in infection status was detected related to age, sex, rat species or density of human settlements and zoological gardens. In conclusion, our investigation shows a broad geographical distribution of ratHEV in Norway and Black rats from Europe and its presence in all settlement types investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Electrocardiography in rats: a comparison to human.

    Science.gov (United States)

    Konopelski, P; Ufnal, M

    2016-11-23

    Electrocardiography (ECG) in rats is a widely applied experimental method in basic cardiovascular research. The technique of ECG recordings is simple; however, the interpretation of electrocardiographic parameters is challenging. This is because the analysis may be biased by experimental settings, such as the type of anesthesia, the strain or age of animals. Here, we aimed to review electrocardiographic parameters in rats, their normal range, as well as the effect of experimental settings on the parameters variation. Furthermore, differences and similarities between rat and human ECG are discussed in the context of translational cardiovascular research.

  2. Oral Gavage in Rats: Animal Welfare Evaluation

    OpenAIRE

    Turner, Patricia V.; Vaughn, Elizabeth; Sunohara-Neilson, Janet; Ovari, Jelena; Leri, Francesco

    2012-01-01

    The effect of chronic daily orogastric gavage with water (5 mL/kg) on behavior and physiology was evaluated in male Sprague–Dawley rats. Treatment groups included: unmanipulated control, restraint control, dry gavage, and gavage, with all rats singly housed (n = 9 or 10 per group). In addition, a group of pair-housed rats (n = 18) was included to determine whether social housing affected response to gavage. Weekly body weights and food consumption were recorded as well as use of a nylon chew ...

  3. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats

    Science.gov (United States)

    TANAKA, Masami; WATANABE, Minoru; YOKOMI, Izuru; MATSUMOTO, Naoki; SUDO, Katsuko; SATOH, Hitoshi; IGARASHI, Tsuneo; SEKI, Azusa; AMANO, Hitoshi; OHURA, Kiyoshi; RYU, Kakei; SHIBATA, Shunichi; NAGAYAMA, Motohiko; TANUMA, Jun-ichi

    2014-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats. PMID:25736479

  4. How rats combine temporal cues.

    Science.gov (United States)

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M

    2005-05-31

    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  5. Tissue disposition of bifenthrin in the rat

    Data.gov (United States)

    U.S. Environmental Protection Agency — Tissue disposition of bifenthrin in the rat and oral and intravenous administration. This dataset is associated with the following publication: Hughes , M., D. Ross...

  6. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  7. Thermal biology of the laboratory rat.

    Science.gov (United States)

    Gordon, C J

    1990-05-01

    The purpose of this paper is to thoroughly review the literature and present a data base of the basic thermoregulatory parameters of the laboratory rat. This review surveys the pertinent papers dealing with various aspects of the thermal biology of the laboratory rat, including: metabolism, thermoneutrality, core and brain temperature, thermal tolerance, thermal conductance and insulation, thermoregulatory effectors (i.e., thermogenesis, peripheral vasomotor tone, evaporation, and behavior), thermal acclimation, growth and reproduction, ontogeny, aging, motor activity and exercise, circadian rhythm and sleep, gender differences, and other parameters. It is shown that many facets of the thermoregulatory system of the laboratory rat are typical to that of most homeothermic species. However, is several instances the rat exhibits unique thermoregulatory responses which are not comparable to other species.

  8. Comeback of the Rat in Biomedical Research

    NARCIS (Netherlands)

    Homberg, J.R.; Wohr, M.; Alenina, N.

    2017-01-01

    Rats were the first mammalian species domesticated for scientific purposes, and they soon became the most widely used animal model in biomedical sciences, including cardiovascular research and behavioral neuroscience. Yet, after the development of technologies to manipulate genes, researchers

  9. Experimental model to induce obesity in rats

    National Research Council Canada - National Science Library

    Vinicius Von Diemen; Eduardo Neubarth Trindade; Manoel Roberto Maciel Trindade

    2006-01-01

    .... Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models to induce obesity in rats are a lesion of the ventromedial hypothalamic nucleus (VMH...

  10. Reduced graphene oxide: nanotoxicological profile in rats

    National Research Council Canada - National Science Library

    Mendonça, Monique Culturato Padilha; Soares, Edilene Siqueira; de Jesus, Marcelo Bispo; Ceragioli, Helder José; Irazusta, Silvia Pierre; Batista, Ângela Giovana; Vinolo, Marco Aurélio Ramirez; Maróstica Júnior, Mário Roberto; da Cruz-Höfling, Maria Alice

    2016-01-01

    We have previously demonstrated that reduced graphene oxide (rGO) administered intravenously in rats was detected inside the hippocampus after downregulation of the tight and adherens junction proteins of the blood-brain barrier...

  11. Rat Bite Fever Resembling Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ripa Akter

    2016-01-01

    Full Text Available Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated.

  12. Rat sperm motility analysis: methodologic considerations

    Science.gov (United States)

    The objective of these studies was to optimize conditions for computer-assisted sperm analysis (CASA) of rat epididymal spermatozoa. Methodologic issues addressed include sample collection technique, sampling region within the epididymis, type of diluent medium used, and sample c...

  13. Penile autotransplantation in rats: An animal model

    Directory of Open Access Journals (Sweden)

    Raouf M Seyam

    2013-01-01

    Conclusions: Penile autotransplantation in rats is feasible and provides the basis for evaluation of the corpora cavernosa in an allotransplantation model. Long-term urethral continuity and dorsal neurovascular bundle survival in this model is difficult to establish.

  14. Reactive Protein Synthesis in Pregnant Rats

    African Journals Online (AJOL)

    olayemitoyin

    /kg) groups. At terminal gestation day (GD) ranging from 0-20, the rats were sacrificed, and blood samples and amniotic fluids were collected. Thyroid hormone, C-reactive protein (CRP) and leptin assay was carried using the blood samples.

  15. A Focused Microarray for Screening Rat Embryonic Stem Cell Lines

    Science.gov (United States)

    Hong, James; He, Hong; Bui, Phuoc; Ryba-White, Ben; Rumi, Mohammad A.K.; Soares, Michael J.; Dutta, Debasree; Paul, Soumen; Kawamata, Masaki; Ochiya, Takahiro; Ying, Qi-Long; Rajanahalli, Pavan

    2013-01-01

    Here, we describe a focused microarray for screening rat embryonic stem cells (ESCs) and provide validation data that this array can distinguish undifferentiated rat ESCs from rat trophoblast stem (TS) cells, rat extraembryonic endoderm cells, mouse embryonic fibroblast feeder cells, and differentiated rat ESCs. Using this tool, genuine rat ESC lines, which have been expanded in a conventional rat ESC medium containing two inhibitors (2i), for example, glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase (MEK) inhibitors, and leukemia inhibitory factor, and genuine rat ESCs, which have been expanded in rat ESC medium containing four inhibitors (4i), for example, GSK3, MEK, Alk5, and Rho-associated kinase inhibitors were compared; as were genuine rat ESCs from 4 different strains of rats. Expression of Cdx2, a gene associated with trophoblast determination, was observed in genuine, undifferentiated rat ESCs from 4 strains and from both 2i and 4i ESC derivation medium. This finding is in contrast to undifferentiated mouse ESCs that do not express Cdx2. The rat ESC focused microarray described in this report has utility for rapid screening of rat ESCs. This tool will enable optimization of culture conditions in the future. PMID:22889370

  16. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  17. Epidermal growth factor reactivity in rat milk

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Tollund, L

    1990-01-01

    whey elutes as a broad peak corresponding to a Stokes radius of 4.0 nm (an approximate molecular weight of 80 kDa). Almost no 6 kDa EGF is present. Judged by gel filtration of whey pre-incubated with 125I-EGF (6 kDa), no binding protein for EGF is present in rat whey. When rat milk is incubated...

  18. Autoprotection in acetaminophen intoxication in rats

    DEFF Research Database (Denmark)

    Dalhoff, K; Laursen, H; Bangert, K

    2001-01-01

    Autoprotection by acetaminophen, i.e. increased resistance to toxic effects caused by pretreatment, is a well-known phenomenon. The purpose of the present work was to identify mechanisms for increased acetaminophen tolerance induced by pretreatment of rats. One group of female Wistar rats (pretre....... Pretreatment increased the tolerance to acetaminophen toxicity twice, as estimated by mortality. The data indicate that pretreatment may reduce the relative production of toxic metabolites, but it primarily enhances the protection against these metabolites by regenerating hepatocytes....

  19. Hyperlipoproteinemia in streptozotocin-treated rats.

    Science.gov (United States)

    Bar-On, H; Roheim, P S; Eder, H A

    1976-06-01

    In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal dose of streptozotocin was 45 mg/kg body weight for the sucrose-fed rats. With this dose, plasma glucose reached a maximum of over 600 mg/100 ml., and plasma insulin was reduced by 60 per cent. Plasma triglycerides rose in the sucrose-fed rats to over 1,000 mg/100 ml. two days after the streptozotocin was given and then decreased to over 770 mg./100 ml. 12 days after treatment and then to 585 mg./100 ml. 10 weeks after induction of diabetes. With this dose, ketonuria did not occur nor did any of the animals die, as occurred with higher doses. In the chow-fed rats, plasma triglyceride levels were elevated with the induction of diabetes to levels of approximately 300 mg./100 ml. The concentration of all the plasma lipoproteins increased with the induction of diabetes. The concentration of very-low density lipoprotein (VLDL) protein in the sucrose-fed diabetic increased fivefold, the low-density lipoprotein (LDL) protein increased, and especially striking was the increase in high-density lipoprotein (HDL) protein concentration, which became more pronounced with the duration of the diabetes. The diabetes produced by streptozotocin administration to sucrose-fed rats, thus, provides a useful model for the study of the hyperlipoproteinemia of diabetes.

  20. Finding prefrontal cortex in the rat.

    Science.gov (United States)

    Leonard, Christiana M

    2016-08-15

    The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B

  1. Blood platelet serotonin following enterectomy in rats.

    Science.gov (United States)

    Osim, E E; Wyllie, J H

    1991-01-01

    The role of the intestine as a source of platelet serotonin was investigated. Radioactive serotonin precursor. 5-Hydroxytryptophan was injected into enterectomised and sham-operated rats. Blood samples were taken at time intervals and serotonin uptake was estimated by radioactive counting. Soon (1-2 hrs) after surgery and under sodium pentobarbital anaesthesia, platelet 5HT activity was higher in enterectomised rats than in controls. The intestine may not be the major source of platelet serotonin.

  2. Reproductive toxicity of Samanea tubulosa on rats

    Directory of Open Access Journals (Sweden)

    Maria Rafaella Luz de Araújo

    2015-12-01

    Full Text Available Samanea tubulosa is a plant used for medicinal and feeding purposes. However, ingestion of S. tubulosa pods has been associated with bovine abortion. Thus, the aim of this work was to investigate the effects of diet containing 5% of S. tubulosa pod meal on male and female Wistar rats. Diet was administered to male rats (n = 10 for 60 days before mating. Female rats (n = 10 received the treatment for 30 days, during cohabitation and from gestational day (GD 0 to GD20. Treated animals were mated with untreated rats. In male rats, plant consumption caused decreased food consumption and 20% fertility index reduction. Litters from treated males presented lower body weight and crown–rump length. Female rats treated with the plant increased water and food intake and body weight. Decreases in fertility, fecundity and gestation indices and increase of placenta weight and mean number of corpora lutea were found. Thus, owing to the possible general and reproductive toxic effects, long-term consumption of S. tubulosa is not recommended for phytotherapic or food purposes.

  3. Colonic Fermentation Promotes Decompression sickness in Rats.

    Science.gov (United States)

    de Maistre, Sébastien; Vallée, Nicolas; Gempp, Emmanuel; Lambrechts, Kate; Louge, Pierre; Duchamp, Claude; Blatteau, Jean-Eric

    2016-02-08

    Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body's H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production.

  4. Quantity Discrimination in Domestic Rats, Rattus norvegicus.

    Science.gov (United States)

    Cox, Laura; Montrose, V Tamara

    2016-08-03

    Quantity discrimination is a basic form of numerical competence where an animal distinguishes which of two amounts is greater in size. Whilst quantity discrimination in rats has been investigated via training paradigms, rats' natural quantity discrimination abilities without explicit training for a desired response have not been explored. This study investigated domestic rats' ability to perform quantity discrimination. Domestic rats ( n = 12) were examined for their ability to distinguish the larger amount under nine quantity comparisons. One-sample t -tests identified a significant preference for the larger quantity in comparisons of 1 vs. 2, 2 vs. 3, 3 vs. 5, 3 vs. 8, 4 vs. 6, and 4 vs. 8. No preference between quantities was found for comparisons of 3 vs. 4, 4 vs. 5 and 5 vs. 6. Overall, this study drew two key conclusions. Firstly, that domestic rats are capable of performing quantity discrimination without extensive training. Secondly, as subjects adhered to Weber's law, it was concluded that the approximate number system underpins domestic rats' ability to perform spontaneous quantity discrimination.

  5. Hematological Characteristics of the BB Wistar Rat.

    Science.gov (United States)

    Wright, J R; Yates, A J; Shah, N T; Neff, J C; Covey, D W; Thibert, P

    1983-01-01

    Complete blood counts, differential white blood cell and platelet counts were performed on male and female BB Wistar diabetic rats (BBWd), their nondiabetic siblings (BBWnd) and outbred Wistar rats of the line from which the BB Wistar rats were derived. Most of the observed changes were strain-related (those present in both BBWd and BBWnd but not in control rats) rather than diabetes-related (those in BBWd but neither BBWnd nor control rats) and therefore probably due to the inbreeding process. The BBW strain had significantly lower numbers of white cells and platelets, as well as markedly changed differential white cell counts. Differential counts showed a pattern of lymphopenia, neutrophilia, monocytosis and eosinophilia. It is possible that these white blood cell changes contribute to the increased susceptibility to infection reported for the BBW strain. No significant difference in serum immunoglobulin concentrations was found in any of these three groups of rats. There- fore, hypogammaglobutinemia cannot account for the increased susceptibility to infections, but it is not possible to rule out an abnormality in the distribution of immunoglobulin fractions as an etiological factor.

  6. Thermoregulation in hypergravity-acclimated rats

    Science.gov (United States)

    Monson, Conrad B.; Patterson, Susan L.; Horowitz, John M.; Oyama, Jiro

    1989-01-01

    The effect of acclimation to hypergravity on thermoregulatory responses of rats was determined by comparing data on core temperature, T(c), tail temperature, and O2 consumption in rats raised at 1 G (C) and at 2.1 G. It was found that, when C rats were exposed to an ambient temperature of 9 C concurrently with exposure to 2.1 G, the T(c) fell by about 6 C, while in rats acclimated to 2.1 G, the T(c) fell only by 1 C. Results of O2 consumption measurements showed that C rats exposed simultaneously to cold and hypergravity were not activating their thermogenic mechanism sufficiently to prevent a fall in T(c). In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their T(c) when exposed to a 5.8-G field or when cold-stressed at 1 G for extended times.

  7. Hypophysectomyinduced regression of female rat lacrimal glands. Partial restoration/maintenance by dihydrotestosterone and prolactin

    DEFF Research Database (Denmark)

    Bjerrum, Kirsten Birgitte; Azzarolo, A.M.

    1995-01-01

    Ophthalmology, hypophysectomi, rats regression, lacrimal galnds, restoration, dihydrotestosterone, prolactin......Ophthalmology, hypophysectomi, rats regression, lacrimal galnds, restoration, dihydrotestosterone, prolactin...

  8. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    1993-01-01

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  9. [Preventive effects of pueraria on presbycusis in rats].

    Science.gov (United States)

    Chen, Wangyan; Yao, Qi; Liu, Weihong; Zhang, Bibo; Wang, Ying; Liu, Bo

    2009-08-01

    To investigate the preventive effects of Pueraria on presbycusis in rats. Thirty-two 24-26 month old Wistar rats were randomly divided into four groups, and were treated with different dosages of Pueraria (1, 2, 4, 0 g x kg(-1) x d(-1)) separately for 4 weeks. Auditory brainstem response (ABR) was used to detect the change of hearing threshold of rats. Hemorheological items of rats were checked in each group. Compared with control group, the hearing threshold and hemorheological items of rats was significantly improved after treated with Pueraria (Ppresbycusis of rats.

  10. Het domesticeren van de rat : Rat-mens relaties in de twintigste eeuw in het Westen

    NARCIS (Netherlands)

    Beumer, K.

    2009-01-01

    In de afgelopen eeuw heeft zich een opvallende verschuiving voorgedaan in de relatie tussen mens en rat. Terwijl de rat rond het begin van de twintigste eeuw in het algemeen nog ondubbelzinnig als ongedierte werd beschouwd, zijn ratten momenteel zowel een populair huisdier als het ultieme model van

  11. Effects of BCL-2 over-expression on B cells in transgenic rats and rat hybridomas.

    Science.gov (United States)

    Iscache, Anne-Laure; Ménoret, Séverine; Tesson, Laurent; Rémy, Séverine; Usal, Claire; Pedros, Christophe; Saoudi, Abdelhadi; Buelow, Roland; Anegon, Ignacio

    2011-10-01

    The rat is an important biomedical experimental model that benefited from the recent development of new transgenic and knockout techniques. With the goal to optimize rat mAb production and to analyze the impact of Bcl-2 on B-cell development, we generated bcl-2 transgenic rats. Transgenic rats showed Bcl-2 over-expression in B cells, increased B cell numbers in lymphoid organs, elevated production of immunoglobulins (Igs) and prolonged B-cell survival in vitro. Transgenic rats remained healthy, reproduced normally and did not develop autoimmunity. Fusions with bcl-2 transgenic splenocytes did not result in increased hybridoma generation. A comparison of on- and off-rates of 39 mAbs generated with bcl-2 transgenic and wild-type animals revealed no significant differences. Over-expression of Bcl-2 in hybridomas did not change cell proliferation but resulted in increased Ig production. Bcl-2 transgenic rats will be a useful tool for the generation of rat mAbs, the analysis of B cells in different pathophysiological models, such as autoimmunity, cancer or organ transplantation, and the study of rat B-cell biology.

  12. Fish oil versus arachis oil food supplementation in relation to pregnancy duration in rats

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Jensen, B.

    1990-01-01

    Throughout pregnancy, Lewis rats were fed standard rat chow supplemented with 15% (w/w) of either MaxEPA fish oil (FO) or arachis oil (AO); a third group was fed standard rat chow only (St) (n = 15, 15, and 16 rats, respectively). Compared to AO-rats, FO-rats had substantially higher levels of n-3...

  13. Prevention of red cell lysis in artesunate-treated rats: A role for ...

    African Journals Online (AJOL)

    -phosphate dehydrogenase activity in male rats. Twelve (12) male rats were divided into two groups of six (6) rats each. Group 1 rats were control rats which received normal saline while group 2 rats were treated with artesunate orally for five ...

  14. Male rats transmit Brucella abortus biotype 1 through sexual intercourse.

    Science.gov (United States)

    Islam, Md Ariful; Khatun, Mst Minara; Baek, Byeong-Kirl

    2013-08-30

    The aim of this study was to evaluate transmission of Brucella abortus biotype 1 via sexual intercourse in rats. Male and female virgin Sprague-Dawley (SD) rats were experimentally infected intraperitoneally with 1×10(9)colony forming units (CFU) of B. abortus biotype 1, a Korean bovine isolate. At 14 days after infection, infected male rats (n=10) were housed with uninfected female rats (n=10) and infected female rats (n=10) were housed with uninfected male rats (n=10) for a period of one month. During this period all uninfected female rats became pregnant and 6 of 10 infected female rats became pregnant. Serum from two out of 10 female uninfected rats had positive reactions in the Rose Bengal Plate Agglutination Test (RBPAT), Tube Agglutination Test (TAT) or the Enzyme-Linked Immunosorbent Assay (ELISA); whereas none of the uninfected male rat had positive reactions in these tests. Using bacteriological culture and AMOS-PCR assay, B. abortus biotype 1 was isolated and identified from two uninfected female rats and all of the uninfected male rats were found negative for B. abortus biotype 1. It was concluded that transmission of B. abortus biotype 1 from infected male to uninfected female rats resulted from sexual intercourse. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. OSMOTICALLY LYSED RAT LIVER MITOCONDRIA

    Science.gov (United States)

    Vasington, Frank D.; Greenawalt, John W.

    1968-01-01

    Osmotically lysed rat liver mitochondria have been utilized for a study of the biochemical and ultrastructural properties in relation to divalent ion accumulation. Osmotic lysis of mitochondria by suspension and washing in cold, distilled water results in the extraction of about 50% of the mitochondrial protein, the loss of the outer mitochondrial membrane, an increase in respiration, and a marked decrease in the ability to catalyze oxidative phosphorylation. Nevertheless, except for a decrease in the ability to accumulate Sr2+ by an ATP-supported process, these lysed mitochondria retain full capacity to accumulate massive amounts of divalent cations by respiration-dependent and ATP-supported mechanisms. The decreased ability of osmotically lysed mitochondria to accumulate Sr2+ by an ATP-energized process does not appear to be due to a loss or inactivation of a specific Sr2+-activated ATPase. The energy-dependent accumulation processes in lysed mitochondria show an increased sensitivity to inhibition by monovalent cations. Extraction of cytochrome c from osmotically lysed mitochondria results in a complete loss of phosphorylation and the respiration-dependent accumulation of Ca2+; a lesser, but significant, decrease in the ATP-supported accumulation of Ca2+ also was observed. The addition of cytochrome c fully restores the respiration-dependent accumulation of Ca2+ to the level present in unextracted, osmotically lysed mitochondria. The ATP-supported process is not affected by the addition of cytochrome c to extracted mitochondria, indicating that cytochrome c is not involved in ion transport energized by ATP. The osmotically lysed mitochondria are devoid of outer membranes and contain relatively little matrix substance. The accumulation of Ca2+ and Pi by lysed mitochondria under massive loading conditions is accompanied by the formation of electron-opaque deposits within the lysed mitochondria associated with the inner membranes. This finding suggests that the

  16. Leptin responsiveness in chronically decerebrate rats.

    Science.gov (United States)

    Harris, Ruth B S; Bartness, Timothy J; Grill, Harvey J

    2007-10-01

    Peripheral infusions of physiological doses of leptin decrease body fat mass, but it is not known whether this results from direct effects on peripheral tissue or activation of central leptin receptors. In this study, we infused chronically decerebrate (CD) rats, in which the forebrain was surgically isolated from the caudal brainstem, with 60 microg leptin/d or PBS for 14 d from ip mini-osmotic pumps. The CD rats were tube fed an amount of food equivalent to the intake of ad libitum-fed intact controls or 75% of this amount to account for their reduced energy expenditure. Control rats fed ad libitum or tube fed 75, 100, or 125% of their ad libitum intake also were peripherally infused with leptin or PBS. CD rats had a lower serum testosterone, energy expenditure, and lean body mass compared with controls but had increased levels of adiponectin and leptin and were obese. Leptin increased body fat and decreased energy expenditure during the light period in 100%-fed CD rats, but not 75%-fed CD rats. Leptin decreased body fat of ad libitum- and 100%-fed but not 75%-fed or 125%-fed intact controls. Energy expenditure did not change in any control group. These results show that leptin can change body fat independent of a change in food intake or energy expenditure, that the forebrain normally prevents leptin from inhibiting energy expenditure through mechanisms initiated in the caudal brainstem or peripheral tissues, and that the leptin response in both intact and CD rats is determined by the energy status of the animal.

  17. Indomethacin-Induced Gastric Ulcer: Model in Female Wistar Rats ...

    African Journals Online (AJOL)

    Indomethacin-Induced Gastric Ulcer: Model in Female Wistar Rats. ... In this regard, an animal model experiment was carried-out to determine the ulcer-dose of indomethacin on female Wistar rats. Based on this objective, ... from 32 Countries:.

  18. Patterns of blood pressure variability in normotensive and hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; He, J; Wagner, A J

    1995-01-01

    We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR)...... the day; less pronounced in 2K,1C; and not detectable in SHR. There are regular patterns of blood pressure fluctuations and specific modifications to the patterns by different forms of hypertension.......We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR...

  19. fetal contamination with cadmilim following chronic exposure of rat ...

    African Journals Online (AJOL)

    FETAL CONTAMINATION WITH CADMILIM FOLLOWING CHRONIC. EXPOSURE OF RAT DAMS DURING GESTATION ... UNIVERSITY OF PORT HARCOURT, PORT HARCOURT,'NIGERIA. ABSTRACT. Pregnant albino rats (n = 5) ..... Friberg, (1988) Biological monitoring of toxic metals, New York, London, Plenum Press,.

  20. Hepatitis E Virus in Rats, Los Angeles, California, USA

    Science.gov (United States)

    Purcell, Robert H.; Engle, Ronald E.; Rood, Michael P.; Kabrane-Lazizi, Yamina; Nguyen, Hanh T.; Govindarajan, Sugantha; St. Claire, Marisa

    2011-01-01

    The role of rats in human hepatitis E virus (HEV) infections remains controversial. A genetically distinct HEV was recently isolated from rats in Germany, and its genome was sequenced. We have isolated a genetically similar HEV from urban rats in Los Angeles, California, USA, and characterized its ability to infect laboratory rats and nonhuman primates. Two strains of HEV were isolated from serum samples of 134 wild rats that had a seroprevalence of antibodies against HEV of ≈80%. Virus was transmissible to seronegative Sprague-Dawley rats, but transmission was spotty and magnitude and duration of infection were not robust. Viremia was higher in nude rats. Serologic analysis and reverse transcription PCR were comparably sensitive in detecting infection. The sequence of the Los Angeles virus was virtually identical to that of isolates from Germany. Rat HEV was not transmissible to rhesus monkeys, suggesting that it is not a source of human infection. PMID:22172320

  1. Effect of simulated weightlessness on energy metabolism in the rat

    Science.gov (United States)

    Jordan, J. P.; Sykes, H. A.; Crownover, J. C.; Schatte, C. L.; Simmons, J. B., II; Jordan, D. P.

    1982-01-01

    Results of measurements of food uptake and body weight changes occurring in rats suspended from a harness so that the antigravity muscles were not used for locomotion are presented. The rats were tested in pairs, with both in a harness but only one suspended off its hind legs; this section lasted 7 days. A second phase of the experiment involved feeding the nonsuspended rat the same amount of food the experimental rat had consumed the previous day. All rats experienced decreased in body weight and food intake in the first stage, while in the second stage the suspended rat lost more weight. The total oxygen uptake, CO2 output, and rate of C-14O2 production were depressed in the suspended rats, then returned to normal levels once the rats were back on the ground. It is concluded that the gross metabolic processes are unaffected by simulated weightlessness.

  2. Tachykinins and tachykinin-receptors in the rat pineal gland

    DEFF Research Database (Denmark)

    Mukda, S; Chetsawang, B; Govitrapong, P

    2005-01-01

    High-pressure liquid chromatography of extracts of rat pineal glands, followed by radio immunological analysis with antibodies against tachykinins, demonstrated the presence of substance P, neurokinin A and neurokinin B in the superficial rat pineal gland. Immunohistochemistry on perfusion...

  3. Changes in Renal Function and Oxidative Status Associated with the Hypotensive Effects of Oleanolic Acid and Related Synthetic Derivatives in Experimental Animals.

    Directory of Open Access Journals (Sweden)

    Hlengiwe Pretty Madlala

    Full Text Available The triterpene oleanolic acid (OA is known to possess antihypertensive actions. In the present study we to compared the effects of the triterpene on mean arterial blood pressure (MAP and kidney function following acute administration in normotensive animals with those of its related oleanane synthetic derivatives (brominated oleanolic acid, Br-OA and oleanolic acid methyl ester, Me-OA. We also used experimental models of hypertension to further explore the effects of sub-chronic oral OA treatment and evaluated influences on oxidative status.OA was extracted from dried flower buds of Syzygium aromaticum using a previously validated protocol in our laboratory. Me-OA and Br-OA were synthesized according to a method described. Rats were supplemented with lithium chloride (12 mmol L-1 prior to experimentation in order to raise plasma lithium to allow measurements of lithium clearance and fractional excretion (FELi as indices of proximal tubular Na+ handling. Anaesthetized animals were continuously infused via the right jugular with 0.077M NaCl. MAP was measured via a cannula inserted in the carotid artery, and urine was collected through a cannula inserted in the bladder. After a 3.5 h equilibration, MAP, urine flow, electrolyte excretion rates were determined for 4 h of 1 h control, 1.5 h treatment and 1.5 h recovery periods. OA, Me-OA and Br-OA were added to the infusate during the treatment period. We evaluated sub-chronic effects on MAP and kidney function in normotensive Wistar rats and in two animal models of hypertension, spontaneously hypertensive rats (SHR and Dahl salt-sensitive (DSS rats, during 9-week administration of OA (p.o.. Tissue oxidative status was examined in these animals at the end of the study. Increasing evidence suggests that and renal function disturbances and oxidative stress play major roles in the pathogenesis of hypertension.Acute infusion OA and oleanane derivatives displayed qualitatively similar effects in decreasing

  4. High prevalence of rat hepatitis E virus in wild rats in China.

    Science.gov (United States)

    Li, Wei; Guan, Dawei; Su, Juan; Takeda, Naokazu; Wakita, Takaji; Li, Tian-Cheng; Ke, Chang Wen

    2013-08-30

    Serum samples from a total of 713 wild rats captured in Zhanjiang city in China from December 2011 to September 2012 were investigated for the prevalence of rat hepatitis E virus (HEV) by exploring rat HEV-specific antibodies and RNA. By an ELISA based on recombinant rat HEV-like particles (HEV-LPs), 23.3% (166/713) of the rats were positive for anti-HEV IgG, and 8.3% (59/713) were positive for anti-HEV IgM. The IgG-positive rates in Rattus norvegicus, Bandicota indica, Rattus flavipectus, Rattus rattoides losea, and Rattus rattus hainanus, were 27.8% (64/230), 23.0% (40/174), 19.9% (34/171), 21.5% (26/121), and 11.8% (2/17), while the IgM-positive rates were 8.3% (19/230), 6.9% (12/174), 8.2% (14/171), 10.7% (13/121), and 5.9% (1/17), respectively. The IgG-positive rate of the rats captured in rural areas, 24.1% (84/348), was higher than that in the central area of Zhanjiang city, 15.1% (32/212). The highest IgG-positive rates, as high as 45.3% (39/86), were detected in wild rats trapped in the garbage dump. Twelve of the 59 IgM-positive serum samples were positive for HEV RNA, which was detected in all of the wild rat species except R. rattus hainanus. A phylogenetic analysis of the partial genome of rat HEV ORF1 indicated that all of the 12 HEV strains belong to rat HEV, and no other genotype HEV were detected. The rat HEV from Zhangjiang city could be classified into three separated clusters, suggesting that the infection due to rat HEV with a variety of genome entities occurs extensively among wild rats in China. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Clinical Evalualtion in Isoflurane and Sevoflurane Anesthesia in Rat

    OpenAIRE

    Flavia Ruxanda; Lucia Victoria Bel; Cristian Adrian Raţiu; Viorel Miclăuş; Cosmin Peştean; Liviu Ioan Oana

    2016-01-01

    The present study focused on evaluation of induction, maintenance and emergence of inhaled anesthesia and comparison of these anesthetics times for isoflurane and sevoflurane. The biological material consisted of 12 Wistar rats divided into 2 groups, each containing a number of 6 rats. One group was anesthetized with isoflurane and the other with sevoflurane. We monitorized the rats during all stages of anesthesia, observing how the induction established, the state of the rats throughout the ...

  6. Diabetic rat testes: morphological and functional alterations.

    Science.gov (United States)

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M

    2009-12-01

    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  7. A rat model for hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Yannick Debing

    2016-10-01

    Full Text Available Hepatitis E virus (HEV is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans. As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains. Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies.

  8. The queer life of a lab rat.

    Science.gov (United States)

    Pettit, Michael

    2012-08-01

    The laboratory rat is an important, if neglected, actor in the history of sexuality. From the 1920s and 1940s, a series of reports emerged from American psychology laboratories detailing instances of spontaneous "reversals" in sexual behavior within their rat colonies. Frank Beach, then at the American Museum of Natural History, developed a model for the "nature" of sexuality that stressed that all organisms had the neurological capacity to perform behavior of either sex. Beach enrolled his emerging specialty, behavioral endocrinology, in support of Alfred Kinsey's controversial findings. Both scientists highlighted the multitude of potential sexual outlets pursued by organisms and the prevalence of nonprocreative sexual behaviors. This article draws on elements of queer theory to elucidate how the landscape of the comparative psychologist's rat colony with its organisms, apparatus, practices, and rituals served an integral function in the redefinition of sex in the 20th century. Queer theory calls into question easy proclamations about what counts as natural or normal by drawing attention to the presumed binaries that frequently govern the classification of sex. The maintenance of the colony required the careful management of sex with its obstruction devices, hypersexualized indicator animals, segregation cages, and castrated rats injected with hormones. Moreover, Beach's own writings indicate how his own domestic life became entangled with the sex lives of the rats. An irony animates this Rockefeller-funded sexology: Research funded to elucidate the mechanisms underlying heterosexuality came to question its innateness and universality. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  9. Scene and object vision in rats.

    Science.gov (United States)

    Simpson, E L; Gaffan, E A

    1999-02-01

    Dark Agouti rats learned to discriminate large visual displays ("scenes") in a computer-controlled Y-maze. Each scene comprised several shapes ("objects") against a contrasting background. The constant-negative paradigm was used; in each problem, one constant scene was presented on every trial together with a trial-unique variable scene, and rats were rewarded for approaching the variable scene. By varying the manner in which variables differed from the constant, we investigated what aspects of scenes and the objects comprising them were salient. In Experiment 1, rats discriminated constant scenes more easily if they contained four objects rather than six, and they showed a slight attentional bias towards the lower halves of the screens. That bias disappeared in Experiment 2. Experiments 3 and 4 showed that rats could discriminate scenes even if the objects that comprised them were closely matched in position, luminance, and area. Therefore, they encoded the form of individual objects. Rats perceived shapes of the same class (e.g. two ellipses) as more similar than shapes from different classes (e.g. ellipse and polygon) regardless of whether they also differed in area. This paradigm is suitable for studying the neuropsychology of perceiving spatial relationships in multi-object scenes and of identifying visual objects.

  10. Working Memory Systems in the Rat.

    Science.gov (United States)

    Bratch, Alexander; Kann, Spencer; Cain, Joshua A; Wu, Jie-En; Rivera-Reyes, Nilda; Dalecki, Stefan; Arman, Diana; Dunn, Austin; Cooper, Shiloh; Corbin, Hannah E; Doyle, Amanda R; Pizzo, Matthew J; Smith, Alexandra E; Crystal, Jonathon D

    2016-02-08

    A fundamental feature of memory in humans is the ability to simultaneously work with multiple types of information using independent memory systems. Working memory is conceptualized as two independent memory systems under executive control [1, 2]. Although there is a long history of using the term "working memory" to describe short-term memory in animals, it is not known whether multiple, independent memory systems exist in nonhumans. Here, we used two established short-term memory approaches to test the hypothesis that spatial and olfactory memory operate as independent working memory resources in the rat. In the olfactory memory task, rats chose a novel odor from a gradually incrementing set of old odors [3]. In the spatial memory task, rats searched for a depleting food source at multiple locations [4]. We presented rats with information to hold in memory in one domain (e.g., olfactory) while adding a memory load in the other domain (e.g., spatial). Control conditions equated the retention interval delay without adding a second memory load. In a further experiment, we used proactive interference [5-7] in the spatial domain to compromise spatial memory and evaluated the impact of adding an olfactory memory load. Olfactory and spatial memory are resistant to interference from the addition of a memory load in the other domain. Our data suggest that olfactory and spatial memory draw on independent working memory systems in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Renal alterations in prediabetic rats with periodontitis

    DEFF Research Database (Denmark)

    Andersen, Carla Cruvinel Pontes; Holmstrup, Palle; Buschard, Karsten

    2008-01-01

    BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim of the p......BACKGROUND: Periodontitis was shown to have an impact on glucose levels in prediabetic and diabetic rats. The Zucker fatty rat (ZFR) is a well-characterized model of prediabetes presenting with impaired glucose tolerance, hyperinsulinemia, dyslipidemia, and moderate hypertension. The aim...... of the present study was to investigate whether periodontitis influences kidney changes in ZFRs. METHODS: Male adult ZFRs (N = 19) and their lean littermates (N = 18) were studied. Periodontitis was induced with ligatures in half of the ZFRs and lean rats, whereas the other half served as controls. After 4 weeks...... IValpha1, fibronectin, and nephrin. Urinary albumin excretion and creatinine clearance were also evaluated. RESULTS: In prediabetic ZFRs, periodontitis was associated with kidney hypertrophy (P = 0.03) and a tendency for increased glomerular volume (P = 0.06). In lean littermates, elevated fibronectin m...

  12. Middle ear mucosa in rats and humans.

    Science.gov (United States)

    Albiin, N; Hellström, S; Stenfors, L E; Cerne, A

    1986-01-01

    The purposes of the study were to review thoroughly the literature and summarize it in a standardized fashion; to study the mucosa, including the distribution of mast cells, in all parts of the middle ear cavity in rats; and to compare the experimental findings with those known in humans. Adult, healthy rats were studied by light, scanning electron, and transmission electron microscopic techniques. The ciliated and secretory cells of the rat tympanic cavity are confined to two tracts, one anterior and one inferoposterior to the promontory. The tracts connect the epitympanum with the eustachian tube. The pars flaccida exhibits the highest density of mast cells, but mast cells are also distributed in the subepithelial layer of the tracts and in the floor of the tympanic bulla. The structure of the rat mucosa shows striking similarities to that of humans. Thus, from a morphological point of view, the rat seems to be a suitable model for middle ear studies. However, to be able to compare results obtained in different species and/or different laboratories, the areas of the middle ear from which the specimens have been taken must be carefully defined and presented in a standardized manner.

  13. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  14. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Science.gov (United States)

    Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

  15. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation.

    Science.gov (United States)

    Yderstraede, K B; Starklint, H; Steinbruchel, D; Jørgensen, T W; Gotfredsen, C F

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding.

  16. Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Linton, EA; Sargent, IL; Redman, CWG

    OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 mu g/kg body weight). For comparison, rats with normal

  17. Histological changes of the adult albino rats entorhinal cortex under ...

    African Journals Online (AJOL)

    Ibrahim K. Ragab

    2016-06-03

    Jun 3, 2016 ... entorhinal cortex of the adult male albino rats. Materials and methods: The study was carried out on 40 adult male rats. The rats were divided equally into two groups: control group, ..... cerebral cortex consequently leads to development of oxida- tive stress.37. In this study, light microscopic examination of ...

  18. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats

    NARCIS (Netherlands)

    Waalkens-Berendsen, D.H.; Kuilman-Wahls, M.E.M.; Bär, A.

    2004-01-01

    The embryotoxicity/teratogenicity of neohesperidin dihydrochalcone (NHDC) was examined in Wistar Crl:(WI)WU BR rats. NHDC was fed at dietary concentrations of 0, 1.25, 2.5 or 5 to groups of 28 mated female rats from day 0 to 21 of gestation. At Cesarean section 25, 22, 23, and 23 rats were found to

  19. antidiabetic effect of emilia sonchifora in dithizone diabetic rats

    African Journals Online (AJOL)

    The antidiabetic effect of a crude extract of Emilia sanchifora leaves was studied in rats with dithizone induced diabetes in rat. Three different concentrations of the crude chloroform – methanol extract were given orally to both normal and diabetic rats. The percentage blood glucose reduction for ES1 was 33.3, 14.2, 45.9, ...

  20. Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

    NARCIS (Netherlands)

    Price, R.J.; Scott, M.P.; Walters, D.G.; Stierum, R.H.; Groten, J.P.; Meredith, C.; Lake, B.G.

    2004-01-01

    The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets

  1. 1 and CTGF in Rats with Early Diabetic Nephropathy

    African Journals Online (AJOL)

    Methods: Thirty-two rats were divided into 4 groups: normal control (NC), DN, and DN-treated with TG .... were cut at 80 - 90 nm, mounted on copper grids, ... RESULTS. Effect of TG on fasting BG and urine biochemical parameters. After the establishment of DN rat model, the DN rats appeared polydipsia, polyuria and.

  2. Gravimetric and Histologic Changes in Rat Testes Following Oral ...

    African Journals Online (AJOL)

    Hence the effect(s) of orally administered low doses of Congo red (CR) on rat testes was investigated using gravimetric and histologic methods. When compared to CR-free rats, the testes weights of rats exposed to 10, 20, 30 and 40mg CR/kg body weight (once a week for 6 weeks) significantly decreased (p < 0.05).

  3. Rat1p maintains RNA polymerase II CTD phosphorylation balance

    DEFF Research Database (Denmark)

    Jimeno-González, Silvia; Schmid, Manfred; Malagon, Francisco

    2014-01-01

    In S. cerevisiae, the 5'-3' exonuclease Rat1p partakes in transcription termination. Although Rat1p-mediated RNA degradation has been suggested to play a role for this activity, the exact mechanisms by which Rat1p helps release RNA polymerase II (RNAPII) from the DNA template are poorly understoo...

  4. Changes in activities of tissues enzymes in rats administered Ficus ...

    African Journals Online (AJOL)

    This study evaluates the effects of methanolic extract of Ficus exasperata leaf on the activities of some enzymes in the serum, liver, kidney and heart of albino rats. Twenty four rats were sorted into four groups: Group A (control) received distilled water while rats in groups B, C and D were administered graded doses.

  5. Bile secretion in albino rat following chronic honey intake | Alagwu ...

    African Journals Online (AJOL)

    This study was carried out to evaluate the effect of honey intake on bile secretion, bile electrolytes, bilirubin and cholesterol levels including plasma cholesterol in albino rats. 20 male albino rats (200-210g) were used in the study. The rats were assigned randomly into 2 groups (control and honey-fed groups), each group ...

  6. Honey increases sperm count in male albino rats by enhancing ...

    African Journals Online (AJOL)

    We investigated the effects of different doses of honey (H) and testosterone (T) on sperm count and reproductive hormones in male albino rats. Thirty-five male albino rats were randomly divided in a blinded fashion into 7 groups of 5 rats each. Group 1 (control) was given 0.2 ml of distilled water. Groups 2, 3 and 4 were ...

  7. Rat islet isolation yield and function are donor strain dependent

    NARCIS (Netherlands)

    de Groot, M; de Haan, BJ; Schuurs, TA; van Schilfgaarde, R; Leuvenink, HGD; KEIZER, J

    Effective rat islet isolation is pertinent for successful islet transplantation and islet studies in vitro. To determine which rat strain yields the highest number of pure and functional islets, four commonly used rat strains were compared with regard to islet yield, islet purity and islet function.

  8. Biochemical and histological changes in female wistar rats following ...

    African Journals Online (AJOL)

    This study was aimed at investigating the effect of aqueous extract of Mangifera indica leaves on some biochemical parameters and histology of liver, kidney and small intestine of rats. Twenty female rats (142.30 ± 7.56 g) were randomly assigned into four groups A, B, C and D. The rats were administered orally 1 mL of ...

  9. Dichloroacetate prevents hypoxic lactic acidosis in rats | Bosco ...

    African Journals Online (AJOL)

    For the induction of hypoxia, the rats were given to inspire a gas mixture containing 11% O2 during 45 minutes. There were 20 rats in the dichloroacetate group and 20 in the control group. The dichloroacetate group rats were given dichloroacetate 300 mg/kg in slow IV injection before the induction of hypoxia. We measured ...

  10. Pathogenicity of Trypanosoma brucei in African giant rats ...

    African Journals Online (AJOL)

    Pathogenicity of Trypanosoma brucei in African giant rats ( Cricetomys gambianus , Water House) ... The course of trypanosomosis was investigated over a period of two weeks in six African giant rats (Cricetomys gambianus) experimentally infected with Trypanosoma brucei. Six other rats served as uninfected control.

  11. Haematological and Serum Biochemical Variables in rats Treated ...

    African Journals Online (AJOL)

    The haematology and serum biochemical effects of oral administration of the ethanolic extract of the root of Moringa oleifera at 50, 100 and 150 mg/kg were investigated in 30 mated female Wistar rats. The rats were assigned into five groups of six rats each. Group A was given 50mg/kg of the extract; group B, 100mg/kg; ...

  12. Using giant African pouched rats to detect tuberculosis in human ...

    African Journals Online (AJOL)

    Giant African pouched rats previously have detected tuberculosis (TB) in human sputum samples in which the presence of TB was not initially detected by smear microscopy. Operant conditioning principles were used to train these rats to indicate TB-positive samples. In 2010, rats trained in this way evaluated 26,665 ...

  13. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  14. [Auto- and xenotransplantation of testicular organ culture to castrated rats and rats with experimental hypogonadism].

    Science.gov (United States)

    Potikha, O P; Chelnakova, I S; Turchin, I S

    1993-01-01

    The organ culture from the testes of newborn pigs able to produce the basic androgens such as testosterone, dehydroepiandrosterone, androstenedione and androstenediol has been obtained. CdCl2 administration to the rats in a dose of 0.055 mg/100 g of body weight and gonadectomy resulted in the development of two experimental models of hypogonadism. Autotransplantation of organ culture from the rat testes and xenotransplantation of the testes from newborn pigs to the rats with experimental hypogonadism provoked an increase in blood plasma testosterone for 1.5 and 3 months, respectively. Organ cultures from the testes of newborn pigs can be recommended for clinical purposes.

  15. Efficacy of antimicrobial therapy in experimental rat pneumonia: antibiotic treatment schedules in rats with impaired phagocytosis.

    Science.gov (United States)

    Bakker-Woudenberg, I A; van Gerwen, A L; Michel, M F

    1979-07-01

    Pneumococcal pneumonia in rats with intact host defense mechanisms could be successfully cured by penicillin. The efficacy of this antibiotic therapy was lost in cobra venom factor-treated rats which had selectively impaired phagocytic functions. In these animals the effect of penicillin therapy was improved by increasing the daily dose and the frequency of injections and by earlier initiation of the therapy. The efficacy of penicillin in the cobra venom facttor-treated rats was restored either by markedly increasing the daily dose of penicillin or by increasing the daily dose in combination with a reduced interval of the penicillin injections.

  16. Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

    Science.gov (United States)

    Díaz-Morán, Sira; Palència, Marta; Mont-Cardona, Carme; Cañete, Toni; Blázquez, Gloria; Martínez-Membrives, Esther; López-Aumatell, Regina; Tobeña, Adolf; Fernández-Teruel, Alberto

    2012-03-01

    The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Opportunity Leaves a Trail of 'Rat' Holes

    Science.gov (United States)

    2004-01-01

    NASA's Mars Exploration Rover Opportunity's rock abrasion tool, known informally as the 'Rat,' has nibbled seven holes into the slope of 'Endurance Crater.' This image from the rover's navigation camera was released previously (PIA06716) without the Rat holes labeled so that viewers could try to find the holes themselves. Here, the holes have been identified. Starting from the uppermost pictured (closest to the crater rim) to the lowest, the Rat hole targets are: 'Tennessee,' 'Cobblehill,' 'Virginia,' 'London,' 'Grindstone,' 'Kettlestone,' and 'Drammensfjorden.' These holes were drilled on sols 138 (June 13, 2004), 143 (June 18), 145 (June 20), 148 (June 23), 151 (June 26), 153 (June 28) and 161 (July 7), respectively. Each hole is 4.5 centimeters (1.8 inches) in diameter.

  18. Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands

    NARCIS (Netherlands)

    Franssen, Frits; Swart, Arno; van Knapen, Frans|info:eu-repo/dai/nl/070114749; van der Giessen, Joke

    2016-01-01

    BACKGROUND: Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We

  19. Rat pancreatic beta cells and cytomegalovirus infection.

    Science.gov (United States)

    Smelt, Maaike J; Faas, Marijke M; de Haan, Bart J; Hofstede, Jeroen; Cheung, Chi-Wai; van der Iest, Hanna; de Haan, Aalzen; de Vos, Paul

    2010-01-01

    Cytomegalovirus (CMV) infection has been suggested to accelerate beta-cell destruction and thereby to contribute to new-onset diabetes and failure of islet allografts in both humans and rodents. Surprisingly, direct CMV infection of beta cells has received only minor attention. Therefore, we investigated the susceptibility of rat beta cells for rat CMV (RCMV) infection and the direct effects on the regulation of immune cell-activating ligands. Primary rat beta cells, the rat beta-cell line Rin-m5F, and fibroblasts were RCMV-infected in vitro. The viral gene and protein expression levels were determined as a measure for RCMV susceptibility. Gene expression levels of intracellular adhesion molecule 1, lymphocyte function associated antigen 3, rat major histocompatibility complex region A, rat major histocompatibility complex region E, toll like receptor 2, and clustered domain 14 were determined as a measure for cellular immunogenicity. We demonstrate that beta cells are susceptible for RCMV infection but allow only low levels of viral gene expression. In contrast, infected fibroblasts demonstrated productive viral infection and formation of viral progeny. After RCMV infection, beta-cell immunogenicity was markedly increased, as demonstrated by the increased cellular expression of immune cell-activating ligands. Direct beta-cell infection by RCMV and subsequent low-grade viral gene expression may lead to increased immunogenicity of native or transplanted beta cells in vivo. An infection-induced enhanced beta-cell recognizability may have important consequences for beta-cell survival and the development of diabetes or rejection of islet grafts.

  20. [Vitamins in rat experimental diets].

    Science.gov (United States)

    Kodentsova, V M; Beketova, N A; Vrzhesinskaia, O A

    2012-01-01

    A comparison of full semisynthetic diets used in different laboratories has shown that its vitamin content covers physiological requirements of rats in these micronutrients. The significant fluctuations in group B vitamin concentrations may take place when one uses brewer's yeast as a source of these vitamins. A preliminary assessment of vitamin content in brewer's yeasts is required in this case. An essential contribution of basic components in diet vitamin content must be taken in consideration when one creates a vitamin-deficient diet. Casein contains substantial amounts of group B vitamins and vitamin D. Therefore decontamination of casein from water and / or fat-soluble vitamins or the use of commercial purified casein is required. Vegetable oils are usually used as a fatty component of a diet and they simultaneously serve as an additional source of vitamin E. A choice of naturally containing vitamin E oil as a fat component of a diet is crucial for the creating an alimentary deficiency of vitamin E. The content of fat-soluble vitamins in the diet of control group (group of comparison) and vitamin level in the diet of experimental group of animals must be equivalent in investigations with modified (quality and quantitative) fat diet component. Caloric restriction by simple reducing of food without increasing the amount of vitamins to an adequate level is incorrect. With these considerations in mind proper attention to the equivalence of vitamin content in the diet of animals in experimental and control groups should be paid during experiments scheduling. Otherwise, the studies carried out under deficient or excessive intake of vitamins can lead to incorrect interpretation of the results and difficulties in their comparison with the data obtained under different conditions.

  1. Characterization of rat lung ICAM-1

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Schmal, H

    1998-01-01

    studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression. TREATMENT: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor alpha...... (TNFalpha). In vivo immunoglobulin G (IgG) immune complex-induced lung injury was employed. METHODS: Enzyme-linked immunoassay (ELISA) Western and Northern blot analyses and immunohistochemical evaluations were performed. All experiments were done at least in duplicate. Data were analyzed by two...

  2. Tryptophan depletion affects compulsive behaviour in rats

    DEFF Research Database (Denmark)

    Merchán, A; Navarro, S V; Klein, A B

    2017-01-01

    RATIONALE: Compulsive behaviour, present in different psychiatric disorders, such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of monoamines, particularly serotonin (5-hydroxytryptamine) and its receptor system. OBJECTIVES: The present study......-free diet (T-) or a TRP-supplemented diet (T+) RESULTS: The TRP depletion diet effectively reduced 5-HT levels in the frontal cortex, amygdala and hippocampus in both strains of rats. The TRP-depleted HD Wistar rats were more sensitive to 5-HT manipulation, exhibiting more licks on SIP than did the non...

  3. [Asenic accumulation following realgar administration in rats].

    Science.gov (United States)

    Li, Chunying; Liang, Aihua; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bin; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg; Zhang, Boli

    2011-07-01

    To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic. The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing. Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain. Asenic can be

  4. Oxidative stress in normal and diabetic rats.

    Science.gov (United States)

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pC18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

  5. Nerve excitability in the rat forelimb

    DEFF Research Database (Denmark)

    Arnold, Ria; Moldovan, Mihai; Rosberg, Mette Romer

    2017-01-01

    a novel setup to explore the ulnar nerve excitability in rodents. We provide normative ulnar data in 11 adult female Long Evans rats under anaesthesia by comparison with tibial and caudal nerves. Additionally, these measures were repeated weekly on 3 occasions to determine the repeatability of these tests....... Results Nerve excitability assessment of ulnar nerve proved to be a longitudinally repeatable measure of axonal function mature in rats, as were measures in tibial and caudal nerves. Comparison with existing method: Ulnar nerve motor excitability measures were different from the caudal and tibial...

  6. Guanethidine-induced sympathectomy in the nude rat

    DEFF Research Database (Denmark)

    Juul, A; Juul, P; Christensen, H B

    1989-01-01

    part of the nerve cells accompanied by an increased number of small mononuclear inflammatory cells. The extent of chromatolysis and nerve cell death induced by guanethidine did not differ between normal and nude rats, whereas the increase of the number of mononuclear cells was lower in the nude rats...... than in the normal rats (163 and 268 per cent respectively of the saline treated controls, P less than 0.01). Since guanethidine induced nerve cell death in the T-cell deficient nude rat to the same extent as in normal rats, it is concluded, that the effect is caused by either a thymus...

  7. The oncogenic action of ionizing radiation on rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.

    1991-01-01

    Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs.

  8. Effect of lactoferrin on rat osteoblast proliferation

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2016-10-01

    Full Text Available Objective: To investigate the effect of lactoferrin on osteoblastic proliferation of rats and to explore the possible mechanisms. Methods: Isolation and purification of rat osteoblasts were performed, the second generation of osteoblasts in the logarithmic growth phase were tested. Osteoblast cells were seeded into the porous plate, adding lactoferrin solution to the final concentration 0.1 μg/mL, 1 μg/mL, 10 μg/mL and 100 μg/mL, respectively, set up the control group (lactoferrin concentration was 0 μg/mL, rat osteoblast cells proliferation was detected by MTT method, insulin-like growth factor-1 (IGF-1 mRNA expression was detected by fluorescence quantitative PCR (real-time PCR. Results: MTT results showed that compared with the 0 μg/mL group, the number of rat osteoblast cells in the other concentration groups increased significantly (P<0.05 except in the 0.1 μg/mL group; The number of 3 d and 5 d rat osteoblasts in 1 μg/mL group was significantly higher than that in 0 μg/mL group, the number of 1 d, 3 d, 5 d and 7 d rat osteoblasts in 10 μg/mL and 100 μg/mL group was significantly higher than that in 0 μg/mL group (P<0.05; With the extension of time, the number of rat osteoblasts in each concentration group was significantly increased with the increase of the concentration, the number of 7 d rat osteoblasts in the 100 μg/mL group was the highest. Real-time PCR results showed that different concentrations of lactoferrin could promote rat osteoblast cells IGF-1 mRNA expression and was dose dependent. The 7 d IGF-1 mRNA expression in 0.1 μg/mL group was significantly higher than that in 0 μg/mL group, the 3 d, 5 d and 7 d IGF-1 mRNA expression in 1 μg/mL and 10 μg/mL were significantly higher than that in 0 μg/mL group, the 1 d, 3 d, 5 d and 7 d IGF-1 mRNA expression in 100 μg/mL were significantly higher than that in 0 μg/mL group (P<0.05; With the extension of time, the expression of rat osteoblasts IGF-1 mRNA in each

  9. Rat hepatitis E virus: geographical clustering within Germany and serological detection in wild Norway rats (Rattus norvegicus).

    Science.gov (United States)

    Johne, Reimar; Dremsek, Paul; Kindler, Eveline; Schielke, Anika; Plenge-Bönig, Anita; Gregersen, Henrike; Wessels, Ute; Schmidt, Katja; Rietschel, Wolfram; Groschup, Martin H; Guenther, Sebastian; Heckel, Gerald; Ulrich, Rainer G

    2012-07-01

    Zoonotic hepatitis E virus (HEV) infection in industrialised countries is thought to be caused by transmission from wild boar, domestic pig and deer as reservoir hosts. The detection of HEV-specific antibodies in rats and other rodents has suggested that these animals may represent an additional source for HEV transmission to human. Recently, a novel HEV (ratHEV) was detected in Norway rats from Hamburg, Germany, showing the typical genome organisation but a high nucleotide and amino acid sequence divergence to other mammalian and to avian HEV strains. Here we describe the multiple detection of ratHEV RNA and HEV-specific antibodies in Norway rats from additional cities in north-east and south-west Germany. The complete genome analysis of two novel strains from Berlin and Stuttgart confirmed the association of ratHEV to Norway rats. The present data indicated a continuing existence of this virus in the rat populations from Berlin and Hamburg. The phylogenetic analysis of a short segment of the open reading frame 1 confirmed a geographical clustering of the corresponding sequences. Serological investigations using recombinant ratHEV and genotype 3 capsid protein derivatives demonstrated antigenic differences which might be caused by the high amino acid sequence divergence in the immunodominant region. The high amount of animals showing exclusively ratHEV RNA or anti-ratHEV antibodies suggested a non-persistent infection in the Norway rat. Future studies have to prove the transmission routes of the virus in rat populations and its zoonotic potential. The recombinant ratHEV antigen generated here will allow future seroepidemiological studies to differentiate ratHEV and genotype 3 infections in humans and animals. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Sympathetically-mediated thermogenic response to food in rats.

    Science.gov (United States)

    Liverini, G; Iossa, S; Lionetti, L; Mollica, M P; Barletta, A

    1995-02-01

    The aim of this work was to assess the participation of the sympathetic nervous system in the thermogenic response to food in control and hyperphagic rats. Rats were fed either a control (CD) or energy dense (ED) diet. After 15 days, CD rats received a small (7 kJ) meal composed of either control or energy dense diet, while ED rats received a small meal composed of energy dense diet. The experiment was then repeated, with the exception that rats received a larger portion (35 kJ) of the test meal. The postprandial increase in oxygen consumption was measured for 30 min after the small meal and 90-180 min after the completion of the large meal. The measurements were made in saline-injected and propranolol-injected rats. ED rats exhibited hyperphagia as well as an increase of 32% in resting metabolic rate after a 16 h fast. The sympathetically-mediated postprandial increase in oxygen consumption was greater after an energy dense meal than after a control meal in CD rats, and was higher in ED rats than in CD rats fed an energy dense meal. It was concluded that the sympathetically-mediated increase in the thermogenic response to food, as well as the increase in fasting metabolic rate can help prevent obesity development in hyperphagic rats.

  11. Oxytocin and vasopressin in rat hypophysial portal blood: experimental studies in normal and Brattleboro rats.

    Science.gov (United States)

    Horn, A M; Robinson, I C; Fink, G

    1985-02-01

    Oxytocin (OT) and vasopressin (VP) were measured by radioimmunoassay in hypophysial portal and peripheral blood from male Wistar rats and heterozygous and homozygous Brattleboro rats anaesthetized with urethane. In Wistar rats the concentrations of OT and VP were about 50 times greater than the concentrations in peripheral blood, whether or not the pituitary gland was left in situ during collection, and also considerably greater than the reported concentrations of the peptides in the cerebrospinal fluid. The release of both peptides was increased significantly by a lesion of the supraoptico-hypophysial tract that led to diabetes insipidus, but which left intact the external layer of the median eminence (ME). Concentrations of VP were undetectable in plasma from homozygous Brattleboro rats, but the portal plasma concentrations of VP in heterozygous Brattleboro rats were not significantly lower than in Wistar rats. The concentrations of OT in portal plasma from both types of Brattleboro rat were significantly higher than in Wistar rats. The output of VP and OT into hypophysial portal blood of Wistar rats was not significantly affected by electrical stimulation of the suprachiasmatic, supraoptic or paraventricular nuclei or the ME using two types of stimuli, one of which produced an increase in peripheral plasma concentrations of VP and OT in intact rats and a significant increase in the release of LH-releasing hormone into hypophysial portal blood. The output of VP and OT into portal blood was also not significantly affected by either adrenalectomy with or without injection of dexamethasone or the injection of either the 5-hydroxytryptamine (5-HT) synthesis blocker, parachlorophenylalanine, or the 5-HT uptake blockers, alaproclate or zimelidine. These results show that large amounts of OT as well as VP are released into hypophysial portal blood from fibres of the hypothalamo-neurohypophysial system that terminate in the external layer of the ME. Although distinct

  12. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes......, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe...... in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable...

  13. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    was normalized. Rat PTH 1-84 stimulated in vitro the PHA-induced proliferation of T cells in a dose dependent manner. This effect was significant in CRF rat lymphocytes, but not in lymphocytes obtained from normal rats. Based upon the present results it is suggested that the secondary hyperparathyroidism......Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...... and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After...

  14. Effects of electromagnetic radiation on the hemorheology of rats

    Science.gov (United States)

    Huang, Zhiwei; Tian, Tian; Xiao, Bo; Li, Wen

    2017-01-01

    The current work examines the effects of electromagnetic radiation on the hemorheology to provide an experimental basis for radiation protection. Electromagnetic radiation was generated by a Helmholtz coil constructed from copper wire. There were six rats altogether: three rats in the experimental group, and three rats in the control group. The rats in the experimental group were continuously exposed to radiation for 10 hours every day, and rats in the control group remained in a normal environment. After 30 days, the characteristics of hemorheology of the two groups were compared. The average plasma viscosity, whole blood high shear velocity, and whole blood low shear viscosity were lower in rats in the experimental group than in rats in the control group, while the whole blood shear viscosity was higher in the experimental group than in the control group. Results suggest that long term exposure to electromagnetic radiation does have certain impacts on the cardiovascular system, deeming it necessary to take preventative measures.

  15. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

    Czech Academy of Sciences Publication Activity Database

    Holubová, M.; Zemenová, J.; Mikulášková, Barbora; Panajotová, V.; Stöhr, J.; Haluzík, M.; Kuneš, Jaroslav; Železná, B.; Maletínská, L.

    2016-01-01

    Roč. 229, č. 2 (2016), s. 85-96 ISSN 0022-0795 R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * diet-induced obesity * ZDF rats * food intake rat Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

  16. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

    Czech Academy of Sciences Publication Activity Database

    Holubová, Martina; Zemenová, Jana; Mikulášková, Barbora; Panajotová, V.; Stöhr, J.; Haluzík, M.; Kuneš, Jaroslav; Železná, Blanka; Maletínská, Lenka

    2016-01-01

    Roč. 229, č. 2 (2016), s. 85-96 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * diet-induced obesity * ZDF rats * food intake * rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

  17. Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart control Wistar rats

    OpenAIRE

    Park, Ji Min; Bong, Ha Yoon; Jeong, Hye In; Kim, Yeon Kyoung; Kim, Ji Yeon; Kwon, Oran

    2009-01-01

    Postprandial hypoglycemic effect of mulberry leaf (Morus alba L.) was compared in two animal models: Goto-Kakizaki (GK) rats, a spontaneous non-obese animal model for type II diabetes, and their counterpart control Wistar rats. First, the effect of a single oral administration of mulberry leaf aqueous extract (MLE) on postprandial glucose responses was determined using maltose or glucose as substrate. With maltose-loading, MLE reduced peak responses of blood glucose significantly in both GK a...

  18. Derivation of rat embryonic stem cells and generation of protease-activated receptor-2 knockout rats.

    Science.gov (United States)

    Yamamoto, Satoshi; Nakata, Mitsugu; Sasada, Reiko; Ooshima, Yuki; Yano, Takashi; Shinozawa, Tadahiro; Tsukimi, Yasuhiro; Takeyama, Michiyasu; Matsumoto, Yoshio; Hashimoto, Tadatoshi

    2012-08-01

    One of the remarkable achievements in knockout (KO) rat production reported during the period 2008-2010 is the derivation of authentic embryonic stem (ES) cells from rat blastocysts using a novel culture medium containing glycogen synthase kinase 3 and mitogen-activated protein kinase kinase inhibitors (2i medium). Here, we report gene-targeting technology via homologous recombination in rat ES cells, demonstrating its use through production of a protease-activated receptor-2 gene (Par-2) KO rat. We began by generating germline-competent ES cells from Dark Agouti rats using 2i medium. These ES cells, which differentiate into cardiomyocytes in vitro, can produce chimeras with high ES cell contribution when injected into blastocysts. We then introduced a targeting vector with a neomycin-resistant gene driven by the CAG promoter to disrupt Par-2. After a 7-day drug selection, 489 neomycin-resistant colonies were obtained. Following screening by polymerase chain reaction (PCR) genotyping and quantitative PCR analysis, we confirmed three homologous recombinant clones, resulting in chimeras that transmitted the Par-2 targeted allele to offspring. Par-2 KO rats showed a loss of Par-2 messenger RNA expression in their stomach cells and a lack of PAR-2 mediated smooth muscle relaxation in the aorta as indicated by pharmacological testing. Compared with mice, rats offer many advantages in biomedical research, including a larger body size; consequently, they are widely used in scientific investigation. Thus, the establishment of a gene-targeting technology using rat ES cells will be a valuable tool in human disease model production and drug discovery.

  19. Subretinal transplantation of rat MSCs and erythropoietin gene modified rat MSCs for protecting and rescuing degenerative retina in rats.

    Science.gov (United States)

    Guan, Y; Cui, L; Qu, Z; Lu, L; Wang, F; Wu, Y; Zhang, J; Gao, F; Tian, H; Xu, L; Xu, G; Li, W; Jin, Y; Xu, G-T

    2013-11-01

    For degenerative retinal diseases, like the acquired form exemplified by age-related macular degeneration (AMD), there is currently no cure. This study was to explore a stem cell therapy and a stem cell based gene therapy for sodium iodate (SI)-induced retinal degeneration in rats. Three cell types, i.e., rat mesenchymal stem cells (rMSCs) alone, erythropoietin (EPO) gene modified rMSCs (EPO-rMSCs) or doxycycline (DOX) inducible EPO expression rMSCs (Tet-on EPO-rMSCs), were transplanted into the subretinal spaces of SI-treated rats. The rMSCs were prepared for transplantation after 3 to 5 passages or modified with EPO gene. During the 8 weeks after the transplantation, the rats treated with rMSCs alone or with two types of EPO-rMSCs were all monitored with fundus examination, fundus fluorescein angiography (FFA) and electroretinogram. The transplantation efficiency of donor cells was examined for their survival, integration and differentiation. Following the transplantation, labeled donor cells were observed in subretinal space and adopted RPE morphology. EPO concentration in vitreous and retina of SI-treated rats which were transplanted with EPO-rMSCs or Tet-on EPO-rMSCs was markedly increased, in parallel with the improvement of retinal morphology and function. These findings suggest that rMSCs transplantation could be a new therapy for degenerative retinal diseases since it can protect and rescue RPE and retinal neurons, while EPO gene modification to rMSCs could be an even better option.

  20. Witnessing traumatic events causes severe behavioral impairments in rats.

    Science.gov (United States)

    Patki, Gaurav; Solanki, Naimesh; Salim, Samina

    2014-12-01

    Witnessing a traumatic event but not directly experiencing it can be psychologically quite damaging. In North America alone, ∼30% of individuals who witness a traumatic event develop post-traumatic stress disorder (PTSD). While effects of direct trauma are evident, consequences of indirect or secondary trauma are often ignored. Also unclear is the role of social support in the consequences of these experiences. The social defeat paradigm, which involves aggressive encounters by a large Long-Evans male rat (resident) towards a smaller Sprague-Dawley male rat (intruder), is considered a rodent model of PTSD. We have modified this model to create a trauma witness model (TWM) and have used our TWM model to also evaluate social support effects. Basically, when an intruder rat is placed into the home cage of a resident rat, it encounters an agonistic behavior resulting in intruder subordination. The socially defeated intruder is designated the SD rat. A second rat, the cage mate of the SD, is positioned to witness the event and is the trauma witnessing (TW) rat. Experiments were performed in two different experimental conditions. In one, the SD and TW rats were cagemates and acclimatized together. Then, one SD rat was subjected to three sessions of social defeat for 7 d. TW rat witnessed these events. After each social defeat exposure, the TW and SD rats were housed together. In the second, the TW and SD rats were housed separately starting after the first defeat. At the end of each protocol, depression-anxiety-like behavior and memory tests were conducted on the SD and TW rats, blood withdrawn and specific organs collected. Witnessing traumatic events led to depression- and anxiety-like behavior and produced memory deficits in TW rats associated with elevated corticosterone levels.

  1. Survey for zoonotic pathogens in Norway rat populations from Europe.

    Science.gov (United States)

    Heuser, Elisa; Fischer, Stefan; Ryll, René; Mayer-Scholl, Anne; Hoffmann, Donata; Spahr, Carina; Imholt, Christian; Alfa, Dewi Murni; Fröhlich, Andreas; Lüschow, Dörte; Johne, Reimar; Ehlers, Bernhard; Essbauer, Sandra; Nöckler, Karsten; Ulrich, Rainer G

    2017-02-01

    The Norway rat Rattus norvegicus is an important reservoir of various zoonotic pathogens, such as cowpox virus and Leptospira, but also for agents of no or unknown zoonotic potential. We describe a survey of 426 Norway rats originating from five European countries and different habitats for Leptospira spp., rickettsiae, orthopoxvirus (OPV), avian metapneumovirus subtypes A and B (aMPV) and rat polyomavirus (rat PyV). Leptospira DNA was detected in 60 out of 420 (14.3%) rats, and Rickettsia DNA was found in three out of 369 (0.8%) rats investigated. PCR-based typing resulted in the identification of L. interrogans sequence type 17, which corresponds to the serogroup Icterohaemorrhagiae, and Rickettsia helvetica respectively. Rat PyV DNA was detected in 103 out of 421 (24.5%) rats. OPV DNA and aMPV RNA were detected in none of the rats, but OPV-specific antibodies were detected in three out of 388 (0.8%) rats. The frequency of single Leptospira and rat PyV infections and coinfections was, independent of sex, greater for adults compared with juveniles/subadults and greater at rural sites compared with urban areas. Study results indicate a broad geographical distribution of Leptospira DNA in rats within Europe, underlining the need to investigate further the potential mechanisms leading to increased prevalence in rural habitats and to assess the relevance to public health. In contrast, rickettsia and OPV infections rarely occurred in wild rat populations. The potential influence of rat PyV on the susceptibility to infections with other pathogens should be investigated in future studies. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  2. Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats.

    Science.gov (United States)

    Holubová, Martina; Zemenová, Jana; Mikulášková, Barbora; Panajotova, Vladimíra; Stöhr, Jiří; Haluzík, Martin; Kuneš, Jaroslav; Železná, Blanka; Maletínská, Lenka

    2016-05-01

    Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity, but are ineffective after peripheral application, owing to a limited ability to cross the blood-brain barrier. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both Prrp-knockout and Prrp receptor-knockout mice. The aim of this study was to characterize the subchronic effect of a palmitoylated PrRP analog in two rat models of obesity and diabetes: diet-induced obese Sprague-Dawley rats and leptin receptor-deficient Zucker diabetic (ZDF) rats. In the rats with diet-induced obesity (DIO), a two-week intraperitoneal treatment with palmitoylated PrRP lowered food intake by 24% and body weight by 8%. This treatment also improved glucose tolerance and tended to decrease leptin levels and adipose tissue masses in a dose-dependent manner. In contrast, in ZDF rats, the same treatment with palmitoylated PrRP lowered food intake but did not significantly affect body weight or glucose tolerance, probably in consequence of severe leptin resistance due to a nonfunctional leptin receptor. Our data indicate a good efficacy of lipidized PrRP in DIO rats. Thus, the strong anorexigenic, body weight-reducing, and glucose tolerance-improving effects make palmitoylated PrRP an attractive candidate for anti-obesity treatment. © 2016 Society for Endocrinology.

  3. Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart control Wistar rats.

    Science.gov (United States)

    Park, Ji Min; Bong, Ha Yoon; Jeong, Hye In; Kim, Yeon Kyoung; Kim, Ji Yeon; Kwon, Oran

    2009-01-01

    Postprandial hypoglycemic effect of mulberry leaf (Morus alba L.) was compared in two animal models: Goto-Kakizaki (GK) rats, a spontaneous non-obese animal model for type II diabetes, and their counterpart control Wistar rats. First, the effect of a single oral administration of mulberry leaf aqueous extract (MLE) on postprandial glucose responses was determined using maltose or glucose as substrate. With maltose-loading, MLE reduced peak responses of blood glucose significantly in both GK and Wistar rats (P glucose-loading, MLE also significantly reduced blood glucose concentrations, measured at 30 min, in both animal models (P glucose transport by MLE. Next, dried mulberry leaf powder (MLP) was administered for 8 weeks by inclusion in the diet. By MLP administration, fasting blood glucose was significantly reduced at weeks 4 and 5 (P rats. Insulin, HOMA-IR, C-reactive protein, and triglycerides tended to be decreased by MLP treatment in GK rats. All other biochemical parameters were not changed by MLP administration in GK rats. Collectively, these findings support that MLE has significant postprandial hypoglycemic effect in both non-obese diabetic and healthy animals, which may be beneficial as food supplement to manage postprandial blood glucose. Inhibitions of glucose transport as well as alpha-glucosidase in the small intestine were suggested as possible mechanisms related with the postprandial hypoglycemic effect of MLE.

  4. A phytooxysterol, 28-homobrassinolide modulates rat testicular steroidogenesis in normal and diabetic rats.

    Science.gov (United States)

    Premalatha, R; Jubendradass, Rajamanickam; Rani, S Judith Amala; Srikumar, K; Mathur, Premendu Prakash

    2013-05-01

    Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3β-hydroxysteroid dehydrogenase (3β-HSD, 17β-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 µg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3β-HSD and 17β-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis.

  5. Sympathoadrenal Function in Genetically Obese Zucker Rats

    NARCIS (Netherlands)

    Scheurink, Anton J.W.; Steffens, Anton B.; Roossien, Bert; Balkan, Börk

    1992-01-01

    The effects of genetic obesity on the actions and alterations of the sympathetic nervous system were studied in 10-12-month-old obese (fa/fa) and lean (Fa/-) Zucker rats. Blood glucose, plasma insulin, epinephrine (E), norepinephrine (NE), and free fatty acids (FFA) concentrations were measured in

  6. Morphological and neurohistological changes in adolescent rats ...

    African Journals Online (AJOL)

    olayemitoyin

    resistance, this effect is not likely to be seen in healthy subjects (Xu et al., 2012). Studies by Liu et al. (2003) observed that long-term oral nicotine administration reduces insulin resistance in obese rats. The current study examined the effect of prenatal nicotine on the morphology and the histology of the cerebral cortex of ...

  7. Nonneurogenic hypoxia sensitivity in rat adrenal slices.

    Science.gov (United States)

    Takeuchi, Y; Mochizuki-Oda, N; Yamada, H; Kurokawa, K; Watanabe, Y

    2001-11-23

    A change in the intracellular Ca(2+) ([Ca(2+)](i)) level induced by hypoxia was detected in rat adrenal slices by use of fura-2/AM. After hypoxic stress, an increase in [Ca(2+)](i) was observed only in the adrenal medulla. This increase was inhibited by nifedipine, but not modified by the cholinergic receptor blockers. The hypoxia-induced increase in [Ca(2+)](i) was observed in all postnatal developmental stages to a similar extent, whereas the nicotine and high K(+) sensitivities increased along with postnatal development. A 10 nM ryanodine enhanced the hypoxia-induced [Ca(2+)](i) increase in adult but not in neonatal rat slices. These results suggest the existence of an oxygen-sensing mechanism in adult rat adrenals even after sympathetic innervation. Hypoxic responses seemed to be similar both in neonate and in adult rat adrenals and were triggered by the influx of Ca(2+) via L-type voltage-sensitive Ca(2+) channels. However, the sustained [Ca(2+)](i) increase caused by hypoxia might depend on postnatal development and be triggered by Ca(2+)-induced Ca(2+) release (CICR). Copyright 2001 Academic Press.

  8. Swelling of rat hepatocytes stimulates glycogen synthesis

    NARCIS (Netherlands)

    Baquet, A.; Hue, L.; Meijer, A. J.; van Woerkom, G. M.; Plomp, P. J.

    1990-01-01

    In hepatocytes from fasted rats, several amino acids are known to stimulate glycogen synthesis via activation of glycogen synthase. The hypothesis that an increase in cell volume resulting from amino acid uptake may be involved in the stimulation of glycogen synthesis is supported by the following

  9. ULTRASTRUCTURE OF THE RAT MESENCEPHALIC TRIGEMINAL NUCLEUS

    NARCIS (Netherlands)

    LIEM, RSB; COPRAY, JCVM; VANWILLIGEN, JD

    The subcellular morphology of the mesencephalic trigeminal (Me5) nucleus in the rat was studied by transmission electron microscopy. Most neurons in the thin rostral as well as in the major caudal part of Me5 appeared as large (40-50-mu-m), round-to ovoid-shaped unipolar cells. A few neurons

  10. Voluntary Oral Administration of Losartan in Rats.

    Science.gov (United States)

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.

  11. Acetaminophen modulation of hydrocodone reward in rats.

    Science.gov (United States)

    Nazarian, Arbi; Are, Deepthi; Tenayuca, John M

    2011-09-01

    Abuse of prescription opioid analgesics in non-medical context has been on the rise over the past decade. The most commonly abused analgesic in this drug class consists of a combined formulation of hydrocodone and acetaminophen. The present study was aimed to determine the rewarding effects of hydrocodone, acetaminophen, and their combination using the conditioned place preference (CPP) paradigm. Using a 6-day CPP paradigm, rats were paired with hydrocodone (0.5, 1.0 or 5.0 mg/kg) or acetaminophen (50, 100 or 300 mg/kg) to determine whether the drugs given alone would produce a CPP. Rats conditioned with the highest dose of hydrocodone exhibited place preference, whereas rats conditioned with acetaminophen did not demonstrate place preference. In a second experiment, varying doses of hydrocodone and acetaminophen were combined to determine whether acetaminophen would enhance hydrocodone reward. Acetaminophen (100 mg/kg) enhanced the rewarding effects of hydrocodone (1mg/kg), although the effect was unique to this particular dose combination. Higher or lower doses of acetaminophen combined with hydrocodone did not alter hydrocodone CPP. The present findings suggest that acetaminophen has a limited potential of modulating the rewarding properties of hydrocodone in rats. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Following Exhaustive Exercise in Male Rats

    Directory of Open Access Journals (Sweden)

    reza Badalzadeh

    2014-12-01

    Conclusion: Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.

  13. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    Science.gov (United States)

    1991-12-01

    Each animal was kept in an unused, quiet room. Food and water were checked daily, and female estrus cycles were monitored by daily vaginal smears...Independence of ultrasonic vocali- zation and thermogenic responses in infant rats. Behavioral Neuroscience, 105, 41-48 (1991). Hofer, M.A., and

  14. Prenatal Caffeine Exposure Impairs Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Yadegari

    2016-12-01

    Full Text Available Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world’s population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL and abnormality in pregnant rats. Materials and Methods: In this experimental study, 40 female albino rats (170-190 g were randomly divided into two experimental and two control groups (n=10/each group. In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05. There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

  15. The rat incisor in toxicologic pathology

    NARCIS (Netherlands)

    Kuijpers, M.H.M.; Kooij, A.J. van de; Slootweg, P.J.

    1996-01-01

    Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors

  16. Lipogenesis in maintenance cultures of rat hepatocytes

    NARCIS (Netherlands)

    Geelen, Math J.H.; Gibson, David M.

    1975-01-01

    Induction of the several enzymes in the liver cytosol catalyzing de novo synthesis of fatty acids from glucose has been demonstrated in intact animals. When carbohydrate is provided to previously starved rats the metabolism of liver switches from a gluconeogenic-ketogenic economy to a

  17. Vldlr overexpression causes hyperactivity in rats

    Directory of Open Access Journals (Sweden)

    Iwata Keiko

    2012-10-01

    Full Text Available Abstract Background Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients. Methods We generated transgenic (Tg rats overexpressing Vldlr, and examined their histological and behavioral features. Results Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function. Conclusions Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities.

  18. Excretion of bisphenol A into rat milk.

    Science.gov (United States)

    Okabayashi, Ken; Watanabe, Toshi

    2010-03-01

    Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the production of polycarbonate plastic and epoxy resins. This study analyzed the BPA concentration in rat milk, in order to assess the risk of BPA transfer to the offspring via milk. The rats ingested BPA by oral administration or by drinking the water in a polycarbonate bottle, and the milk samples were collected using an automated experimental milker. The BPA concentration in the samples of milk, drinking water, and food was analyzed by LC/MS. In the case of milk samples obtained from rats injected with BPA at 2, 4, 8, and 24 h prior to milking, the BPA concentrations were 0.462 +/- 0.182 ppm, 0.138 +/- 0.0185 ppm, 0.080 +/- 0.0197 ppm, and 0.0232 +/- 0.0051 ppm, respectively. Also, in the cases of the water sample left in polycarbonate bottle and the milk sample obtained from rats provided it as drinking water, the concentrations of BPA were 0.000332 +/- 0.00015 ppm and 0.0184 +/- 0.0050 ppm, respectively. The results indicate that the BPA administered to the dams was transferred to their milk, and that BPA concentration in milk was higher at the early period after the single bolus dose. Additionally, these results reveal that sequential elution of BPA from polycarbonate containers in a much diluted form would undergo bioaccumulation in dams and likely be transferred to pups via milk in a much concentrated form.

  19. Rat Lungworm Expands into North America

    Centers for Disease Control (CDC) Podcasts

    2016-01-21

    Emily York, integrated pest management specialist at the Sam Noble Museum of Natural History, discusses the rat lungworm expansion in North America.  Created: 1/21/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/21/2016.

  20. Motor development after vestibular deprivation in rats

    NARCIS (Netherlands)

    Geisler, HC; Gramsbergen, A

    This review summarizes the postural development in the rat and the influences of vestibular deprivation from the 5th postnatal day on this development. Vestibular deprivation leads to a delay in motor development. Most probably this delay is caused by a delay in the development of postural control,

  1. Cloning and biosynthetic studies of rat somatostatin.

    Science.gov (United States)

    Dixon, J E; Andrews, P C; Collier, K; Deschenes, R; Funckes, C; Lorenz, L; Magazin, M; Minth, C D; Nichols, R; Tavianini, M

    1983-01-01

    The predicted amino acid sequence of rat preprosomatostatin has been obtained by cloning and subsequent DNA sequence analysis of a cDNA obtained from mRNA prepared from a rat medullary thyroid carcinoma (MTC). The predicted preprosomatostatin is 116 amino acid residues in length. Somatostatin-14 is located at the C-terminus of the preprohormone and the amino terminus contains a 'signal' peptide of 24 amino acids. A somatostatin amino terminal protein of 78 residues is found between the signal peptide and somatostatin-14. Both somatostatin-14 and somatostatin-28 are observed in the thyroid tumour C-cells. A comparison of the rat and human preprosomatostatin amino acid sequences shows only 4 substitutions observed in 116 amino acids. Patients with localized MTC often exhibit high serum calcitonin levels while patients showing cellular heterogeneity in the MTC appear to have lower calcitonin levels and a virulent neoplasia with a grave prognosis. Numerous rat MTCs have been examined by two dimensional gel electrophoresis. It is possible to distinguish characteristic differences in protein profiles of tumours producing high levels of calcitonin from those showing low calcitonin and high somatostatin levels. This analysis can be done with less than 1 mg of tissue and may represent a valuable prognostic tool in evaluating the clinical variability of MTC.

  2. Neuroglobin in the rat brain: localization

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Allen, Gregg C; Nyengaard, Jens Randel

    2008-01-01

    in the rat brain using immunohistochemistry, in situ hybridization, and quantitative real-time PCR (qRT-PCR). This revealed the interesting finding that Ngb expression is restricted to a few neurone populations, many of which are involved in the sleep-wake cycle, circadian regulation or food regulation...

  3. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  4. Rat gastric banding model for bariatric surgery.

    Science.gov (United States)

    Kanno, Hitoshi; Kiyama, Teruo; Fujita, Itsuo; Kato, Shunji; Yoshiyuki, Toshiro; Tajiri, Takashi

    2008-08-01

    Adjustable gastric banding is a surgical approach to weight reduction. In this study we created a gastric banding model in rats to better understand the mechanism of body weight loss. Male Sprague-Dawley rats weighing 260 to 280 g were subjected to gastric banding (band group) (n=8) or to a sham operation (control group) (n=8). Body weights were monitored for 14 days, and daily food and water intake and nitrogen balance were monitored for 7 days. Two rats in the band group died of malnutrition due to gastric stomal stenosis and obstruction caused by the gastric banding. Body weight gain during the 14 days after the operation was less in the band group than in the control group (pwater intake during the 7 days after the operation was significantly less in the band group than in the control group (pbalance was significantly less in the band group than in the control group (p<0.01). Gastric banding decreased the body weight gain of rats by decreasing the amount of food intake because of the creation of a small gastric pouch.

  5. and Impair Spermatogenesis in Male Rats

    African Journals Online (AJOL)

    However, serum concentrations of testosterone and LH were not significantly different in all the groups. We conclude that diabetes mellitus and insulin resistance affect semen parameters and impair distinct phases of spermatogenesis in male rats Sonne mechanisms responsible for this impairment are suggested. (Afi].

  6. In Utero Hepatocellular Transplantation in Rats

    Directory of Open Access Journals (Sweden)

    Emma Muñoz-Sáez

    2013-01-01

    Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

  7. Toxicological investigation of diethylphthalate in rats

    NARCIS (Netherlands)

    Jansen EHJM; van den Ham WA; de Fluiter P; van Leeuwen FXR

    1993-01-01

    In a study in which male rats have been exposed to 0, 200, 600, 2000, 6000 and 20000 mg diethylphthalate (DEP)/kg diet for 2 weeks, body weight and liver weight and a number of enzyme parameters which are related with peroxisome proliferation (palmitoyl coenzyme-A oxidase (PCO), enoyl coenzyme-A

  8. Toxicological investigation of dibutylphthalate in rats

    NARCIS (Netherlands)

    Jansen EHJM; van den Ham WA; de Fluiter P; van Leeuwen FXR

    1993-01-01

    In a study in which male rats have been exposed to 0, 20, 60, 200, 600 and 2000 mg dibutylphthalate (DBP)/kg diet for 2 weeks, body weight and liver weight and a number of enzyme parameters which are related with peroxisome proliferation (palmitoyl coenzyme-A oxidase (PCO, enoyl coenzyme-A hydratase

  9. Spatial Memory in Spontaneously Hypertensive Rats (SHR)

    NARCIS (Netherlands)

    Sontag, Thomas-A.; Fuermaier, Anselm B. M.; Hauser, Joachim; Kaunzinger, Ivo; Tucha, Oliver; Lange, Klaus W.

    2013-01-01

    The spontaneously hypertensive rat (SHR) is an established animal model of ADHD. It has been suggested that ADHD symptoms arise from deficits in executive functions such as working memory, attentional control and decision making. Both ADHD patients and SHRs show deficits in spatial working memory.

  10. gonadal axis in male Wistar rats

    African Journals Online (AJOL)

    USER

    assessed the effect of the single and combined administration of vigabatrin (VIG) and carbamazepine. (CBZ) on the pituitary-gonadal axis of male ..... possible that the active reversal of sperm characteristics that was observed was ... weights, sex hormones and biochemical profiles of male rats. Neuroendocrinology Letters.

  11. Estrogen induces glomerulosclerosis in analbuminemic rats

    NARCIS (Netherlands)

    Joles, JA; van Goor, H; Koomans, HA

    Progression of chronic renal disease: is usually more rapid in males, both In humans and in experimental animals. Estrogen-replacement studies indicate that this may be related to the beneficial effects of estrogen on the lipoprotein profile. However, in hyperlipidemic analbuminemic rats (NAR),

  12. developing cerebellum of wistar rat (Rattus Novergicus)

    African Journals Online (AJOL)

    trol animals were fed a standard diet of mice cubes, while the experimental animals were fed 500 ppm potas- .... is responsible for the rapid and fatal toxic effect of cya- nide'°. Considering the important function of the ..... tion bctween Vitamin E and glutathione in rat brain — effect of acute alcohol administration. Journal of ...

  13. New isoforms of rat Aquaporin-4

    DEFF Research Database (Denmark)

    Moe, Svein Erik; Sorbo, Jan Gunnar; Søgaard, Rikke

    2008-01-01

    Aquaporin-4 (AQP4) is a brain aquaporin implicated in the pathophysiology of numerous clinical conditions including brain edema. Here we show that rat AQP4 has six cDNA isoforms, formed by alternative splicing. These are named AQP4a-f, where AQP4a and AQP4c correspond to the two classical M1 and M...

  14. Pulmonary cryptococcosis induces chitinase in the rat

    Directory of Open Access Journals (Sweden)

    Casadevall Arturo

    2008-05-01

    Full Text Available Abstract Background We previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Because the cell wall of C. neoformans consists of chitin, and since acidic mammalian chitinase (AMCase has recently been implicated as a novel mediator of asthma, we sought to determine whether such infection induces chitinase activity and expression of AMCase in the rat. Methods We utilized a previously-established model of chronic C. neoformans pulmonary infection in the rat to analyze the activity, expression and localization of AMCase. Results Our studies indicate that intratracheal inoculation of C. neoformans induces chitinase activity within the lung and bronchoalveolar lavage fluid of infected rats. Chitinase activity is also elicited by pulmonary infection with other fungi (e.g. C. albicans, but not by the inoculation of dead organisms. Enhanced chitinase activity reflects increased AMCase expression by airway epithelial cells and alveolar macrophages. Systemic cryptococcosis is not associated with increased pulmonary chitinase activity or AMCase expression. Conclusion Our findings indicate a possible link between respiratory fungal infections, including C. neoformans, and asthma through the induction of AMCase.

  15. Behavioral effects of etiracetam in rats

    NARCIS (Netherlands)

    Wolthuis, O.L.

    1981-01-01

    The effects of etiracetam, a structural analogue or piracetam, were investigated in rats on Y-maze discrimination acquisition, on open field behavior, on one-trial passive avoidance learning and on shuttlebox acquisition and extinction. The results indicate that this drug significantly enhances

  16. Prior access to a sweet is more protective against cocaine self-administration in female rats than male rats

    Science.gov (United States)

    Cason, Angie M.; Grigson, Patricia S.

    2013-01-01

    It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson & Twining, 2002). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior. PMID:23474135

  17. Juvenile female rats, but not male rats, show renewal, reinstatement, and spontaneous recovery following extinction of conditioned fear.

    Science.gov (United States)

    Park, Chun Hui J; Ganella, Despina E; Kim, Jee Hyun

    2017-12-01

    Anxiety disorders emerge early, and girls are significantly more likely to develop anxiety compared to boys. However, sex differences in fear during development are poorly understood. Therefore, we investigated juvenile male and female rats in the relapse behaviors following extinction of conditioned fear. In all experiments, 18-d-old rats first received three white-noise-footshock pairings on day 1. On day 2, extinction involved 60 white-noise alone trials. In experiment 1, we examined renewal by testing the rats in either the same or different context as extinction on day 3. Male rats did not show renewal, however, female rats showed renewal. Experiment 2 investigated reinstatement by giving rats either a mild reminder footshock or context exposure on day 3. When tested the next day, male rats did not show reinstatement, whereas female rats showed reinstatement. Experiment 3 investigated spontaneous recovery by testing the rats either 1 or 5 d following extinction. Male rats did not show any spontaneous recovery whereas female rats did. Taken together, fear regulation appear to be different in males versus females from early in development, which may explain why girls are more prone to suffer from anxiety disorders compared to boys. © 2017 Park et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Rats do not eat alone in public: Food-deprived rats socialize rather than competing for baits.

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    Omri Weiss

    Full Text Available Limited resources result in competition among social animals. Nevertheless, social animals also have innate preferences for cooperative behavior. In the present study, 12 dyads of food-deprived rats were tested in four successive trials, and then re-tested as eight triads of food-deprived rats that were unfamiliar to each other. We found that the food-deprived dyads or triads of rats did not compete for the food available to them at regular spatially-marked locations that they had previously learnt. Rather, these rats traveled together to collect the baits. One rat, or two rats in some triads, lead (ran ahead to collect most of the baits, but "leaders" differed across trials so that, on average, each rat ultimately collected similar amounts of baits. Regardless of which rat collected the baits, the rats traveled together with no substantial difference among them in terms of their total activity. We suggest that rats, which are a social species that has been found to display reciprocity, have evolved to travel and forage together and to share limited resources. Consequently, they displayed a sort of 'peace economy' that on average resulted in equal access to the baits across trials. For social animals, this type of dynamics is more relaxed, tolerant, and effective in the management of conflicts. Rather than competing for the limited available food, the food-deprived rats socialized and coexisted peacefully.

  19. Effect of orlistat on fat absorption in rats: A comparison of normal rats and rats with diverted bile and pancreatic juice

    DEFF Research Database (Denmark)

    Porsgaard, Trine; Straarup, Ellen Marie; Mu, Huiling

    2003-01-01

    this with the transport in normal rats and rats with fat malabsorption. Rats were subjected to cannulation of the main mesenteric lymph duct, and a feeding catheter was inserted into the stomach. In addition, malabsorbing rats were cannulated in the common bile and pancreatic duct. Emulsified safflower, fish...... and furthermore that the source of fat had no influence on the inhibitory effect of orlistat. Orlistat did not interfere with the absorption of the hydrolysis products, since high absorption of sn-2 MAG and FFA (oleic acid) mixed with orlistat was observed. The baseline lymphatic transport in the orlistat group...

  20. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

    Directory of Open Access Journals (Sweden)

    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  1. Effect of dietary soy isoflavones on bone loss in ovariectomized rats ...

    African Journals Online (AJOL)

    Purpose: To determine the effect of dietary soy isoflavone supplementation on bone loss in ovariectomized (OVX) rats. Methods: Forty-eight rats were assigned randomly to groups of OVX rats receiving soy isoflavones (20, 30, or 40 mg/kg of body weight daily), untreated OVX rats, or untreated intact rats. After 8 weeks, bone ...

  2. NMR characteristics of rat mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Osbakken, M.; Kreider, J.; Taczanowsky, P.

    1984-01-01

    12 rats were injected intradermally with 13762A rat mammary adenocarcinoma (1 x 10/sup 6/ cells). 3 rats died before completion of the study and 2 rat had tumor regression; the first 3 were excluded from data analysis. NMR imaging with a 1.5K gauss resistive magnet at 2, 3, 4, and 5 weeks after injection demonstrated increasing tumor mass. Saturation recovery (SR), inversion recovery (IR), and spin echo (SE) pulse sequence images and T/sub 1/ calculation were done for tumor characterization. (Tumor size was too small to identify at 2 weeks.) 3 rats were sacrificed after the last 3 imaging periods for histological studies, done to distinguish solid tumor mass from necrosis. Planimetry of tumor areas showed that as tumors grew in size, the ratio of necrotic area to area of solid tumor increased (week 3 = .3 +- .11; week 4 = .45 +- .07; week 5 = .51 +- 05); simultaneous calculated T/sub 1/ values also increased (week 3 = .35 +- .15; week 4 = .45 +- .06; week 5 = .42 +- 03). Qualitative NMR image T/sub 1/ values also increased as evidenced by progression of SR and IR tumor image intensity from very bright compared to the rest of the body at week 3 to less intense than other structures at week 5. These findings indicate that change in T/sub 1/ may be secondary to the pathophysiological change in the tumor (the increasing in necrosis, associated with increased free water). Thus, the range of T/sub 1/ values obtained in tumors in this study (and in previous studies) may be due to change in tumor physiology and anatomy. Careful correlation of histological with NMR data may allow ultimate use of NMR relaxation characteristics for determination of the physiological state of tumors.

  3. [Functional recovery in hemifacial transplants in rats].

    Science.gov (United States)

    González-García, E; Landín-Jarillo, L; Piqueras-Del Rey, A

    There are a number of different options open to the surgeon for the reconstruction of the face and scalp, but when tissue loss is very extensive, good aesthetic and functional recovery is not possible. Not only must the damaged tissues be replaced, but motor and sensorial functioning also has to be restored. To evaluate the functional recovery of hemifacial allografts in rats. Twenty-one hemifacial flaps were transplanted from Long-Evans rats to Wistar-Lewis rats, under immunosuppression monotherapy with tacrolimus. Prior to the operation, anatomical and allograft viability studies were conducted. Two groups of transplanted rats were formed: with or without nerve repair. In the nerve repair group, end-to-end suture was employed to repair the infraorbital branch of the trigeminal nerve and the buccolabial, upper mandibular marginal and zygomatico-orbital branches of the facial nerve. Sensory recovery was evaluated by filming traction of the whiskers, whereas motor recovery was assessed by blind tests using electromyography studies of the mystacial muscles and electroneurography of the facial nerve. At eight weeks, the animals were sacrificed and biopsy samples were taken from the mystacial region. The facial flap was successfully lifted in 10 cases. In the nerve repair group both clinical and electrophysiological recovery were observed at six weeks, whereas biopsy samples taken in the eighth week showed recovery of the nerve fascicles. The hemifacial flap can be transplanted. By repairing the nerves of the allograft, it is possible to achieve its functional recovery, as can be confirmed clinically, electrophysiologically and histopathologically. To date, this is the first evidence of functional recovery following a hemifacial transplant in rats.

  4. Hypercholesterolemia downregulates autophagy in the rat heart.

    Science.gov (United States)

    Giricz, Zoltán; Koncsos, Gábor; Rajtík, Tomáš; Varga, Zoltán V; Baranyai, Tamás; Csonka, Csaba; Szobi, Adrián; Adameová, Adriana; Gottlieb, Roberta A; Ferdinandy, Péter

    2017-03-23

    We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Male Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the

  5. Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands.

    Science.gov (United States)

    Franssen, Frits; Swart, Arno; van Knapen, Frans; van der Giessen, Joke

    2016-01-01

    Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We aimed to study the intestinal and intramuscular helminths in wild rats from three different environments to assess the relevance of rats as carrier of zoonotic parasites for public health. Wild brown rats (117 individuals) and black rats (44 individuals) were captured at farms, in suburban and in rural environments in the Netherlands. Intestinal helminths were isolated and identified morphologically. Artificial digestion was used to isolate muscle larvae. Morphological analysis of rat intestinal contents yielded six nematode species (Syphacia muris, Heterakis spumosa, Aonchotheca murissylvatici, Trichuris muris, Nippostrongylus brasiliensis, and Strongyloides sp.), three cestode species (Hymenolepis diminuta, H. nana and Hymenolepis (=Rodentolepis) fraterna), and four trematode species (Plagiorchis muris, Plagiorchis proximus, Echinostoma chloropodis, and Notocotylus imbricatus).Black rats at farms displayed the lowest intestinal helminth species variation (six species) and carried overall on average 0.93 species simultaneously. In comparison, brown rats at farms carried seven helminth species and 1.91 species simultaneously. Brown rats from suburban environments displayed the highest species variation (11 species) at 1.82 simultaneous helminth species. Absence of trematodes from rats at farms may suggest limited exchange of rats between farms and surrounding wet rural environments. We report four species of veterinary (Syphacia muris) or zoonotic relevance (Hymenolepis diminuta, Hymenolepis nana and Plagiorchis muris). We did not find Trichinella muscle larvae, consistent with long-term prevalence in Dutch wild rats.

  6. Helminth parasites in black rats (Rattus rattus and brown rats (Rattus norvegicus from different environments in the Netherlands

    Directory of Open Access Journals (Sweden)

    Frits Franssen

    2016-05-01

    Full Text Available Background: Rattus norvegicus (brown rat and Rattus rattus (black rat are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We aimed to study the intestinal and intramuscular helminths in wild rats from three different environments to assess the relevance of rats as carrier of zoonotic parasites for public health. Materials and methods: Wild brown rats (117 individuals and black rats (44 individuals were captured at farms, in suburban and in rural environments in the Netherlands. Intestinal helminths were isolated and identified morphologically. Artificial digestion was used to isolate muscle larvae. Results and discussion: Morphological analysis of rat intestinal contents yielded six nematode species (Syphacia muris, Heterakis spumosa, Aonchotheca murissylvatici, Trichuris muris, Nippostrongylus brasiliensis, and Strongyloides sp., three cestode species (Hymenolepis diminuta, H. nana and Hymenolepis (=Rodentolepis fraterna, and four trematode species (Plagiorchis muris, Plagiorchis proximus, Echinostoma chloropodis, and Notocotylus imbricatus.Black rats at farms displayed the lowest intestinal helminth species variation (six species and carried overall on average 0.93 species simultaneously. In comparison, brown rats at farms carried seven helminth species and 1.91 species simultaneously. Brown rats from suburban environments displayed the highest species variation (11 species at 1.82 simultaneous helminth species. Absence of trematodes from rats at farms may suggest limited exchange of rats between farms and surrounding wet rural environments. We report four species of veterinary (Syphacia muris or zoonotic relevance (Hymenolepis diminuta, Hymenolepis nana and Plagiorchis muris. We did not find Trichinella muscle larvae, consistent with long-term prevalence in Dutch wild rats.

  7. Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol.

    Science.gov (United States)

    Németi, Balázs; Gregus, Zoltán

    2013-03-18

    Dimethylarsinic acid (DMAs(V)), the major urinary metabolite of inorganic arsenic, is weakly cytotoxic, whereas its reduced form, dimethylarsinous acid (DMAs(III)), is highly toxic. Although glutathione S-transferase omega 1 (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze DMAs(V) reduction, their role in DMAs(V) reduction in vivo, or in cell extracts is uncertain. Therefore, the reduction of DMAs(V) to DMAs(III) in rats and in rat liver cytosol was studied to better understand its mechanism. To assess DMAs(V) reduction in rats, a novel procedure was devised based on following the accumulation of red blood cell (RBC)-bound dimethylarsenic (DMAs), which represents DMAs(III), in the blood of DMAs(V)-injected anesthetized rats. These studies indicated that rats reduced DMAs(V) to DMAs(III) to a significant extent, as in 90 min 31% of the injected 50 μmol/kg DMAs(V) dose was converted to DMAs(III) that was sequestered by the circulating erythrocytes. Pretreatment of rats with glutathione (GSH) depletors (phorone or BSO) delayed the elimination of DMAs(V) and the accumulation of RBC-bound DMAs, whereas the indirect methyltransferase inhibitor periodate-oxidized adenosine was without effect. Assessment of DMAs(V)-reducing activity of rat liver cytosol revealed that reduction of DMAs(V) required cytosolic protein and GSH and was inhibited by thiol reagents, GSSG and dehydroascorbate. Although thioredoxin reductase (TRR) inhibitors (aurothioglucose and Sb(III)) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction. On ultrafiltration of the cytosol through a 3 kDa filter, the reducing activity in the retentate was lost but was largely restored by NADPH. Such experiments also suggested that the reducing enzyme was larger than 100 kDa and was not GSTO1. In summary, reduction of DMAs(V) to the highly toxic DMAs(III) in rats and rat liver cytosol is a GSH

  8. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

    Directory of Open Access Journals (Sweden)

    Kenichiro Sato

    2013-10-01

    Full Text Available The number of diabetes mellitus (DM patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1 are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson’s test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF. The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

  9. Intracerebroventricular injection of ghrelin decreases wheel running activity in rats.

    Science.gov (United States)

    Miyatake, Yumiko; Shiuchi, Tetsuya; Mawatari, Kazuaki; Toda, Satomi; Taniguchi, Yasuko; Futami, Akari; Sato, Fukiko; Kuroda, Masashi; Sebe, Mayu; Tsutsumi, Rie; Harada, Nagakatsu; Minokoshi, Yasuhiko; Kitamura, Tadahiro; Gotoh, Koro; Ueno, Masaki; Nakaya, Yutaka; Sakaue, Hiroshi

    2017-01-01

    There is an increasing interest in elucidating the molecular mechanisms by which voluntary exercise is regulated. In this study, we examined how the central nervous system regulates exercise. We used SPORTS rats, which were established in our laboratory as a highly voluntary murine exercise model. SPORTS rats showed lower levels of serum ghrelin compared with those of the parental line of Wistar rats. Intracerebroventricular and intraperitoneal injection of ghrelin decreased wheel-running activity in SPORTS rats. In addition, daily injection of the ghrelin inhibitor JMV3002 into the lateral ventricles of Wistar rats increased wheel-running activity. Co-administration of obestatin inhibited ghrelin-induced increases in food intake but did not inhibit ghrelin-induced suppression of voluntary exercise in rats. Growth hormone secretagogue receptor (GHSR) in the hypothalamus and hippocampus of SPORTS rats was not difference that in control rats. We created an arcuate nucleus destruction model by administering monosodium glutamate (MSG) to neonatal SPORTS rats. Injection of ghrelin into MSG-treated rats decreased voluntary exercise but did not increase food intake, suggesting that wheel-running activity is not controlled by the arcuate nucleus neurons that regulate feeding. These results provide new insights into the mechanism by which ghrelin regulates voluntary activity independent of arcuate nucleus neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Functional adaptation in female rats: the role of estrogen signaling.

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    Susannah J Sample

    Full Text Available Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERβ, a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER. GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females.We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17β-estradiol, or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG gene expression of ERα, ERβ, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced.Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on adaptive bone formation in estrogen-deficient female rats.

  11. Comparison Of Cardiovascular Characteristics In Normotensive And Hypertensive Rat Strains.

    Science.gov (United States)

    Zemancíková, Anna; Török, Jozef

    2015-01-01

    Hypertensive rats serve as valuable tools for studies of dysregulations in cardiovascular functions before and during pathological elevation of blood pressure. They exhibit many defects in structure and function of heart and vessels which are often related to severity of hypertension. The relationship of blood pressure level and manifestation of aberrations in selected cardiovascular and metabolic parameters were determined in 20-week-old normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and in their F1 offspring borderline hypertensive rats (BHR), and also in normotensive Wistar rats which are genetically less compatible with the other mentioned rat strains. Systolic blood pressure and heart rate were measured in conscious rats by the non-invasive tail-cuff method. At the end of the treatment, rats were sacrificed, relative weight of their left heart ventricle and liver were determined and plasma concentration of glucose and triglycerides were measured. Thoracic aorta and superior mesenteric artery were isolated and prepared for isometric tension recording. Neurogenic contractions were elicited by electrical stimulation of perivascular adrenergic nerves. The level of systolic blood pressure in WKY rats (106.0 ± 0.4 mmHg), BHR (149.5 ± 2.5 mmHg) and SHR (186.4 ± 3.9 mmHg) corresponded with the impairment of acetylcholine-induced relaxation of isolated thoracic aorta and with the increase in sensitivity of contractile responses to exogenous noradrenaline and to electrical stimulation of perivascular adrenergic nerves in mesenteric artery. However, rats of the normotensive strain Wistar (118.1 ± 2.0 mmHg) exhibited arterial contractions similar to those obtained in hypertensive rats. Wistar rats had also the highest relative liver weight and plasma triglyceride concentration. These observations indicate that when comparing non-related rat strains the higher magnitude of arterial contractions and abnormal lipid parameters may not

  12. Intravenous infusion of mesenteric lymph from severe intraperitoneal infection rats causes lung injury in healthy rats.

    Science.gov (United States)

    Zhang, Yan-Min; Zhang, Shu-Kun; Cui, Nai-Qiang

    2014-04-28

    To investigate whether mesenteric lymph from rats with severe intraperitoneal infection (SII) induces lung injury in healthy rats. Twenty adult male specific pathogen-free Wistar rats were divided into two groups. Animals in the SII group received intraperitoneal injection of Escherichia coli (E. coli) at a dose of 0.3 mL/100 g. Control rats underwent the same procedure, but were injected with normal saline rather than E. coli. We ligated and drained the mesenteric lymphatic vessels and collected the mesenteric lymph. Mesenteric lymph collected from SII or control rats was infused intravenously into male healthy rats at a rate of 1 mL/h for 4 h. At the end of the infusion, all rats were sacrificed. Lungs were removed and examined histologically, and wet-to-dry weight (W/D) ratio and myeloperoxidase (MPO) activity were determined. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the levels of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. We performed Western blot to investigate the activation of Toll-like receptor (TLR)-4, and nuclear factor (NF)-κB p65. Compared with the control infusion group, there were obvious pathological changes in the SII group. The W/D ratio was significantly increased in the SII compared to control infusion group (5.86 ± 0.06 vs 5.37 ± 0.06, P lung injury. The results indicate that SII lymph is sufficient to induce acute lung injury.

  13. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

    Directory of Open Access Journals (Sweden)

    Takashi Kuramoto

    Full Text Available Albino and hooded (or piebald rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

  14. A set of highly informative rat simple sequence length polymorphism (SSLP markers and genetically defined rat strains

    Directory of Open Access Journals (Sweden)

    Yamasaki Ken-ichi

    2006-04-01

    Full Text Available Abstract Background The National Bio Resource Project for the Rat in Japan (NBRP-Rat is focusing on collecting, preserving and distributing various rat strains, including spontaneous mutant, transgenic, congenic, and recombinant inbred (RI strains. To evaluate their value as models of human diseases, we are characterizing them using 109 phenotypic parameters, such as clinical measurements, internal anatomy, metabolic parameters, and behavioral tests, as part of the Rat Phenome Project. Here, we report on a set of 357 simple sequence length polymorphism (SSLP markers and 122 rat strains, which were genotyped by the marker set. Results The SSLP markers were selected according to their distribution patterns throughout the whole rat genome with an average spacing of 7.59 Mb. The average number of informative markers between all possible pairs of strains was 259 (72.5% of 357 markers, showing their high degree of polymorphism. From the genetic profile of these rat inbred strains, we constructed a rat family tree to clarify their genetic background. Conclusion These highly informative SSLP markers as well as genetically and phenotypically defined rat strains are useful for designing experiments for quantitative trait loci (QTL analysis and to choose strategies for developing new genetic resources. The data and resources are freely available at the NBRP-Rat web site 1.

  15. Trophic garnishes: cat-rat interactions in an urban environment.

    Directory of Open Access Journals (Sweden)

    Gregory E Glass

    Full Text Available BACKGROUND: Community interactions can produce complex dynamics with counterintuitive responses. Synanthropic community members are of increasing practical interest for their effects on biodiversity and public health. Most studies incorporating introduced species have been performed on islands where they may pose a risk to the native fauna. Few have examined their interactions in urban environments where they represent the majority of species. We characterized house cat (Felis catus predation on wild Norway rats (Rattus norvegicus, and its population effects in an urban area as a model system. Three aspects of predation likely to influence population dynamics were examined; the stratum of the prey population killed by predators, the intensity of the predation, and the size of the predator population. METHODOLOGY/PRINCIPAL FINDINGS: Predation pressure was estimated from the sizes of the rat and cat populations, and the characteristics of rats killed in 20 alleys. Short and long term responses of rat population to perturbations were examined by removal trapping. Perturbations removed an average of 56% of the rats/alley but had no negative long-term impact on the size of the rat population (49.6+/-12.5 rats/alley and 123.8+/-42.2 rats/alley over two years. The sizes of the cat population during two years (3.5 animals/alley and 2.7 animals/alley also were unaffected by rat population perturbations. Predation by cats occurred in 9/20 alleys. Predated rats were predominantly juveniles and significantly smaller (144.6 g+/-17.8 g than the trapped rats (385.0 g+/-135.6 g. Cats rarely preyed on the larger, older portion of the rat population. CONCLUSIONS/SIGNIFICANCE: The rat population appears resilient to perturbation from even substantial population reduction using targeted removal. In this area there is a relatively low population density of cats and they only occasionally prey on the rat population. This occasional predation primarily removes the

  16. Trophic garnishes: cat-rat interactions in an urban environment.

    Science.gov (United States)

    Glass, Gregory E; Gardner-Santana, Lynne C; Holt, Robert D; Chen, Jessica; Shields, Timothy M; Roy, Manojit; Schachterle, Stephen; Klein, Sabra L

    2009-06-03

    Community interactions can produce complex dynamics with counterintuitive responses. Synanthropic community members are of increasing practical interest for their effects on biodiversity and public health. Most studies incorporating introduced species have been performed on islands where they may pose a risk to the native fauna. Few have examined their interactions in urban environments where they represent the majority of species. We characterized house cat (Felis catus) predation on wild Norway rats (Rattus norvegicus), and its population effects in an urban area as a model system. Three aspects of predation likely to influence population dynamics were examined; the stratum of the prey population killed by predators, the intensity of the predation, and the size of the predator population. Predation pressure was estimated from the sizes of the rat and cat populations, and the characteristics of rats killed in 20 alleys. Short and long term responses of rat population to perturbations were examined by removal trapping. Perturbations removed an average of 56% of the rats/alley but had no negative long-term impact on the size of the rat population (49.6+/-12.5 rats/alley and 123.8+/-42.2 rats/alley over two years). The sizes of the cat population during two years (3.5 animals/alley and 2.7 animals/alley) also were unaffected by rat population perturbations. Predation by cats occurred in 9/20 alleys. Predated rats were predominantly juveniles and significantly smaller (144.6 g+/-17.8 g) than the trapped rats (385.0 g+/-135.6 g). Cats rarely preyed on the larger, older portion of the rat population. The rat population appears resilient to perturbation from even substantial population reduction using targeted removal. In this area there is a relatively low population density of cats and they only occasionally prey on the rat population. This occasional predation primarily removes the juvenile proportion of the rat population. The top predator in this urban ecosystem

  17. Prevention of anemia alleviates heart hypertrophy in copper deficient rats

    Energy Technology Data Exchange (ETDEWEB)

    Lure, M.D.; Fields, M.; Lewis, C.G. (Dept. of Agriculture, Beltsville, MD (United States) Univ. of Maryland, College Park (United States) Georgetown Univ., Washington, DC (United States))

    1991-03-11

    The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severe signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.

  18. Taurine in the osmoregulation of the Brattleboro rat

    Energy Technology Data Exchange (ETDEWEB)

    Nieminen, M.J.; Tuomisto, L.; Solatunturi, E.; Eriksson, L.; Paasonen, M.K.

    1988-01-01

    The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and /sup 3/H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

  19. Stimulus processing and associative learning in Wistar and WKHA rats.

    Science.gov (United States)

    Chess, Amy C; Keene, Christopher S; Wyzik, Elizabeth C; Bucci, David J

    2005-06-01

    This study assessed basic learning and attention abilities in Wistar-Kyoto hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hind legs), and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning, but not extinction, was impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as in learning stimulus-reward relationships. (c) 2005 APA, all rights reserved.

  20. City rats: insight from rat spatial behavior into human cognition in urban environments.

    Science.gov (United States)

    Yaski, Osnat; Portugali, Juval; Eilam, David

    2011-09-01

    The structure and shape of the urban environment influence our ability to find our way about in the city. Understanding how the physical properties of the environment affect spatial behavior and cognition is therefore a necessity. However, there are inherent difficulties in empirically studying complex and large-scale urban environments. These include the need to isolate the impact of specific urban features and to acquire data on the physical activity of individuals. In the present study, we attempted to overcome the above obstacles and examine the relation between urban environments and spatial cognition by testing the spatial behavior of rats. This idea originated from the resemblance in the operative brain functions and in the mechanisms and strategies employed by humans and other animals when acquiring spatial information and establishing an internal representation, as revealed in past studies. Accordingly, we tested rats in arenas that simulated a grid urban layout (e.g. Manhattan streets) and an irregular urban layout (e.g. Jerusalem streets). We found that in the grid layout, rat movement was more structured and extended over a greater area compared with their restricted movement in the irregular layout. These movement patterns recall those of humans in respective urban environments, illustrating that the structure and shape of the environment affect spatial behavior similarly in humans and rats. Overall, testing rats in environments that simulate facets of urban environments can provide new insights into human spatial cognition in urban environments.

  1. Germline transmission of a novel rat embryonic stem cell line derived from transgenic rats.

    Science.gov (United States)

    Men, Hongsheng; Bauer, Beth A; Bryda, Elizabeth C

    2012-09-20

    Germline-competent rat embryonic stem (ES) cell lines are important resources for the creation of mutant rat models using ES-cell-based gene targeting technology. The ability to isolate germline-competent ES cell lines from any rat strain, including genetically modified strains, would allow for more sophisticated genetic manipulations without extensive breeding. Sprague Dawley (SD) males carrying an enhanced green fluorescent protein (EGFP) transgene were used as the founder animals for the derivation of ES cell lines. A number of ES cell lines were established and subjected to rigorous quality control testing that included assessment of pluripotency factor expression, karyotype analysis, and pathogen/sterility testing. Two male ES cell lines, SD-Tg.EC1/Rrrc and SD-Tg.EC8/Rrrc, were injected into blastocysts recovered from a cross of Dark Agouti (DA) males with SD females. Resulting chimeric animals were bred with wild-type SD mates to verify the germline transmissibility of the ES cell lines by identifying pups carrying the ES cell line-derived EGFP transgene. While both ES cell lines gave rise to chimeric animals, only SD-Tg.EC1 was germline competent. This confirms the feasibility of deriving germline-competent ES cell lines from transgenic rat strains and provides a novel ES cell line with a stable green fluorescent protein (GFP) reporter for future genetic manipulations to create new rat models.

  2. The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

    OpenAIRE

    Yuwei Wang; Qianjin Feng; Xin Niu; Xinshe Liu; Kaixia Xu; Xiangzhu Yang; Huifeng Wang; Qiuju Li

    2014-01-01

    In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can cha...

  3. Altered mandibular growth under functional posterior displacement in rats

    OpenAIRE

    Farias-Neto, A; Martins, APVB; Figueroba, SR; Groppo, FC; Almeida, SM; Rizzatti-Barbosa, CM

    2012-01-01

    Objective: To test the null hypothesis that there is no difference in mandibular growth between growing rats with posterior functional mandibular displacement and growing rats without functional mandibular displacement. Materials and Methods: Twenty female Wistar rats (5 weeks old) were randomized into two groups: (1) control and (2) mandible posterior displacement in the occluded condition induced by an occlusal guiding appliance. After 8 weeks all animals were sacrificed, cone beam computed...

  4. Thujone corrects cholesterol and triglyceride profiles in diabetic rat model.

    Science.gov (United States)

    Baddar, Nour W Al-Haj; Aburjai, Talal A; Taha, Mutasem O; Disi, Ahmad M

    2011-07-01

    Thujone, which is the major constituent in Salvia sp. (Lamiaceae), was found to correct the lipid profile (cholesterol and triglycerides) in diabetic rats. Oral treatment with thujone (5 mg kg⁻¹ body weight dose) significantly adjusted cholesterol and triglyceride levels in diabetic rats (p ≤ 0.05) to normal levels compared to diabetic untreated rats. This provides a premise in the field of finding new agents to treat diabetic complications.

  5. Epidermal growth factor in rat milk is dependent on insulin

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexo, E

    1993-01-01

    Epidermal growth factor (EGF) was measured in milk from four groups of rats: untreated diabetic, insulin-treated diabetic, insulin-treated normal and control rats. In the untreated diabetic group the volume of milk, and the concentration of EGF and the total output of EGF were significantly decre...... of EGF from the mammary glands is dependent on insulin and that the decrement in milk-EGF from diabetic rats is selective when compared to the content of protein in milk....

  6. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development....

  7. An electrophoretic study of urinary protein in the rat.

    Science.gov (United States)

    SELLERS, A L; ROBERTS, S; RASK, I; SMITH, S; MARMORSTON, J; GOODMAN, H C

    1952-05-01

    The nature of the proteins present in the urine of the normal rat has been investigated by electrophoretic analysis and by fractional precipitation of these proteins by ammonium sulfate. Components similar to serum alpha- and beta-globulin constitute the major portion of the urinary protein in both male and female rats. Following the intraperitoneal injection of renin, a massive proteinuria occurs. The proteins excreted are similar in proportion and electric mobility to those of normal rat serum.

  8. The oncogenic action of ionizing radiation on rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.; Garte, S.J.

    1990-01-01

    An extensive experiment involving approximately 400 rats exposed to the neon ion beam at the Bevalac in Berkeley, CA and to electrons is nearing completion. Progress is described in three areas corresponding to the specific aims of the proposal: (1) carcinogenesis and DNA strand breaks in rat skin following exposure by the neon ions or electrons; (2) oncogene activation in radiation-induced rat skin cancers; (3) DNA strand breaks in the epidermis as a function of radiation penetration. 59 refs., 4 tabs.

  9. Effect of ozone on colon anastomoses in rat peritonitis model

    OpenAIRE

    Çakır,Tuğrul; Aslaner, Arif; Tekeli,Seçkin Özgür; Avcı,Sema; Doğan,Uğur; Tekeli,Feyza; Soylu,Hakan; Akyüz, Cebrail; Koç,Süleyman; Üstünel,İsmail; Yılmaz,Necat

    2016-01-01

    PURPOSE: To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. METHODS: Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were ob...

  10. The laboratory rat: Relating its age with human′s

    OpenAIRE

    Pallav Sengupta

    2013-01-01

    By late 18 th or early 19 th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and ...

  11. Sweet Taste Receptors in Normal and Pathological Rat Brain

    OpenAIRE

    YI, Chenju

    2011-01-01

    The mammalian sweet taste receptors (T1Rs) are G protein-coupled receptor complexes, which have recently been proposed to be associated with the brain glucose sensor. Here, we investigated the expression of sweet taste receptors T1R1 and T1R3 in normal and pathological rat brain, including tissue libraries of C6 rat glioma and rat brain of middle cerebral artery occlusion (MCAO), by immunohistological methods. The results demonstrated that neurons located in different brain regions, including...

  12. Diazinon and Cadmium Neurotoxicity in Rats after an Experimental Administration

    OpenAIRE

    Róbert Toman; Svätoslav Hluchý; Jozef Golian; Michal Cabaj; Mária Adamkovičová

    2012-01-01

    The aim of this study was to describe the changes in cholinesterase activity in separate doses and after coadministration of cadmium and diazinon intraperitoneally and to assess toxicity and interactions of diazinon and cadmium on the nervous system in male rats. 40 male rats were randomly divided into three experimental and one control group (10 rats in each group). Blood analyzes were performed 36 hours after an intraperitoneal administration of observed compounds. The statistical evaluatio...

  13. Muscle fragments on a scaffold in rats

    DEFF Research Database (Denmark)

    Jangö, Hanna; Gräs, Søren; Christensen, Lise

    2015-01-01

    with autologous muscle fiber fragments (MFF), as an adjunct to native tissue POP repair, is a potential new alternative. METHODS: A rat abdominal wall model of native repair was used with six animals in each of three groups: native repair, native repair + MPEG-PLGA, and native repair + MPEG-PLGA + MFF. MFF were...... labeled with PKH26-fluorescence dye. After 8 weeks labeled cells were identified in tissue samples and histopathological and immunohistochemical analyses of connective tissue organization and desmin reactivity of muscle cells were performed. Fresh tissue samples were subjected to uniaxial biomechanical......-PLGA scaffolds seeded with autologous MFF affected some histological and biomechanical properties of native tissue repair in an abdominal wall defect model in rats. The method thus appears to be a simple tissue engineering concept with potential relevance for native tissue repair of POP....

  14. DOPA, norepinephrine, and dopamine in rat tissues

    DEFF Research Database (Denmark)

    Eldrup, E; Richter, Erik; Christensen, N J

    1989-01-01

    obtained from stomach, small and large intestine, kidney, and lung. In conclusion, endogenous DOPA in muscle tissue is not located in sympathetic nerve terminals but probably in muscle cells. DA concentrations in the gastrointestinal tract and in the kidneys were greater than could be ascribed to its role......We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were...... measured by reverse-phase high-performance liquid chromatography with electrochemical detection. Sympathectomy decreased NE and DA concentrations of muscles to approximately 10% of control values, whereas the DOPA concentration tended to increase. Relatively high concentrations of DOPA were found...

  15. Adrenergic blockade in diabetic and uninephrectomized rats

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Jørgensen, P E

    1999-01-01

    The present study reports on the effects of adrenergic blocking agents on the renal growth and on the renal content and urinary excretion of epidermal growth factor (EGF) in streptozotocin-induced diabetic or uninephrectomized rats. Diabetic and uninephrectomized rats were allocated to groups...... an increase of 33% in kidney weight when compared to controls. The adrenergic antagonist treated diabetic groups had a significantly lower increase of 15%. Postnephrectomized renal growth was not affected by adrenergic antagonists. The total renal content of EGF was comparable in the saline-treated diabetic...... was not affected by adrenergic blocking agents. These results provide evidence for fundamental differences between diabetes-related renal growth and that observed in compensation to nephrectomy and suggest a connection between adrenergic activity, renal growth, and EGF in diabetes....

  16. Longevity of exercising obese hypertensive rats.

    Science.gov (United States)

    Booth, F W; MacKenzie, W F; Seider, M J; Gould, E W

    1980-10-01

    The purpose of this study was to determine whether daily running lengthens the life-span of animals dying prematurely due to cardiovascular disease. We used a strain of rat that is genetically hypertensive and obese and is reported to develop atherosclerosis (Exp. Mol. Pathol. 19: 53--60, 1973). These animals were divided into three groups consisting of runners exercised daily on treadmills from an early age life, food-restricted sedentary rats, and libitum eaters that were sedentary. This latter group had significantly higher average daily food intakes and body weights than either of the other two groups. The average life-span of both sedentary groups was significantly longer than the running group. Runners had a greater frequency of focal myocardial necrosis, but atherosclerosis was absent in all three groups. We speculate that daily running may have accentuated the development of factor s that may have contributed to the early death of runners.

  17. Antiallodynic Effects of Acupuncture in Neuropathic Rats

    OpenAIRE

    Cha, Myeoung Hoon; Choi, Ji Soo; Bai, Sun Joon; Shim, Insop; Lee, Hye-Jung; Choi, Sun Mi; Lee, Bae Hwan

    2006-01-01

    Peripheral nerve injury often results in abnormal neuropathic pain such as allodynia or hyperalgesia. Acupuncture, a traditional Oriental medicine, has been used to relieve pain and related symptoms. However, the efficiency of acupuncture in relieving neuropathic pain is not clear. The aim of this study was to investigate the anti-allodynic effects of acupuncture through behavioral and electrophysiological examinations. Male Sprague-Dawley rats were subjected to neuropathic surgery consisting...

  18. Transgenic Rat Models for Breast Cancer Research

    Science.gov (United States)

    1999-10-01

    medium). Using bovine embryos, cytochalasin B has been shown to increase the rigidity of the membranes and to restrict the movement of the pronuclei with...non surgical transfer of frozen- thawed bovine embryos. Theriogenology 1984; 21: 767-790. 16. Papaioannou VE, Fox JG. Efficacy of tribromoethanol...0, Tsunoda Y. Cryopreservation of rat blastocysts by vitrification . Cryobiology 1988; 25: 170-173. 24 Helmuth and Griep FIGURE LEGENDS Figure 1

  19. Chemical Renal Denervation in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  20. Real-Ear Attenuation Testing System (RATS)

    Science.gov (United States)

    1991-01-01

    OF TABLES 1. Ambient Noise SPL (in dB) inside Measurement Chamber 2. Reverberation Time in Measurement Chamber in Seconds 6 3. Sound Pressure Level...Chamber New Work Detail 42 9. RATS Measurment System Block Diagram 43 10. Ambient Noise Measurement Block Diagram 44 11. Reverberation Time Measurement...noise level, reverberation time , sound pressure level (SPL) ’uniformity about the subject’s head position, and direc- tionality of the sound field

  1. Renal alterations in prediabetic rats with periodontitis

    DEFF Research Database (Denmark)

    Pontes Andersen, Carla C; Holmstrup, Palle; Buschard, Karsten

    2008-01-01

    , the rats were sacrificed, and the kidneys, liver, and heart were removed and weighed. Kidneys were evaluated histologically for glomerular volume and renal mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptor 2, transforming growth factor-beta, connective tissue growth factor, collagen......RNA levels (P = 0.03) were noted in the presence of periodontitis. CONCLUSION: Our findings suggest the participation of periodontitis in the development of early renal changes in ZFRs....

  2. Rabbiteye blueberry prevents osteoporosis in ovariectomized rats.

    Science.gov (United States)

    Li, Tao; Wu, Shou-Mian; Xu, Zhi-Yuan; Ou-Yang, Sheng

    2014-08-08

    It has been forecasted that the rabbiteye blueberry could inhibit osteoporosis. However, the inhibition and prevention of osteoporosis via rabbiteye blueberry are still elusive. This study was aim to evaluate the anti-osteoporosis effects of rabbiteye blueberry in ovariectomized rats. Thirty rats were randomly divided into three groups of ten rats each as follows: sham-operated group (SG), ovariectomized model control group (OMG), and ovariectomized rabbiteye blueberry treatment group (OBG). The blood mineral levels, the alkaline phosphatase (ALP) activity, and osteoprotegerin (OPG) level were determined. The expression analyses of type I collagen, integrin-β1, and focal adhesion kinase (FAK) were performed. Besides, the bone mineral density (BMD) and bone histomorphometry (BH) were measured. The ALP activity in SG and OBG was significantly lower than that in OMG. For the OPG level, the significant increase of OPG level in OBG was indicated compared with the other groups. The mRNA expression levels of type I collagen, integrin-β1, and FAK in OMG were significantly lower than those in other groups. The BMD in OMG were all significantly lower than those in SG and OBG. For BH, blueberry significantly improved the trabecular bone volume fraction, trabecular thickness, mean trabecular bone number, and bone formation rate, and decreased the trabecular separation, the percent of bone resorption perimeter, and mean osteoclast number in OBG compared with OMG. The rabbiteye blueberries had an effective inhibition in bone resorption, bone loss, and reduction of bone strength of ovariectomized rats and could improve the BMD, osteogenic activity, and trabecular bone structure.

  3. Motor development after vestibular deprivation in rats.

    Science.gov (United States)

    Geisler, H C; Gramsbergen, A

    1998-07-01

    This review summarizes the postural development in the rat and the influences of vestibular deprivation from the 5th postnatal day on this development. Vestibular deprivation leads to a delay in motor development. Most probably this delay is caused by a delay in the development of postural control, which is characterized by a retarded EMG development in postural muscles. Our results indicate that the developing nervous system cannot compensate for a vestibular deficit during the early phase of ontogeny.

  4. Oral Gavage in Rats: Animal Welfare Evaluation

    Science.gov (United States)

    Turner, Patricia V; Vaughn, Elizabeth; Sunohara-Neilson, Janet; Ovari, Jelena; Leri, Francesco

    2012-01-01

    The effect of chronic daily orogastric gavage with water (5 mL/kg) on behavior and physiology was evaluated in male Sprague–Dawley rats. Treatment groups included: unmanipulated control, restraint control, dry gavage, and gavage, with all rats singly housed (n = 9 or 10 per group). In addition, a group of pair-housed rats (n = 18) was included to determine whether social housing affected response to gavage. Weekly body weights and food consumption were recorded as well as use of a nylon chew toy for enrichment. Feces were collected biweekly at the end of the light and dark phases for fecal corticoid metabolite determinations. After 28 d of treatment, animals underwent conditioned place preference testing to evaluate sensitivity to motivational properties of the anxiolytic drug chlordiazepoxide (5.6 mg/kg SC). Brain and paired adrenal gland weights were collected at necropsy. Week 2 total fecal corticosterone levels were elevated in all groups and attributed to a fire alarm accidentally tripped during building renovations. No differences occurred in body weight or food consumption between any groups. All groups used a nylon chew toy given for enrichment and demonstrated mild preference for the drug-associated chamber. Fecal weights and corticoid metabolite levels were similar between all groups at week 4 and showed normal diurnal variation. No biologically significant variations were noted in brain or paired adrenal gland to body weight ratios. We conclude that orogastric gavage of aqueous solutions at 5 mL/kg does not negatively affect the welfare of laboratory rats acclimated to handling. PMID:22330864

  5. Morphological and neurohistological changes in adolescent rats ...

    African Journals Online (AJOL)

    Pregnancy was confirmed and the pregnant rats were divided into 3 groups based on the 3 trimesters (A, B, C), with each group having a control and a treated subgroup. The Control Groups (A1, B1, C1) were given 0.1 ml of normal saline i. p., while the Treated Groups (A2, B2, C2) received 0.06 mg/kg/0.1 ml of nicotine ...

  6. Effects of fencamfamine withdrawal in rats.

    Science.gov (United States)

    Planeta, C S; DeLucia, R; Aizenstein, M L

    1994-09-01

    1. The effects produced by discontinuation of long-term treatment with fencamfamine (FCF) were evaluated recording behavioral and body weight changes. 2. 48 hr after withdrawal of FCF rats showed a significant decrease in exploratory behavior when compared to saline-treated ones. 3. Discontinuation of treatment with FCF resulted in a significant increase in body weight on days of drug withdrawal. 4. These results suggest that FCF caused signs of withdrawal similar to other psychostimulant drugs.

  7. Characterizing a Rat Brca2 Knockout Model

    Science.gov (United States)

    2007-05-01

    gel. m Yeast transformation and sequencing. yIG397 (ref. 15) yeast was cultured overnight at 30 OC in YPD medium supplemented with adenine (200...colonies when plated on selective medium . In the absence VOLUME 21 NUMBER 6 JUNE 2003 NATURE BIOTECHNOLOGY Table 2 ENU-induced heritable phenotypes mately...and a PCR product enriched for BrcaZfragment 2 (nucleotides 3518-5204) were plated on selective medium . When gDNA obtained from a rat (SD) with two

  8. Aggregation of rat neutrophils by nucleotide triphosphates.

    OpenAIRE

    Ford-Hutchinson, A. W.

    1982-01-01

    1 Adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) at concentrations of 3 x 10(-7)M and greater cause a rapid partially reversible aggregation of rat polymorphonuclear leucocytes. 2 Other nucleotide phosphates are much less active at producing aggregation responses; the agonist potencies being UTP greater than ATP greater than guanosine 5'-triphosphate, cytidine 5'-triphosphate, thymidine 5'-triphosphate; ATP greater than adenosine 5'-diphosphate (ADP) greater than adenosine ...

  9. A new neurological rat mutant "mutilated foot".

    OpenAIRE

    Jacobs, J M; Scaravilli, F; Duchen, L W; Mertin, J

    1981-01-01

    A new autosomal recessive mutant rat (mutilated foot) with a neurological disorder is described. Affected animals become ataxic and the feet, generally of the hind limbs, are mutilated. Quantitative studies show a severe reduction in numbers of sensory ganglion cells and fibres, including unmyelinated fibres. The numbers of ventral root fibres, particularly those of small diameter, are also reduced. Markedly decreased numbers of spindles are found in the limb muscles. These quantitative abnor...

  10. Proteomic profiling of the rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Pedroso Amanda P

    2012-04-01

    Full Text Available Abstract Background The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE profile of rat hypothalamus proteins. Results As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development. Conclusion The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.

  11. Platelet mitochondrial dysfunction of DM rats and DM patients.

    Science.gov (United States)

    Wu, Fengming; Liu, Yuhan; Luo, Li; Lu, Yinghong; Yew, David T; Xu, Jie; Guo, Kaihua

    2015-01-01

    It is known that cardiovascular complications plays important roles in the development of diabetes mellitus (DM) and platelet dysfunction is one of the key reasons which led to microangiopathy. This study was designed to investigate the mitochondria function changes of platelet in DM rats and DM patients. The results showed that the platelets viability, platelet adenosine triphosphate (ATP) content and platelet mitochondrial ATP content of DM rats were lower than that of normal rats; when incubated in vitro for 24 h, platelet number and mitochondrial membrane potential (MMP) of DM rats were lower than that of normal rats, reactive oxygen species (ROS) was higher than that of normal rats. For DM patients, their platelet number and ROS were higher and MMP was lower than those of normal people; when incubated in vitro for 24 h, platelet viability of DM patients was lower than that of normal people. Platelet ultra-microstructures of DM rats and DM patients were abnormal. These results suggested that platelet mitochondrial function of both DM rats and DM patients was impaired when compared to normal rats and normal people, respectively. Platelets may be applied as a biomarker to observe the mitochondrial changes during DM.

  12. Calcium balance in mature male rats with unloaded hindlimbs

    Science.gov (United States)

    Navidi, Meena; Evans, Juliann; Wolinsky, Ira; Arnaud, Sara B.

    2004-01-01

    BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

  13. Experimental vaccination of rats with Dermatophilus congolensis zoospores.

    Science.gov (United States)

    Davis, D

    1988-05-01

    The number of zoospores recoverable from the skin of rats five days after challenge with Dermatophilus congolensis, was reduced if the rats had been injected intradermally with zoospores of this bacterium two weeks previously. The difference between zoospore recovery in vaccinated and control rats was increased when the challenge was applied to scarified skin. Assays involving a 24-hour delay between scarification and challenge gave the greatest difference in zoospore recovery. In rats which had been vaccinated 12 weeks before challenge protection was reduced.

  14. Atherogenesis and metabolic dysregulation in LDL receptor-knockout rats.

    Science.gov (United States)

    Sithu, Srinivas D; Malovichko, Marina V; Riggs, Krista A; Wickramasinghe, Nalinie S; Winner, Millicent G; Agarwal, Abhinav; Hamed-Berair, Rihab E; Kalani, Anuradha; Riggs, Daniel W; Bhatnagar, Aruni; Srivastava, Sanjay

    2017-05-04

    Mechanisms of atherogenesis have been studied extensively in genetically engineered mice with disturbed cholesterol metabolism such as those lacking either the LDL receptor (Ldlr) or apolipoprotein E (apoe). Few other animal models of atherosclerosis are available. WT rabbits or rats, even on high-fat or high-cholesterol diets, develop sparse atherosclerotic lesions. We examined the effects of Ldlr deletion on lipoprotein metabolism and atherosclerotic lesion formation in Sprague-Dawley rats. Deletion of Ldlr resulted in the loss of the LDLR protein and caused a significant increase in plasma total cholesterol and triglycerides. On normal chow, Ldlr-KO rats gained more weight and were more glucose intolerant than WT rats. Plasma proprotein convertase subtilisin kexin 9 (PCSK9) and leptin levels were higher and adiponectin levels were lower in KO than WT rats. On the Western diet, the KO rats displayed exaggerated obesity and age-dependent increases in glucose intolerance. No appreciable aortic lesions were observed in KO rats fed normal chow for 64 weeks or Western diet for 16 weeks; however, after 34-52 weeks of Western diet, the KO rats developed exuberant atherosclerotic lesions in the aortic arch and throughout the abdominal aorta. The Ldlr-KO rat may be a useful model for studying obesity, insulin resistance, and early-stage atherosclerosis.

  15. Diuretic activity of coleus aromaticus benth on rats.

    Science.gov (United States)

    Sur, T K; Pandit, S; Biswas, T K; Ghosh, R B; Bhattacharyya, D

    2003-04-01

    Water extract of the leaves of Coleus Aromaticus Benth was tested for its diuretic activity in male albino rats. The study was carried out on normal rats using furosemide as a standard reference drug. Rats were treated with furosemide (4 mg/kg. p.o) and Coleus aromaticus (0.5 g/kg and 1.0 g/kg, p/o). Urine was collected and its volume was recorded. Urinary levels of sodium, potassium and chloride were estimated. Treatment with Coleus aromaticus produced diuresis. The urine output and electrolytes concentration was significantly increased. Hence, it is suggested, Coleus aromaticus leaves has diuretic activity on rats.

  16. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    DEFF Research Database (Denmark)

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo

    2013-01-01

    INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats overexpress......INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats...

  17. Inhalation carcinogenicity of dichloromethane in rats and mice.

    Science.gov (United States)

    Aiso, Shigetoshi; Take, Makoto; Kasai, Tatsuya; Senoh, Hideki; Umeda, Yumi; Matsumoto, Michiharu; Fukushima, Shoji

    2014-07-01

    The carcinogenicity of inhaled dichloromethane (DCM) was examined by exposing groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of both sexes to 0, 1000, 2000, or 4000 ppm (w/w) DCM-containing aerosol for 2 years. Inhalation of DCM resulted in increased incidences of subcutis fibromas, mammary gland fibroadenoma, and peritoneum mesotheliomas in male rats; mammary gland fibroadenomas in female rats; and bronchiolar-alveolar adenomas and carcinomas in the lung and hepatocellular adenomas and carcinomas in male and female mice. These results clearly indicate that inhaled DCM is carcinogenic in F344/DuCrj (SPF) rats and Crj: BDF1 (SPF) mice.

  18. Database of Physiological Parameters for Early Life Rats and Mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...

  19. Cloning and regulation of the rat mdr2 gene.

    OpenAIRE

    Brown, P C; Thorgeirsson, S.S.; Silverman, J A

    1993-01-01

    We have cloned the complete cDNA encoding the rat mdr2 gene by a combination of library screening and the polymerase chain reaction. The sequence of rat mdr2 cDNA is highly similar to other members of the mdr gene family but the initiation of transcription, tissue distribution and regulation of expression of rat mdr2 diverge from the other isoforms. Primer extension analysis showed rat mdr2 mRNA to have a major transcription start point at -277 and a minor one at approximately -518. We constr...

  20. Diabetogenic Effects of Ochratoxin A in Female Rats

    OpenAIRE

    Mor, Firdevs; Sengul, Omur; Topsakal, Senay; KILIC, Mehmet Akif; Ozmen, Ozlem

    2017-01-01

    In this study, the diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated, and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into three different study and control groups according to the duration of the OTA administration. The rats received 45 ?g OTA daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups were also used for the same time per...