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Sample records for hypertensive mice strain

  1. Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex

    NARCIS (Netherlands)

    Taherzadeh, Zhila; VanBavel, Ed; de Vos, Judith; Matlung, Hanke L.; van Montfrans, Gert; Brewster, Lizzy M.; Seghers, Leonard; Quax, Paul H. A.; Bakker, Erik N. T. P.

    2010-01-01

    Taherzadeh Z, VanBavel E, de Vos J, Matlung HL, van Montfrans G, Brewster LM, Seghers L, Quax PH, Bakker EN. Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex. Am J Physiol Heart Circ Physiol 298: H1273-H1282, 2010. First published February 12, 2010;

  2. Energy metabolism in BPH/2J genetically hypertensive mice.

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    Jackson, Kristy L; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

    2014-05-01

    Recent evidence indicates that genetic hypertension in BPH/2J mice is sympathetically mediated, but these mice also have lower body weight (BW) and elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of metabolic abnormalities. The aim of the present study was to determine whether hypertension in BPH/2J mice is associated with metabolic differences. Whole-body metabolic and cardiovascular parameters were measured over 24 h by indirect calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure (BP) was greater in BPH/2J compared with both normotensive strains at both ages (PBPH/2J compared with BPN/3J mice (PBPH/2J and normotensive mice when adjusted for activity (P>0.1) suggesting differences in this relationship are not responsible for hypertension. EchoMRI revealed that percentage body composition was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight similarly with age (P=0.3). Taken together, the present findings indicate that hypertension in BPH/2J mice does not appear to be related to altered energy metabolism.

  3. Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice.

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    Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

    2014-03-01

    BPH/2J hypertensive mice have an exaggerated sympathetic contribution to blood pressure (BP). Premotor sympathetic neurons within the rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor tone and major site of action of the centrally acting sympatholytic agent, rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM in the sympathetic contribution to hypertension in BPH/2J mice. BPH/2J and BPN/3J mice were pre-implanted with telemetry devices to measure BP in conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group), orally for 14 days, at a wide range of doses (n=5/group), and also infused intracerebroventricularly for 7 days (n=6/group). Acute intraperitoneal rilmenidine induced greater depressor and bradycardic responses in BPH/2J than BPN/3J mice (PstrainBPH/2J mice during the dark (active) period (-6.5 ± 2 mmHg; P=0.006). Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal effect on 24-h BP in both strains (P>0.16). The sympathetic vasomotor inhibitory effect of rilmenidine is minimal in both strains and similar in hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not likely mediated by greater neuronal activity in the RVLM, and agents such as rilmenidine would be an ineffective treatment for this form of neurogenic hypertension.

  4. Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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    Kashyap, Sonu; Warner, Gina; Hu, Zeng; Gao, Feng; Osman, Mazen; Al Saiegh, Yousif; Lien, Karen R; Nath, Karl; Grande, Joseph P

    2017-01-01

    Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

  5. Major contribution of the medial amygdala to hypertension in BPH/2J genetically hypertensive mice.

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    Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

    2014-04-01

    BPH/2J mice are recognized as a neurogenic model of hypertension primarily based on overactivity of the sympathetic nervous system and greater neuronal activity in key autonomic cardiovascular regulatory brain regions. The medial amygdala (MeAm) is a forebrain region that integrates the autonomic response to stress and is the only region found to have greater Fos during the night and daytime in BPH/2J compared with BPN/3J mice. To determine the contribution of the MeAm to hypertension, the effect of neuronal ablation on blood pressure (BP) was assessed in BPH/2J (n=7) and normotensive BPN/3J mice (n=7). Mice were preimplanted with radiotelemetry devices to measure 24-hour BP and cardiovascular responses to stress, before and 1 to 3 weeks after bilateral lesions of the MeAm. Baseline BP was 121±4 mm Hg in BPH/2J and 101±2 mm Hg in BPN/3J mice (PstrainBPH/2J mice (PlesionBPH/2J mice was similar during both day and night, suggesting that the MeAm has tonic effects on BP, but the pressor response to stress was maintained in both strains. Midfrequency BP power was attenuated in both strains (PlesionBPH/2J mice (PlesionBPH/2J mice, which is independent of its role in stress reactivity or circadian BP influences.

  6. Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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    Sonu Kashyap

    Full Text Available Renovascular hypertension (RVH has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO protects the stenotic kidney (STK from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS was established in Wild-type (WT and Smad3 KO mice (129 genetic background by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

  7. IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

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    Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2014-12-01

    Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

  8. Cerium-144-induced lung gumors in two strains of mice

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.F.; Griffith, W.C.

    1995-12-01

    A major problem in the extrapolation of radiation cancer risk factors from one species or population to another is the choice of the risk model to use, either absolute or relative. The purpose of this study was to compare absolute and relative risk models in predicting the lung-tumor risks between a low lung-tumor incidence strain of mice and a high-incidence strain of mice. The conclusion from this study is that absolute risk is more accurate than relative risk for predicting lung tumor risk from high to low lung-tumor incidence strains of mice.

  9. [Immunodepressant action of cyclophosphamide in different strains of mice].

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    Pevnitskiĭ, L A; Telegin, L Iu; Bol'shev, V N

    1977-04-01

    A study was made of the immunodepressive effect of cyclophosphamide (CP) on mice of 3 strains (BALB/c, CBA, and DBA/2) immunized with sheep red blood cells (SRBC). With the optimal immunizing dose of the antigen (5 X 10(8) SRBC) the most pronounced immunodepression was noted in DBA/2 mice, and with the high dose (6.2 X 10(9))--in DBA/2 and CBA mice. The CP action proved to depend on the dose of the antigen administered; in BALB/c mice a reduction in the number of the antibody-forming cells was the same with both SRBC doses, in DBA/2 mice an increase of the antigen dose led to reduction of immunode pression, and in CBA mice -- to its enhancement (with sufficiently high CP doses). Determination of the rate of oxidative CP hydroxylation by the liver microsomes of mice showed it to be comparatively low in DBA/2 and CBA mice, and much greater in BALB/c mice. It is supposed that the detected differences in the immunodepressive action of CP could be connected with different sensitivity of the target cells and (or) with the peculiarities of its metabolism in mice belonging to different strains.

  10. Immobilization induced osteopenia is strain specific in mice

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    Andreas Lodberg

    2015-06-01

    Full Text Available Immobilization causes rapid and massive bone loss. By comparing Botulinum Toxin A (BTX-induced bone loss in mouse strains with different genetic backgrounds we investigated whether the genetic background had an influence on the severity of the osteopenia. Secondly, we investigated whether BTX had systemic effects on bone. Female mice from four inbred mouse strains (BALB/cJ, C57BL/6 J, DBA/2 J, and C3H/HeN were injected unilaterally with BTX (n = 10/group or unilaterally with saline (n = 10/group. Mice were euthanized after 21 days, and the bone properties evaluated using μCT, DXA, bone histomorphometry, and mechanical testing. BTX resulted in substantially lower trabecular bone volume fraction (BV/TV and trabecular thickness in all mouse strains. The deterioration of BV/TV was significantly greater in C57BL/6 J (−57% and DBA/2 J (−60% than in BALB/cJ (−45% and C3H/HeN (−34% mice. The loss of femoral neck fracture strength was significantly greater in C57BL/6 J (−47% and DBA/2 J (−45% than in C3H (−25% mice and likewise the loss of mid-femoral fracture strength was greater in C57BL/6 J (−17%, DBA/2 J (−12%, and BALB/cJ (−9% than in C3H/HeN (−1% mice, which were unaffected. Using high resolution μCT we found no evidence of a systemic effect on any of the microstructural parameters of the contralateral limb. Likewise, there was no evidence of a systemic effect on the bone strength in any mouse strain. We did, however, find a small systemic effect on aBMD in DBA/2 J and C3H/HeN mice. The present study shows that BTX-induced immobilization causes the greatest loss of cortical and trabecular bone in C57BL/6 J and DBA/2 J mice. A smaller loss of bone microstructure and fracture strength was seen in BALB/cJ mice, while the bone microstructure and fracture strength of C3H/HeN mice were markedly less affected. This indicates that BTX-induced loss of bone is mouse strain dependent. We found only minimal systemic

  11. Immobilization induced osteopenia is strain specific in mice

    DEFF Research Database (Denmark)

    Lodberg, Andreas; Vegger, Jens Bay; Jensen, Michael Vinkel

    2015-01-01

    systemic effects on bone. Female mice from four inbred mouse strains (BALB/cJ, C57BL/6 J, DBA/2 J, and C3H/HeN) were injected unilaterally with BTX (n = 10/group) or unilaterally with saline (n = 10/group). Mice were euthanized after 21 days, and the bone properties evaluated using μCT, DXA, bone...... resolution μCT we found no evidence of a systemic effect on any of the microstructural parameters of the contralateral limb. Likewise, there was no evidence of a systemic effect on the bone strength in any mouse strain. We did, however, find a small systemic effect on aBMD in DBA/2 J and C3H/HeN mice...

  12. Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

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    Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

    2018-01-01

    The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

  13. Job Strain, Workplace Discrimination, and Hypertension among Older Workers: The Health and Retirement Study.

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    Mezuk, Briana; Kershaw, Kiarri N; Hudson, Darrell; Lim, Kyuang Ah; Ratliff, Scott

    2011-03-01

    Job strain has been associated with hypertension among younger workers; however, whether this relationship persists among older workers, particularly older racial/ethnic minorities, is unresolved. This study evaluated whether job strain and workplace discrimination are associated with hypertension and poor blood pressure control among older workers and whether these relationships vary by gender and race/ethnicity. Data were drawn from the Health and Retirement Study, and analysis was restricted to employed participants with complete information on job strain and blood pressure (N = 3,794). In adjusted models, high job strain was associated with lower likelihood of hypertension (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.63, 0.89) relative to low job strain. Stratified analyses indicated this association was only significant among white (OR: 0.71, 95% CI: 0.58, 0.86) and male (OR: 0.61, 95% CI: 0.47, 0.79) workers. High job strain was not significantly associated with hypertension among African American (OR: 1.14, 95% CI: 0.63, 2.07) or Hispanic (OR: 0.56, 95% CI: 0.29, 1.09) workers. Workplace discrimination was not associated with hypertension among any group. Neither job strain nor discrimination was associated with poor blood pressure control. These findings suggest that persistence in work characterized by high job strain in later life may signal resilience to the influence of work-related stressors on health. Future research efforts should examine the factors that contribute to gender and racial differences in these relationships.

  14. Genetic variation within and between strains of outbred Swiss mice.

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    Cui, S; Chesson, C; Hope, R

    1993-04-01

    The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains.

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

    DEFF Research Database (Denmark)

    Carlström, M; Sällström, J; Skøtt, O

    2007-01-01

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

  16. Contribution of Orexin to the Neurogenic Hypertension in BPH/2J Mice.

    Science.gov (United States)

    Jackson, Kristy L; Dampney, Bruno W; Moretti, John-Luis; Stevenson, Emily R; Davern, Pamela J; Carrive, Pascal; Head, Geoffrey A

    2016-05-01

    BPH/2J mice are a genetic model of hypertension associated with an overactive sympathetic nervous system. Orexin is a neuropeptide which influences sympathetic activity and blood pressure. Orexin precursor mRNA expression is greater in hypothalamic tissue of BPH/2J compared with normotensive BPN/3J mice. To determine whether enhanced orexinergic signaling contributes to the hypertension, BPH/2J and BPN/3J mice were preimplanted with radiotelemetry probes to compare blood pressure 1 hour before and 5 hours after administration of almorexant, an orexin receptor antagonist. Mid frequency mean arterial pressure power and the depressor response to ganglion blockade were also used as indicators of sympathetic nervous system activity. Administration of almorexant at 100 (IP) and 300 mg/kg (oral) in BPH/2J mice during the dark-active period (2 hours after lights off) markedly reduced blood pressure (-16.1 ± 1.6 and -11.0 ± 1.1 mm Hg, respectively;PBPH/2J mice (PBPH/2J mice have 29% more orexin neurons than BPN/3J mice which are preferentially located in the lateral hypothalamus. The results suggest that enhanced orexinergic signaling contributes to sympathetic overactivity and hypertension during the dark period in BPH/2J mice. © 2016 American Heart Association, Inc.

  17. Lymphoma of SJL/J mice strain, 3

    International Nuclear Information System (INIS)

    Takahashi, Masanori; Takeichi, Sanae; Otsuka, Hisashi

    1976-01-01

    This paper describes influences of 7, 12-dimethylbenz (α) anthracene (DMBA) and 60 Co irradiation in lymphoma, together with the past results. The influences of DMBA in the lymphoma were studied 265 days (an average) after the subcutaneous administration of 1 mg/day of DMBA in 35 mice, and 246 days after it accompanied with the extraction of the thymus. Eight hundred rads (200 rads/ week four times) intermittent systemic irradiation was given to 26 mice, and to 16 mice after the extraction of the thymus. The influences on the lymphoma were studied 233 days later (an average) in the former and 544 days later (an average) in the latter. Lymphoma occurred 242 days later (an average) in 20 of the 35 mice with the administration of DMBA (57.1%), and 260 days later (an average) in 13 of the 42 mice with the administration of DMBA accompanied with the extraction of the thymus (30.9%). It occurred 231 days later (an average) in 22 of the 26 mice with 60 Co irradiation (84.6%), and 561 days later (an average) in 12 of the 16 mice with 60 Co irradiation accompanied with the extraction of the thymus (75%). Lymphosarcoma occurred 211 days after the administration of DMBA in 37%, and 208 days after the irradiation of 60 Co in 53.8%. However, it did not occur in animals in which the thymus had been extracted. The frequency of thymic lymphoma was high in animals with the administration of N-nitrosobutylurea. Although the occurrence of lymphosarcoma was controlled after the extraction of the thymus, reticulosarcoma occurred. The time of occurrence of lymphoma and the frequency of its occurrence by tissues were the same in the mice with extraction of the thymus as in controls. The SJL/J strain mice seemed to be independent of the thymus. (Kanao, N.)

  18. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

    Science.gov (United States)

    La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

    2016-11-01

    Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

  19. Job strain and risk of cardiovascular events in treated hypertensive Japanese workers: hypertension follow-up group study.

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    Uchiyama, Shuji; Kurasawa, Takashi; Sekizawa, Toshihiro; Nakatsuka, Hiroshi

    2005-03-01

    In Japan, Karoshi, which means "death from overwork", has become a focus of social concern. However, no previous study has examined long working hours and job strain simultaneously in relation to incidence of cardiovascular events (CVE) in Japanese workers. We prospectively evaluated the relation between job strain or long working hours and risk of CVE in treated hypertensives during the years 1994-2000. In this study, we followed a sample of 1,615 participants (908 men and 707 women) aged 40-65 yr who were working more than 5 working hours per day. Participants completed questions about work-related conditions and lifestyle variables at baseline, and were free of diagnosed cardiovascular disease, stroke or cancer. Job strain (the combination of job demands and job control) was assessed using a simple questionnaire developed with reference to Karasek's model. The main outcome measure was incidence of CVE. During the mean follow-up period of 5.6 yr, we documented 38 cases of initial CVE. Analyses were conducted using the Cox proportional hazard model. We found a significant association between incidence of CVE and job strain categories, but not long working hours. Multivariate relative risks for CVE in active jobs and high strain jobs overall were 2.89 (95% CI: 1.33-6.28) and 2.45 (95% CI: 0.87-6.93); for men 2.94 (95% CI: 1.29-6.73) and 1.86 (95% CI: 0.51-6.75), and for women 3.97 (95% CI: 0.34-46.88) and 9.05 (95% CI: 1.17-69.86), respectively. In conclusion, active jobs and high strain jobs were associated with increased risk of CVE for treated hypertensive workers.

  20. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

    Science.gov (United States)

    Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

    2017-01-01

    Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. © FASEB.

  1. Aldosterone Inhibits the Fetal Program and Increases Hypertrophy in the Heart of Hypertensive Mice

    Science.gov (United States)

    Azibani, Feriel; Devaux, Yvan; Coutance, Guillaume; Schlossarek, Saskia; Polidano, Evelyne; Fazal, Loubina; Merval, Regine; Carrier, Lucie; Solal, Alain Cohen; Chatziantoniou, Christos; Launay, Jean-Marie; Samuel, Jane-Lise; Delcayre, Claude

    2012-01-01

    Background Arterial hypertension (AH) induces cardiac hypertrophy and reactivation of “fetal” gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC) and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. Methodology/Principal Findings RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren) with cardiac hyperaldosteronism (AS mice) and systemic hypertension (Ren). AS-Ren mice had increased (x2) angiotensin II in plasma and increased (x2) aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70%) versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41%) in AS-Ren mice (P<0.05 vs Ren). The increase of ANP (x 2.5; P<0.01) mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (−75%, p<0.001) in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05), an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. Conclusions/Significance Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction of

  2. Aldosterone inhibits the fetal program and increases hypertrophy in the heart of hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Feriel Azibani

    Full Text Available BACKGROUND: Arterial hypertension (AH induces cardiac hypertrophy and reactivation of "fetal" gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren with cardiac hyperaldosteronism (AS mice and systemic hypertension (Ren. AS-Ren mice had increased (x2 angiotensin II in plasma and increased (x2 aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70% versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41% in AS-Ren mice (P<0.05 vs Ren. The increase of ANP (x 2.5; P<0.01 mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (-75%, p<0.001 in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05, an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. CONCLUSIONS/SIGNIFICANCE: Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction

  3. Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice.

    Science.gov (United States)

    Cero, Fadila Telarevic; Hillestad, Vigdis; Sjaastad, Ivar; Yndestad, Arne; Aukrust, Pål; Ranheim, Trine; Lunde, Ida Gjervold; Olsen, Maria Belland; Lien, Egil; Zhang, Lili; Haugstad, Solveig Bjærum; Løberg, Else Marit; Christensen, Geir; Larsen, Karl-Otto; Skjønsberg, Ole Henning

    2015-08-15

    Pulmonary hypertension is a serious condition that can lead to premature death. The mechanisms involved are incompletely understood although a role for the immune system has been suggested. Inflammasomes are part of the innate immune system and consist of the effector caspase-1 and a receptor, where nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) is the best characterized and interacts with the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC). To investigate whether ASC and NLRP3 inflammasome components are involved in hypoxia-induced pulmonary hypertension, we utilized mice deficient in ASC and NLRP3. Active caspase-1, IL-18, and IL-1β, which are regulated by inflammasomes, were measured in lung homogenates in wild-type (WT), ASC(-/-), and NLRP3(-/-) mice, and phenotypical changes related to pulmonary hypertension and right ventricular remodeling were characterized after hypoxic exposure. Right ventricular systolic pressure (RVSP) of ASC(-/-) mice was significantly lower than in WT exposed to hypoxia (40.8 ± 1.5 mmHg vs. 55.8 ± 2.4 mmHg, P right ventricular remodeling. RVSP of NLRP3(-/-) mice exposed to hypoxia was not significantly altered compared with WT hypoxia. Whereas hypoxia increased protein levels of caspase-1, IL-18, and IL-1β in WT and NLRP3(-/-) mice, this response was absent in ASC(-/-) mice. Moreover, ASC(-/-) mice displayed reduced muscularization and collagen deposition around arteries. In conclusion, hypoxia-induced elevated right ventricular pressure and remodeling were attenuated in mice lacking the inflammasome adaptor protein ASC, suggesting that inflammasomes play an important role in the pathogenesis of pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  4. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

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    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  5. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

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    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

  6. Hypertension

    Science.gov (United States)

    ... role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such as kidney ... the body can greatly improve or even cure secondary hypertension. Obstructive sleep apnea is a potentially serious sleep ...

  7. T-cells contribute to hypertension but not to renal injury in mice with subtotal nephrectomy

    NARCIS (Netherlands)

    Oosterhuis, Nynke R.; Papazova, Diana A.; Gremmels, Hendrik; Joles, Jaap A.; Verhaar, Marianne C.

    2017-01-01

    Background: The pathological condition of chronic kidney disease may not be adequately recapitulated in immunocompromised mice due to the lack of T-cells, which are important for the development of hypertension and renal injury. We studied the role of the immune system in relation to salt-sensitive

  8. Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive

    Science.gov (United States)

    Garver, Hannah; Galligan, James J.; Fink, Gregory D.

    2011-01-01

    Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. PMID:21131476

  9. Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

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    Min Yu

    Full Text Available Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined.Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia.Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

  10. Pulmonary hypertension and vascular remodeling in mice exposed to crystalline silica.

    Science.gov (United States)

    Zelko, Igor N; Zhu, Jianxin; Ritzenthaler, Jeffrey D; Roman, Jesse

    2016-11-28

    Occupational and environmental exposure to crystalline silica may lead to the development of silicosis, which is characterized by inflammation and progressive fibrosis. A substantial number of patients diagnosed with silicosis develop pulmonary hypertension. Pulmonary hypertension associated with silicosis and with related restrictive lung diseases significantly reduces survival in affected subjects. An animal model of silicosis has been described previously however, the magnitude of vascular remodeling and hemodynamic effects of inhaled silica are largely unknown. Considering the importance of such information, this study investigated whether mice exposed to silica develop pulmonary hypertension and vascular remodeling. C57BL6 mice were intratracheally injected with either saline or crystalline silica at doses 0.2 g/kg, 0.3 g/kg and 0.4 g/kg and then studied at day 28 post-exposure. Pulmonary hypertension was characterized by changes in right ventricular systolic pressure and lung histopathology. Mice exposed to saline showed normal lung histology and hemodynamic parameters while mice exposed to silica showed increased right ventricular systolic pressure and marked lung pathology characterized by a granulomatous inflammatory reaction and increased collagen deposition. Silica-exposed mice also showed signs of vascular remodeling with pulmonary artery muscularization, vascular occlusion, and medial thickening. The expression of pro-inflammatory genes such as TNF-α and MCP-1 was significantly upregulated as well as the expression of the pro-remodeling genes collagen type I, fibronectin and the metalloproteinases MMP-2 and TIMP-1. On the other hand, the expression of several vasculature specific genes involved in the regulation of endothelial function was significantly attenuated. We characterized a new animal model of pulmonary hypertension secondary to pulmonary fibrosis induced by crystalline silica. Our data suggest that silica promotes the damage of the

  11. Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

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    Upa Kukongviriyapan

    2014-03-01

    Full Text Available Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L in drinking water for eight weeks. Curcumin (50 or 100 mg/kg was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.

  12. Pathophysiologic assessment of left ventricular hypertrophy and strain in asymptomatic patients with essential hypertension

    International Nuclear Information System (INIS)

    Pringle, S.D.; Macfarlane, P.W.; McKillop, J.H.; Lorimer, A.R.; Dunn, F.G.

    1989-01-01

    To investigate the significance of the electrocardiographic (ECG) pattern of left ventricular hypertrophy and strain, two groups of asymptomatic patients with essential hypertension were compared. The patients were similar in terms of age, smoking habit, serum cholesterol and blood pressure levels, but differed in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG pattern of left ventricular hypertrophy and strain. Group I patients had significantly more episodes of exercise-induced ST segment depression (14 versus 4, p less than 0.05) and reversible thallium perfusion abnormalities (11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity and absence of chest pain. Nonsustained ventricular tachycardia was detected on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient in Group II. Coronary arteriography performed in 20 Group I patients demonstrated significant coronary artery disease in 8 patients. This study has shown that there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy and strain who have covert coronary artery disease. This can be detected by thallium perfusion scintigraphy, and may contribute to the increased risk known to be associated with this ECG abnormality

  13. 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

  14. Treatment with salvianolic acid B restores endothelial function in angiotensin II-induced hypertensive mice.

    Science.gov (United States)

    Ling, Wei Chih; Liu, Jian; Lau, Chi Wai; Murugan, Dharmani Devi; Mustafa, Mohd Rais; Huang, Yu

    2017-07-15

    Salvianolic acid B (Sal B) is one of the most abundant phenolic acids derived from the root of Danshen with potent anti-oxidative properties. The present study examined the vasoprotective effect of Sal B in hypertensive mice induced by angiotensin II (Ang II). Sal B (25mg/kg/day) was administered via oral gavage for 11days to Ang II (1.2mg/kg/day)-infused C57BL/6J mice (8-10weeks old). The vascular reactivity (both endothelium-dependent relaxations and contractions) in mouse arteries was examined by wire myography. The production of reactive oxygen species (ROS), protein level and localization of angiotensin AT 1 receptors and the proteins involved in ROS formation were evaluated using dihydroethidium (DHE) fluorescence, lucigenin-enhanced chemiluminescence, immunohistochemistry and Western blotting, respectively. The changes of ROS generating proteins were also assessed in vitro in human umbilical vein endothelial cells (HUVECs) exposed to Ang II with and without co-treatment with Sal B (0.1-10nM). Oral administration of Sal B reversed the Ang II-induced elevation of arterial systolic blood pressure in mice, augmented the impaired endothelium-dependent relaxations and attenuated the exaggerated endothelium-dependent contractions in both aortas and renal arteries of Ang II-infused mice. In addition, Sal B treatment normalized the elevated levels of AT 1 receptors, NADPH oxidase subunits (NOx-2 and NOx-4) and nitrotyrosine in arteries of Ang II-infused mice or in Ang II-treated HUVECs. In summary, the present study provided additional evidence demonstrating that Sal B treatment for 11days reverses the impaired endothelial function and with a marked inhibition of AT 1 receptor-dependent vascular oxidative stress. This vasoprotective and anti-oxidative action of Sal B most likely contributes to the anti-hypertensive action of the plant-derived compound. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. hypertension

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    Emine Hatipoglu

    2013-05-01

    Full Text Available Hypertension is a common disease associated with important cardiovascular complications. Persistent blood pressure of 140/90 or higher despite combined use of a reninangiotensin system blocker, calcium channel blocker and a diuretic at highest tolerated doses constitutes resistant hypertension. Excess sympathetic activity plays an important pathogenic role in resistant hypertension in addition to contributing to the development of metabolic problems, in particular diabetes. Reduction of renal sympathetic activity by percutaneous catheter-based radiofrequency ablation via the renal arteries has been shown in several studies to decrease blood pressure in patients with resistant hypertension, and importantly is largely free of significant complications. However, longer term follow-up is required to confirm both long-term safety and efficacy.

  16. Hypertension

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for hypertension hyperlipidemia. The data is provided by three managed care organizations in Allegheny County...

  17. Hypertension

    OpenAIRE

    Farrugia, Emanuel

    2004-01-01

    Hypertension is a rapidly moving clinical field with frequent developments in new pharmacologic agents and management strategies. Perhaps more importantly, there have been substantial improvements in our understanding of how best to use the drugs available to us. In this article, I will review some of the more important advances in our understanding of hypertension over the past two years, specifically by reviewing six important trials, one survey and two sets of guidelines, all published bet...

  18. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

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    Izziki Mohamed

    2009-01-01

    Full Text Available Abstract Background Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH. Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6. Methods To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/- and wild-type (IL-6+/+ mice exposed to hypoxia for 2 weeks. Results Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines. Conclusion These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.

  19. Strain-specific patterns of autonomic nervous system activity and heart failure susceptibility in mice.

    Science.gov (United States)

    Shusterman, Vladimir; Usiene, Irmute; Harrigal, Chivonne; Lee, Joon Sup; Kubota, Toru; Feldman, Arthur M; London, Barry

    2002-06-01

    Transgenic mice are widely used to study cardiac function, but strain-dependent differences in autonomic nervous system activity (ANSA) have not been explored. We compared 1) short-term pharmacological responses of cardiac rhythm in FVB vs. C57Black6/SV129 wild-type mice and 2) long-term physiological dynamics of cardiac rhythm and survival in tumor necrosis factor (TNF)-alpha transgenic mice with heart failure (TNF-alpha mice) on defined backgrounds. Ambulatory telemetry electrocardiographic recordings and response to saline, adrenergic, and cholinergic agents were examined in FVB and C57Black6/SV129 mice. In FVB mice, baseline heart rate (HR) was higher and did not change after injection of isoproterenol or atropine but decreased with propranolol. In C57Black6/SV129 mice, HR did not change with propranolol but increased with isoproterenol or atropine. Mean HR, but not indexes of HR variability, was an excellent predictor of response to autonomic agents. The proportion of surviving animals was higher in TNF-alpha mice on an FVB background than on a mixed FVB/C57Black6 background. The homeostatic states of ANSA are strain specific, which can explain the interstrain differences in mean HR, pharmacological responses, and survival of animals with congestive heart failure. Strain-specific differences should be considered in selecting the strains of mice used for transgenic and gene targeting experiments.

  20. Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice

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    Sonia G. Andrade

    1990-03-01

    Full Text Available The murine model of chronic Chaga's myocardiopathy was developed in 201 inbred and outbred mice. The experimental groups consisted of 1st: 73 inbred AKR and A/J mice inoculated with one of the following. Trypanosoma cruzi strains: Peruvian (Type I, 12 SF (Type II or Colombian (Type III; 2nd: 128 outbred Swiss mice, chronically infected either with Type II or Type III strains isolated from human patients from different geographical areas. All T. cruzi strains were previoulsly characterized by their morphobiological behaviour in mice and by isoenzymatic patterns. For the 1st group the inoculum was 5 x 10**4 for the Peruvian strain and 1 x 10**5 for the 12 SF and Colombian strains. In the 2nd group-Swiss mice the inoculum size varied from 2 x 10**4 to 2 x 10**5. The inbred animals were killed at a 3 time-point scale (90, 180 and 240 days post-infection. The Swiss mice were killed from 180 to 660 days after infection. The evaluation of parasitemia and serology (xeodiagnosis and indirect immunofluorescent test was performed. The incidence of macroscopic alterations of the heart and cardiac index were evaluated. Histopathological lesions of the myocardium were graded. The influence of T. cruzi strain on the intensity of cardiac lesions was evaluated by the Chi-square test; the incidence of inflammatory lesions and its relationship to the parasite strain was evaluated by the Fisher test. The influence of the duration of infection was evaluated by using the Gamma Coefficient of Kruskal and Goodman and its measure of significance. Slight to severe microscopic alterations occurred in 85% of the chronically infected nice. There were a clear predominance on the incidence and intensity of inflammatory and fibrotic alterations for the mice infected with Type III strains. Statistical analysis has shown significant differences among the infected groups, in the inflammatory and fibrotic lesions. Macroscopic alterations (right cavities dilatation and apex

  1. Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

    Science.gov (United States)

    Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

    2017-07-01

    The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

  2. EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

    Directory of Open Access Journals (Sweden)

    Zhan-Li Shi

    2018-01-01

    Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

  3. Cocaine locomotor activation, sensitization and place preference in six inbred strains of mice

    Science.gov (United States)

    2011-01-01

    Background The expanding set of genomics tools available for inbred mouse strains has renewed interest in phenotyping larger sets of strains. The present study aims to explore phenotypic variability among six commonly-used inbred mouse strains to both the rewarding and locomotor stimulating effects of cocaine in a place conditioning task, including several strains or substrains that have not yet been characterized for some or all of these behaviors. Methods C57BL/6J (B6), BALB/cJ (BALB), C3H/HeJ (C3H), DBA/2J (D2), FVB/NJ (FVB) and 129S1/SvImJ (129) mice were tested for conditioned place preference to 20 mg/kg cocaine. Results Place preference was observed in most strains with the exception of D2 and 129. All strains showed a marked increase in locomotor activity in response to cocaine. In BALB mice, however, locomotor activation was context-dependent. Locomotor sensitization to repeated exposure to cocaine was most significant in 129 and D2 mice but was absent in FVB mice. Conclusions Genetic correlations suggest that no significant correlation between conditioned place preference, acute locomotor activation, and locomotor sensitization exists among these strains indicating that separate mechanisms underlie the psychomotor and rewarding effects of cocaine. PMID:21806802

  4. Layer-specific systolic and diastolic strain in  hypertensive patients with and without mild diastolic dysfunction

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    Hisham Sharif PhD

    2018-03-01

    Full Text Available This study sought to examine layer-specific longitudinal and circumferential systolic and diastolic strain, strain rate (SR and diastolic time intervals in hypertensive patients with and without diastolic dysfunction. Fifty-eight treated hypertensive patients were assigned to normal diastolic function (NDF, N = 39 or mild diastolic dysfunction (DD, N = 19 group. Layer-specific systolic and diastolic longitudinal and circumferential strains and SR were assessed. Results showed no between-group difference in left ventricular mass index (DD: 92.1 ± 18.1 vs NDF: 88.4 ± 16.3; P = 0.44. Patients with DD had a proportional reduction in longitudinal strain across the myocardium (endocardial for DD −13 ± 4%; vs NDF −17 ± 3, P < 0.01; epicardial for DD −10 ± 3% vs NDF −13 ± 3%, P < 0.01; global for DD: −12 ± 3% vs NDF: −15 ± 3, P = 0.01, and longitudinal mechanical diastolic impairments as evidenced by reduced longitudinal strain rate of early diastole (DD 0.7 ± 0.2 L/s vs NDF 1.0 ± 0.3 L/s, P < 0.01 and absence of a transmural gradient in the duration of diastolic strain (DD endocardial: 547 ± 105 ms vs epicardial: 542 ± 113 ms, P = 0.24; NDF endocardial: 566 ± 86 ms vs epicardial: 553 ± 77 ms, P = 0.03. Patients with DD also demonstrate a longer duration of early circumferential diastolic strain (231 ± 71 ms vs 189 ± 58 ms, P = 0.02. In conclusion, hypertensive patients with mild DD demonstrate a proportional reduction in longitudinal strain across the myocardium, as well as longitudinal mechanical diastolic impairment, and prolonging duration of circumferential mechanical relaxation.

  5. 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

    Science.gov (United States)

    Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

    2017-06-01

    Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

  6. TSE strain differentiation in mice by immunohistochemical PrP(Sc) profiles and triplex Western blot.

    Science.gov (United States)

    van Keulen, Lucien J M; Langeveld, Jan P M; Dolstra, Corry H; Jacobs, Jorg; Bossers, Alex; van Zijderveld, Fred G

    2015-10-01

    TSE strains are routinely identified by their incubation period and vacuolation profile in the brain after intracerebral inoculation and serial passaging in inbred mouse lines. There are some major drawbacks to this method that are related to the variation in vacuolation that exists in the brains of mice infected with the same TSE strain and to variation between observers and laboratories in scoring vacuolation and determining the final incubation period. We investigated the potential of PrP(Sc) immunohistochemistry and triplex Western blotting as possible alternative methods to differentiate between TSE strains. TSE reference strains ME7, 87A/87V, 22A/22C, 79A/79V and 301C/301V were intracerebrally inoculated in RIII or VM inbred mice that differ in their PrP genotype. Immunohistochemical PrP(Sc) profiles were drawn up by scanning light microscopy both on coronal and sagittal sections. On the basis of the localization of PrP(Sc) in the cerebral cortex, hippocampus, and cerebellar cortex and the overall type of PrP(Sc) staining, all TSE strains could be well differentiated from each other through their typical strain dependent characteristics. In addition, Western blot showed that the combination of glycosylation profile and 12B2 epitope content of PrP(Sc) allowed to distinguish between all reference strains except for ME7 and 22A in VM mice. TSE strains in mice can be identified on the basis of their PrP(Sc) profile alone. The potential to identify TSE strains in ruminants with these PrP(Sc) profiles after a single primary passage in mice will be the topic of future studies. © 2014 British Neuropathological Society.

  7. Effects of strain and age on ear wound healing and regeneration in mice

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    R.A. Costa

    2009-12-01

    Full Text Available Round holes in the ears of MRL mice tend to close with characteristics of regeneration believed to be absent in other mouse strains (e.g., C57BL/6. We evaluated the kinetics and the histopathology of ear wound closure in young (8 weeks old C57BL/6 and BALB/c mice. We also used middle-aged (40 weeks old C57BL/6 mice to evaluate the influence of aging on this process. A circular through-and-through hole was made in the ear, photographs were taken at different times after injury and wound area was measured with digital analysis software. The percentages of closed area measured on day 100 were: 23.57 ± 8.66% for young BALB/c mice, 56.47 ± 7.39% for young C57BL/6 mice, and 75.31 ± 23.65% for middle-aged C57BL/6 mice. Mice were sacrificed on days 1, 3, 5, 25, 44, and 100 for histological evaluation with hematoxylin and eosin, Gomori’s trichrome, periodic acid-Schiff, or picrosirius red staining. In young mice of both strains, healing included re-epithelialization, chondrogenesis, myogenesis, and collagen deposition. Young C57BL/6 and BALB/c mice differed in the organization of collagen fibers visualized using picrosirius-polarization. Sebaceous glands and hair follicles regenerated and chondrogenesis was greater in young C57BL/6 mice. In middle-aged C57BL/6 mice all aspects of regeneration were depressed. The characteristics of regeneration were present during ear wound healing in both young BALB/c and young C57BL/6 mice although they differed in intensity and pattern. Greater ear wound closure in middle-aged C57BL/6 mice was not correlated with regeneration.

  8. Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

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    Schouenborg Jens

    2008-05-01

    Full Text Available Abstract Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1 if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2 if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.

  9. Genetic analysis of resistance to radiation lymphomagenesis with recombinant inbred strains of mice

    International Nuclear Information System (INIS)

    Okumoto, M.; Nishikawa, R.; Imai, S.; Hilgers, J.

    1990-01-01

    Induction of lymphomas by radiation in mice is controlled by genetic factors. We analyzed the genetic control of radiation lymphomagenesis using the CXS series of recombinant inbred strains derived from two progenitor strains: one highly susceptible to radiation induction of lymphoma [BALB/cHeA (C)] and one extremely resistant [STS/A (S)]. The best concordances between strain distribution patterns of genetic markers and resistance (or susceptibility) to radiation lymphomagenesis were observed in a region with the b and Ifa genes on chromosome 4. This indicates that one major locus controls the incidence of radiogenic lymphomas in mice. We designated this locus as the Lyr (lymphoma resistance) locus. Backcrosses of (CXS)F1 to the two progenitor strains showed an intermediate incidence of lymphomas between their parental mice and did not significantly differ from (CXS)F1 mice. This and previous observations that (CXS)F1 mice also showed an intermediate incidence, differing from both progenitor strains, indicate that more genes are involved in the resistance (or susceptibility) to lymphoma induced by irradiation

  10. Pathogenicity and genetic variation of 3 strains of Corynebacterium bovis in immunodeficient mice.

    Science.gov (United States)

    Dole, Vandana S; Henderson, Kenneth S; Fister, Richard D; Pietrowski, Michael T; Maldonado, Geomaris; Clifford, Charles B

    2013-07-01

    Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice.

  11. Left ventricular strain and strain rate by 2D speckle tracking in chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy

    Directory of Open Access Journals (Sweden)

    Waltman Thomas J

    2010-09-01

    Full Text Available Abstract Background Echocardiographic evaluation of left ventricular (LV strain and strain rate (SR by 2D speckle tracking may be useful tools to assess chronic thromboembolic pulmonary hypertension (CTEPH severity as well as response to successful pulmonary thromboendarterectomy (PTE. Methods We evaluated 30 patients with CTEPH before and after PTE using 2D speckle tracking measurements of LV radial and circumferential strain and SR in the short axis, and correlated the data with right heart catheterization (RHC. Results PTE resulted in a decrease in mean PA pressure (44 ± 15 to 29 ± 9 mmHg, decrease in PVR (950 ± 550 to 31 ± 160 [dyne-sec]/cm5, and an increase in cardiac output (3.9 ± 1.0 to 5.0 ± 1.0 L/min, p change in circumferential strain and change in posterior wall radial strain correlated moderately well with changes in PVR, mean PA pressure and cardiac output (r = 0.69, 0.76, and 0.51 for circumferential strain [p Conclusions LV circumferential and posterior wall radial strain change after relief of pulmonary arterial obstruction in patients with CTEPH, and these improvements occur rapidly. These changes in LV strain may reflect effects from improved LV diastolic filling, and may be useful non-invasive markers of successful PTE.

  12. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

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    Chuanyu Wei

    Full Text Available Pulmonary hypertension (PH is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC dysfunction and pulmonary arterial smooth muscle cell (PASMC proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4 is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.

  13. Depressor effect of the young leaves of Polygonum hydropiper Linn. in high-salt induced hypertensive mice.

    Science.gov (United States)

    Devarajan, Sankar; Yahiro, Eiji; Uehara, Yoshinari; Kuroda, Rieko; Hirano, Yoshio; Nagata, Kaori; Miura, Shinichiro; Saku, Keijiro; Urata, Hidenori

    2018-06-01

    A novel chymase inhibitor has been reported to have depressor effect in salt-induced hypertension. Therefore, we examined the hypothesis that chymase inhibitory dried young leaves of Polygonum hydropiper (PPH) or young leaves extract of Polygonum hydropiper (PHE) could reduce salt-induced hypertension. In this study, 8-wk old wild-type mice were allocated into three experiments and experiment I included groups, I- normal water drinking, II- high salt (2% NaCl) water (HSW) drinking, and III- HSW plus PPH (500 mg kg -1 , orally) for 12-wk. Blood pressure (BP) and heart rate (HR) were measured at baseline and weekly up to wk-12. In experiment II, mice were given HSW for 12-wk followed by 8-wk treatment with PPH plus HSW (62.5, 125, 250 and 500 mg kg -1 for groups I, II, III and IV, respectively). BP and HR were measured at baseline and monthly until wk-12, following weekly for 8-wk. Experiment III comprised of four groups of mice for 12-wk HSW and 8-wk treatment with PHE plus HSW (2.5, 5, 10 and 20 mg kg -1 for groups I-IV, respectively). BP and HR were measured at baseline and monthly up to wk-12, following weekly for 8-wk. Significant reduction in BP and HR were observed in mice treated with PPH (500 mg kg -1 ) compared to HSW control. PPH reduced BP and HR dose dependently in hypertensive mice and the higher dose showed maximum reduction. PHE at its maximum dose (20 mg kg -1 ) significantly suppressed BP and HR. Over all, we found that the young leaves of Polygonum hydropiper suppressed salt-induced hypertension. Copyright © 2018. Published by Elsevier Masson SAS.

  14. Strain-typical patterns of pregnancy-induced nestbuilding in mice: maternal and experiential influences.

    Science.gov (United States)

    Broida, J; Svare, B

    1982-07-01

    Pregnant C57BL/6J mice incorporate less material into maternal nests and build fewer fully enclosed nests than do pregnant DBA/2J mice. These strain differences are not ameliorated by additional reproductive experience since multiparous animals also exhibit a similar pattern. Reciprocally-crossed hybrid females exhibit DBA-like levels of pregnancy-induced nestbuilding and cross-fostered C57BL and DBA females retain the phenotype of their strain. Experiential and maternal environmental factors apparently are not responsible for strain differences in pregnancy-induced nestbuilding. Differences in ovarian function and/or central neural tissue sensitivity to ovarian hormones may modulate strain differences in pregnancy-induced nestbuilding.

  15. Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice.

    Science.gov (United States)

    Inui, Yosuke; Mochida, Hideki; Yamairi, Fumiko; Okada, Miyoko; Ishida, Junji; Fukamizu, Akiyoshi; Arakawa, Kenji

    2013-05-01

    Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyper-filtration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb/Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction.

  16. Strain differences in the somnogenic effects of interferon inducers in mice.

    Science.gov (United States)

    Toth, L A

    1996-12-01

    Increased slow-wave sleep accompanies influenza infection in C57BL/6 mice but not BALB/c mice. These strains of mice possess different alleles of the genetic lucus If-1, which codes for high (If-1h; C57BL/6) and low (If-1(1); BALB/c) production of interferon (IFN), a putative sleep-inducing cytokine. To evaluate the contribution of the If-1 gene to differences in murine sleep propensity, sleep patterns were evaluated in mice treated with the IFN inducers polyinosinic:polycytidilic acid (pIC) or Newcastle disease virus (NDV), with influenza virus, or with murine interferon (IFN-alpha) or IFN-alpha/beta. As compared with baseline values, C57BL/6 mice exhibited increased slow-wave sleep after all three challenges, but BALB/c mice did not. Congenic B6.C-H28c mice, which bear the BALB/c allele for low IFN production on the C57BL/6 genetic background, showed enhanced slow-wave sleep after influenza infection but not after NDV. Exogenous IFN did not enhance slow-wave sleep in either C57BL/6 or BALB/c mice. These data suggest that the If-1 allele may influence the somnogenic responsiveness of mice under some conditions but that additional mechanisms may contribute to sleep enhancement during infectious disease.

  17. Radiation-induced pulmonary endothelial dysfunction and hydroxyproline accumulation in four strains of mice

    International Nuclear Information System (INIS)

    Ward, W.F.; Sharplin, J.; Franko, A.J.; Hinz, J.M.

    1989-01-01

    C57BL mice exposed to 14 Gy of whole-thorax irradiation develop significant histologic lung fibrosis within 52 weeks, whereas CBA and C3H mice do not exhibit substantial fibrosis during this time. The purpose of the present study was to determine whether this strain-dependent difference in radiation histopathology is associated with genetic differences in pulmonary endothelial metabolic activity or in endothelial radioresponsiveness. C57BL/6J, C57BL/10J, CBA/J, and C3H/HeJ mice were sacrificed 12 weeks after exposure to 0 or 14 Gy of 300-kV X rays to the whole thorax. Lung angiotensin converting enzyme (ACE) activity and plasminogen activator (PLA) activity were measured as indices of pulmonary endothelial function; and lung hydroxyproline (HP) content served as an index of pulmonary fibrosis. Lung ACE and PLA activities in sham-irradiated C57BL/6J and CB57BL/10J mice were only half as high as those in sham-irradiated CBA/J and C3H/HeJ mice. Exposure to 14 Gy of X rays produced a slight but nonsignificant reduction in lung ACE and PLA activity in the C57BL strains, and a significant reduction in the CBA/J and C3H/HeJ mice. Even after 14 Gy, however, lung ACE and PLA activities in CBA/J and C3H/HeJ mice were higher than those in sham-irradiated C57BL/6J and C57BL/10J mice. Lung HP content in all four strains increased significantly after irradiation, but this increase was accompanied by an increase in lung wet weight. As a result, HP concentration (per milligram wet weight) remained constant or increased slightly in both C57BL strains and actually decreased in the CBA/J and C3H/HeJ mice. These data demonstrate significant genetic differences in both intrinsic pulmonary endothelial enzyme activity and endothelial radioresponsiveness among the four strains of mice

  18. ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study.

    Science.gov (United States)

    Rodrigues, Jonathan C L; Amadu, Antonio Matteo; Ghosh Dastidar, Amardeep; McIntyre, Bethannie; Szantho, Gergley V; Lyen, Stephen; Godsave, Cattleya; Ratcliffe, Laura E K; Burchell, Amy E; Hart, Emma C; Hamilton, Mark C K; Nightingale, Angus K; Paton, Julian F R; Manghat, Nathan E; Bucciarelli-Ducci, Chiara

    2017-04-01

    In hypertension, the presence of left ventricular (LV) strain pattern on 12-lead electrocardiogram (ECG) carries adverse cardiovascular prognosis. The underlying mechanisms are poorly understood. We investigated whether hypertensive ECG strain is associated with myocardial interstitial fibrosis and impaired myocardial strain, assessed by multi-parametric cardiac magnetic resonance (CMR). A total of 100 hypertensive patients [50 ± 14 years, male: 58%, office systolic blood pressure (SBP): 170 ± 30 mmHg, office diastolic blood pressure (DBP): 97 ± 14 mmHg) underwent ECG and 1.5T CMR and were compared with 25 normotensive controls (46 ± 14 years, 60% male, SBP: 124 ± 8 mmHg, DBP: 76 ± 7 mmHg). Native T1 and extracellular volume fraction (ECV) were calculated with the modified look-locker inversion-recovery sequence. Myocardial strain values were estimated with voxel-tracking software. ECG strain (n = 20) was associated with significantly higher indexed LV mass (LVM) (119 ± 32 vs. 80 ± 17 g/m2, P ECG strain (n = 80). ECG strain subjects had significantly impaired circumferential strain compared with hypertensive subjects without ECG strain and controls (-15.2 ± 4.7 vs. -17.0 ± 3.3 vs. -17.3 ± 2.4%, P ECG strain subjects to hypertensive subjects with elevated LVM but no ECG strain, a significantly higher ECV (30 ± 4 vs. 28 ± 3%, P ECG strain in multivariate logistic regression analysis [odds ratio (95th confidence interval): 1.07 (1.02-1.12), P ECG strain is a marker of advanced LVH associated with increased interstitial fibrosis and associated with significant myocardial circumferential strain impairment. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  19. Genetic basis of resistance to trauma in inbred strains of mice

    International Nuclear Information System (INIS)

    Radojicic, C.; Andric, B.; Simovic, M.; Dujic, A.; Marinkovic, D.

    1990-01-01

    In this study the resistance to mechanical, thermal, and radiation trauma in four inbred strains of mice (AKR, BALB/c, CBA, and C57Bl/6) was compared with the degree of genetic resemblance, by analyzing the allozyme variabilities of these strains. It was shown that the highest degree of genetic resemblance was among CBA and AKR strains, which correlated with a similar degree of resistance to trauma. On the other hand, BALB/c and C57Bl/6 strains expressed significant differences, both genetically and with respect to the responses to trauma. The hypothesis is introduced that the genetic determination of the resistance to trauma is based on: (a) a polygenic control of general physiological homeostasis, with the possibility that (b) some specific genes or single loci may contribute more than others to such adaptations of the strains tested

  20. Biochemical behavior of Trypanosoma cruzi strains isolated from mice submitted to specific chemotherapy

    Directory of Open Access Journals (Sweden)

    Jesila Pinto M. Marretto

    1994-12-01

    Full Text Available To investigate the influence of chemotherapy on the biochemical beha vior of Trypanosoma cruzi strains, three groups of mice were infected with one of three strains of T. cruzi of different biological and isoenzymic patterns (Peruvian, 21 SF and Colombian strains. Each group was subdivided into subgroups: 1 - treated with nifurtimox; 2 - treated with benznidazole and 3 - untreated infected controls. At the end of treatment, that lasted for 90 days, xenodiagnosis, sub inoculation of blood into new born mice and haemoculture were performed as tests of cure. From the positive tests, 22 samples of T. cruzi were isolated from all subgroups. Electrophoretic analysis of the isoenzymes PGM, GP1, ALAT and AS AT failed to show any difference between parasite strains isolated from treated and untreated mice, which indicates that no detectable clonal selection or parasite genetic markers alterations concerning the isoenzymes analysed have been determined by treatment with drugs of recognized antiparasitic effect, suggesting stability of the phenotypic characteristics of the three biological types of T. cruzi strains.

  1. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice.

    Directory of Open Access Journals (Sweden)

    Melissa K Friswell

    2010-01-01

    Full Text Available The gastrointestinal tract microbiota (GTM of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables.The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57. Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie embryos produced highly similar GTM profiles (c. 95% concordance between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions.Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions.

  2. Differentiation of strains of yellow fever virus in γ-irradiated mice

    International Nuclear Information System (INIS)

    Fitzgeorge, R.; Bradish, C.J.

    1980-01-01

    The mouse sensitized by optimal, sub-lethal γ-irradiation has been used for the differentiation of strains of yellow fever virus and for the resolution of their immunogenicity and pathogenicity as distinct characteristics. For different strains of yellow fever virus, the patterns of antibody-synthesis, regulatory immunity (pre-challenge) and protective immunity (post-challenge) are differentially sensitive to γ-irradiation. These critical differentiations of strains of yellow fever virus in γ-irradiated mice have been compared with those shown in normal athymic and immature mice in order to elucidate the range of quantifiable in vivo characteristics and the course of the virus-host interaction. This is discussed as a basis for the comparisons of the responses of model and principal hosts to vaccines and pathogens. (author)

  3. Intra-strain polymorphisms are detected but no genomic alteration is found in cloned mice

    International Nuclear Information System (INIS)

    Gotoh, Koshichi; Inoue, Kimiko; Ogura, Atsuo; Oishi, Michio

    2006-01-01

    In-gel competitive reassociation (IGCR) is a method for differential subtraction of polymorphic (RFLP) DNA fragments between two DNA samples of interest without probes or specific sequence information. Here, we applied the IGCR procedure to two cloned mice derived from an F1 hybrid of the C57BL/6Cr and DBA/2 strains, in order to investigate the possibility of genomic alteration in the cloned mouse genomes. Each of the five of the genomic alterations we detected between the two cloned mice corresponded to the 'intra-strain' polymorphisms in the C57BL/6Cr and DBA/2 mouse strains. Our result suggests that no severe aberration of genome sequences occurs due to somatic cell nuclear transfer

  4. Improvement of diabetes, obesity and hypertension in type 2 diabetic KKAy mice by bis(allixinato)oxovanadium(IV) complex

    International Nuclear Information System (INIS)

    Adachi, Yusuke; Yoshikawa, Yutaka; Yoshida, Jiro; Kodera, Yukihiro; Katoh, Akira; Takada, Jitsuya; Sakurai, Hiromu

    2006-01-01

    Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx) 2 ) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx) 2 was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx) 2 was examined in obesity-linked type 2 diabetic KKA y mice. Treatment of VO(alx) 2 for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA y mice; however, it had no effect on hypoadiponectinemia. VO(alx) 2 also improved hyperleptinemia, following attenuation of obesity in KKA y mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx) 2 is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal

  5. Absence of strong strain effects in behavioral analyses of Shank3-deficient mice

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    Elodie Drapeau

    2014-06-01

    Full Text Available Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid syndrome, symptoms of which can include absent or delayed speech, intellectual disability, neurological changes and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin-repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions, in Shank3 heterozygous mice. Changes in phenotype owing to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype owing to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3 heterozygous, knockout and wild-type mice, using C57BL/6, 129SVE and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent.

  6. Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension.

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    Richard B Rothman

    Full Text Available The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/- mice were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(-/- mice. We postulated that: 1 Tph1(-/- mice express lower levels of pulmonary 5-HT transporter (SERT when compared to wild-type controls, and 2 Tph1(-/- mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR. Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(-/- mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(-/- mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(-/- mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized.

  7. Cognitive assessment of mice strains heterozygous for cell-adhesion genes reveals strain-specific alterations in timing.

    Science.gov (United States)

    Gallistel, C R; Tucci, Valter; Nolan, Patrick M; Schachner, Melitta; Jakovcevski, Igor; Kheifets, Aaron; Barboza, Luendro

    2014-03-05

    We used a fully automated system for the behavioural measurement of physiologically meaningful properties of basic mechanisms of cognition to test two strains of heterozygous mutant mice, Bfc (batface) and L1, and their wild-type littermate controls. Both of the target genes are involved in the establishment and maintenance of synapses. We find that the Bfc heterozygotes show reduced precision in their representation of interval duration, whereas the L1 heterozygotes show increased precision. These effects are functionally specific, because many other measures made on the same mice are unaffected, namely: the accuracy of matching temporal investment ratios to income ratios in a matching protocol, the rate of instrumental and classical conditioning, the latency to initiate a cued instrumental response, the trials on task and the impulsivity in a switch paradigm, the accuracy with which mice adjust timed switches to changes in the temporal constraints, the days to acquisition, and mean onset time and onset variability in the circadian anticipation of food availability.

  8. Abnormalities in the WFU strain of Taenia crassiceps (Cyclophyllidea: Taeniidae) following years of propagation in mice.

    Science.gov (United States)

    Aguilar-Vega, L; García-Prieto, L; Zurabian, R

    2016-09-01

    Asexually proliferating Taenia crassiceps (Zeder, 1800) metacestodes isolated within past decades have been successfully sub-cultured under experimental conditions using Mus musculus Linnaeus, 1758 mice. However, during their development, morphological irregularities of scolex structures have been reported in two of the three strains of this cestode species maintained in mice - ORF and KBS. The main goal of this work is to describe the abnormalities observed in a sample of 118 cysticerci of the third T. crassiceps strain used at present - WFU. Morphological abnormalities were detected in 39.8% of the evaginated scoleces; they consisted of supernumerary suckers (n= 2), duplicated (n= 2) or absent rostellum (n= 1), as well as absent or aberrant (n= 29) hooks, which were significantly shorter when compared to the large and short hook lengths referred to in the literature.

  9. Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

    Science.gov (United States)

    Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

    2013-05-01

    Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

  10. Brain cystogenesis capacity of Toxoplasma gondii, avirulent Tehran strain in mice

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    Mehrzad Saraei

    2014-09-01

    Full Text Available Objective: To investigate the brain cystogenesis capacity of Tehran strain of Toxoplasma gondii (T. gondii that had been isolated from a patient with lymphadenitis in 1973. Methods: A volume of 0.5 mL mice brain suspension containing 20 tissue cysts of Tehran strain of T. gondii was inoculated intraperitoneally to each of 25 male BALB/c mice. The number of brain cysts was counted in unstained squash-smears for 10 mice during weeks 7-9 and for 15 mice during weeks 13-14 post-infection. Nonparametric test of Mann-Whitney was used to demonstrate means differences. Results: There was a significant difference in the means for the number of brain cysts between weeks 7-9 (228.3依144.8 and weeks 13-14 (1 239.8依429.3 post-infection (P<0.05. The minimum and the maximum of cysts were 70 and 1 531 during weeks 7-9 post-infection, and 12 and 5 170 during weeks 13-14 post-infection, respectively. The mean number of brain cysts in the right cerebral hemisphere was insignificantly higher than that of the left cerebral hemisphere. Furthermore, the number of cysts counted in the right or the left hemispheres was significantly higher than those enumerated for cerebellum+brain stem altogether. Conclusions: It is concluded that the brain cystogenesis capacity of T. gondii, Tehran strain shows enormous variation in mice regarding the duration of infection. In addition, the cystogenesis observed in cerebellum+brain stem is lower than the right and left cerebral hemispheres.

  11. Strain differences in the influence of open field exposure on sleep in mice.

    Science.gov (United States)

    Tang, Xiangdong; Xiao, Jihua; Liu, Xianling; Sanford, Larry D

    2004-09-23

    The open field (OF) is thought to induce anxiety in rodents. It also allows an opportunity for exploration in a novel environment. Less activity in the OF is thought to indicate greater anxiety whereas more activity may reflect greater exploration, and possibly greater exploratory learning. Anxiety and learning have poorly understood relationships to sleep. In order to determine how anxiety and exploration in the OF could influence sleep, we recorded sleep in mouse strains (C57BL/6J (B6), BALB/cJ (C), DBA/2J (D2), and CB6F1/J (CB6)) with different levels of anxiety and exploration after 30 min in an OF. In all strains, OF exposure induced immediate decreases in rapid eye movement sleep (REM) followed by longer latency increases in REM. The time course and amount of REM decreases and increases varied among strains. Compared to less anxious B6, D2 and CB6 mice, C mice had greater and longer lasting immediate decreases in REM. C mice also displayed longer periods of decreases REM and a smaller, longer latency increase in REM. OF exploratory activity was positively correlated to percentage of REM increases from 6 to 10h after OF exposure. The results suggest that the anxiogenic component of the OF produced an immediate decrease in REM that was greater in more "anxious" mice. In contrast, exploration in the OF was associated with increased REM, with the increase greater in less anxious mice. The results are discussed with respect to the potential influences of anxiety and learning on sleep.

  12. Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

    DEFF Research Database (Denmark)

    Mitchell, Sarah J.; Madrigal-Matute, Julio; Scheibye-Knudsen, Morten

    2016-01-01

    Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with li...... of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions....

  13. Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with mild pulmonary hypertension induced by monocrotaline.

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    Francesca Seta

    Full Text Available The aim of this study was to examine the role of cyclooxygenase-2 (COX-2 and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD mice, characterized by 80-90% suppression of COX-2, and wild-type (WT control mice were treated weekly with monocrotaline (MCT over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1 expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ∼4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ∼85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling.

  14. Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

    Science.gov (United States)

    de Amorim Corrêa, Ricardo; de Oliveira, Fernanda Brito; Barbosa, Marcia M; Barbosa, Jose Augusto A; Carvalho, Taís Soares; Barreto, Michele Campos; Campos, Frederico Thadeu A F; Nunes, Maria Carmo Pereira

    2016-09-01

    Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction. © 2016, Wiley Periodicals, Inc.

  15. A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

    Science.gov (United States)

    Jackson, Kristy L; Marques, Francine Z; Watson, Anna M D; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Morris, Brian J; Charchar, Fadi J; Davern, Pamela J; Head, Geoffrey A

    2013-10-01

    Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.

  16. Application of a naturalistic psychogenic stressor in periadolescent mice: effect on serum corticosterone levels differs by strain but not sex

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    Klein Laura C

    2010-06-01

    Full Text Available Abstract Background As a first step in determining whether psychogenic stressors might be incorporated into periadolescent mouse models of stress, we evaluated whether a commonly used psychogenic stressor, exposure to red fox urine, alters serum corticosterone levels in periadolescent C57BL/6J and DBA/2J mice. Findings In a 1-day experiment, forty-eight 38-day-old C57BL/6J (N = 12 males; N = 12 females and DBA/2J (N = 12 males; N = 12 females mice were exposed to 10-min of red fox urine via cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice or to a non-saturated cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice. All mice were sacrificed 15-min after cotton ball exposure and serum was collected for corticosterone assessment. Overall, there was a main effect for strain such that C57BL/6J male and female mice displayed higher corticosterone levels than did male and female DBA/2J mice. There were no main effects for sex or odor exposure. However, there was a significant strain by odor exposure interaction, whereby, within odor-exposed mice, DBA/2J mice displayed lower corticosterone levels (ng/mL compared to C57BL/6J mice, regardless of sex. Further, among DBA/2J mice, predator odor exposure reduced corticosterone levels compared to no odor exposure. Conclusions Findings indicate that mouse strain, but not sex, may play an important role in the efficacy of a predator odor among periadolescent mice.

  17. High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice.

    Science.gov (United States)

    Marques, Francine Z; Nelson, Erin; Chu, Po-Yin; Horlock, Duncan; Fiedler, April; Ziemann, Mark; Tan, Jian K; Kuruppu, Sanjaya; Rajapakse, Niwanthi W; El-Osta, Assam; Mackay, Charles R; Kaye, David M

    2017-03-07

    Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease. Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess-treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets. We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens . Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1 , a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart. A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut

  18. Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-³ and IL-10

    OpenAIRE

    Brandão,Geane Peroni; Melo,Maria Norma; Gazzinelli,Ricardo Tostes; Caetano,Braulia Costa; Ferreira,Adriana Melo; Silva,Letícia Azevedo; Vitor,Ricardo Wagner Almeida

    2009-01-01

    To assess reinfection of BALB/c mice with different Toxoplasma gondii strains, the animals were prime infected with the non-virulent D8 strain and challenged with virulent recombinant strains. Thirty days after challenge, brain cysts were obtained from surviving BALB/c mice and inoculated in Swiss mice to obtain tachyzoites for DNA extraction and PCR-RFLP analysis to distinguish the different T. gondii strains present in possible co-infections. Anti-Toxoplasma immune responses were evaluated ...

  19. Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.

    Science.gov (United States)

    Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D; Hughson, Andrew G; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S; Miller, Michael W; Race, Richard E; Caughey, Byron

    2007-04-01

    In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

  20. Pulmonary Hypertension in Wild Type Mice and Animals with Genetic Deficit in KCa2.3 and KCa3.1 Channels

    DEFF Research Database (Denmark)

    Wandall-Frostholm, Christine; Skaarup, Lykke Moran; Sadda, Veeranjaneyulu

    2014-01-01

    to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections....... Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The K(Ca)3.1(-/-)/K(Ca)2.3(T/T(+DOX)) mice developed structural alterations in the heart with increased right ventricular wall thickness as well...

  1. Macrophage activation and histopathological findings in Calomys callosus and Swiss mice infected with several strains of Trypanosoma cruzi

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    Monamaris Marques Borges

    1992-12-01

    Full Text Available Peritoneal macrophage activation as measured by H2O2 release and histopathology was compared between Swiss mice and Calomys callosus, a wild rodent, reservoir of Trypanosoma cruzi, during the course of infection with four strains of this parasite. In mice F and Y strain infections result in high parasitemia and mortality while with silvatic strains Costalimai and M226 parasitemia is sub-patent, with very low mortality. H2O2 release peaked at 33,6 and 59 nM/2 x 10(elevado a sexta potência cells for strains Y and F, respectively, 48 and 50 nM/2 x 10 (elevado a sexta potência for strains Costalimai and M226, at different days after infection. Histopathological findings of myositis, myocarditis, necrotizing artheritis and abscence of macrophage parasitism were foud for strains F and Costalimai. Y strain infection presented moderate myocarditis and myositis, with parasites multiplying within macrophages. In C. callosus all four strains resulted in patent parasitemia wich was eventually overcome, with scarce mortality. H2O2 release for strains Y or F was comparable to that of mice-peaks of 27 and 53 nM/2 x 10 (elevado a sexta potência cells, with lower values for strains Costalimai and M226 - 16.5 and 4.6 nM/2 x 10(elevado a sexta potênciacells, respectively. Histopathological lesions with Y and F strain injected animals were comparable to those of mice at the onset of infections; they subsided completely at the later stages with Y strain and partially with F strain infected C. callosus. In Costalimai infected C. callosus practically no histopathological alterations were observed.

  2. Effects of bone marrow-derived cells on monocrotaline- and hypoxia-induced pulmonary hypertension in mice

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    Vainchenker William

    2007-01-01

    Full Text Available Abstract Background Bone marrow -derived cells (BMDCs can either limit or contribute to the process of pulmonary vascular remodeling. Whether the difference in their effects depends on the mechanism of pulmonary hypertension (PH remains unknown. Objectives We investigated the effect of BMDCs on PH induced in mice by either monocrotaline or exposure to chronic hypoxia. Methods Intravenous administration of the active monocrotaline metabolite (monocrotaline pyrrole, MCTp to C57BL/6 mice induced PH within 15 days, due to remodeling of small distal vessels. Three days after the MCTp injection, the mice were injected with BMDCs harvested from femurs and tibias of donor mice treated with 5-fluorouracil (3.5 mg IP/animal to deplete mature cells and to allow proliferation of progenitor cells. Results BMDCs significantly attenuated PH as assessed by reductions in right ventricular systolic pressure (20 ± 1 mmHg vs. 27 ± 1 mmHg, P ≤ 0.01, right ventricle weight/left ventricle+septum weight ratio (0.29 ± 0.02 vs. 0.36 ± 0.01, P ≤ 0.03, and percentage of muscularized vessels (26.4% vs. 33.5%, P ≤ 0.05, compared to control animals treated with irradiated BMDCs. Tracking cells from constitutive GFP-expressing male donor mice with anti-GFP antibodies or chromosome Y level measurement by quantitative real-time PCR showed BMDCs in the lung. In contrast, chronically hypoxic mice subjected to the same procedure failed to show improvement in PH. Conclusion These results show that BMDCs limit pulmonary vascular remodeling induced by vascular injury but not by hypoxia.

  3. Sequence analysis of chromosome 1 revealed different selection patterns between Chinese wild mice and laboratory strains.

    Science.gov (United States)

    Xu, Fuyi; Hu, Shixian; Chao, Tianzhu; Wang, Maochun; Li, Kai; Zhou, Yuxun; Xu, Hongyan; Xiao, Junhua

    2017-10-01

    Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1. For the differentiation between the C1SLs and MGP, 110 candidate selection regions containing 47 protein coding genes were detected. A total of 149 selection regions which encompass 7.215 Mb were identified in the C1SLs by Tajima's D approach. While for the MGP, we identified nearly twice selection regions (243) compared with the C1SLs which accounted for 13.27 Mb Chr 1 sequence. Through functional annotation, we identified several biological processes with significant enrichment including seven genes in the olfactory transduction pathway. In addition, we searched the phenotypes associated with the 47 candidate selection genes identified by Fst. These genes were involved in behavior, growth or body weight, mortality or aging, and immune systems which align well with the phenotypic differences between wild and laboratory mice. Therefore, the findings would be helpful for our understanding of the phenotypic differences between wild and laboratory mice and applications for using this new mouse resource (C1SLs) for further genetics studies.

  4. Mixed Lactobacillus plantarum Strains Inhibit Staphylococcus aureus Induced Inflammation and Ameliorate Intestinal Microflora in Mice.

    Science.gov (United States)

    Ren, Dayong; Gong, Shengjie; Shu, Jingyan; Zhu, Jianwei; Rong, Fengjun; Zhang, Zhenye; Wang, Di; Gao, Liangfeng; Qu, Tianming; Liu, Hongyan; Chen, Ping

    2017-01-01

    Objective . Staphylococcus aureus is an important pathogen that causes intestinal infection. We examined the immunomodulatory function of single and mixed Lactobacillus plantarum strains, as well as their impacts on the structure of the microbiome in mice infected with Staphylococcus aureus . The experiment was divided into three groups: protection, treatment, and control. Serum IFN- γ and IL-4 levels, as well as intestinal sIgA levels, were measured during and 1 week after infection with Staphylococcus aureus with and without Lactobacillus plantarum treatment. We used 16s rRNA tagged sequencing to analyze microbiome composition. IFN- γ /IL-4 ratio decreased significantly from infection to convalescence, especially in the mixed Lactobacillus plantarum group. In the mixed Lactobacillus plantarum group the secretion of sIgA in the intestine of mice (9.4-9.7 ug/mL) was significantly higher than in the single lactic acid bacteria group. The dominant phyla in mice are Firmicutes , Bacteroidetes , and Proteobacteria . Treatment with mixed lactic acid bacteria increased the anti-inflammatory factor and the secretion of sIgA in the intestine of mice infected with Staphylococcus aureus and inhibited inflammation.

  5. Immunological aspects of Giardia muris and Spironucleus muris infections in inbred and outbred strains of laboratory mice: a comparative study.

    Science.gov (United States)

    Brett, S J; Cox, F E

    1982-08-01

    The intestinal flagellates, Giardia muris and Spironucleus muris, cause similar infections in CBA mice as determined by trophozoite and cyst counts. Both parasites occur all along the small intestine with G. muris, being mainly present in the anterior part and S. muris towards the posterior. The early stages of infection are similar in all strains of mice examined and peak levels of both trophozoites and cysts occur 1-2 weeks after infection. All strains of mice overcome the infection but the rate of recovery varies considerably between strains, being most rapid in BALB/c and slowest in A and C57BL.B10. Outbred mice are more variable in their recovery than inbred mice. After recovery, mice are partially resistant to reinfection with the homologous but not the heterologous parasite. Resistance to reinfection with S. muris is greatest in those strains that eliminate the primary infection most rapidly. Giardia muris and S. muris cause similar changes in the mucosa of the small intestine of BALB/c mice with increased intra-epithelial lymphocyte counts from 3 weeks onwards corresponding with the start of the elimination of the parasites from the gut. A reduction in villus height and increase in crypt depth is also characteristic of these infections.

  6. Biochemical behavior of Trypanosoma cruzi strains isolated from mice submitted to specific chemotherapy

    Directory of Open Access Journals (Sweden)

    Jesila Pinto M. Marretto

    1994-12-01

    Full Text Available To investigate the influence of chemotherapy on the biochemical beha vior of Trypanosoma cruzi strains, three groups of mice were infected with one of three strains of T. cruzi of different biological and isoenzymic patterns (Peruvian, 21 SF and Colombian strains. Each group was subdivided into subgroups: 1 - treated with nifurtimox; 2 - treated with benznidazole and 3 - untreated infected controls. At the end of treatment, that lasted for 90 days, xenodiagnosis, sub inoculation of blood into new born mice and haemoculture were performed as tests of cure. From the positive tests, 22 samples of T. cruzi were isolated from all subgroups. Electrophoretic analysis of the isoenzymes PGM, GP1, ALAT and AS AT failed to show any difference between parasite strains isolated from treated and untreated mice, which indicates that no detectable clonal selection or parasite genetic markers alterations concerning the isoenzymes analysed have been determined by treatment with drugs of recognized antiparasitic effect, suggesting stability of the phenotypic characteristics of the three biological types of T. cruzi strains.Com o objetivo de investigar a influência da quimioterapia no padrão bioquímico de diferentes cepas do Trypanosoma cruzi, três grupos de camundongos foram infectados respectivamente com as cepas Peruana, 21 SF e Colombiana, que correspondem a diferentes padrões biológicos e isoenzimáticos. Cada grupo foi subdividido em subgrupos: 1 - tratados com nifurtimox; 2 - tratados com benzonidazol; 3- controles infectados não tratados. Ao final do tratamento que durou 90 dias, os animais foram submetidos a testes parasitológicos de cura: xenodiagnóstico, subinoculação do sangue em camundongos recém-nascidos e hemocultura em meio Warren. A partir da positivação destes testes, foram isoladas 22 amostras do T. cruzi dos três subgrupos. A análise eletroforética dos extratos enzimáticos obtidos após cultura para as enzimas PGM, GPI, ALAT e

  7. Environmental Burkholderia cenocepacia Strain Enhances Fitness by Serial Passages during Long-Term Chronic Airways Infection in Mice

    Directory of Open Access Journals (Sweden)

    Alessandra Bragonzi

    2017-11-01

    Full Text Available Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from clinical strains in some pathogenic traits. Here, we investigated the ability of the environmental B. cenocepacia Mex1 strain, isolated from the maize rhizosphere, to persist and increase its virulence after serial passages in a mouse model of chronic infection. B. cenocepacia Mex1 strain, belonging to the recA lineage IIIA, was embedded in agar beads and challenged into the lung of C57Bl/6 mice. The mice were sacrificed after 28 days from infection and their lungs were tested for bacterial loads. Agar beads containing the pool of B. cenocepacia colonies from the four sequential passages were used to infect the mice. The environmental B. cenocepacia strain showed a low incidence of chronic infection after the first passage; after the second, third and fourth passages in mice, its ability to establish chronic infection increased significantly and progressively up to 100%. Colonial morphology analysis and genetic profiling of the Mex1-derived clones recovered after the fourth passage from infected mice revealed that they were indistinguishable from the challenged strain both at phenotypic and genetic level. By testing the virulence of single clones in the Galleria mellonella infection model, we found that two Mex1-derived clones significantly increased their pathogenicity compared to the parental Mex1 strain and behaved similarly to the clinical and epidemic B. cenocepacia LMG16656T. Our findings suggest that serial passages of the environmental B. cenocepacia Mex1 strain in mice resulted in an increased ability to determine chronic lung infection and the appearance of clonal variants with increased virulence in non-vertebrate hosts.

  8. Reduced infectivity of waterborne viable but nonculturable Helicobacter pylori strain SS1 in mice.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Fontaine, Clinton; Brewster, Rebecca; Wu, Jianfeng; Eisenberg, Joseph N S; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2017-08-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of viable but nonculturable (VBNC) H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne VBNCH. pylori could cause gastric infection. We performed five mouse experiments to assess the infectivity of VBNCH. pylori in various exposure scenarios. VBNC viability was examined using Live/Dead staining and Biolog phenotype metabolism arrays. High doses of VBNCH. pylori in water were chosen to test the "worst-case" scenario for different periods of time. One experiment also investigated the infectious capabilities of VBNC SS1 using gavage. Further, immunocompromised mice were exposed to examine infectivity among potentially vulnerable groups. After exposure, mice were euthanized and their stomachs were examined for H. pylori infection using culture and PCR methodology. VBNC cells were membrane intact and retained metabolic activity. Mice exposed to VBNCH. pylori via drinking water and gavage were not infected, despite the various exposure scenarios (immunocompromised, high doses) that might have permitted infection with VBNCH. pylori. The positive controls exposed to viable, culturable H. pylori did become infected. While other studies that have used viable, culturable SS1 via gavage or drinking water exposures to successfully infect mice, in our study, waterborne VBNC SS1 failed to colonize mice under all test conditions. Future studies could examine different H. pylori strains in similar exposure scenarios to compare the relative infectivity of the VBNC vs the viable, culturable state, which would help inform future risk assessments of H. pylori in water. © 2017 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

  9. 'Obligate' anaerobic Salmonella strain YB1 suppresses liver tumor growth and metastasis in nude mice.

    Science.gov (United States)

    Li, Chang-Xian; Yu, Bin; Shi, Lei; Geng, Wei; Lin, Qiu-Bin; Ling, Chang-Chun; Yang, Mei; Ng, Kevin T P; Huang, Jian-Dong; Man, Kwan

    2017-01-01

    The antitumor properties of bacteria have been demonstrated over the past decades. However, the efficacy is limited and unclear. Furthermore, systemic infection remains a serious concern in bacteria treatment. In this study, the effect of YB1, a rationally designed 'obligate' anaerobic Salmonella typhimurium strain, on liver tumor growth and metastasis in a nude mouse orthotopic liver tumor model was investigated. The orthotopic liver tumor model was established in nude mice using the hepatocellular carcinoma cell line MHCC-97L. Two weeks after orthotopic liver tumor implantation, YB1, SL7207 and saline were respectively administered through the tail vein of the mice. Longitudinal monitoring of tumor growth and metastasis was performed using Xenogen IVIS, and direct measurements of tumor volume were taken 3 weeks after treatment. In vitro , MHCC-97L and PLC cells were incubated with YB1 or SL7207 under anaerobic conditions. YB1 was observed to invade tumor cells and induce tumor cell apoptosis and death. The results revealed that all mice in the YB1 group were alive 3 weeks after YB1 injection while all mice in the SL7207 group died within 11 days of the SL7207 injection. The body weight decreased by ~9% on day 1 after YB1 injection and but subsequently recovered. Liver tumor growth and metastases were significantly inhibited following YB1 treatment. By contrast to the control group, a large number of Gr1-positive cells were detected on days 1 to 21 following YB1 treatment. Furthermore, YB1 also effectively invaded tumor cells and induced tumor cell apoptosis and death. In conclusion, YB1 suppressed liver tumor growth and metastasis in a nude mice liver tumor model. The potential mechanism may be through enhancing innate immune response and inducing tumor cell apoptosis and cell death.

  10. Adrenocortical changes and arterial hypertension in lipoatrophic A-ZIP/F-1 mice

    Czech Academy of Sciences Publication Activity Database

    Lamounier-Zepter, V.; Bornstein, S.R.; Kuneš, Jaroslav; Zicha, Josef; Kršek, M.; Ehrhart-Bornstein, M.; Ziegler, Ch.G.; Kiessling, A.; Funk, R.H.; Haluzík, M.

    2008-01-01

    Roč. 280, 1-2 (2008), s. 39-46 ISSN 0303-7207 Grant - others:-(DE) EH161/4-1 Institutional research plan: CEZ:AV0Z50110509 Keywords : adrenal gland * adipose tissue * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.611, year: 2008

  11. Optimized protocols for Mycobacterium leprae strain management: frozen stock preservation and maintenance in athymic nude mice.

    Science.gov (United States)

    Trombone, Ana Paula Fávaro; Pedrini, Sílvia Cristina Barbosa; Diório, Suzana Madeira; Belone, Andréa de Faria Fernandes; Fachin, Luciana Raquel Vicenzi; do Nascimento, Dejair Caitano; Rosa, Patricia Sammarco

    2014-03-23

    Leprosy, caused by Mycobacterium leprae, is an important infectious disease that is still endemic in many countries around the world, including Brazil. There are currently no known methods for growing M. leprae in vitro, presenting a major obstacle in the study of this pathogen in the laboratory. Therefore, the maintenance and growth of M. leprae strains are preferably performed in athymic nude mice (NU-Foxn1(nu)). The laboratory conditions for using mice are readily available, easy to perform, and allow standardization and development of protocols for achieving reproducible results. In the present report, we describe a simple protocol for purification of bacilli from nude mouse footpads using trypsin, which yields a suspension with minimum cell debris and with high bacterial viability index, as determined by fluorescent microscopy. A modification to the standard method for bacillary counting by Ziehl-Neelsen staining and light microscopy is also demonstrated. Additionally, we describe a protocol for freezing and thawing bacillary stocks as an alternative protocol for maintenance and storage of M. leprae strains.

  12. [Immunogenicity of attenuated Salmonella choleraesuis vaccine strain expressing immunogenic genes of Mycoplasma hyopneumoniae in mice].

    Science.gov (United States)

    Ma, Fengying; Zou, Haoyong; He, Qigai

    2011-09-01

    The study was carried out to construct and characterize Salmonella choleraesuis vaccine strain expressing immunogenic genes of Mycoplasma hyopneumoniae and to test its immunogenicity in mice. We made p36, p46, p65 and p97R1-Nrdf, the main immunogenic genes of Mycoplasma hyopneumoniae, to insert into the prokaryotic expression plasmid pYA3493. Then these recombinant plasmids and pYA3493 were electroporated into C500 asd-mutant, resulting in the recombinant Salmonella choleraesuis vaccine strains C36 (pYA-36), C46 (pYA-46), C65 (pYA-65), C97R1-Nrdf(pYA-97R1-Nrdf) and CpYA(pYA3493). We characterized these recombinant Salmonella choleraesuis vaccine strains and tested the immunogenicity in mice by intramuscular injection or orally immunized. The results of the immunogenicity in mice indicated that the group orally immunized with C36, C46, C65, C97R1-Nrdf showed significantly higher Mycoplasma pneumoniae antibody than both the group orally immunized with C36, C46, C65 and the group intramuscular injected with the Mycoplasma hyopneumoniae bacterin (M + PAC) (P Mycoplasma hyopneumoniae bacterin (M + PAC) (P 0.05). The highest level of IL-4 was found in the group orally immunized with C36, C46, C65; higher levels of IL-4 was observed in the group orally immunized with C36, C46, C65, C97R1-Nrdf than the group injected with the Mycoplasma hyopneumoniae bacterin (M + PAC); and the lowest IL-4 level was found in the group injected with C36, C46, C65. There were no significant differences among them (P > 0.05). The Mycoplasma pneumoniae antibody, IFN-gamma or IL-4 production of the each group was obviously higher than the control group (P Mycoplasma hyopneumoniae which has immunogenicity in mice especially by intramuscular injection could probably serve as a vaccine against mycoplasmal pneumonia of swine.

  13. Marginal level dystrophin expression improves clinical outcome in a strain of dystrophin/utrophin double knockout mice.

    Directory of Open Access Journals (Sweden)

    Dejia Li

    2010-12-01

    Full Text Available Inactivation of all utrophin isoforms in dystrophin-deficient mdx mice results in a strain of utrophin knockout mdx (uko/mdx mice. Uko/mdx mice display severe clinical symptoms and die prematurely as in Duchenne muscular dystrophy (DMD patients. Here we tested the hypothesis that marginal level dystrophin expression may improve the clinical outcome of uko/mdx mice. It is well established that mdx3cv (3cv mice express a near-full length dystrophin protein at ∼5% of the normal level. We crossed utrophin-null mutation to the 3cv background. The resulting uko/3cv mice expressed the same level of dystrophin as 3cv mice but utrophin expression was completely eliminated. Surprisingly, uko/3cv mice showed a much milder phenotype. Compared to uko/mdx mice, uko/3cv mice had significantly higher body weight and stronger specific muscle force. Most importantly, uko/3cv outlived uko/mdx mice by several folds. Our results suggest that a threshold level dystrophin expression may provide vital clinical support in a severely affected DMD mouse model. This finding may hold clinical implications in developing novel DMD therapies.

  14. Pulmonary hypertension in wild type mice and animals with genetic deficit in KCa2.3 and KCa3.1 channels.

    Directory of Open Access Journals (Sweden)

    Christine Wandall-Frostholm

    Full Text Available In vascular biology, endothelial KCa2.3 and KCa3.1 channels contribute to arterial blood pressure regulation by producing membrane hyperpolarization and smooth muscle relaxation. The role of KCa2.3 and KCa3.1 channels in the pulmonary circulation is not fully established. Using mice with genetically encoded deficit of KCa2.3 and KCa3.1 channels, this study investigated the effect of loss of the channels in hypoxia-induced pulmonary hypertension.Male wild type and KCa3.1-/-/KCa2.3T/T(+DOX mice were exposed to chronic hypoxia for four weeks to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The KCa3.1-/-/KCa2.3T/T(+DOX mice developed structural alterations in the heart with increased right ventricular wall thickness as well as in pulmonary vessels with increased lumen size in partially- and fully-muscularized vessels and decreased wall area, not seen in wild type mice. Exposure to chronic hypoxia up-regulated the gene expression of the KCa2.3 channel by twofold in wild type mice and increased by 2.5-fold the relaxation evoked by the KCa2.3 and KCa3.1 channel activator NS309, whereas the acetylcholine-induced relaxation - sensitive to the combination of KCa2.3 and KCa3.1 channel blockers, apamin and charybdotoxin - was reduced by 2.5-fold in chronic hypoxic mice of either genotype.Despite the deficits of the KCa2.3 and KCa3.1 channels failed to change hypoxia-induced pulmonary hypertension, the up-regulation of KCa2.3-gene expression and increased NS309-induced relaxation in wild-type mice point to a novel mechanism to counteract pulmonary

  15. Comparison of antibody and cytokine responses to primary Giardia muris infection in H-2 congenic strains of mice.

    Science.gov (United States)

    Venkatesan, P; Finch, R G; Wakelin, D

    1996-11-01

    The course of primary infections with Giardia muris differs between BALB and B10 H-2 congenic strains of mice. In the first 3 weeks of infection, there is a more rapid decline in intestinal trophozoite and fecal cyst counts in B10 strains than in BALB strains. To determine whether this difference could be explained by variation in specific antibody responses, both secretory immunoglobulin A (IgA) and serum antibody responses were compared between these strains. No significant differences in the timing, titer, or specificity of secretory or serum antibodies were found. However, on comparing specific anti-G. muris serum IgG subclass responses, we found that B10 strains produced IgG2a while BALB strains produced IgG1, suggesting differential involvement of T helper 1 and 2 subsets of lymphocytes. When cells harvested from mesenteric lymph nodes were stimulated with concanavalin A in vitro, both gamma interferon and interleukin-5 were secreted by cells from B10 mice, but only interleukin-5 was secreted by cells from BALB/c mice. Specific blockade of gamma interferon by monoclonal antibody administered to B10 mice resulted in an enhanced intensity of infection.

  16. Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothrops jararaca.

    Science.gov (United States)

    Silva, Carlos A; Portaro, Fernanda C V; Fernandes, Beatriz L; Ianzer, Danielle A; Guerreiro, Juliano R; Gomes, Claudiana L; Konno, Katsuhiro; Serrano, Solange M T; Nascimento, Nanci; Camargo, Antonio C M

    2008-03-15

    The snake venom proline-rich peptide BPP 10c is an active somatic angiotensin-converting enzyme (sACE) inhibitors. Recently we demonstrated that the anti-hypertensive effect of BPP 10c is not related to the inhibition of sACE alone, thus suggesting that this enzyme is not its only target for blood pressure reduction. In the present work, a biodistribution study in Swiss mice of [(125)I]-BPP 10c in the absence or in the presence of a saturating concentration of captopril, a selective active-site inhibitor of sACE, demonstrated that: (1) [(125)I]-BPP 10c was present in several organs and the renal absorption was significantly high; (2) [(125)I]-BPP 10c showed a clear preference for the kidney, maintaining a high concentration in this organ in the presence of captopril for at least 3h; (3) The residual amount of [(125)I]-BPP 10c in the kidney of animals simultaneously treated with captopril suggest that the peptide can interact with other targets different from sACE in this organ. We also showed that Cy3-labeled BPP 10c was internalized by human embryonic kidney cells (HEK-293T). Taken together, these results suggest that sACE inhibition by captopril affects the tissue distribution of [(125)I]-BPP 10c and that the anti-hypertensive effects of BPP 10c are not only dependent on sACE inhibition.

  17. Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice.

    Science.gov (United States)

    Kim, Ahreum; Hur, Yun-Gyoung; Gu, Sunwha; Cho, Sang-Nae

    2017-11-01

    The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis -infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses ( P tuberculosis Beijing/K-strain is frequently isolated from TB patients. Copyright © 2017 American Society for Microbiology.

  18. Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational De-repression of HIF2α

    Science.gov (United States)

    Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Noguchi, Audrey; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Graham, Brian B.; Tuder, Rubin M.; Yu, Zu-Xi; Eckhaus, Michael; Lee, Jaekwon; Springer, Danielle A.; Rouault, Tracey A.

    2013-01-01

    SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. PMID:23395173

  19. Lifespan studies on different strains of mice exposed chronically to low levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    Fox, L.A.; Klein, A.K.; Cain, G.R.; Rosenblatt, L.S.

    1982-01-01

    Several strains of mice, chosen for their predisposition to immunohematological disorders, were exposed to low levels of 60 irradiation continuously for four weeks. All individuals were subsequently followed throughout their lifetimes. W/W/sup v/ mice, which are tyically subject to a stem cell deficiency, had a lower cumulative survival rate for the irradiated group than for the unirradiated controls. Irradiated RF/sub j/ mice had a dramatically lower cumulative survival rate than their unirradiated controls. Conversely, BXSB mice, which have a lumphoproliferative autoimmune disorder, had a higher cumulative survival rate after chronic irradiation than did unirradiated BXSBs. Irradiation had no effect upon the survival rate curves of the NZB strain, the murine model for Lupus Erythematosus

  20. Innate and Adaptive Immune Response to Pneumonia Virus of Mice in a Resistant and a Susceptible Mouse Strain

    Directory of Open Access Journals (Sweden)

    Ellen R. T. Watkiss

    2013-01-01

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM.

  1. Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain.

    Science.gov (United States)

    Tikhonova, Maria; Kulikov, Alexander V

    2012-08-31

    Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: [1] BDNF is effective in the treatment of some genetically defined behavioral disturbances; [2] BDNF influences sexually-motivated behavior; [3] Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; [4] ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on

  2. A pilot study using laser-based technique for non-invasive diagnostics of hypertensive conditions in mice

    Science.gov (United States)

    Litvinova, Karina S.; Ahmad, Shakil; Wang, Keqing; Rafailov, Ilya E.; Sokolovski, Sergei G.; Zhang, Lin; Rafailov, Edik U.; Ahmed, Asif

    2016-02-01

    Endothelial dysfunction is directly linked to preeclampsia, a maternal hypertensive condition that is life threating for both the mother and the baby. Epidemiological studies show that women with a history of pre-eclampsia have an elevated risk for cardiovascular disease. Here we report a new non-invasive diagnostic test for preeclampsia in mice that allows us to non-invasively assess the condition of the animals during the experiment and treatment in established models of preeclampsia. A laser-based multifunctional diagnostics system (LAKK-M) was chosen to carry out non-invasive analysis of multiple parameters. The device was used to simultaneously record the microcirculatory blood flow and oxygen saturation, as well as fluorescence levels of endogenous fluorophores. Preliminary experiments were conducted on adenoviral (Ad-)- mediated overexpression of sFlt-1 (Ad-sFlt-1) to mimic preeclampsialike symptoms in mice. The recorded data displayed the ability of the LAKK-M diagnostics device to detect significant differences in perfusion measurements between the control and Ad-sFlt-1 treatment. Preliminary results provide a potential avenue to employ these diagnostics technology to monitor and aid in maintaining control of live animal conditions throughout the experiment and treatment.

  3. Mice: progesterone and the regulation of strain differences in pregnancy-induced nest building.

    Science.gov (United States)

    Broida, J; Svare, B

    1983-12-01

    Pregnant DBA/2J females built significantly larger and more completely enclosed nests than did pregnant C57BL/6J mice. This strain difference was restricted to the last half of gestation and was not observed during either the virgin state or lactation. Genotype-based differences in pregnancy-induced nest building were not related to circulating levels of progesterone (P), core temperature, or body weight. Exposure to supplemented P during pregnancy elevated nest building exhibited by pregnant C57BL females but did not induce DBA-like levels of the behavior. Also, virgin DBA females built larger nests in response to P than did C57BL females. These findings suggest that differences in the sensitivity of central neural tissue to steroid hormones may account for genotypically determined variation in patterns of pregnancy-induced nest building.

  4. Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice

    Science.gov (United States)

    Pichl, Alexandra; Bednorz, Mariola; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo; Seeger, Werner; Grimminger, Friedrich; Weissmann, Norbert

    2015-01-01

    Rationale Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available. Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease. Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice. We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects. Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both. Methods C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both. Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar and vascular morphometry) as well as the heart ratio were determined after 6 months of tobacco smoke exposure. In addition, the number of alveolar macrophages in the respective lungs was counted. Results Preventive treatment with Tadalafil, Piclamilast or a combination of both almost completely prevented the development of emphysema, the increase in lung compliance, tidal volume, structural remodeling of the lung vasculature, right ventricular systolic pressure, and right ventricular hypertrophy induced by cigarette smoke exposure. Single, but not combination treatment prevented or reduced smoke-induced increase in alveolar macrophages. Conclusion Cigarette smoke-induced emphysema and PH could be prevented by inhibition of the phosphodiesterases 4 and 5 in mice. PMID:26058042

  5. Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice

    NARCIS (Netherlands)

    Rensen, Sander S.; Niessen, Petra M.; van Deursen, Jan M.; Janssen, Ben J.; Heijman, Edwin; Hermeling, Evelien; Meens, Merlijn; Lie, Natascha; Gijbels, Marion J.; Strijkers, Gustav J.; Doevendans, Pieter A.; Hofker, Marten H.; de Mey, Jo G. R.; van Eys, Guillaume J.

    2008-01-01

    Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-)

  6. Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm

    DEFF Research Database (Denmark)

    Waeckel, L.; Badier-Commander, C.; Damery, T.

    2015-01-01

    Angiotensin-II and oxidative stress are involved in the genesis of aortic aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS) deletion or uncoupling. The purpose of this work was to study the endothelial function in wild-type C57BL/6 (BL) and transgenic mice expressing...

  7. Studies on radiation-induced thymic lymphomagenesis in B10 strain mice

    International Nuclear Information System (INIS)

    Muto, Masahiro

    1989-01-01

    Using B10.Thy 1 congenic strain mice, we reexamined the earlier results by Kaplan and others that lymphomas could develop from lymphocytes present in the nonirradiated parental thymuses grafted into thymectomized, fractionally irradiated H-2 semiincompatible recipient mice. The results indicated that 37 out of 91 thymectomized and irradiated B10.Thy 1.2 mice developed lymphomas of which 75 % were shown to have originated from grafted thymuses. The evidence was not obtained that supported the involvement of endogenous MuLV or some kind of transmissible agents during thymic lymphomagenesis. We found, with intrathymic injection assay, that 'preneoplastic' cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment first appeared in the thymuses about 4-8 days after irradiation. These thymic prelymphoma cells 'thymus-dependent' preneoplastic cells were detected in 26.1 % of the test donor thymuses when examined at 14 days and in more than 63 % 21 and 31 days after irradiation. It was found that lymphomagenic irradiation resulted in the anomalous appearance of CD4 + and/or CD8 + thymocytes bearing IL-2 receptor (IL-2R) which were different from normal thymocyte subpopulations. Thymic prelymphoma cells existed mainly in CD4 - CD8 - and CD4 - CD8 + thymocyted subpopulations and also in CD4 + CD8 + subpopulation. T cell lymphomas derived from CD4 - CD8 - prelymphoma cells had mainly CD4 - CD8 - or CD4 - CD8 + phenotypes. T cell lymphomas developed from CD4 - CD8 + prelymphoma cells mainly expressed CD4 - CD8 + or CD4 + CD8 + phenotype. T cell lymphomas originated from CD4 + CD8 + prelymphoma cells were mainly CD4 + CD8 + but some CD4 - CD8 + or CD4 + CD8 - cells were also present. These T cell lymphomas expressed IL-2R on various levels. The development of thymic prelymphoma cells is discussed in view of thymocyte differentiation. (J.P.N)

  8. Sarcocystis neurona infection in gamma interferon gene knockout (KO) mice: comparative infectivity of sporocysts in two strains of KO mice, effect of trypsin digestion on merozoite viability, and infectivity of bradyzoites to KO mice and cell culture.

    Science.gov (United States)

    Dubey, J P; Sundar, N; Kwok, O C H; Saville, W J A

    2013-09-01

    The protozoan Sarcocystis neurona is the primary cause of Equine Protozoal Myeloencephalitis (EPM). EPM or EPM-like illness has been reported in horses, sea otters, and several other mammals. The gamma interferon gene knockout (KO) mouse is often used as a model to study biology and discovery of new therapies against S. neurona because it is difficult to induce clinical EPM in other hosts, including horses. In the present study, infectivity of three life cycle stages (merozoites, bradyzoites, sporozoites) to KO mice and cell culture was studied. Two strains of KO mice (C57-black, and BALB/c-derived, referred here as black or white) were inoculated orally graded doses of S. neurona sporocysts; 12 sporocysts were infective to both strains of mice and all infected mice died or became ill within 70 days post-inoculation. Although there was no difference in infectivity of sporocysts to the two strains of KO mice, the disease was more severe in black mice. S. neurona bradyzoites were not infectious to KO mice and cell culture. S. neurona merozoites survived 120 min incubation in 0.25% trypsin, indicating that trypsin digestion can be used to recover S. neurona from tissues of acutely infected animals. Published by Elsevier B.V.

  9. Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance

    NARCIS (Netherlands)

    McCarthy, J.; O'Mahony, L.; O'Callaghan, L.; Sheil, B.; Vaughan, E.E.; Fitzsimons, N.A.; Fitzgibbon, J.; O'Sullivan, G.C.; Kiely, B.; Collins, J.K.; Shanahan, F.

    2003-01-01

    Background: Prophylactic efficacy against colitis following lactobacillus consumption in interleukin 10 (IL-10) knockout ( KO) mice has been reported. Whether this applies equally to other probiotic strains is unknown, and the mechanism is unclear. Aims: ( 1) To compare the effect of feeding

  10. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

  11. Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

    Science.gov (United States)

    Massé, Ian O; Guillemette, Sonia; Laramée, Marie-Eve; Bronchti, Gilles; Boire, Denis

    2014-11-07

    Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Motor coordination and balance measurements reveal differential pathogenicity of currently spreading enterovirus 71 strains in human SCARB2 transgenic mice.

    Science.gov (United States)

    Chen, Mei-Feng; Shih, Shin-Ru

    2016-12-01

    Enterovirus 71 (EV71) has caused large-scale epidemics with neurological complications in the Asia-Pacific region. The C4a and B5 strains are the two major genotypes circulating in many countries recently. This study used a new protocol, a motor coordination task, to assess the differential pathogenicity of C4a and B5 strains in human SCARB2 transgenic mice. We found that the pathogenicity of C4a viruses was more severe than that of B5 viruses. Moreover, we discovered that an increased level of monocyte chemoattractant protein-1 was positively correlated with severely deficient motor function. This study provides a new method for evaluating EV71 infection in mice and distinguishing the severity of the symptoms caused by different clinical strains, which would contribute to studies of pathogenesis and development of vaccines and antivirals in EV71 infections.

  13. Genetic control of oromotor phenotypes: A survey of licking and ingestive behaviors in highly diverse strains of mice.

    Science.gov (United States)

    St John, Steven J; Lu, Lu; Williams, Robert W; Saputra, Jennifer; Boughter, John D

    2017-08-01

    In order to examine genetic influences on fluid ingestion, 20-min intake of either water or 0.1M sucrose was measured in a lickometer in 18 isogenic strains of mice, including 15 inbred strains and 3 F 1 hybrid crosses. Intake and licking data were examined at a number of levels, including lick rate as defined by mean or median interlick interval, as well as several microstructural parameters (i.e. burst-pause structure). In general, strain variation for ingestive phenotypes were correlated across water and sucrose in all strains, indicating fundamental, rather than stimulus-specific, mechanisms of intake. Strain variation was substantial and robust, with heritabilities for phenotypes ranging from 0.22 to 0.73. For mean interlick interval (MPI; a measure of lick rate) strains varied continuously from 94.3 to 127.0ms, a range consistent with previous studies. Furthermore, variation among strains for microstructural traits such as burst size and number suggested that strains possess different overall ingestive strategies, with some favoring more short bursts, and others favoring fewer, long bursts. Strains also varied in cumulative intake functions, exhibiting both linear and decelerated rates of intake across the session. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Incremental value of right atrial strain for early diagnosis of hemodynamic deterioration in pulmonary hypertension: a new noninvasive tool for a more comprehensive diagnostic paradigma.

    Science.gov (United States)

    Piccinino, Cristina; Giubertoni, Ailia; Zanaboni, Jacopo; Gravellone, Miriam; Sola, Daniele; Rosso, Roberta; Ferrarotti, Lorena; Marino, Paolo Nicola

    2017-11-01

    Increased right atrial size is related to adverse prognosis in pulmonary hypertension. The potential incremental value of right atrial function assessment is still unclear. We tested the relationship between right atrial two-dimensional speckle-tracking echocardiography impairment and hemodynamic, functional and clinical deterioration in patients with pulmonary hypertension. We prospectively evaluated 36 patients (27 female, 9 male; mean age 68 ± 13 years) with suspected pulmonary hypertension undergoing right heart catheterization and 16 matched controls. All patients underwent baseline evaluation by New York Heart Association functional class, 6-min walking test, brain natriuretic peptide (BNP), and standard two-dimensional echocardiography in less than 48 h of right heart catheterization. Right atrial two-dimensional speckle-tracking echocardiography was assessed by averaging all segments in standard four-chamber apical view. Right atrial global integral strain was significantly lower in patients compared with controls (11.40 ± 5.22% vs. 25.72 ± 5.95 P < 0.001). Moreover, right atrial global strain, but not right atrial area or volume, was correlated with invasively measured cardiac index (CI) (r = 0.72; P < 0.0001) and pulmonary vascular resistances in all patients, even though stronger in subjects with precapillary pulmonary hypertension (r = -0.42, P = 0.018; r = -0.54, P = 0.007 respectively; P = 0.007). It was also correlated with New York Heart Association (P = 0.027), BNP (P = 0.002), and 6-min walking test (P = 0.006). After multivariate analysis including right atrial volume, tricuspid annular plane systolic excursion, left atrial strain, and BNP, right atrial global strain showed the strongest correlation with CI. Area under the curve optimal cutoff for predicting CI at least 2.4 l/min/m was 17% (area under the curve: 0.83, sensitivity: 90%, specificity: 54%). Right atrial global strain can

  15. Assessment of strain and strain rate by two-dimensional speckle tracking in mice: comparison with tissue Doppler echocardiography and conductance catheter measurements.

    Science.gov (United States)

    Ferferieva, V; Van den Bergh, A; Claus, P; Jasaityte, R; La Gerche, A; Rademakers, F; Herijgers, P; D'hooge, J

    2013-08-01

    This study was designed in order to compare the strain and strain rate deformation parameters assessed by speckle tracking imaging (STI) with those of tissue Doppler imaging (TDI) and conductance catheter measurements in chronic murine models of left ventricular (LV) dysfunction. Twenty-four male C57BL/6J mice were assigned to wild-type (n = 8), myocardial infarction (n = 8) and transaortic constriction (n = 8) groups. Echocardiographic and conductance measurements were simultaneously performed at rest and during dobutamine infusion (5 µg/kg/min) in all animals 10 weeks post-surgery. The LV circumferential strain (Scirc) and the strain rate (SRcirc) were derived from grey scale and tissue Doppler data at frame rates of 224 and 375 Hz, respectively. Scirc and SRcirc by TDI/STI correlated well with the preload recruitable stroke work (PRSW) (r = -0.64 and -0.71 for TDI; r = -0.46 and -0.50 for STI, P < 0.05). Both modalities showed a good agreement with respect to Scirc and SRcirc (r = 0.60 and r = 0.63, P < 0.05). During stress, however, TDI-estimated Scirc and SRcirc values were predominantly higher than those measured by STI (P < 0.05). The similarity of Scirc and SRcirc measurements with respect to the STI/TDI data was examined by the Bland-Altman analysis. In mice, the STI- and TDI-derived strain and strain rate deformation parameters relate closely to intrinsic myocardial function. At low heart rate-to-frame rate ratios (HR/FR), both STI and TDI are equally acceptable for assessing the LV function non-invasively in these animals. At HR/FR (e.g. dobutamine challenge), however, these methods cannot be used interchangeably as STI underestimates S and SR at high values.

  16. Quantitative effects of diet on fecal corticosterone metabolites in two strains of laboratory mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten Rosenmaj; Teilmann, Anne Charlotte

    2012-01-01

    /6 mice. Furthermore, throughout the experiment, the C57bl/6 mice excreted significantly higher levels of FCM compared to the BALB/c mice. The mice were also challenged with synthetic adrenocorticotropic hormone (ACTH) and dexamethasone (DEX). The effect of the challenges could readily be detected...

  17. Whole exome sequencing of wild-derived inbred strains of mice improves power to link phenotype and genotype.

    Science.gov (United States)

    Chang, Peter L; Kopania, Emily; Keeble, Sara; Sarver, Brice A J; Larson, Erica; Orth, Annie; Belkhir, Khalid; Boursot, Pierre; Bonhomme, François; Good, Jeffrey M; Dean, Matthew D

    2017-10-01

    The house mouse is a powerful model to dissect the genetic basis of phenotypic variation, and serves as a model to study human diseases. Despite a wealth of discoveries, most classical laboratory strains have captured only a small fraction of genetic variation known to segregate in their wild progenitors, and existing strains are often related to each other in complex ways. Inbred strains of mice independently derived from natural populations have the potential to increase power in genetic studies with the addition of novel genetic variation. Here, we perform exome-enrichment and high-throughput sequencing (~8× coverage) of 26 wild-derived strains known in the mouse research community as the "Montpellier strains." We identified 1.46 million SNPs in our dataset, approximately 19% of which have not been detected from other inbred strains. This novel genetic variation is expected to contribute to phenotypic variation, as they include 18,496 nonsynonymous variants and 262 early stop codons. Simulations demonstrate that the higher density of genetic variation in the Montpellier strains provides increased power for quantitative genetic studies. Inasmuch as the power to connect genotype to phenotype depends on genetic variation, it is important to incorporate these additional genetic strains into future research programs.

  18. Impairment of the natriuretic peptide system in follitropin receptor knockout mice and reversal by estradiol: implications for obesity-associated hypertension in menopause.

    Science.gov (United States)

    Belo, Najara O; Sairam, M Ram; Dos Reis, Adelina M

    2008-03-01

    Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.

  19. Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

    Science.gov (United States)

    Jin, Li; Lin, Ming Quan; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho

    2017-07-01

    Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

  20. Atypical patterns of neural infection produced in mice by drug-resistant strains of herpes simplex virus.

    Science.gov (United States)

    Field, H J; Anderson, J R; Wildy, P

    1982-03-01

    Mice inoculated intracerebrally (i.c.) with a mutant strain of HSV were found to develop cataracts 1 to 2 months after inoculation. Cataract formation was subsequently shown to follow an acute retinitis which commenced within 1 week of inoculation. The mutant had been selected for high resistance to the nucleoside analogue acyclovir and has been shown previously to be defective in the induction of thymidine kinase and also to express an altered DNA polymerase. The LD50 for mice inoculated i.c. was greater than 10(5) p.f.u. compared with approx 7 p.f.u. for the parental strain. Studies of virus replication following i.c. inoculation with a sublethal dose of the mutant revealed that only small amounts of infectious virus were produced in the brain, but during a period from 6 to 12 days after inoculation vigorous replication occurred in retinal tissue, producing very high titres of virus.

  1. Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams

    DEFF Research Database (Denmark)

    Holch, Anne; Ingmer, Hanne; Licht, Tine Rask

    2013-01-01

    potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10...... % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlAm* (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal...... case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas...

  2. X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses

    Science.gov (United States)

    Kamiya, Mana; Kawase, Tomoyuki; Hayama, Kazuhide; Tsuchimochi, Makoto; Okuda, Kazuhiro; Yoshie, Hiromasa

    2015-01-01

    Abstract Radiation therapy for head and neck cancers often causes xerostomia (dry mouth) by acutely damaging the salivary glands through the induction of severe acute inflammation. By contrast, the mechanism underlying the X-ray-induced delayed salivary dysfunction is unknown and has attracted increasing attention. To identify and develop a mouse model that distinguishes the delayed from the acute effects, we examined three different mouse strains (C57BL/6, ICR, and ICR-nu/nu) that showed distinct T-cell activities to comparatively analyze their responses to X-ray irradiation. Three strains were irradiated with X-rays (25 Gy), and functional changes of the submandibular glands were examined by determining pilocarpine-induced saliva secretion. Structural changes were evaluated using histopathological and immunohistochemical examinations of CD3, cleaved poly (ADP-ribose) polymerase (PARP), and Bcl-xL. In C57BL/6 mice, the X-ray irradiation induced acute inflammation accompanied by severe inflammatory cell infiltration at 4 days postirradiation, causing substantial destruction and significant dysfunction at 2 weeks. Fibrotic repair was observed at 16 weeks. In ICR-nu/nu mice, the inflammation and organ destruction were much milder than in the other mice strains, but increased apoptotic cells and a significant reduction in salivary secretion were observed at 4 and 8 weeks and beyond, respectively. These results suggest that in C57BL/6 mice, X-ray-induced functional and structural damage to the salivary glands is caused mainly by acute inflammation. By contrast, although neither acute inflammation nor organ destruction was observed in ICR-nu/nu mice, apoptotic cell death preceded the dysfunction in salivary secretion in the later phase. These data suggest that the X-ray-irradiated ICR-nu/nu mouse may be a useful animal model for developing more specific therapeutic methods for the delayed dysfunction of salivary glands. PMID:26309806

  3. Bifidobacterium adolescentis Exerts Strain-Specific Effects on Constipation Induced by Loperamide in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    2017-02-01

    Full Text Available Constipation is one of the most common gastrointestinal complaints worldwide. This study was performed to determine whether Bifidobacterium adolescentis exerts inter-strain differences in alleviating constipation induced by loperamide in BALB/c mice and to analyze the main reasons for these differences. BALB/c mice underwent gavage with B. adolescentis (CCFM 626, 667, and 669 once per day for 17 days. The primary outcome measures included related constipation indicators, and the secondary outcome measures were the basic biological characteristics of the strains, the concentration changes of short-chain fatty acids in feces, and the changes in the fecal flora. B. adolescentis CCFM 669 and 667 relieved constipation symptoms by adhering to intestinal epithelial cells, growing quickly in vitro and increasing the concentrations of propionic and butyric acids. The effect of B. adolescentis on the gut microbiota in mice with constipation was investigated via 16S rRNA metagenomic analysis. The results revealed that the relative abundance of Lactobacillus increased and the amount of Clostridium decreased in the B. adolescentis CCFM 669 and 667 treatment groups. In conclusion, B. adolescentis exhibits strain-specific effects in the alleviation of constipation, mostly due to the strains’ growth rates, adhesive capacity and effects on the gut microbiome and microenvironment.

  4. Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice

    Directory of Open Access Journals (Sweden)

    Sandra L. Rebholz

    Full Text Available Perfluorooctanoic acid (PFOA is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet. When fed these high fat diets, PFOA ingestion resulted in marked hypercholesterolemia in male and female C57BL/6 mice and less robust hypercholesterolemia in male BALB/c mice. The PFOA-induced hypercholesterolemia appeared to be the result of increased liver masses and altered expression of genes associated with hepatic sterol output, specifically bile acid production. mRNA levels of genes associated with sterol input were reduced only in C57BL/6 females, the mice with the greatest increase in plasma cholesterol levels. Strain-specific PFOA-induced changes in cholesterol concentrations in mammary tissues and ovaries paralleled changes in plasma cholesterol levels. mRNA levels of sterol-related genes were reduced in ovaries of C57BL/6 but not in BALB/c mice and not in mammary tissues. Our data suggest that PFOA ingestion leads to hypercholesterolemia in mice fed fat and cholesterol and effects are dependent upon the genetic background and gender of the mice with C57BL/6 female mice being most responsive to PFOA. Keywords: Perfluorooctanoic acid, C8, PFC, PFAS, Cholesterol, Dietary fat

  5. Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice.

    Directory of Open Access Journals (Sweden)

    Frida Fåk

    Full Text Available OBJECTIVE: To investigate whether the specific strains of Lactobacillus reuteri modulates the metabolic syndrome in Apoe-/- mice. METHODS: 8 week-old Apoe-/- mice were subdivided into four groups who received either L. reuteri ATCC PTA 4659 (ATCC, DSM 17938 (DSM, L6798, or no bacterial supplement in the drinking water for 12 weeks. The mice were fed a high-fat Western diet with 0.2% cholesterol and body weights were monitored weekly. At the end of the study, oral glucose and insulin tolerance tests were conducted. In addition, adipose and liver weights were recorded along with analyses of mRNA expression of ileal Angiopoietin-like protein 4 (Angptl4, the macrophage marker F4/80 encoded by the gene Emr1 and liver Acetyl-CoA carboxylase 1 (Acc1, Fatty acid synthase (Fas and Carnitine palmitoyltransferase 1a (Cpt1a. Atherosclerosis was assessed in the aortic root region of the heart. RESULTS AND CONCLUSIONS: Mice receiving L. reuteri ATCC gained significantly less body weight than the control mice, whereas the L6798 mice gained significantly more. Adipose and liver weights were also reduced in the ATCC group. Serum insulin levels were lower in the ATCC group, but no significant effects were observed in the glucose or insulin tolerance tests. Lipogenic genes in the liver were not altered by any of the bacterial treatments, however, increased expression of Cpt1a was found in the ATCC group, indicating increased β-oxidation. Correspondingly, the liver trended towards having lower fat content. There were no effects on inflammatory markers, blood cholesterol or atherosclerosis. In conclusion, the probiotic L. reuteri strain ATCC PTA 4659 partly prevented diet-induced obesity, possibly via a previously unknown mechanism of inducing liver expression of Cpt1a.

  6. Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-gamma and IL-10.

    Science.gov (United States)

    Brandão, Geane Peroni; Melo, Maria Norma; Gazzinelli, Ricardo Tostes; Caetano, Braulia Costa; Ferreira, Adriana Melo; Silva, Letícia Azevedo; Vitor, Ricardo Wagner Almeida

    2009-03-01

    To assess reinfection of BALB/c mice with different Toxoplasma gondii strains, the animals were prime infected with the non-virulent D8 strain and challenged with virulent recombinant strains. Thirty days after challenge, brain cysts were obtained from surviving BALB/c mice and inoculated in Swiss mice to obtain tachyzoites for DNA extraction and PCR-RFLP analysis to distinguish the different T. gondii strains present in possible co-infections. Anti-Toxoplasma immune responses were evaluated in D8-primed BALB/c mice by detecting IFN-gamma and IL-10 produced by T cells and measuring immunoglobulin levels in serum samples. PCR-RFLP demonstrated that BALB/c mice were reinfected with the EGS strain at 45 days post prime infection (dpi) and with the EGS and CH3 strains at 180 dpi. High levels of IFN-gamma were detected after D8 infection, with no significant difference between 45 and 180-day intervals. However, higher IL-10 levels and higher plasmatic IgG1 and IgA were detected from samples obtained 180 days after infection. BALB/c mice were susceptible to reinfection with different recombinant T. gondii strains and this susceptibility correlated with enhancement of IL-10 production.

  7. Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-³ and IL-10

    Directory of Open Access Journals (Sweden)

    Geane Peroni Brandão

    2009-03-01

    Full Text Available To assess reinfection of BALB/c mice with different Toxoplasma gondii strains, the animals were prime infected with the non-virulent D8 strain and challenged with virulent recombinant strains. Thirty days after challenge, brain cysts were obtained from surviving BALB/c mice and inoculated in Swiss mice to obtain tachyzoites for DNA extraction and PCR-RFLP analysis to distinguish the different T. gondii strains present in possible co-infections. Anti-Toxoplasma immune responses were evaluated in D8-primed BALB/c mice by detecting IFN-³ and IL-10 produced by T cells and measuring immunoglobulin levels in serum samples. PCR-RFLP demonstrated that BALB/c mice were reinfected with the EGS strain at 45 days post prime infection (dpi and with the EGS and CH3 strains at 180 dpi. High levels of IFN-³ were detected after D8 infection, with no significant difference between 45 and 180-day intervals. However, higher IL-10 levels and higher plasmatic IgG1 and IgA were detected from samples obtained 180 days after infection. BALB/c mice were susceptible to reinfection with different recombinant T. gondii strains and this susceptibility correlated with enhancement of IL-10 production.

  8. Discovery of a new strain of murine rotavirus that is consistently shed in large quantities after oral inoculation of adult mice

    International Nuclear Information System (INIS)

    McNeal, Monica M.; Belli, Janine; Basu, Mitali; Choi, Anthony H.-C.; Ward, Richard L.

    2004-01-01

    In 1990, we developed the adult mouse model for studies on active immunity against shedding of the EDIM strain of murine rotavirus. Low and inconsistent levels of EDIM shedding in some strains of adult mice, particularly those on C57BL/6 backgrounds, established the need for an alternative murine rotavirus strain for these studies. Fortuitously, such a rotavirus strain was obtained from mice housed within the conventional colony at Children's Hospital. This strain, named EMcN, was clearly distinguishable from EDIM based on electropherotype. Furthermore, sequence analyses of VP4 and VP7 genes of EMcN revealed non-identities in 5% of the amino acids of both proteins relative to EDIM but established EMcN as another G3P[16] strain of murine rotavirus. Subgroup analysis showed EMcN belonged to SG1 while EDIM was found to be non-SG1/SG2. Similarly, unlike EDIM, the EMcN strain was identified as serotype G3 based on neutralization by hyperimmune antisera developed against prototype human and simian G3 rotavirus strains. Although EDIM produced more days of diarrhea and was shed in greater quantities in neonatal BALB/c mice, EMcN was shed in much greater quantities in adult BALB/c mice. More importantly, in contrast to the EDIM strain, EMcN was shown to be consistently shed in large quantities in adult C57BL/6 mice and ko mice on this background. Therefore, it is recommended that the EMcN strain be used for future challenge studies with mice on this background

  9. A novel system for tracking social preference dynamics in mice reveals sex- and strain-specific characteristics.

    Science.gov (United States)

    Netser, Shai; Haskal, Shani; Magalnik, Hen; Wagner, Shlomo

    2017-01-01

    Deciphering the biological mechanisms underlying social behavior in animal models requires standard behavioral paradigms that can be unbiasedly employed in an observer- and laboratory-independent manner. During the past decade, the three-chamber test has become such a standard paradigm used to evaluate social preference (sociability) and social novelty preference in mice. This test suffers from several caveats, including its reliance on spatial navigation skills and negligence of behavioral dynamics. Here, we present a novel experimental apparatus and an automated analysis system which offer an alternative to the three-chamber test while solving the aforementioned caveats. The custom-made apparatus is simple for production, and the analysis system is publically available as an open-source software, enabling its free use. We used this system to compare the dynamics of social behavior during the social preference and social novelty preference tests between male and female C57BL/6J mice. We found that in both tests, male mice keep their preference towards one of the stimuli for longer periods than females. We then employed our system to define several new parameters of social behavioral dynamics in mice and revealed that social preference behavior is segregated in time into two distinct phases. An early exploration phase, characterized by high rate of transitions between stimuli and short bouts of stimulus investigation, is followed by an interaction phase with low transition rate and prolonged interactions, mainly with the preferred stimulus. Finally, we compared the dynamics of social behavior between C57BL/6J and BTBR male mice, the latter of which are considered as asocial strain serving as a model for autism spectrum disorder. We found that BTBR mice ( n  = 8) showed a specific deficit in transition from the exploration phase to the interaction phase in the social preference test, suggesting a reduced tendency towards social interaction. We successfully

  10. An immunological analysis of natural resistance to moise hepatitis virus (JHMV strain) infection in C3H mice

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, C A; Pickel, K [Wurzburg Univ. (Germany, F.R.). Inst. fuer Virologie und Immunbiologie

    1987-01-01

    Since the development of resistance against mouse hepatitis virus (JHMV strain) coincides with the maturation of the immune system, we studied the possible role of distinct immunological components in the resistance of adult mice during JHMV infection. Adult C3H mice naturally resistant to JHMV were rendered susceptible to infection by lethal {sup 60}Co-irradiation and were subsequently reconstituted with limiting numbers of syngeneic bone marrow cells or spleen cells. Resistance or susceptibility dependend on the number of cells used for reconstitution and the interval between reconsitution and infection. Spleen cells from suckling mice affected neither resistance nor susceptibility and peritoneal cells from adult mice and thymus cells reduced resistance. Persistence of JHMV was demonstrated by virus reactivation. Animals infected with JHMV only once before being rendered immunoincompetent showed a different pattern of resistance. One to four months after infection, 15 to 35% of the animals died after reconstitution without having been reinfected, and persisting JHMV was found in their liver, spleen and peritoneal exudate. The survivors (47 to 87%) were resistant to further JHMV infection during immunodeficiency. Animals immunized 3 times with JHMV before irradiation did not show virus reactivation and were fully resistant to JHMV reinfection after reconstitution. The level of neutralizing anti JHMV serum antibodies in the group of mice immunized only once was comparable with the level of those immunized 3 times. The role of macrophage activation and cell-mediated immunity in this model are discused as an explanation for the resistance to, and persistence of, JHMV. (author).

  11. An immunological analysis of natural resistance to moise hepatitis virus (JHMV strain) infection in C3H mice

    International Nuclear Information System (INIS)

    Pereira, C.A.; Pickel, K.

    1987-01-01

    Since the development of resistance against mouse hepatitis virus (JHMV strain) coincides with the maturation of the immune system, we studied the possible role of distinct immunological components in the resistance of adult mice during JHMV infection. Adult C3H mice naturally resistant to JHMV were rendered susceptible to infection by lethal 60 Co-irradiation and were subsequently reconstituted with limiting numbers of syngeneic bone marrow cells or spleen cells. Resistance or susceptibility dependend on the number of cells used for reconstitution and the interval between reconsitution and infection. Spleen cells from suckling mice affected neither resistance nor susceptibility and peritoneal cells from adult mice and thymus cells reduced resistance. Persistence of JHMV was demonstrated by virus reactivation. Animals infected with JHMV only once before being rendered immunoincompetent showed a different pattern of resistance. One to four months after infection, 15 to 35% of the animals died after reconstitution without having been reinfected, and persisting JHMV was found in their liver, spleen and peritoneal exudate. The survivors (47 to 87%) were resistant to further JHMV infection during immunodeficiency. Animals immunized 3 times with JHMV before irradiation did not show virus reactivation and were fully resistant to JHMV reinfection after reconstitution. The level of neutralizing anti JHMV serum antibodies in the group of mice immunized only once was comparable with the level of those immunized 3 times. The role of macrophage activation and cell-mediated immunity in this model are discused as an explanation for the resistance to, and persistence of, JHMV. (author) [pt

  12. Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

    Science.gov (United States)

    Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

    2014-10-01

    This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

    International Nuclear Information System (INIS)

    Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia; Yu, Xue-Zhong; Xia, Chang-Qing

    2014-01-01

    Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT

  14. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2014-04-18

    Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

  15. Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice.

    Science.gov (United States)

    Bath, Kevin G; Pimentel, Tiare

    2017-05-01

    Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we tested the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate exposure led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7-8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain- and dose-dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate exposure had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampal BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region-specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. [Immunosuppressant effect of cyclophosphamide activated in vitro by liver microsomes from different strains of mice].

    Science.gov (United States)

    Telegin, L Iu; Zhirnov, G F; Mazurov, A V; Pevnitskiĭ, L A

    1981-07-01

    The paper is concerned with activation of cyclophosphamide by mouse liver microsomes in vitro. Liver microsomes from BALB/c mice metabolize cyclophosphamide more effectively as compared with those from DBA/2 mice, which manifested by a more intense output of products having alkylating or immunodepressant properties. This seems likely to be a consequence of the increased P-450 cytochrome content in liver microsomes from BALB/c mice, as well as of its structural characteristics in the mouse. The relationship between the immunodepressant effect of cyclophosphamide in vivo and in vitro in mice of varied genotypes is discussed.

  17. Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice.

    Science.gov (United States)

    Diniz, Lívia de Figueiredo; Mazzeti, Ana Lia; Caldas, Ivo Santana; Ribeiro, Isabela; Bahia, Maria Terezinha

    2018-06-01

    Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. The first set of experiments assessed the range of E1224 doses required to induce parasitological cure using Trypanosoma cruzi strains with different susceptibilities to benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing death; however, parasitological cure was observed only in mice infected with Y strain. Considering these results, we evaluated the effect of combined treatment against Colombian, a multidrug-resistant T. cruzi strain. After exclusion of antagonistic effects using in vitro assays, infected mice were treated with E1224 and benznidazole in monotherapy or in combination at day 4 or 10 postinoculation. All treatments were well tolerated and effective in suppressing parasitemia; however, parasitological and PCR assays indicated no cure among mice treated with monotherapies. Intriguingly, the outcome of combination therapy was dependent on treatment onset. Early treatment using optimal doses of E1224-benznidazole induced a 100% cure rate, but this association could not eliminate a well-established infection. The beneficial effect of combination therapy was evidenced by further reductions of the patent parasitemia period in the group receiving combined therapy compared with monotherapies. Our results demonstrated a positive interaction between E1224 and benznidazole against murine T. cruzi infection using a multidrug-resistant strain and highlighted the importance of a stringent experimental model in the evaluation of new therapies. Copyright © 2018 Diniz et al.

  18. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.

    Directory of Open Access Journals (Sweden)

    Niwanthi W Rajapakse

    Full Text Available Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1 can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13 and CAT1 overexpressing mice (CAT+; n=13 were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p. on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%. The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001, but was similar in obese and lean CAT+ (P = 0.65. In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001. Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001, but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%, but greater in obese CAT+ (37 ± 2%, when compared to respective lean WT (31 ± 3% and lean CAT+ controls (27 ± 2%; P ≤ 0.02. We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.

  19. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.

    Science.gov (United States)

    Rajapakse, Niwanthi W; Karim, Florian; Evans, Roger G; Kaye, David M; Head, Geoffrey A

    2015-01-01

    Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ≤ 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.

  20. Comparison of Ehrlichia muris Strains Isolated from Wild Mice and Ticks and Serologic Survey of Humans and Animals with E. muris as Antigen

    OpenAIRE

    Kawahara, Makoto; Ito, Tadahiko; Suto, Chiharu; Shibata, Shinichiro; Rikihisa, Yasuko; Hata, Kazuhisa; Hirai, Katsuya

    1999-01-01

    In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had...

  1. Strain-specific aggressive behavior of male mice submitted to different husbandry procedures

    NARCIS (Netherlands)

    Loo, P.L.P. van; Meer, E. van der; Kruitwagen, C.L.J.J.; Koolhaas, J.M.; Zutphen, L.F.M. van; Baumans, V.

    Severe aggression within groups of male laboratory mice can cause serious welfare problems. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study,

  2. Effect of Supplementation with n-3 Fatty Acids Extracted from Microalgae on Inflammation Biomarkers from Two Different Strains of Mice

    Directory of Open Access Journals (Sweden)

    L. E. Gutiérrez-Pliego

    2018-01-01

    Full Text Available Background. Diabetes mellitus is considered a chronic noncommunicable disease in which inflammation plays a main role in the progression of the disease and it is known that n-3 fatty acids have anti-inflammatory properties. One of the most recent approaches is the study of the fatty acids of microalgae as a substitute for fish oil and a source rich in fatty acids EPA and DHA. Objective. To analyze the effect of supplementation with n-3 fatty acids extracted from microalgae on the inflammatory markers from two different strains of mice. Methods. Mice of two strains, db/db and CD1, were supplemented with n-3 fatty acids extracted from microalgae in lyophilized form and added to food; the experiment was carried out from week 8 to 16 of life. Flow cytometry was performed to determine the percentage of TCD4+ cells producing Th1 and Th2 cytokines. Results. Supplementation with microalgae fatty acids decreased the percentage of TCD4+ cells producing IFN-γ and TNF-α and increased the ones producing IL-17A and IL-12 in both strains; on the other hand, supplementation decreased percentage of TCD4+ cells producing IL-4 and increased the ones producing TGF-β. Conclusions. Microalgae n-3 fatty acids could be a useful tool in the treatment of diabetes as well as in the prevention of the appearance of health complications caused by inflammatory states.

  3. Strain differences in paroxetine-induced reduction of immobility time in the forced swimming test in mice: role of serotonin.

    Science.gov (United States)

    Guzzetti, Sara; Calcagno, Eleonora; Canetta, Alessandro; Sacchetti, Giuseppina; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

    2008-10-10

    We studied the antidepressant-like effect of paroxetine in strains of mice carrying different isoforms of tryptophan hydroxylase-2 (TPH-2), the enzyme responsible for the synthesis of brain serotonin (5-HT). The effect of paroxetine alone and in combination with pharmacological treatments enhancing or lowering 5-HT synthesis or melatonin was assessed in the forced swimming test in mice carrying allelic variants of TPH-2 (1473C in C57BL/6 and 1473G in DBA/2 and BALB/c). Changes in brain 5-hydroxytryptophan (5-HTP) accumulation and melatonin levels were measured by high-performance liquid chromatography. Paroxetine (2.5 and 5 mg/kg) reduced immobility time in C57BL/6J and C57BL/6N mice but had no such effect in DBA/2J, DBA/2N and BALB/c mice, even at 10 mg/kg. Enhancing 5-HT synthesis with tryptophan reinstated the antidepressant-like effect of paroxetine in DBA/2J, DBA/2N and BALB/c mice whereas inhibition of 5-HT synthesis prevented the effect of paroxetine in C57BL/6N mice. The response to paroxetine was not associated with changes in locomotor activity, brain melatonin or brain levels of the drug measured at the end of the behavioral test. These results support the importance of 5-HT synthesis in the response to SSRIs and suggest that melatonin does not contribute to the ability of tryptophan to rescue the antidepressant-like effect of paroxetine.

  4. Elements determination of clinical relevance in biological tissues Dmdmdx/J dystrophic mice strains investigated by NAA

    International Nuclear Information System (INIS)

    Metairon, Sabrina

    2012-01-01

    In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMD mdx /J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (Sao Paulo, Brazil). The concentrations of these elements in biological tissues of Dmd mdx /J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

  5. Variable Suppression of Serum Thyroxine in Female Mice of Different Inbred Strains by Triiodothyronine Administered in Drinking Water

    Science.gov (United States)

    Hamidi, Sepehr; Aliesky, Holly; Chen, Chun-Rong; Rapoport, Basil

    2010-01-01

    Background Recombinant-inbred mouse strains differ in their susceptibility to Graves'-like hyperthyroidism induced by immunization with adenovirus expressing the human thyrotropin (TSH) receptor. Because one genetic component contributing to this susceptibility is altered thyroid sensitivity to TSH receptor agonist stimulation, we wished to quantify thyroid responsiveness to TSH. For such studies, it is necessary to suppress endogenous TSH by administering L-3,5,3′-triiodothyronine (L-T3), with the subsequent decrease in serum thyroxine (T4) reflecting endogenous TSH suppression. Our two objectives were to assess in different inbred strains of mice (i) the extent of serum T4 suppression after L-T3 administration and (ii) the magnitude of serum T4 increase induced by TSH. Methods Mice were tail-bled to establish baseline-serum T4 before L-T3 administration. We initially employed a protocol of L-T3-supplemented drinking water for 7 days. In subsequent experiments, we injected L-T3 intraperitoneally (i.p.) daily for 3 days. Mice were then injected i.p. with bovine TSH (10 mU) and euthanized 5 hours later. Serum T4 was assayed before L-T3 administration, and before and after TSH injection. In some experiments, serum T3 and estradiol were measured in pooled sera. Results Oral L-T3 (3 or 5 μg/mL) suppressed serum T4 levels by 26%–64% in female BALB/c mice but >95% in males. T4 suppression in female B6 mice ranged from 0% to 90%. In C3H mice, L-T3 at 3 μg/mL was ineffective but 5 μg/mL achieved >80% serum T4 reduction. Unlike inbred mice, in outbred CF1 mice the same protocol was more effective: 83% in females and 100% suppression in males. The degree of T4 suppression was unrelated to baseline T4, T3, or estradiol, but was related to mouse weight and postmortem T3, with greater suppression in larger mice (outbred CF1 animals and inbred males). Among females with serum T4 suppression >80%, the increase in serum T4 after TSH injection was greater for BALB

  6. Oral immunization of mice with engineered Lactobacillus gasseri NM713 strain expressing Streptococcus pyogenes M6 antigen.

    Science.gov (United States)

    Mansour, Nahla M; Abdelaziz, Sahar A

    2016-08-01

    The aim of this in vivo study was to evaluate the effects of a recombinant probiotic strain, Lactobacillus gasseri NM713, which expresses the conserved region of streptococcal M6 protein (CRR6), as an oral vaccine against Streptococcus pyogenes. A dose of 10(9) cells of the recombinant strain in 150 μL PBS buffer was administered orally to a group of mice. One control group received an equivalent dose of Lb. gasseri NM613 (containing the empty plasmid without insert) or and another control group received PBS buffer. Each group contained 30 mice. The immunization protocol was followed on three consecutive days, after which two booster doses were administered at two week intervals. Fecal and serum samples were collected from the mice on Days 18, 32, 46, 58 after the first immunization and Day 0 prior to immunization. Anti-CRR6 IgA and IgG concentrations were measured by ELISA in fecal and sera samples, respectively, to assess immune responses. Vaccination with the recombinant Lb. gasseri NM713 strain induced significant protection after nasal challenge with S. pyogenes, only a small percentage of this group developing streptococcal infection (10%) or dying of it (3.3%) compared with the NM613 and PBS control groups, high percentages of which developed streptococcal infection (43.3% and 46.7%, respectively) and died of it (46.7% and 53%, respectively). These results indicate that recombinant Lb. gasseri NM713 has potential as an oral delivery vaccine against streptococcus group A. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  7. Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Carlos A. Alba-Fierro

    2016-01-01

    Full Text Available Cell wall (CW components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60 has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

  8. Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis.

    Science.gov (United States)

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Pulido-Camarillo, Evelyn; López-Romero, Everardo; Romo-Lozano, Yolanda; Gutiérrez-Sánchez, Gerardo; Ruiz-Baca, Estela

    2016-01-01

    Cell wall (CW) components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60) has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

  9. Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice.

    Science.gov (United States)

    Cheon, Eric C; Strouch, Matthew J; Barron, Morgan R; Ding, Yongzeng; Melstrom, Laleh G; Krantz, Seth B; Mullapudi, Bhargava; Adrian, Kevin; Rao, Sambasiva; Adrian, Thomas E; Bentrem, David J; Grippo, Paul J

    2011-06-15

    Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-Kras(G12D) (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid. Copyright © 2010 UICC.

  10. HSV-1 strain McKrae is more neuroinvasive than HSV-1 KOS after corneal or vaginal inoculation in mice.

    Science.gov (United States)

    Wang, Hong; Davido, David J; Morrison, Lynda A

    2013-05-01

    Strains of HSV-1 have been noted to vary in their pathogenesis. We compared the replication of strains KOS and McKrae in mice by two routes of infection, ocular and vaginal. Peripheral replication of KOS was similar (cornea) or attenuated over time (vagina) compared with McKrae; however, McKrae replicated in the nervous system to significantly higher levels than KOS after inoculation by either route. Host genetic background strongly influenced the capacity for virus entry into the nervous system from the vagina. KOS and McKrae replicated equivalently after intracranial inoculation, indicating that McKrae's pathogenic phenotype is linked to neuroinvasiveness rather than neurovirulence. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Radiosensitivity of spermatogenous epithelium stem cells of mice of different strains and age

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.; Konoplyannikov, A.G.

    1988-01-01

    In experiments on CBA and BALB/c male mices (3 months of age) and F 1 (CBAxC57BL/6) hybrides (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenous epithelium stem cells displayed by the changes in their colony-forming ability to testicular tubules 42 days following local 60 Co-γ-irradiation. The older the hybrid mice the smaller was the number of spermatogenous epithelium stem cells

  12. Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assay.

    Science.gov (United States)

    Takeyoshi, Masahiro; Noda, Shuji; Yamasaki, Kanji; Kimber, Ian

    2006-01-01

    The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or alpha-hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method. 2005 John Wiley & Sons, Ltd.

  13. Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension

    International Nuclear Information System (INIS)

    Yu Lunyin; Quinn, Deborah A.; Garg, Hari G.; Hales, Charles A.

    2006-01-01

    The balance between cell proliferation and cell quiescence is regulated delicately by a variety of mediators, in which cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) play a very important role. Heparin which inhibits pulmonary artery smooth muscle cell (PASMC) proliferation increases the levels of two CDKIs, p21 and p27, although only p27 is important in inhibition of PASMC growth in vitro and in vivo. In the present study we investigated the expression profile of all the cell cycle regulating genes, including all seven CDKIs (p21, p27, p57, p15, p16, p18, and p19), in the lungs of mice with hypoxia-induced pulmonary hypertension. A cell cycle pathway specific gene microarray was used to profile the 96 genes involved in cell cycle regulation. We also observed the effect of heparin on gene expression. We found that (a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p18 activity, showing a 98% decrease in p27 and 81% increase in p18; (b) other CDKIs, p21, p57, p15, p16, and p19 were not affected significantly in response to hypoxia; (c) heparin treatment restored p27 expression, but did not influence p18; (d) ERK1/2 and p38 were mediators in heparin upregulation of p27. This study provides an expression profile of cell cycle regulating genes under hypoxia in mice with hypoxia-induced pulmonary hypertension and strengthens the previous finding that p27 is the only CDKI involved in heparin regulation of PASMC proliferation and hypoxia-induced pulmonary hypertension

  14. Genetics of the α 1,6-dextran response: expression of the QUPC52 idiotype in different inbred and congenic strains of mice

    International Nuclear Information System (INIS)

    D'Hoostelaere, L.; Potter, M.

    1982-01-01

    Antibodies to dextran B512 were raised in various strains of mice and were assayed by a radioimunoassay procedure. Idiotypic antibodies to the IgA(k) dextran B512 binding myeloma proteins QUOC52 and W3129 of BALB/c origin were prepred in rabbits. After adsorption, each antiserum was specific for the immunizing myeloma protein and did not react with hundreds of other myeloma proteins; nonetheless, antibodies to dextran B512 from various strains of mice cross-reacted in these test systems. Of the 2 idiotypes tested, the W3129 idiotype was more universally expressed in different strains of mice. The QUPC52 idiotype was the predominant idiotype in BALB/c anti-dextran B512 antibodies and was found in only a few other inbred strains. Using a battery of congenic and inbred strains, it was shown that the QUPC52 idiotype was controlled by genes linked to the Igh complex locus (chromosome 12) and to the Ig k complex locus (chromosome 6). The W3129 idiotype was found in a number of stocks of mice in the genus Mus recently isolated from the wild. The QUPC52 idiotype thus far was found only in inbred mice

  15. Antigenic variants of influenza A virus, PR8 strain. I. Their development during serial passage in the lungs of partially immune mice.

    Science.gov (United States)

    GERBER, P; LOOSLI, C G; HAMBRE, D

    1955-06-01

    Antigenically different strains of mouse-adapted PR8 influenza A virus have been produced by 17 serial passages of the virus in the lungs of mice immunized with the homologous agent. Comparative serological tests show that the variant strains share antigenic components with the parent strain but the dominant antigen is different. By means of antibody absorption it was shown that the "new" antigenic component of the variant was already present in minor amounts up to the eighth passage and thereafter gained prominence with continued passage in vaccinated mice. Groups of mice vaccinated with either the PR8-S or T(21) virus and having comparable antibody titers showed no growth of virus in the lungs following aid-borne challenge with homologous strains. On the other hand, following heterologous air-borne challenge no deaths occurred, but virus grew in the lungs of both groups of vaccinated mice. Almost unrestricted virus multiplication took place in the lungs of mice vaccinated with the parent strain and challenged with the PR8-T(21) virus which resulted in extensive consolidation. Less virus grew in the lungs of the mice vaccinated with the variant strains and challenged with the PR8-S virus. In these animals only microscopic evidence of changes due to virus growth in the lungs was observed. The successful serial passage of PR8 influenza A virus in immunized animals was dependent on the initial selection of mice with uniformly low H.I. antibody titers as determined on tail blood, and the intranasal instillation of sufficient virus to favor the survival of those virus particles least related to the antibodies present. The epidemiological implications of these observations are discussed briefly.

  16. Assessment of right ventricular longitudinal strain by 2D speckle tracking imaging compared with RV function and hemodynamics in pulmonary hypertension.

    Science.gov (United States)

    Li, Yidan; Wang, Yidan; Meng, Xiangli; Zhu, Weiwei; Lu, Xiuzhang

    2017-11-01

    The right ventricular longitudinal strain (RVLS) of pulmonary hypertension (PH) patients and its relationship with RV function parameters measured by echocardiography and hemodynamic parameters measured by right heart catheterization was investigated. According to the WHO functional class (FC), 66 PH patients were divided into FC I/II (group 1) and III/IV (group 2). RV function parameters were measured by echocardiographic examinations. Hemodynamic parameters were obtained by right heart catheterization. Patients in group 2 had higher systolic pulmonary artery pressure (sPAP; P good sensitivity and specificity. Evidence has shown that RVLS measurement can provide the much-needed and reliable information on RV function and hemodynamics. Therefore, this qualifies as a patient-friendly approach for the clinical management of PH patients.

  17. Characteristics of histocompatibility barriers in congenis strains of mice. III. Passive enhancement of skin allografts in x-irradiated hosts

    International Nuclear Information System (INIS)

    Cantrell, J.L.; Kaliss, N.; Hildemann, W.H.

    1975-01-01

    Passive immunological enhancement of skin allografts was investigated in three donor-host combinations of congenic mice disparate at non-H-2 loci. Serum against the graft donor was derived from mice that had received donor strain lymphoid cells as neonates, and thereby were rendered specifically tolerant of a skin allograft. We refer to this serum as ''allograft-tolerant'' serum. Each strain combination was chosen to provide only two non-H-2 histoincompatibilities present in the donor and absent in the host. The differences are categorized as immunogenetically strong, moderate, or weak, on the basis of skin allograft survival times. With passively administered allograft-tolerant serum, significantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal x-irradiation and allograft-tolerant serum significantly prolonged graft survival in both the moderate and weak combinations, with the largest effect present in the weakest disparity. A hyperimmune alloantiserum (produced in adults) directed against the graft donor prolonged allograft survival in the strongest disparity when given in combination with irradiation. In this combination, graft survival time was increased in hosts exposed to x-ray alone, but joint treatment with x-ray and the alloantiserum gave the largest increment. In contrast, combined treatment with the serum and an antithymocyte alloantiserum did not affect graft survival times. Treatment with both radiation and antithymocyte serum did not prolong graft survival beyond that in mice given only x-radiation. Immunological enhancement with central inhibition is assumed as the mechanism underlying prolonged graft survival, and it is suggested that a population of thymus-derived killer cells, sensitive to x-irradiation, is required for normal graft rejection. (U.S.)

  18. A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice.

    Directory of Open Access Journals (Sweden)

    Grace K Tan

    Full Text Available The spread of dengue (DEN worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable small animal model. Most of the DEN clinical isolates and cell culture-passaged DEN virus strains reported so far require either host adaptation, inoculation with a high dose and/or intravenous administration to elicit a virulent phenotype in mice which results, at best, in a productive infection with no, few, or irrelevant disease manifestations, and with mice dying within few days at the peak of viremia. Here we describe a non-mouse-adapted DEN2 virus strain (D2Y98P that is highly infectious in AG129 mice (lacking interferon-alpha/beta and -gamma receptors upon intraperitoneal administration. Infection with a high dose of D2Y98P induced cytokine storm, massive organ damage, and severe vascular leakage, leading to haemorrhage and rapid death of the animals at the peak of viremia. In contrast, very interestingly and uniquely, infection with a low dose of D2Y98P led to asymptomatic viral dissemination and replication in relevant organs, followed by non-paralytic death of the animals few days after virus clearance, similar to the disease kinetic in humans. Spleen damage, liver dysfunction and increased vascular permeability, but no haemorrhage, were observed in moribund animals, suggesting intact vascular integrity, a cardinal feature in DEN shock syndrome. Infection with D2Y98P thus offers the opportunity to further decipher some of the aspects of dengue pathogenesis and provides a new platform for drug and vaccine testing.

  19. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

    NARCIS (Netherlands)

    Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Genevieve; Wenzel, Ulrich

    Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is

  20. Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.

    Directory of Open Access Journals (Sweden)

    Lukas E Dow

    Full Text Available Tetracycline or doxycycline (dox-regulated control of genetic elements allows inducible, reversible and tissue specific regulation of gene expression in mice. This approach provides a means to investigate protein function in specific cell lineages and at defined periods of development and disease. Efficient and stable regulation of cDNAs or non-coding elements (e.g. shRNAs downstream of the tetracycline-regulated element (TRE requires the robust expression of a tet-transactivator protein, commonly the reverse tet-transactivator, rtTA. Most rtTA strains rely on tissue specific promoters that often do not provide sufficient rtTA levels for optimal inducible expression. Here we describe the generation of two mouse strains that enable Cre-dependent, robust expression of rtTA3, providing tissue-restricted and consistent induction of TRE-controlled transgenes. We show that these transgenic strains can be effectively combined with established mouse models of disease, including both Cre/LoxP-based approaches and non Cre-dependent disease models. The integration of these new tools with established mouse models promises the development of more flexible genetic systems to uncover the mechanisms of development and disease pathogenesis.

  1. Virulent variants emerging in mice infected with the apathogenic prototype strain of the parvovirus minute virus of mice exhibit a capsid with low avidity for a primary receptor.

    Science.gov (United States)

    Rubio, Mari-Paz; López-Bueno, Alberto; Almendral, José M

    2005-09-01

    The mechanisms involved in the emergence of virulent mammalian viruses were investigated in the adult immunodeficient SCID mouse infected by the attenuated prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp intravenously inoculated in mice consistently evolved during weeks of subclinical infection to variants showing altered plaque phenotypes. All the isolated large-plaque variants spread systemically from the oronasal cavity and replicated in major organs (brain, kidney, liver), in sharp contrast to the absolute inability of the MVMp and small-plaque variants to productively invade SCID organs by this natural route of infection. The virulent variants retained the MVMp capacity to infect mouse fibroblasts, consistent with the lack of genetic changes across the 220-to-335 amino acid sequence of VP2, a capsid domain containing main determinants of MVM tropism. However, the capsid of the virulent variants shared a lower affinity than the wild type for a primary receptor used in the cytotoxic infection. The capsid gene of a virulent variant engineered in the MVMp background endowed the recombinant virus with a large-plaque phenotype, lower affinity for the receptor, and productive invasiveness by the oronasal route in SCID mice, eventually leading to 100% mortality. In the analysis of virulence in mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2 days postoronasal inoculation and remained infectious when adsorbed to blood cells in vitro. However, the wild-type MVMp was cleared from circulation a few days afterwards, in contrast to the viremia of the recombinant virus, which was sustained for life. Significantly, attachment to an abundant receptor of primary mouse kidney epithelial cells by both viruses could be quantitatively competed by wild-type MVMp capsids, indicating that virulence is not due to an extended receptor usage in target tissues. We conclude that the selection of capsid-receptor interactions of

  2. Variations in ventral root axon morphology and locomotor behavior components across different inbred strains of mice

    NARCIS (Netherlands)

    de Mooij-van Malsen, J. G.; Yu, K. L.; Veldman, H.; Oppelaar, H; van den Berg, L. H.; Olivier, B.; Kas, M. J. H.

    2009-01-01

    Locomotion is a complex behavior affected by many different brain- and spinal cord systems, as well as by variations in the peripheral nervous system. Recently, we found increased gene expression for EphA4, a gene intricately involved in motor neuron development, between high-active parental strain

  3. TEMPORAL STRUCTURE OF OPEN-FIELD BEHAVIOR IN INBRED STRAINS OF MICE

    NARCIS (Netherlands)

    MAKINO, J; KATO, K; MAES, FW

    1991-01-01

    Behavior of the inbred mouse strains BALB, C3H, DBA and C57BL in an open field was directly observed for 10 min by a multi-event time sampling method. It was coded into nine behavioral items, the occurrence or absence of which in consecutive 5-s time bins was called a behavioral state. Fourteen

  4. No postnatal maternal effect on male aggressiveness in wild-derived strains of house mice

    Czech Academy of Sciences Publication Activity Database

    Ďureje, Ľudovít; Vošlajerová Bímová, Barbora; Piálek, Jaroslav

    2011-01-01

    Roč. 37, č. 1 (2011), s. 48-55 ISSN 0096-140X R&D Projects: GA AV ČR KJB600930701 Institutional research plan: CEZ:AV0Z60930519 Keywords : aggression * cross-fostering * wild-derived inbred strains * house mouse Subject RIV: EG - Zoology Impact factor: 2.630, year: 2011

  5. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension.

    Science.gov (United States)

    Bruder-Nascimento, Thiago; Butler, Benjamin R; Herren, David J; Brands, Michael W; Bence, Kendra K; Belin de Chantemèle, Eric J

    2015-12-01

    Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Diagnostic and prognostic value of right ventricular strain in patients with pulmonary arterial hypertension and relatively preserved functional capacity studied with echocardiography and magnetic resonance.

    Science.gov (United States)

    da Costa Junior, Augusto Alberto; Ota-Arakaki, Jaquelina Sonoe; Ramos, Roberta Pulcheri; Uellendahl, Marly; Mancuso, Frederico José Neves; Gil, Manuel Adan; Fischer, Cláudio Henrique; Moises, Valdir Ambrosio; de Camargo Carvalho, Antonio Carlos; Campos, Orlando

    2017-01-01

    Right ventricular (RV) dysfunction harbingers adverse prognosis in pulmonary arterial hypertension (PAH). Although conventional two-dimensional echocardiography (2DE) is limited for RV systolic function quantitation, RV strain can be a useful tool. The diagnostic and prognostic impact of 2DE speckle-tracking RV longitudinal strain was evaluated, including other 2DE systolic indexes, in a group of PAH patients without severe impairment of functional capacity, chronic pulmonary thromboembolism or left ventricular dysfunction. Sixty-six group I PAH patients, 67 % NYHA functional class I or II (none in IV) were studied by 2DE to obtain: RV fractional area change, tricuspid annular plane systolic excursion, RV myocardial performance index, tissue Doppler tricuspid annulus systolic velocity. Global, free wall (RVFreeWSt) and septal RV longitudinal systolic strain were obtained. RV ejection fraction by cardiac magnetic resonance (CMR-RVEF) was also assessed. All patients were followed up to 3.9 years (mean 3.3 years). Combined endpoints were hospitalization for worsening PAH or cardiovascular death. Among all the 2DE indexes of RV systolic function, RVFreeWSt exhibited the best correlation with CMR-RVEF (r = 0.83; p < 0.005). Combined endpoints occurred in 15 (22.7 %) patients (6 hospitalizations and 9 deaths). Multivariate analysis identified RVFreeWSt ≤-14 % as the only 2DE independent variable associated with combined endpoints [HR 4.66 (1.25-17.37); p < 0.05]. We conclude that RVFreeWSt may be a suitable non-geometric 2DE surrogate of CMR-RVEF in PAH patients, constituting a powerful independent predictor of long-term outcome in this cohort with relatively preserved functional capacity.

  7. Characterization of in vitro phenotypes of Burkholderia pseudomallei and Burkholderia mallei strains potentially associated with persistent infection in mice.

    Science.gov (United States)

    Bernhards, R C; Cote, C K; Amemiya, K; Waag, D M; Klimko, C P; Worsham, P L; Welkos, S L

    2017-03-01

    Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the agents of melioidosis and glanders, respectively, are Tier 1 biothreats. They infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. Chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. First, a phenotyping strategy was developed employing colony morphotyping, chemical sensitivity testing, macrophage infection, and lipopolysaccharide fingerprint analyses to distinguish Burkholderia strains. Then mouse spleen isolates collected 3-180 days after infection were characterized phenotypically. Isolates from long-term infections often exhibited increased colony morphology differences and altered patterns of antimicrobial sensitivity and macrophage infection. Some of the Bp and Bm persistent infection isolates clearly displayed enhanced virulence in mice. Future studies will evaluate the potential role and significance of these phenotypic markers in signaling the establishment of a chronic infection.

  8. Genetic influences on ovulation of primary oocytes in LT/Sv strain mice.

    Science.gov (United States)

    Everett, Clare A; Auchincloss, Catherine A; Kaufman, Matthew H; Abbott, Catherine M; West, John D

    2004-11-01

    A high proportion of LT/Sv strain oocytes arrest in meiotic metaphase I (MI) and are ovulated as diploid primary oocytes rather than haploid secondary oocytes. (Mus musculus castaneus x LT/SvKau)F1 x LT/SvKau backcross females were analysed for the proportion of oocytes that arrested in MI and typed by PCR for a panel of microsatellite DNA sequences (simple sequence repeat polymorphisms) that differed between strain LT/SvKau and M. m. castaneus. This provided a whole genome scan of 86 genetic markers distributed over all 19 autosomes and the X chromosome, and revealed genetic linkage of the MI arrest phenotype to markers on chromosomes 1 and 9. Identification of these two chromosomal regions should facilitate the identification of genes involved in mammalian oocyte maturation and the control of meiosis.

  9. [Establishment of Social Stress Induced Depression-like Animal Model in Mice of C57BL/6 Strain and Behavioral Assessments].

    Science.gov (United States)

    Li, Mi-hui; Wu, Xiao; Wei Ying; Dong, Jing-cheng

    2016-02-01

    To establish social stress induced depression-like model in mice of C57BL/6 strain, and to assess its reliability using differenf behavioral methods. Totally 20 male mice of C57BL/6 strain were divided into the normal group and the stress model group by random digit table,10 in each group. Another 10 CD1 mice were subjected to social stress. Mice in the normal control group received no stress, while those in the model group received social stress for 10 successive days. Behavioral assessment was performed using social interaction test (SIT), the elevated plus-maze (EPM) test, tail suspension test (TST), respectively. Serum cortisol level was detected by ELISA to assess the reliability of the model. In the social interaction test when the social target (CDI mice) was inexistent, mice in the normal control group spent longer time in the social interaction zone and less time in the corner zone (P stress induced depression-like animal model in mice of C57BL/6 straineasquite reliable and possibly suitable to be used in integrative medicine research of combination of disease and syndrome model.

  10. Derivation of hybrid ES cell lines from two different strains of mice

    Directory of Open Access Journals (Sweden)

    Ho-Tak Lau

    2016-03-01

    Full Text Available Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds. The blastocyst-derived ES clones displayed largely intact DNA methylation imprint at the tested imprinted regions. These hybrid ES clones will be useful for future studies to examine the allelic expression of the imprinted genes in ES cells and their differentiated progeny.

  11. Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure

    Directory of Open Access Journals (Sweden)

    Kikuchi Mihoko

    2009-05-01

    Full Text Available Abstract Background Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. Methodology To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated. Results Upon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%, which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively. Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6, followed by C57BL/6 (8.6, CBA (6.9 and NZW (4.0, p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p Conclusion The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also

  12. Influence of radon (222Rn) on hypothalamus, hypophysis, ovaries and uterus in Balb C strain mice

    International Nuclear Information System (INIS)

    Koziorowski, A.

    1997-01-01

    Curative properties of radon waters have been applied in balneotherapy for a long time. Therapeutic action is connected with radioactive properties of radon and the products of its degradation. All of them are the source of ionizing radiation, the alpha rays in particular. Radon therapy is widely applied to the treatment of many illnesses, especially of the circulatory system, rheumatism, and arthritis, bronchial asthma and many others. Good therapeutic results have also been achieved in gynecology to mention chronic inflammation of female reproductive organs and endocrinological disorders (of the ovary and during the period of sterilization). Positive results of radon therapy can also be associated with the influence of ionizing radiation on the activity of endocrine glands, mainly the axis hypothalamus - hypophysis - adrenal gland - ovary. There has been neither regular investigation into this problem nor into the morphology of the organs mentioned above. The present paper is an attempt to evaluate the influence of radon inhalations on the structure and function of hypothalamus, hypophysis ovary and uterus. This investigation was performed on hypothalamus, hypophysis, ovary and uterus in Balb C virgin mice. The total population of the mice under study was 140; with a control group of 40. The mice inhalated radon for 30 min. a day, starting with a single irradiation up to a 30-fold. I applied traditional histological techniques and immunocytochemical localization of selected hormones (FSH, LH, ADH). I also tried to evaluate the quantitative activity of mentioned glands by means of the computer morphometric and densitometric analyses of the immunocytochemical slides using an image analyzer Vidas 25 manufactured by Kontron. The results underwent statistical analysis. In order to examine the uterus the ultrastructural evaluation of its functioning was made. Moreover, I analyzed the concentration of FSH, LH, estrogens and progesterone in the serum by means of the

  13. Recombinant M. bovis BCG expressing the PLD protein promotes survival in mice challenged with a C. pseudotuberculosis virulent strain.

    Science.gov (United States)

    Leal, Karen Silva; de Oliveira Silva, Mara Thais; de Fátima Silva Rezende, Andréa; Bezerra, Francisco Silvestre Brilhante; Begnini, Karine; Seixas, Fabiana; Collares, Tiago; Dellagostin, Odir; Portela, Ricardo Wagner; de Carvalho Azevedo, Vasco Ariston; Borsuk, Sibele

    2018-06-14

    The aim of this study was to evaluate the survival of mice inoculated with M. bovis BCG Pasteur recombinant expressing the PLD protein and challenged with a C. pseudotuberculosis virulent strain. Four groups were immunized with a sterile 0.9% saline solution (G1), 10 6  CFU of M. bovis BCG Pasteur (G2), 10 6  CFU of M. bovis BCG/pld (G3) or 10 6  CFU of M. bovis BCG/pld with a booster with rPLD (G4) and challenged with 10 4 CFU of C. pseudotuberculosis MIC-6 strain. The highest survival rate of 88% was observed in G4, followed by 77% in G3 and 66% in G2. A significant statistical difference was observed in the levels of cytokines IFN-γ and IL-10 in vaccinated groups (G3 and G4) when compared with the control group (G1) (p < 0.05). The results seem promising as the recombinant vaccine elicited a cellular immune response and provided significant survival after a high virulent challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Ocular Hypertension

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Ocular Hypertension Sections What Is Ocular Hypertension? Ocular Hypertension Causes ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Leer en Español: ¿Qué es la hipertensión ocular? ...

  15. [Testicular testosterone production in male mice of inbred strains PT and CBA/Lac after a long-term period of stable social hierarchy].

    Science.gov (United States)

    Osadchuk, L V; Gutorova, N V; Kleshchev, M A

    2014-04-01

    Social dominance can alter testicular testosterone production, although there is pronounced variability in the relationship between social status and pattern of the testosterone response. The study designed to investigate how a long-term period of stable social hierarchy effects on testicular testosterone production in male mice of inbred strains PT and CBA/Lac. Paired males of different genotypes were housed together for 32 days beginning 38 day of age. Dyadic interactions of males generated dominance-subordination relationships during the first day after a social group has been produced and the social rank of each opponent was assessed by asymmetry in agonistic behaviour. Serum level of testosterone and its testicular content were evaluated in male mice of both inbred strains at 70 day of age after pair housing. Control animals were age- and genotype-matched single males that were housed in conventional cages. After a long-term period of pair housing, the serum testosterone level and its testicular content in males of both PT and CBA/Lac strains were not significantly different from the control. There were no significant differences in androgenic parameters between social ranks in male mice of both strains. The results indicate that in laboratory mice the pattern of testicular testosterone response to social hierarchy determined by a social situation, for example, a stability of social interactions, when the importance of aggressive competition for rank is minimal.

  16. Response of white mice to inoculation of irradiated organisms of the Toxoplasma strain RH

    International Nuclear Information System (INIS)

    Mas Bakal, P.; Veld, N. in't

    1979-01-01

    Chemoterapeutic agents available for use against toxoplasmosis are usually not suitable for prophylatic purposes because of their toxicity. The observed increasing number of activated latent infections with Toxoplasma, especially in immune suppressed patients, requires that safe techniques are available for use during the patients' regression period. Pretreatment of mice with Toxoplasma killed by irradiation appeared to induce resistance to challenge with virulent organisms. Survival times of six months have been observed to date. Increasing effectiveness was seen after more than one administration. Further investigation into the duration of effective resistance is needed; the question of at which intervals subsequent inoculations should be performed in order to acquire a booster effect, if any, has still to be solved before application to man can be recommended. (orig.) [de

  17. Enhancing the value of psychiatric mouse models; differential expression of developmental behavioral and cognitive profiles in four inbred strains of mice.

    Science.gov (United States)

    Molenhuis, Remco T; de Visser, Leonie; Bruining, Hilgo; Kas, Martien J

    2014-06-01

    The behavioral characterization of animal models of psychiatric disorders is often based upon independent traits measured at adult age. To model the neurodevelopmental aspects of psychiatric pathogenesis, we introduce a novel approach for a developmental behavioral analysis in mice. C57BL/6J (C57) mice were used as a reference strain and compared with 129S1/SvImJ (129Sv), BTBR T+tf/J (BTBR) and A/J (AJ) strains as marker strains for aberrant development. Mice were assessed at pre-adolescence (4 weeks), adolescence (6 weeks), early adulthood (8 weeks) and in adulthood (10-12 weeks) on a series of behavioral tasks measuring general health, neurological reflexes, locomotor activity, anxiety, short- and long-term memory and cognitive flexibility. Developmental delays in short-term object memory were associated with either a hypo-reactive profile in 129Sv mice or a hyper-reactive profile in BTBR mice. Furthermore, BTBR mice showed persistent high levels of repetitive grooming behavior during all developmental stages that was associated with the adult expression of cognitive rigidity. In addition, strain differences in development were observed in puberty onset, touch escape, and body position. These data showed that this longitudinal testing battery provides sufficient behavioral and cognitive resolution during different development stages and offers the opportunity to address the behavioral developmental trajectory in genetic mouse models for neurodevelopmental disorders. Furthermore, the data revealed that the assessment of multiple behavioral and cognitive domains at different developmental stages is critical to determine confounding factors (e.g., impaired motor behavior) that may interfere with the behavioral testing performance in mouse models for brain disorders. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  18. Comparison of Ehrlichia muris strains isolated from wild mice and ticks and serologic survey of humans and animals with E. muris as antigen.

    Science.gov (United States)

    Kawahara, M; Ito, T; Suto, C; Shibata, S; Rikihisa, Y; Hata, K; Hirai, K

    1999-04-01

    In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had been isolated. These new isolates were compared with the E. muris type strain. The mouse virulence and ultrastructure of the new isolates were similar to those of the type strain, and all of them were cross-reactive with each other, as well as with the type strain, by indirect immunofluorescent-antibody test. The levels of similarity of the base sequences of the 16S rRNA gene of one of the A. speciosus isolates and one of the tick isolates to that of the E. muris type strain were 99.79 and 99.93%, respectively. We suggest that all of these isolates are E. muris; that E. muris is not limited to Eothenomys kageus but infects other species of mice; and that E. muris is present at locations other than Aichi Prefecture. It appears that H. flava is a potential vector of E. muris. Twenty (1%) of 1803 humans from metropolitan Tokyo were found to be seropositive for E. muris antibodies. A serological survey revealed that exposure to E. muris or organisms antigenically cross-reactive to E. muris occurred among dogs, wild mice, monkeys, bears, deer, and wild boars in Gifu Prefecture, nearby prefectures, and Nagoya City, central Japan. However, human beings and Rattus norvegicus rats in this area were seronegative. These results indicate broader geographic distribution of and human and animal species exposure to E. muris or related Ehrlichia spp. in Japan.

  19. Mixed-strain housing for female C57BL/6, DBA/2, and BALB/c mice: validating a split-plot design that promotes refinement and reduction.

    Science.gov (United States)

    Walker, Michael; Fureix, Carole; Palme, Rupert; Newman, Jonathan A; Ahloy Dallaire, Jamie; Mason, Georgia

    2016-01-27

    Inefficient experimental designs are common in animal-based biomedical research, wasting resources and potentially leading to unreplicable results. Here we illustrate the intrinsic statistical power of split-plot designs, wherein three or more sub-units (e.g. individual subjects) differing in a variable of interest (e.g. genotype) share an experimental unit (e.g. a cage or litter) to which a treatment is applied (e.g. a drug, diet, or cage manipulation). We also empirically validate one example of such a design, mixing different mouse strains -- C57BL/6, DBA/2, and BALB/c -- within cages varying in degree of enrichment. As well as boosting statistical power, no other manipulations are needed for individual identification if co-housed strains are differentially pigmented, so also sparing mice from stressful marking procedures. The validation involved housing 240 females from weaning to 5 months of age in single- or mixed- strain trios, in cages allocated to enriched or standard treatments. Mice were screened for a range of 26 commonly-measured behavioural, physiological and haematological variables. Living in mixed-strain trios did not compromise mouse welfare (assessed via corticosterone metabolite output, stereotypic behaviour, signs of aggression, and other variables). It also did not alter the direction or magnitude of any strain- or enrichment-typical difference across the 26 measured variables, or increase variance in the data: indeed variance was significantly decreased by mixed- strain housing. Furthermore, using Monte Carlo simulations to quantify the statistical power benefits of this approach over a conventional design demonstrated that for our effect sizes, the split- plot design would require significantly fewer mice (under half in most cases) to achieve a power of 80%. Mixed-strain housing allows several strains to be tested at once, and potentially refines traditional marking practices for research mice. Furthermore, it dramatically illustrates the

  20. Mixed-strain housing for female C57BL/6, DBA/2, and BALB/c mice: validating a split-plot design that promotes refinement and reduction

    Directory of Open Access Journals (Sweden)

    Michael Walker

    2016-01-01

    Full Text Available Abstract Background Inefficient experimental designs are common in animal-based biomedical research, wasting resources and potentially leading to unreplicable results. Here we illustrate the intrinsic statistical power of split-plot designs, wherein three or more sub-units (e.g. individual subjects differing in a variable of interest (e.g. genotype share an experimental unit (e.g. a cage or litter to which a treatment is applied (e.g. a drug, diet, or cage manipulation. We also empirically validate one example of such a design, mixing different mouse strains -- C57BL/6, DBA/2, and BALB/c -- within cages varying in degree of enrichment. As well as boosting statistical power, no other manipulations are needed for individual identification if co-housed strains are differentially pigmented, so also sparing mice from stressful marking procedures. Methods The validation involved housing 240 females from weaning to 5 months of age in single- or mixed- strain trios, in cages allocated to enriched or standard treatments. Mice were screened for a range of 26 commonly-measured behavioural, physiological and haematological variables. Results Living in mixed-strain trios did not compromise mouse welfare (assessed via corticosterone metabolite output, stereotypic behaviour, signs of aggression, and other variables. It also did not alter the direction or magnitude of any strain- or enrichment-typical difference across the 26 measured variables, or increase variance in the data: indeed variance was significantly decreased by mixed- strain housing. Furthermore, using Monte Carlo simulations to quantify the statistical power benefits of this approach over a conventional design demonstrated that for our effect sizes, the split- plot design would require significantly fewer mice (under half in most cases to achieve a power of 80 %. Conclusions Mixed-strain housing allows several strains to be tested at once, and potentially refines traditional marking practices

  1. Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis

    Science.gov (United States)

    Fang, Fan; Du, Ying; Ma, Rui; Li, Xiang-Yang; Yu, Qian; Meng, Di; Tang, Ren-Xian; Zheng, Kui-Yang

    2017-01-01

    Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells) and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice) induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson’s trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (Psinensis-infected mice. PMID:28151995

  2. Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis.

    Directory of Open Access Journals (Sweden)

    Bei-Bei Zhang

    Full Text Available Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson's trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (P<0.01. Importantly, increased Th2 subset and Treg subset all positively correlated with hydroxyproline contents (P<0.01. This result for the first time implied that the increased hepatic Th2 and Treg cell subsets were likely to play potential roles in the formation of biliary fibrosis in C. sinensis-infected mice.

  3. Emotion and cognition in high and low stress sensitive mouse strains: a combined neuroendocrine and behavioral study in BALB/c and C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Vera Brinks

    2007-12-01

    Full Text Available Emotionally arousing experiences and stress influence cognitive processes and vice versa. Understanding the relations and interactions between these three systems forms the core of this study. We tested two inbred mouse strains (BALB/c, C57BL/6J; male; 3-month-old for glucocorticoid stress system markers (expression of MR and GR mRNA and protein in hippocampus, amygdala, and prefrontal cortex; blood plasma corticosterone, used behavioral tasks for emotions and cognitive performance (elevated plus maze, holeboard to assess the interdependence of these factors. We hypothesize that BALB/c mice have a stress-vulnerable neuroendocrine phenotype and that emotional expressions in BALB/c and C57BL/6J mice will differentially contribute to learning and memory. We applied factor analyses on emotional and cognitive parameters to determine the behavioral structure of BALB/c and C57BL/6J mice. Glucocorticoid stress system markers indeed show that BALB/c mice are more stress-vulnerable than C57BL/6J mice. Moreover, emotional and explorative factors differed between naïve BALB/c and C57BL/6J mice. BALB/c mice display high movement in anxiogenic zones and high risk assessment, while C57BL/6J mice show little movement in anxiogenic zones and display high vertical exploration. Furthermore, BALB/c mice are superior learners, showing learning related behavior which is highly structured and emotionally biased when exposed to a novel or changing situation. In contrast, C57BL/6J mice display a rather ‘‘chaotic’’ behavioral structure during learning in absence of an emotional factor. These results show that stress vulnerability coincides with more emotionality, which drives well orchestrated goal directed behavior to the benefit of cognition. Both phenotypes have their advantage depending on environmental demands.

  4. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu

    2005-01-01

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  5. Effect of Oxidized Dextran on Cytokine Production and Activation of IRF3 Transcription Factor in Macrophages from Mice of Opposite Strains with Different Sensitivity to Tuberculosis Infection.

    Science.gov (United States)

    Chechushkov, A V; Kozhin, P M; Zaitseva, N S; Gainutdinov, P I; Men'shchikova, E B; Troitskii, A V; Shkurupy, V A

    2018-04-16

    We studied differences in the production of pro- and anti-inflammatory cytokines and IRF3 transcription factor by peritoneal macrophages from mice of opposite strains CBA/J and C57Bl/6 and the effect of 60-kDa oxidized dextran on these parameters. Macrophages from C57Bl/6 mice were mainly characterized by the production of proinflammatory cytokines TNFα, IL-12, and MCP-1 (markers of M1 polarization). By contrast, CBA/J mice exhibited a relatively high level of anti-inflammatory cytokine IL-10 and lower expression of proinflammatory cytokines (M2 phenotype). IRF3 content in peritoneal macrophages of CBA/J mice was higher than in C57Bl/6 mice. Oxidized dextran decreased the expression of IRF3 upon stimulation of cells from CBA/J mice with LPS, but increased this process in C57Bl/6 mice. Despite a diversity of oxidized dextran-induced changes in cytokine production, the data confirm our hypothesis that this agent can stimulate the alternative activation of macrophages.

  6. A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes.

    Directory of Open Access Journals (Sweden)

    Iñigo Angulo-Barturen

    Full Text Available To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NOD(scid/beta2m-/- mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NOD(scid/beta2m-/- mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D7(0087/N9 as a reference strain for model development. Pf3D7(0087/N9 caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods.

  7. Portal Hypertension

    Science.gov (United States)

    ... Overview of Gallbladder Cancer Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD, Professor of Medicine, ... Liver Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension Portal hypertension is abnormally high blood pressure in ...

  8. [Secondary hypertension].

    Science.gov (United States)

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice.

  9. Secondary Hypertension

    Science.gov (United States)

    Secondary hypertension Overview Secondary hypertension (secondary high blood pressure) is high blood pressure that's caused by another medical condition. Secondary hypertension can be caused by conditions that affect your kidneys, ...

  10. Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.

    Science.gov (United States)

    McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min; Loguinov, Alex; Valore, Erika; Hui, Simon T; Jung, Grace; Zhou, Jie; Lusis, Aldons J; Fuqua, Brie; Ganz, Tomas; Nemeth, Elizabeta; Vulpe, Chris D

    2017-11-01

    Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin ( Hamp1 ) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least

  11. The Protective Effect of Antarctic Krill Oil on Cognitive Function by Inhibiting Oxidative Stress in the Brain of Senescence-Accelerated Prone Mouse Strain 8 (SAMP8) Mice.

    Science.gov (United States)

    Li, Qian; Wu, Fengjuan; Wen, Min; Yanagita, Teruyoshi; Xue, Changhu; Zhang, Tiantian; Wang, Yuming

    2018-02-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative stress plays a vital role in its progression. Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids, which has various biological activities, such as improving insulin sensitivity, alleviating inflammation and ameliorating oxidative stress. In this study, the protective effect of AKO against AD were investigated in senescence-accelerated prone mouse strain 8 (SAMP8) mice. Results showed that treatment with AKO could effectively ameliorate learning and memory deficits and ease the anxiety in SAMP8 mice by Morris water maze, Barnes maze test and open-field test. Further analysis indicated that AKO might reduce β-amyloid (Aβ) accumulation in hippocampus through decreasing the contents of malondialdehyde (MDA) and 7,8-dihydro-8-oxoguanine (8-oxo-G), increasing the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain of SAMP8 mice. The results of Morris water maze, Barnes maze test and open-field test indicated that Antarctic krill oil (AKO) improved the cognitive function and anxiety of SAMP8 mice. AKO reduced the Aβ 42 level in hippocampus of SAMP8 mice. AKO ameliorated oxidative stress in brain rather than in serum and liver of SAMP8 mice. © 2018 Institute of Food Technologists®.

  12. Immunization of Mice with a Live Transconjugant Shigella Hybrid Strain Induced Th1 and Th17 Cell-Mediated Immune Responses and Confirmed Passive Protection Against Heterologous Shigellae.

    Science.gov (United States)

    Nag, D; Koley, H; Sinha, R; Mukherjee, P; Sarkar, C; Withey, J H; Gachhui, R

    2016-02-01

    An avirulent, live transconjugant Shigella hybrid (LTSHΔstx) strain was constructed in our earlier study by introducing a plasmid vector, pPR1347, into a Shiga toxin gene deleted Shigella dysenteriae 1. Three successive oral administrations of LTSHΔstx to female adult mice produced comprehensive passive heterologous protection in their offspring against challenge with wild-type shigellae. Production of NO and different cytokines such asIL-12p70, IL-1β and IL-23 in peritoneal mice macrophages indicated that LTSHΔstx induced innate and adaptive immunity in mice. Furthermore, production of IFN-γ, IL-10 and IL-17 in LTSH-primed splenic CD4+ T cell suggested that LTSHΔstx may induce Th1 and Th17 cell-mediated immune responses. Exponential increase of the serum IgG and IgA titre against whole shigellae was observed in immunized adult mice during and after the immunization with the highest peak on day 35. Antigen-specific sIgA was also determined from intestinal lavage of immunized mice. The stomach extracts of neonates from immunized mice, mainly containing mother's milk, contained significant levels of anti-LTSHΔstx immunoglobulin. These studies suggest that the LTSHΔstx could be a new live oral vaccine candidate against shigellosis in the near future. © 2015 The Foundation for the Scandinavian Journal of Immunology.

  13. Colony formation of C57BL/6J mice in visible burrow system: Identification of eusocial behaviors in a background strain for genetic animal models of autism

    OpenAIRE

    Arakawa, Hiroyuki; Blanchard, D. Caroline; Blanchard, Robert J.

    2006-01-01

    Deficits in social interaction are primary characteristics of autism, which has strong genetic components. Genetically-manipulated mouse models may provide a useful research tool to advance the investigation of genes associated with autism. To identify these genes using mouse models, behavioral assays for social relationships in the background strains must be developed. The present study examined colony formation in groups of one male and three female mice (Experiment 1) and, groups of three ...

  14. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

    Directory of Open Access Journals (Sweden)

    Yosuke Kikuchi

    Full Text Available The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

  15. Babassu aqueous extract (BAE as an adjuvant for T helper (Th1-dependent immune responses in mice of a Th2 immune response-prone strain

    Directory of Open Access Journals (Sweden)

    Nascimento Flavia RF

    2011-01-01

    Full Text Available Abstract Background The aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE exerts a clear immunostimulative activity in vivo. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of Leishmania amazonensis promastigote extract (LE, adsorbed or not to Al(OH3, and in the presence or not of BAE, were used as immunogens. LE and Al(OH3 have been shown to preferentially elicit Th2 immune responses. Results The addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH3, clearly promoted the in vitro production of interferon γ (IFN-γ, a major Th1-dependent cytokine, and not of interleukin (IL-4 (a Th2-dependent cytokine, by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the in vivo formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH3-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH3-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were in vitro stimulated with BAE or which received no specific in vitro stimulus. No differences in IL-10 (an immunoregulatory cytokine levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous ex vivo production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by

  16. Immunization with 60 kD Ro peptide produces different stages of preclinical autoimmunity in a Sjögren's syndrome model among multiple strains of inbred mice.

    Science.gov (United States)

    Kurien, B T; Dsouza, A; Igoe, A; Lee, Y J; Maier-Moore, J S; Gordon, T; Jackson, M; Scofield, R H

    2013-07-01

    Sjögren's syndrome is a chronic illness manifested characteristically by immune injury to the salivary and lacrimal glands, resulting in dry mouth/eyes. Anti-Ro [Sjögren's syndrome antigen A (SSA)] and anti-La [Sjögren's syndrome antigen B (SSB)] autoantibodies are found frequently in Sjögren's subjects as well as in individuals who will go on to develop the disease. Immunization of BALB/c mice with Ro60 peptides results in epitope spreading with anti-Ro and anti-La along with lymphocyte infiltration of salivary glands similar to human Sjögren's. In addition, these animals have poor salivary function/low saliva volume. In this study, we examined whether Ro-peptide immunization produces a Sjögren's-like illness in other strains of mice. BALB/c, DBA-2, PL/J, SJL/J and C57BL/6 mice were immunized with Ro60 peptide-274. Sera from these mice were studied by immunoblot and enzyme-linked immunosorbent assay for autoantibodies. Timed salivary flow was determined after pharmacological stimulation, and salivary glands were examined pathologically. We found that SJL/J mice had no immune response to the peptide from Ro60, while C57BL/6 mice produced antibodies that bound the peptide but had no epitope spreading. PL/J mice had epitope spreading to other structures of Ro60 as well as to La, but like C57BL/6 and SJL/J had no salivary gland lymphocytic infiltration and no decrement of salivary function. DBA-2 and BALB/c mice had infiltration but only BALB/c had decreased salivary function. The immunological processes leading to a Sjögren's-like illness after Ro-peptide immunization were interrupted in a stepwise fashion in these differing mice strains. These data suggest that this is a model of preclinical disease with genetic control for epitope spreading, lymphocytic infiltration and glandular dysfunction. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  17. Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition

    Science.gov (United States)

    Zukerman, Steven; Ackroff, Karen

    2014-01-01

    Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS−) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. PMID:25320345

  18. Booster vaccination with safe, modified, live-attenuated mutants of Brucella abortus strain RB51 vaccine confers protective immunity against virulent strains of B. abortus and Brucella canis in BALB/c mice.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Kim, Kiju; Park, Bo-Kyoung; Hahn, Tae-Wook

    2015-11-01

    Brucella abortus attenuated strain RB51 vaccine (RB51) is widely used in prevention of bovine brucellosis. Although vaccination with this strain has been shown to be effective in conferring protection against bovine brucellosis, RB51 has several drawbacks, including residual virulence for animals and humans. Therefore, a safe and efficacious vaccine is needed to overcome these disadvantages. In this study, we constructed several gene deletion mutants (ΔcydC, ΔcydD and ΔpurD single mutants, and ΔcydCΔcydD and ΔcydCΔpurD double mutants) of RB51 with the aim of increasing the safety of the possible use of these mutants as vaccine candidates. The RB51ΔcydC, RB51ΔcydD, RB51ΔpurD, RB51ΔcydCΔcydD and RB51ΔcydCΔpurD mutants exhibited significant attenuation of virulence when assayed in murine macrophages in vitro or in BALB/c mice. A single intraperitoneal immunization with RB51ΔcydC, RB51ΔcydD, RB51ΔcydCΔcydD or RB51ΔcydCΔpurD mutants was rapidly cleared from mice within 3 weeks, whereas the RB51ΔpurD mutant and RB51 were detectable in spleens until 4 and 7 weeks, respectively. Vaccination with a single dose of RB51 mutants induced lower protective immunity in mice than did parental RB51. However, a booster dose of these mutants provided significant levels of protection in mice against challenge with either the virulent homologous B. abortus strain 2308 or the heterologous Brucella canis strain 26. In addition, these mutants were found to induce a mixed but T-helper-1-biased humoral and cellular immune response in immunized mice. These data suggest that immunization with a booster dose of attenuated RB51 mutants provides an attractive strategy to protect against either bovine or canine brucellosis.

  19. A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain.

    Science.gov (United States)

    Thibodeaux, Brett A; Garbino, Nina C; Liss, Nathan M; Piper, Joseph; Blair, Carol D; Roehrig, John T

    2012-05-02

    Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains to be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually. Besides vaccination, there are no other prophylactic or therapeutic strategies approved for use in human YF. Current small animal models of YF require either intra-cranial inoculation of YF vaccine to establish infection, or use of wt strains (e.g., Asibi) in order to achieve pathology. We have developed and characterized a BSL2, adult mouse peripheral challenge model for YFV infection in mice lacking receptors for interferons α, β, and γ (strain AG129). Intraperitoneal challenge of AG129 mice with 17D-204 is a uniformly lethal in a dose-dependent manner, and 17D-204-infected AG129 mice exhibit high viral titers in both brain and liver suggesting this infection is both neurotropic and viscerotropic. Furthermore the use of a mouse model permitted the construction of a 59-biomarker multi-analyte profile (MAP) using samples of brain, liver, and serum taken at multiple time points over the course of infection. This MAP serves as a baseline for evaluating novel therapeutics and their effect on disease progression. Changes (4-fold or greater) in serum and tissue levels of pro- and anti-inflammatory mediators as well as other factors associated with tissue damage were noted in AG129 mice infected with 17D-204 as compared to mock-infected control animals. Published by Elsevier Ltd.

  20. [Sensitivity of BALB/c and WR strain mice to the immunodepressive action of cyclophosphamide and thiophosphamide].

    Science.gov (United States)

    Ir, K N; Telegin, L Iu; Pevnitskiĭ, L A; Malashenko, A M

    1984-05-01

    Experiments were made on BALB/cJ YSto and WR/Y mice to study the immunosuppressant action of cyclophosphamide (CP) and thiophosphamide (thiotepa) in vivo. WR mice were found to be significantly more sensitive to the immunosuppressant action of thiotepa than BALB/c mice and to have similar sensitivity to the action of CP. BALB/c mice appeared highly resistant to the action of both the drugs. Based on the data obtained and those reported in the literature a possible parallelism is suggested between the mutagenic and immunosuppressant action of CP and thiotepa.

  1. A BALB/c congenic strain of mice that carries a genetic locus (Ityr) controlling resistance to intracellular parasites.

    OpenAIRE

    Potter, M; O'Brien, A D; Skamene, E; Gros, P; Forget, A; Kongshavn, P A; Wax, J S

    1983-01-01

    BALB/c.DBA/2 Idh-1b-Ityr-Pep-3b congenic mice were developed by introgressively backcrossing the Idh-1b and Pep-3b markers of DBA/2 mice onto the BALB/c pi mice. This introduced a 30-centimorgan chromosome 1 segment of DBA/2 chromatin that contained the Ityr gene. BALB/c.DBA/2 Idh-1b-Ityr-Pep-3b mice were resistant to in vivo infections by Salmonella typhimurium, Mycobacterium bovis, and Leishmania donovani.

  2. Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species

    Directory of Open Access Journals (Sweden)

    Charles A. Specht

    2017-11-01

    Full Text Available Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus-derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii. The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1 were selected, recombinantly expressed in Escherichia coli, purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4 were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1 afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii. Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific.

  3. Vascular inflammatory cells in hypertension

    Directory of Open Access Journals (Sweden)

    David G. Harrison

    2012-05-01

    Full Text Available Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease.

  4. Phenotypic characterization of a novel virulence-factor deletion strain of Burkholderia mallei that provides partial protection against inhalational glanders in mice

    Directory of Open Access Journals (Sweden)

    Joel A. Bozue

    2016-02-01

    Full Text Available Burkholderia mallei (Bm is a highly infectious intracellular pathogen classified as a category B biological agent by the Centers for Disease Control and Prevention. After respiratory exposure, Bm establishes itself within host macrophages before spreading into major organ systems, which can lead to chronic infection, sepsis, and death. Previously, we combined computational prediction of host-pathogen interactions with yeast two-hybrid experiments and identified novel virulence factor genes in Bm, including BMAA0553, BMAA0728 (tssN, and BMAA1865. In the present study, we used recombinant allelic exchange to construct deletion mutants of BMAA0553 and tssN (ΔBMAA0553 and ΔTssN, respectively and showed that both deletions completely abrogated virulence at doses of >100 times the LD50 of the wild-type Bm strain. Analysis of ΔBMAA0553- and ΔTssN-infected mice showed starkly reduced bacterial dissemination relative to wild-type Bm, and subsequent in vitro experiments characterized pathogenic phenotypes with respect to intracellular growth, macrophage uptake and phagosomal escape, actin-based motility, and multinucleated giant cell formation. Based on observed in vitro and in vivo phenotypes, we explored the use of ΔTssN as a candidate live-attenuated vaccine. Mice immunized with aerosolized ΔTssN showed a 21-day survival rate of 67% after a high-dose aerosol challenge with the wild-type Bm ATCC 23344 strain, compared to a 0% survival rate for unvaccinated mice. However, analysis of histopathology and bacterial burden showed that while the surviving vaccinated mice were protected from acute infection, Bm was still able to establish a chronic infection. Vaccinated mice showed a modest IgG response, suggesting a limited potential of ΔTssN as a vaccine candidate, but also showed prolonged elevation of pro-inflammatory cytokines, underscoring the role of cellular and innate immunity in mitigating acute infection in inhalational glanders.

  5. Androgen-sensitive hypertension associated with soluble guanylate cyclase-α1 deficiency is mediated by 20-HETE.

    Science.gov (United States)

    Dordea, Ana C; Vandenwijngaert, Sara; Garcia, Victor; Tainsh, Robert E T; Nathan, Daniel I; Allen, Kaitlin; Raher, Michael J; Tainsh, Laurel T; Zhang, Fan; Lieb, Wolfgang S; Mikelman, Sarah; Kirby, Andrew; Stevens, Christine; Thoonen, Robrecht; Hindle, Allyson G; Sips, Patrick Y; Falck, John R; Daly, Mark J; Brouckaert, Peter; Bloch, Kenneth D; Bloch, Donald B; Malhotra, Rajeev; Schwartzman, Michal L; Buys, Emmanuel S

    2016-06-01

    Dysregulated nitric oxide (NO) signaling contributes to the pathogenesis of hypertension, a prevalent and often sex-specific risk factor for cardiovascular disease. We previously reported that mice deficient in the α1-subunit of the NO receptor soluble guanylate cyclase (sGCα1 (-/-) mice) display sex- and strain-specific hypertension: male but not female sGCα1 (-/-) mice are hypertensive on an 129S6 (S6) but not a C57BL6/J (B6) background. We aimed to uncover the genetic and molecular basis of the observed sex- and strain-specific blood pressure phenotype. Via linkage analysis, we identified a suggestive quantitative trait locus associated with elevated blood pressure in male sGCα1 (-/-)S6 mice. This locus encompasses Cyp4a12a, encoding the predominant murine synthase of the vasoconstrictor 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE). Renal expression of Cyp4a12a in mice was associated with genetic background, sex, and testosterone levels. In addition, 20-HETE levels were higher in renal preglomerular microvessels of male sGCα1 (-/-)S6 than of male sGCα1 (-/-)B6 mice. Furthermore, treating male sGCα1 (-/-)S6 mice with the 20-HETE antagonist 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) lowered blood pressure. Finally, 20-HEDE rescued the genetic background- and testosterone-dependent impairment of acetylcholine-induced relaxation in renal interlobar arteries associated with sGCα1 deficiency. Elevated Cyp4a12a expression and 20-HETE levels render mice susceptible to hypertension and vascular dysfunction in a setting of sGCα1 deficiency. Our data identify Cyp4a12a as a candidate sex-specific blood pressure-modifying gene in the context of deficient NO-sGC signaling. Copyright © 2016 the American Physiological Society.

  6. Different mechanisms for the resistance of C3H and STS strain mice to the development of thymic lymphomas following fractionated whole-body irradiation

    International Nuclear Information System (INIS)

    Aizawa, Shiro; Kamisaku, Hitoko

    1999-01-01

    B10 strain mice are extremely susceptible for induction of thymic lymphomas by fractionated whole-body irradiation (FI), whereas C3H and STS mice are fairly resistant. In the present study, we constructed radiation bone marrow chimeras in the reciprocal donor-host combinations of susceptible and resistant mice with use of Thy1 markers that allow to determine genetic origins of donor- and host-type thymocytes, and then to analyze the influence of host/thymic environment on the strain-dependent susceptibility to thymic lymphomagenesis. B10.Thy1.1→C3H, B10.Thy1.1→STS as well as B10.Thy1.1→B10 bone marrow chimeras manifested a high incidence of thymic lymphomas after FI-treatment, whereas C3H. Thy1.1→B10 and STS→B10 as well as C3H→C3H and STS→STS chimeras manifested a low incidence of thymic lymphoma. Furthermore, FI-treatment of [B10.Thy1.1+C3H]→B10 mixed chimeras resulted in the generation of similar numbers of thymic lymphomas of B10 and C3H origins, whereas FI-treatment of [B10.Thy1.1+STS]→B10 mixed chimeras preferentially induced thymic lymphomas of B10 origin. These results indicated that host environments of C3H and STS resistant mice are not inhibitory for the development of thymic lymphomas, genetic factors responsible for the strain-dependent susceptibility and/or resistance to FI-induced lymphomagenesis exert their effects entirely on bone-marrow derived cells, and the resistance of STS mice to FI-induced thymic lymphomagenesis is an intrinsic property of thymocytes as the targets of thymic lymphoma induction, whereas bone marrow-derived thymic stroma cells seem to play a significant role in the resistance of C3H mice for the induction of thymic lymphomas. (author)

  7. Association of immunity and tolerance of host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain

    International Nuclear Information System (INIS)

    Sprent, J.; von Boehmer, H.; Nabholz, M.

    1975-01-01

    Semiallogeneic radiation chimeras were prepared by injecting heavily irradiated F 1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 x 10 7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100 percent of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemagglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes

  8. Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

    Science.gov (United States)

    Kimitsuki, Kazunori; Yamada, Kentaro; Shiwa, Nozomi; Inoue, Satoshi; Nishizono, Akira; Park, Chun-Ho

    2017-06-10

    Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10 6 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

  9. Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.

    Science.gov (United States)

    Liu, Shiliang A; Stanfield, Brent A; Chouljenko, Vladimir N; Naidu, Shan; Langohr, Ingeborg; Del Piero, Fabio; Ferracone, Jacqueline; Roy, Alma A; Kousoulas, Konstantin G

    2017-06-15

    Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals ( P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations ( P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge ( P < 0.01 or P < 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4 + T cells and CD8 + T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus

  10. Use of a recombinant Salmonella enterica serovar Typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in mice

    International Nuclear Information System (INIS)

    Gentschev, Ivaylo; Fensterle, Joachim; Schmidt, Andreas; Potapenko, Tamara; Troppmair, Jakob; Goebel, Werner; Rapp, Ulf R

    2005-01-01

    Serine-threonine kinases of the Raf family (A-Raf, B-Raf, C-Raf) are central players in cellular signal transduction, and thus often causally involved in the development of cancer when mutated or over-expressed. Therefore these proteins are potential targets for immunotherapy and a possible basis for vaccine development against tumors. In this study we analyzed the functionality of a new live C-Raf vaccine based on an attenuated Salmonella enterica serovar Typhimurium aroA strain in two Raf dependent lung tumor mouse models. The antigen C-Raf has been fused to the C-terminal secretion signal of Escherichia coli α-hemolysin and expressed in secreted form by an attenuated aroA Salmonella enterica serovar Typhimurium strain via the α-hemolysin secretion pathway. The effect of the immunization with this recombinant C-Raf strain on wild-type C57BL/6 or lung tumor bearing transgenic BxB mice was analyzed using western blot and FACS analysis as well as specific tumor growth assays. C-Raf antigen was successfully expressed in secreted form by an attenuated Salmonella enterica serovar Typhimurium aroA strain using the E. coli hemolysin secretion system. Immunization of wild-type C57BL/6 or tumor bearing mice provoked specific C-Raf antibody and T-cell responses. Most importantly, the vaccine strain significantly reduced tumor growth in two transgenic mouse models of Raf oncogene-induced lung adenomas. The combination of the C-Raf antigen, hemolysin secretion system and Salmonella enterica serovar Typhimurium could form the basis for a new generation of live bacterial vaccines for the treatment of Raf dependent human malignancies

  11. Elemental analysis of biological tissues of Dmdmdx/J and C57BL/6J mice strains investigated by neutron activation analysis

    International Nuclear Information System (INIS)

    Sabrina Metairon; Zamboni, C.B.; Suzuki, M.F.; Bueno Junior, C.R.; Sant'Anna, O.A.

    2013-01-01

    In order to understand in more details the alterations that Duchenne muscular dystrophy disease may cause in biological tissues (blood, tibia, quadriceps and heart), correlations matrixes of the Dmd mdx /J dystrophic mice as well as C57BL/6J (control group) were generated. These mice were obtained from Jackson Laboratory (Maine, USA) and bred at IPEN (Dmd mdx /J), and at Centro de Estudos do Genoma Humano (C57BL/6J), both research centers at Sao Paulo city. Elements of clinical and nutritional relevance (Br, Ca, Cl, K, Mg, Na and S) were investigated by neutron activation analysis. These measurements were performed using the nuclear reactor IEA-R1 (3.5-4.5 MW, pool type) at IPEN. Comparisons between concentrations and correlations in these biological tissues, of these strains, showed that a Ca and Mg in blood are altered for the dystrophic mice. A significant change in the heart of dystrophic mice was also observed suggesting that a constant monitoring is required. Moreover, these results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

  12. Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    van Gennip, M; Moser, Claus; Christensen, Louise D

    2009-01-01

    : A significant reduction in the number of bacteria was observed when initiating treatment 1 h post-infection compared with initiating treatment after 24 h, although the latest isolate avoided complete clearance. Early antibiotic treatment directed at the mucoid phenotype in mice also reduced the inflammation and......Background: Effects of treatment with tobramycin initiated 1 or 24 h post-infection were investigated in a new version of a pulmonary infection model in mice. The model reflects the differentiated behaviour of Pseudomonas aeruginosa mucoid strains isolated from the lungs of one chronically infected......, histopathology, and measurement of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein 2 (MIP-2). Results: There was a significant reduction of bacteria when comparing treatment initiated 1 h post-infection with treatment initiated after 24 h for isolates 1997 and 2003. Treatment...

  13. Hypertensive Crisis

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Hypertensive Crisis: When You Should Call 9-1-1 for ... Nov 13,2017 A hypertensive ( high blood pressure ) crisis is when blood pressure rises quickly and severely ...

  14. Comparative study of inorganic elements determined in whole blood from Dmd(mdx)/J mice strain by EDXRF and NAA analytical techniques.

    Science.gov (United States)

    Redígolo, M M; Sato, I M; Metairon, S; Zamboni, C B

    2016-04-01

    Several diseases can be diagnosed observing the variation of specific elements concentration in body fluids. In this study the concentration of inorganic elements in blood samples of dystrophic (Dmd(mdx)/J) and C57BL/6J (control group) mice strain were determined. The results obtained from Energy Dispersive X-ray Fluorescence (EDXRF) were compared with Neutron Activation Analysis (NAA) technique. Both analytical techniques showed to be appropriate and complementary offering a new contribution for veterinary medicine as well as detailed knowledge of this pathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

    Science.gov (United States)

    Byrd, Wyatt; Boedeker, Edgar C

    2013-03-15

    Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham

  16. Regression of electrocardiographic left ventricular hypertrophy or strain is associated with lower incidence of cardiovascular morbidity and mortality in hypertensive patients independent of blood pressure reduction - A LIFE review.

    Science.gov (United States)

    Bang, Casper N; Devereux, Richard B; Okin, Peter M

    2014-01-01

    Cornell product criteria, Sokolow-Lyon voltage criteria and electrocardiographic (ECG) strain (secondary ST-T abnormalities) are markers for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, the relationship of regression of ECG LVH and strain during antihypertensive therapy to cardiovascular (CV) risk was unclear before the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. We reviewed findings on ECG LVH regression and strain over time in 9193 hypertensive patients with ECG LVH at baseline enrolled in the LIFE study. The composite endpoint of CV death, nonfatal MI, or stroke occurred in 1096 patients during 4.8±0.9years follow-up. In Cox multivariable models adjusting for randomized treatment, known risk factors including in-treatment blood pressure, and for severity ECG LVH by Cornell product and Sokolow-Lyon voltage, baseline ECG strain was associated with a 33% higher risk of the LIFE composite endpoint (HR. 1.33, 95% CI [1.11-1.59]). Development of new ECG strain between baseline and year-1 was associated with a 2-fold increased risk of the composite endpoint (HR. 2.05, 95% CI [1.51-2.78]), whereas the risk associated with regression or persistence of ECG strain was attenuated and no longer statistically significant (both p>0.05). After controlling for treatment with losartan or atenolol, for baseline Framingham risk score, Cornell product, and Sokolow-Lyon voltage, and for baseline and in-treatment systolic and diastolic blood pressure, 1 standard deviation (SD) lower in-treatment Cornell product was associated with a 14.5% decrease in the composite endpoint (HR. 0.86, 95% CI [0.82-0.90]). In a parallel analysis, 1 SD lower in-treatment Sokolow-Lyon voltage was associated with a 16.6% decrease in the composite endpoint (HR. 0.83, 95% CI [0.78-0.88]). The LIFE study shows that evaluation of both baseline and in-study ECG LVH defined by Cornell product criteria, Sokolow-Lyon voltage criteria or

  17. The distribution of erythropoiesis over the various anatomical regions of the erythropoietic system in some inbred strains of mice

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, J.; Hola, J.; Dungel, J.; Znojil, V.

    1982-10-01

    The extraction of /sup 59/Fe bound to the heme in the erythropoietic organs by means of acid ethylacetate was used to establish the proportion of erythropoiesis for which individual bones and the spleens of some inbred mouse strains are responsible. The proportion of splenic erythropoiesis differs from strain to strain, being in the range 9-42% of total erythropoiesis. In the strain BALB/c erythropoiesis is shifted in comparison with C57B1/10 strain towards the spine and away from the bones of the skull, the long bones of the limbs and the pelvis. Calculations of the erythroid cellularity and/or the intensity of erythropoiesis of the total bone marrow on the basis of a single bone should take into account both these interstrain differences in the participation of different regions and the possibility of various proportions of red and white blood cells and cells containing non-heme iron existing in different regions (bones).

  18. The therapeutic protection of a living and dead Lactobacillus strain against aluminum-induced brain and liver injuries in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Fengwei Tian

    Full Text Available Our previous study found that Lactobacillus plantarum CCFM639 had the ability to alleviate acute aluminum (Al toxicity when the strain was introduced simultaneously with Al exposure. This research was designed to elucidate the therapeutic effects of living and dead L. plantarum CCFM639 against chronic Al toxicity and to gain insight into the protection modes of this strain. Animals were assigned into control, Al only, Al + living CCFM639, and Al + dead CCFM639 groups. The Al exposure model was established by drinking water for the first 4 weeks. The strain was given after Al exposure by oral gavage at 109 colony-forming units once per day for 12 weeks. The results show that the Al binding ability of dead CCFM639 was similar to that of living CCFM639 in vitro. The ingestion of living or dead CCFM639 has similar effects on levels of Al and trace element in tissues, but living strains led to more significant amelioration of oxidative stress and improvement of memory deficits in Al-exposed mice. In conclusion, in addition to intestinal Al sequestration, CCFM639 treatment offers direct protection against chronic Al toxicity by alleviation of oxidative stress. Therefore, L. plantarum CCFM639 has a potential as dietary supplement ingredient that provides protection against Al-induced injury.

  19. Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

    Science.gov (United States)

    Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

    2017-01-01

    Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

  20. Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

    International Nuclear Information System (INIS)

    Reif, A.E.

    1985-01-01

    Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells

  1. The Visible Burrow System: A behavioral paradigm to assess sociability and social withdrawal in BTBR and C57BL/6J mice strains.

    Science.gov (United States)

    Bove, Maria; Ike, Kevin; Eldering, Adriaan; Buwalda, Bauke; de Boer, Sietse F; Morgese, Maria Grazia; Schiavone, Stefania; Cuomo, Vincenzo; Trabace, Luigia; Kas, Martien J H

    2018-05-15

    Disrupted sociability and consequent social withdrawal are (early) symptoms of a wide variety of neuropsychiatric diseases, such as schizophrenia, autism spectrum disorders, depressive disorders and Alzheimer's disease. The paucity of objective measures to translationally assess social withdrawal characteristics has been an important limitation to study this behavioral phenotype, both in human and rodents. The aim of the present study was to investigate sociability and social withdrawal in rodents using an ethologically valid behavioral paradigm, the Visible Burrow System (VBS). The VBS mimics a natural environment, with male and female rodents housed together in an enclosure where a large open arena is connected to a continuously dark burrow system that includes 4 nest boxes. In this study, mixed-sex colonies of C57BL/6J and of BTBR mice have been investigated (n = 8 mice per colony). Results showed marked differences between the two strains, in terms of sociability as well as social withdrawal behaviors. In particular, BTBR mice performed less social behaviors and have a preference for non-social behaviors compared to C57BL/6J mice. Neurobiologically, the decreased sociability of BTBR was accompanied by reduced GABA and increased glutamate concentrations in brain prefrontal cortex (PFC) and amygdala regions. In conclusion, our study validated the use of the VBS as an ethologically relevant behavioral paradigm in group-housed mice to investigate individual sociability and social withdrawal features and their underlying neurobiology. This paradigm may provide new insights to develop new therapeutic treatments for behavioral dysfunctions that may be relevant across neuropsychiatric diseases. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  2. A Lactobacillus plantarum strain isolated from kefir protects against intestinal infection with Yersinia enterocolitica O9 and modulates immunity in mice.

    Science.gov (United States)

    De Montijo-Prieto, Soumi; Moreno, Encarnación; Bergillos-Meca, Triana; Lasserrot, Agustín; Ruiz-López, María-Dolores; Ruiz-Bravo, Alfonso; Jiménez-Valera, María

    2015-10-01

    Lactobacillus plantarum C4, previously isolated from kefir and characterized as a potential probiotic strain, was tested for its protective and immunomodulatory capacity in a murine model of yersiniosis. The inoculation of BALB/c mice with a low pathogenicity serotype O9 strain of Yersinia enterocolitica results in a prolonged intestinal infection with colonization of Peyer's patches. Pretreatment with C4 was without effect on fecal excretion of yersiniae, but shortened the colonization of Peyer's patches. This protective effect was associated with pro-inflammatory status in the intestinal mucosa (TNF-α production in infected mice was increased by C4) and an increase in total IgA secretion. At a systemic level, C4 did not promote a pro-inflammatory response, although production of the immunoregulatory cytokine IFN-γ was enhanced. These findings suggest that L. plantarum C4 can increase resistance to intestinal infections through its immunomodulatory activity. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  3. On the tissular parasitism of Trypanosoma cruzi y strain in swiss mice Sobre o parasitismo tecidual da cepa Y do Trypanosoma cruzi em camundongos albinos (Swiss-Webster

    Directory of Open Access Journals (Sweden)

    Maria Auxiliadora de Sousa

    1984-12-01

    Full Text Available A review of the tissular parasitism of Trypanosoma cruzi Y strain in Swiss mice was carried out. This strain parasitized preferentially smooth, skeletal and cardiac muscle fibers, with low transitory spleen and liver parasitism, as previously found by some Authors, although differing from other reports. These results can be related to the host genetical constitution and/or the degree of the strain virulence at the time of this study. Furthermore, we discuss that the high macrophagotropism reported for this strain in some instances could be an artificially induced condition resulting from its serial maintenance in mice, either for a longer time and/or by using young animals. The heavy parasitism and inflammation observed in the bladder, pancreas and spermatic duct of some inoculated mice, as well as the testis parasitization, were also noteworthy findings.Através deste trabalho fizemos uma revisão do parasitismo tecidual da cepa Y do Trypanosoma cruzi em camundongos albinos (Swiss-Webster. Esta cepa parasitou preferencialmente as fibras musculares lisas, esqueléticas e cardíacas, sendo baixo e transitório seu parasitismo do baço e fígado, conforme já observado por alguns Autores, embora diferindo de outros achados. Estes resultados podem estar relacionados com o padrão genético do hospedeiro e/ou com o grau de virulência da cepa por ocasião deste estudo. Além do mais, discutimos a possibilidade de que o intenso macrofagotropismo descrito para esta cepa em algumas ocasiões possa ser uma condição artificialmente induzida através de sua manutenção seriada em camundongos por tempo prolongado e/ou pelo uso de animais jovens. Também são dignos de nota, o intenso parasitismo e inflamação da bexiga, pâncreas e canal espermático de alguns animais inoculados, assim como, o encontro de ninhos de amastigotas no testículo.

  4. Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.

    Science.gov (United States)

    Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia

    2013-12-26

    The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFNγ-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Resistant Hypertension.

    Science.gov (United States)

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  6. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development

    Directory of Open Access Journals (Sweden)

    Kyle J. Beauchemin

    2016-08-01

    Full Text Available To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ. Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS. Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO archive (GSE74243. Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org.

  7. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.

    Science.gov (United States)

    Beauchemin, Kyle J; Wells, Julie M; Kho, Alvin T; Philip, Vivek M; Kamir, Daniela; Kohane, Isaac S; Graber, Joel H; Bult, Carol J

    2016-01-01

    To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS). Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular) defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO) archive (GSE74243). Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org).

  8. Glucocorticoid cell reception in mice of different strains with natural killer cell activity depressed during immobilization stress

    International Nuclear Information System (INIS)

    Lyashko, V.N.; Sukhikh, G.T.

    1987-01-01

    The authors study differences in stress-induced depression of natural killer cell activity in mice of different inbred lines, depending on parameters of glucocorticoid binding with glucorticoid receptors of spleen cells and on the hormonal status of the animals. In determining the parameters of glucocorticoid binding on intact splenocytes, aliquots of a suspension of washed splenocytes were incubated with tritium-labeled dexamethasone

  9. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Galisteo Junior, Andres [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; E-mail: galisteo@usp.br; Zorgi, Nahiara Esteves; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; Alves, Janaina Baptista; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Hiramoto, Roberto Mitsuyoshi [instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2007-07-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/{sup 60}Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10{sup 7} RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral

  10. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    International Nuclear Information System (INIS)

    Jimenez Galisteo Junior, Andres

    2007-01-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/ 60 Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10 7 RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral vaccines could

  11. Spray-drying process preserves the protective capacity of a breast milk-derived Bifidobacterium lactis strain on acute and chronic colitis in mice

    Science.gov (United States)

    Burns, Patricia; Alard, Jeanne; Hrdỳ, Jiri; Boutillier, Denise; Páez, Roxana; Reinheimer, Jorge; Pot, Bruno; Vinderola, Gabriel; Grangette, Corinne

    2017-01-01

    Gut microbiota dysbiosis plays a central role in the development and perpetuation of chronic inflammation in inflammatory bowel disease (IBD) and therefore is key target for interventions with high quality and functional probiotics. The local production of stable probiotic formulations at limited cost is considered an advantage as it reduces transportation cost and time, thereby increasing the effective period at the consumer side. In the present study, we compared the anti-inflammatory capacities of the Bifidobacterium animalis subsp. lactis (B. lactis) INL1, a probiotic strain isolated in Argentina from human breast milk, with the commercial strain B. animalis subsp. lactis BB12. The impact of spray-drying, a low-cost alternative of bacterial dehydration, on the functionality of both bifidobacteria was also investigated. We showed for both bacteria that the spray-drying process did not impact on bacterial survival nor on their protective capacities against acute and chronic colitis in mice, opening future perspectives for the use of strain INL1 in populations with IBD. PMID:28233848

  12. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    Takahashi R.N.

    2001-01-01

    Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

  13. Mineralocorticoid hypertension

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Hypertension affects about 10 - 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta, aldosterone-producing pathologies (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and 3, non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH syndrome, congenitalvadrenal hyperplasia, and drugs with mineraocorticoid activity (locorice, carbenoxole therapy to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics. Direct aldosterone synthetase antagonists represent a promising future therapy.

  14. Acrolein inhalation causes myocardial strain delay and decreased cardiac performance as detected by high-frequency echocardiography in mice

    Science.gov (United States)

    Acrolein, an unsaturated aldehyde found in air pollution, impairs Ca2+ flux and contraction in cardiomyocytes in vitro. To better define direct and delayed functional cardiac effects, we hypothesized that a single exposure to acrolein would modify myocardial strain and performanc...

  15. Adaptation, allometry, and hypertension.

    Science.gov (United States)

    Weder, A B; Schork, N J

    1994-08-01

    Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure.

  16. Protective effect of Lactobacillus casei strain Shirota against lethal infection with multi-drug resistant Salmonella enterica serovar Typhimurium DT104 in mice.

    Science.gov (United States)

    Asahara, T; Shimizu, K; Takada, T; Kado, S; Yuki, N; Morotomi, M; Tanaka, R; Nomoto, K

    2011-01-01

    The anti-infectious activity of lactobacilli against multi-drug resistant Salmonella enterica serovar Typhimurium DT104 (DT104) was examined in a murine model of an opportunistic antibiotic-induced infection. Explosive intestinal growth and subsequent lethal extra-intestinal translocation after oral infection with DT104 during fosfomycin (FOM) administration was significantly inhibited by continuous oral administration of Lactobacillus casei strain Shirota (LcS), which is naturally resistant to FOM, at a dose of 10(8) colony-forming units per mouse daily to mice. Comparison of the anti-Salmonella activity of several Lactobacillus type strains with natural resistance to FOM revealed that Lactobacillus brevis ATCC 14869(T) , Lactobacillus plantarum ATCC 14917(T) , Lactobacillus reuteri JCM 1112(T) , Lactobacillus rhamnosus ATCC 7469(T) and Lactobacillus salivarius ATCC 11741(T) conferred no activity even when they obtained the high population levels almost similar to those of the effective strains such as LcS, Lact. casei ATCC 334(T) and Lactobacillus zeae ATCC 15820(T) . The increase in concentration of organic acids and maintenance of the lower pH in the intestine because of Lactobacillus colonization were correlated with the anti-infectious activity. Moreover, heat-killed LcS was not protective against the infection, suggesting that the metabolic activity of lactobacilli is important for the anti-infectious activity. These results suggest that certain lactobacilli in combination with antibiotics may be useful for prophylaxis against opportunistic intestinal infections by multi-drug resistant pathogens, such as DT104. Antibiotics such as FOM disrupt the metabolic activity of the intestinal microbiota that produce organic acids, and that only probiotic strains that are metabolically active in vivo should be selected to prevent intestinal infection when used clinically in combination with certain antibiotics. © 2010 The Authors. Journal of Applied Microbiology

  17. Oral supplementation of Bifidobacterium longum strain BR-108 alters cecal microbiota by stimulating gut immune system in mice irrespectively of viability.

    Science.gov (United States)

    Makioka, Yuko; Tsukahara, Takamitsu; Ijichi, Tetsuo; Inoue, Ryo

    2018-03-20

    Effect on cecal microbiota and gene expression of various cytokines in ileal Peyer's patches and cecal tissues were compared between viable and heat-killed Bifidobacterium longum strain BR-108 (BR-108) using a mouse model. Irrespectively of viability, oral supplementation of BR-108 altered the cecal microbiota and stimulated gene expression of cytokines such as IL-6 and IL-10 in ileal Peyer's patches and cecal tissue of mice. In addition, BR-108 supplementation significantly affected the relative abundance of bacterial genera and family, Oscillospira, Bacteroides and S24-7. The abundance of these bacterial genera and family strongly correlated with gene expression induced by BR-108. This study demonstrated that the effect of heat-killed BR-108 on the mouse cecal microbiota is similar to that of viable BR-108, most likely due to stimulation of the gut immune system by both heat-killed and viable BR-108 is also similar.

  18. Hypertension hos gravide

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Johansen, Marianne; Kamper, Anne Lise

    2009-01-01

    There are four major hypertensive disorders in pregnancy: chronic hypertension, gestational hypertension, preeclampsia and chronic hypertension with superimposed preeclampsia. The indications and efficacy of antihypertensive treatment of the different hypertensive disorders are assessed. Advantages...

  19. Comparison of the effects of diet sterilization by irradiation and autoclaving on the equilibrium between eleven microbe strains seeded in the alimentary tracts of axenic mice

    International Nuclear Information System (INIS)

    Ducluzeau, R.; Clara, A.

    1978-01-01

    Eleven obligate or facultative anaerobe strains were seeded successively in the alimentary tracts of 'gnotoxenic' mice. The animals were divided into four groups which received a commercially available diet sterilized by autoclaving or by irradiation (4Mrad) or treated with the two methods in succession and supplemented or not supplemented in vitamins. A series of quantitative differential analyses carried out over a period of seven months on the faeces of the animals did not reveal any significant differences in the equilibrium that became established among the eleven strains in the faecal flora of the four groups of animals. At the end of the experiment quantitative differential analyses were performed of the stomachal and caecal flora of two animals from each group; again no differences were found in the equilibrium of the flora in the animals from the different groups. Any radiolytic products that may have been in the radiation-sterilized diet therefore had no detectable effect on the equilibrium of the microflora that the authors had chosen to establish in the alimentary tract of the 'gnotoxenic' animals. (author)

  20. Coalescence of DNA Double Strand Breaks Induced by Galactic Cosmic Radiation is Modulated by Genetics in 15 Inbred Strains of Mice

    Science.gov (United States)

    Penninckx, Sebastien; Ray, Shayoni; Staatz, Kevin; Degorre, Charlotte; Guiet, Elodie; Viger, Louise; Snijders, Antoine M.; Mao, Jian-Hua; Karpen, Gary; Costes, Sylvain V.

    2018-01-01

    In this manuscript we address the challenges associated with the ability to predict radiation sensitivity associated with exposure to either cosmic radiation or X-rays in a population study, by monitoring DNA damage sensing protein 53BP1 forming small nuclear radiation-induced foci (RIF) as a surrogate biomarker of DNA double strand breaks (DSB). 76 primary skin fibroblasts were isolated from 10 collaborative cross strains and five reference inbred mice (C57Bl/6, BALB/CByJ, B6C3, C3H and CBA/CaJ) and exposed to three different charged nuclei of increasing LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and X-ray. Our data brings strong evidence against the classic "contact-first" model where DSBs are assumed to be immobile and repaired at the lesion site. In contrast, our model suggests nearby DSBs move into single repair unit characterized by large RIF before the repair machinery kicks in. Such model has the advantage of being much more efficient molecularly but is poorly suited to deal with cosmic radiation, where energy is concentrated along the particle trajectory, inducing a large density of DSBs along each particle track. In accordance with this model, RIF quantification after X-ray exposition showed a saturated dose response for early time points post-irradiation for all strains. Similarly, the high-LET response showed that RIF number matched the number of track per cell, not the number of expected DSB per cell (1). At the temporal level, we noted that the percentage of unrepaired high-LET tracks over a 48 hour time-course increased with LET, confirming that the DNA repair process becomes more difficult as more DSB coalesce into single RIF. There was also good agreement between persistent RIF levels measured in-vitro in the primary skin cultures and survival levels of T-cells and B-cells collected in blood samples from 10 CC strains 24 hours after 0.1 Gy whole-body dose of X-ray. This suggests that persistent RIF 24 hour post-IR is a good surrogate in

  1. Sex differences in primary hypertension

    Science.gov (United States)

    2012-01-01

    Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477

  2. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  3. Endokrin hypertension

    DEFF Research Database (Denmark)

    Poulsen, Per Løgstrup; Ibsen, Hans

    2009-01-01

    Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma-aldosterone-to-renin ......Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma...

  4. Resistant hypertension.

    Science.gov (United States)

    Wei, Fang-Fei; Zhang, Zhen-Yu; Huang, Qi-Fang; Yang, Wen-Yi; Staessen, Jan A

    2018-06-15

    The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment-resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure lowering medications. As we demonstrate in this review, this idea so attractive to manufacturers and invasive cardiologists and radiologists overlooked decades of careful pathophysiological research in a disease, which still remains enigmatic but remains the major cause of cardiovascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of the ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices and in the future research. Throughout our review, we focused on new evidence became available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.

  5. Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

    Science.gov (United States)

    Rexhaj, Emrush; Pireva, Agim; Paoloni-Giacobino, Ariane; Allemann, Yves; Cerny, David; Dessen, Pierre; Sartori, Claudio; Scherrer, Urs; Rimoldi, Stefano F

    2015-10-01

    Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans. Copyright © 2015 the American Physiological Society.

  6. Radiation-induced leukemogenesis in RFM/UN strain mice: a potential model for retrovirus sequence transposition

    International Nuclear Information System (INIS)

    Tennant, R.W.; Hand, R.E. Jr.; Otten, J.A.; Liou, R.; Kiggans, J.O. Jr.; Yang, W.K.; Wang, T.W.

    1982-01-01

    Analysis of various tissues from normal and tumor-bearing mice, including bone marrow, spleen, thymus, and embryonic cells, showed low-level expression of viral p 30 protein or an infectious type C virus. However, It was possible to cultivate and establish cell lines from embryonic tissues and adult thymuses that were virus-negative but which could be chemically induced to express retrovirus. In all cases, only ecotropic virus with N-tropic host range was detected, and the production of a similar virus was detected in transplantable myeloid leukemia cells. Virus isolates of RFM/Un endogenous origin showed good infectivity in most Fv-1/sup n/ cells such as NIH Swiss mouse embryo cells but were severely restricted in Fv-1/sub f/ cells, confirming the N-tropic host range; in addition, the replication of this RFM/Un endogenous N-tropic virus (RFV) was preferentially restricted in RFM/Un cells which are of the Fv-1/sup n/ genotype. The restriction of RFM/Un cells for RFV was analyzed at the stage of viral DNA formation by means of a modified Hirt extraction procedure and the electrophoresis/diazobenzyloxymethyl-paper transfer/molecular hybridization method; it was found that synthesis of both linear and covalently closed circular forms of viral DNA, either by RFV or by WN1802B B-tropic virus, was markedly inhibited in RFM/Un cells relative to that of Gross virus. Analysis by restriction endonuclease EcoR1 digestion demonstration that nuclear DNA of RFM/Un cells contained multiple copies of endogenous type C retroviral genes, including distinct retroviral sequence not found in NIH Swiss cells which never express endogenous ecotropic viruses. These results suggest that the RFM/Un mouse may possess only one inducible ecotropic host-range class of inducible virus and a unique gene, possibly an allele of the Fv-1 locus, which specifically restricts endogenous virus

  7. Heat stress proteins in hypertension

    International Nuclear Information System (INIS)

    Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

    1986-01-01

    It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46 0 C during 5 min in a hot water bath. The cells were then labeled with ( 75 Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension

  8. Preserved regulation of renal perfusion pressure by small and intermediate conductance K-Ca channels in hypertensive mice with or without renal failure

    DEFF Research Database (Denmark)

    Waeckel, L.; Bertin, F.; Clavreul, N.

    2015-01-01

    -transgenic female mice expressing human angiotensinogen and renin (AR) genes received either control or a high-salt diet associated to a nitric oxide (NO) synthase inhibitor treatment (BLSL and ARSL). Changes in renal perfusion pressure (RPP) were measured in isolated perfused kidneys. BLSL and AR were moderately...

  9. Renovascular hypertension

    International Nuclear Information System (INIS)

    Thomsen, H.S.; Sos, T.A.; Nielsen, S.L.; Koebenhavns Amts Sygehus, Herlev; Cornell Univ., New York

    1989-01-01

    Hypertension constitutes a major health problem and the challenge is to identify patients having 'surgically' curable renal vascular disease among the majority with so-called essential hypertension. The best of unsatisfactory diagnostic tests are renography and plasma renin activity both before and during angiotensin II blockade. The necessity of better screening tests has increased because of the recent advances in surgical techniques and especially percutaneous transluminal renal angioplasty. The latter has definitely become the method of choice for correction of suspected hemodynamically significant artery stenoses whenever technically feasible. With improved angioplasty techniques the risk of treating renal artery stenosis without hemodynamic and clinical importance (so-called cosmetic repair) has increased. Unfortunately randomized trials including surgery versus angioplasty are not available. It should be kept in mind that only after correction of the stenosis is achieved and the blood pressure has become normal, can the diagnosis of renovascular hypertension be made with certainty. (orig.)

  10. Effects of topiramate and other anti-glutamatergic drugs on the acute intoxicating actions of ethanol in mice: modulation by genetic strain and stress

    Science.gov (United States)

    Chen, Yi-Chyan; Holmes, Andrew

    2008-01-01

    Compounds with anti-glutamatergic properties currently in clinical use for various indications (e.g., Alzheimer's disease, epilepsy, psychosis, mood disorders) have potential utility as novel treatments for alcoholism. Enhanced sensitivity to certain acute intoxicating effects (ataxia, sedative) of alcohol may be one mechanism by which anti-glutamatergic drugs modulate alcohol use. We examined the effects of six compounds (memantine, dextromethorphan, haloperidol, lamotrigine, oxcarbazepine, topiramate) on sensitivity to acute intoxicating effects of ethanol (ataxia, hypothermia, sedation/hypnosis) in C57BL/6J mice. Analysis of topiramate was extended to determine the influence of genetic background (via comparison of the 129S1, BALB/cJ, C57BL/6J, DBA/2J inbred strains) and prior stress history (via chronic exposure of C57BL/6J to swim stress) on topiramate's effects on ethanol-induced sedation/hypnosis. Results showed that one N-methyl-D-aspartate receptor (NMDAR) antagonist, memantine, but not another, dextromethorphan, potentiated the ataxic but not hypothermic or sedative/hypnotic effects of ethanol. Haloperidol increased ethanol-induced ataxia and sedation/hypnosis to a similar extent as the prototypical NMDAR antagonist MK-801. Of the anticonvulsants tested, lamotrigine accentuated ethanol-induced sedation/hypnosis, while oxcarbazepine was without effect. Topiramate was without effect per se under baseline conditions in C57BL/6J, but had a synergistic effect with MK-801 on ethanol-induced sedation/hypnosis. Comparing inbred strains, topiramate was found to significantly potentiated ethanol's sedative/hypnotic effects in BALB/cJ, but not 129S1, C57BL/6J or DBA/2J strains. Topiramate also increased ethanol-induced sedation/hypnosis in C57BL/6J after exposure to chronic stress exposure. Current data demonstrate that, with the exception of MK-801 and haloperidol, the compounds tested had either no significant or assay-selective effects on sensitivity to acute

  11. Exercise Hypertension.

    Science.gov (United States)

    Schultz, Martin G; Sharman, James E

    2014-05-01

    Irrespective of apparent 'normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a 'hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory 'masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.

  12. c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice: a possible target to reduce ganglion cell apoptosis

    Directory of Open Access Journals (Sweden)

    Yue He

    2015-01-01

    Full Text Available Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

  13. Essential hypertension vs. secondary hypertension among children.

    Science.gov (United States)

    Gupta-Malhotra, Monesha; Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E; Barratt, Michelle S; Hecht, Jacqueline T; Milewicz, Diane M; Boerwinkle, Eric

    2015-01-01

    The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the "Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents") from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3-17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08-19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P secondary hypertension. The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Murine respiratory mycoplasmosis (MRM) in C57BL/6N and C3H/HeN mice: strain differences in early host responses and exacerbation by nitrogen dioxide

    International Nuclear Information System (INIS)

    Parker, R.F.

    1987-01-01

    The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO 2 ) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO 2 for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 days after exposure in both mouse strains. NO 2 appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO 2 exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the endpoint measured. Pulmonary clearance of radiolabeled M. pulmonis was determined in both mouse strains, and in C57BL/6N mice exposed to NO 2

  15. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercaria- I. analysis of antibody and T-lymphocyte responses in mouse strains developing differing levels of immunity

    International Nuclear Information System (INIS)

    James, S.L.; Labine, M.; Sher, A.

    1981-01-01

    The kinetics of cellular and humoral responses directed against schistosomula were examined in mice of three inbred strains which demonstrate differences in the degree of resistance induced by immunization with irradiated cercariae. T-Cell reactivity was observed during the first 4 weeks after vaccination but declined to control levels thereafter. Anti-schistosomulum antibody was first detected 2 weeks after vaccination, peaked by 6 weeks, and persisted as late as 15 weeks. In sera obtained at 6 weeks, antibody activity was detected in affinity chromatography-purified fractions containing IgM, IgA, IgG 1 , IgG 2 /sub a/, and IgG 3 immunoglobulins. In general, the cellular and humoral responses observed in C57Bl/6J mice, which consistently developed a high level of immunity after vaccination, were not significantly different from those observed in C3H/HeJ or CBA/J mice, which achieved only low to moderate levels of immunity. Thus, although antibody production appears to correlate more closely than T lymphocyte responsiveness with the typical long-term resistance pattern observed in this model, the absence of striking differences in parasite-specific antibody levels between mice of these different strains suggests that additional mechanisms may be involved in the development of immunity after vaccination

  16. Effects of Lactobacillus plantarum Strain OLL2712 Culture Conditions on the Anti-inflammatory Activities for Murine Immune Cells and Obese and Type 2 Diabetic Mice.

    Science.gov (United States)

    Toshimitsu, T; Ozaki, S; Mochizuki, J; Furuichi, K; Asami, Y

    2017-04-01

    Studies on the health-promoting effects of lactic acid bacteria (LAB) are numerous, but few provide examples of the relationship between LAB function and culture conditions. We verified the effect of differences in culture conditions on Lactobacillus plantarum OLL2712 functionality; this strain exhibits anti-inflammatory activity and preventive effects against metabolic disorders. We measured interleukin-10 (IL-10) and IL-12 production in murine immune cells treated with OLL2712 cells prepared under various culture conditions. The results showed that the IL-10-inducing activities of OLL2712 cells on murine immune cells differed dramatically between OLL2712 groups at different culture phases and using different culture medium components, temperatures, and neutralizing pHs. In particular, exponential-phase cells had much more IL-10-inducing activity than stationary-phase cells. We confirmed that the Toll-like receptor 2 (TLR2) stimulation activity of OLL2712 cells depended on culture conditions in conjunction with IL-10-inducing activity. We also demonstrated functional differences by culture phases in vivo ; OLL2712 cells at exponential phase had more anti-inflammatory activity and anti-metabolic-disorder effects on obese and diabetic mice than those by their stationary-phase counterparts. These results suggest that culture conditions affect the functionality of anti-inflammatory LAB. IMPORTANCE While previous studies demonstrated that culture conditions affected the immunomodulatory properties of lactic acid bacteria (LAB), few have comprehensively investigated the relationship between culture conditions and LAB functionality. In this study, we demonstrated several culture conditions of Lactobacillus plantarum OLL2712 for higher anti-inflammatory activity. We also showed that culture conditions concretely influenced the health-promoting functions of OLL2712 in vivo , particularly against metabolic disorders. Further, we characterized a novel mechanism by which

  17. Hypertension Subtypes among Hypertensive Patients in Ibadan

    OpenAIRE

    Abiodun M. Adeoye; Adewole Adebiyi; Bamidele O. Tayo; Babatunde L. Salako; Adesola Ogunniyi; Richard S. Cooper

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% fema...

  18. Controlling Hypertension

    Centers for Disease Control (CDC) Podcasts

    Hypertension, or high blood pressure, affects one third of U.S. adults and is a leading cause of heart disease and stroke. A recent study found an increase in self-reported high blood pressure among U.S. adults, and an increase in the use of medications to control high blood pressure. In this podcast, Dr. Fleetwood Loustalot discusses the importance of controlling high blood pressure.

  19. Hypertension Subtypes among Hypertensive Patients in Ibadan

    Directory of Open Access Journals (Sweden)

    Abiodun M. Adeoye

    2014-01-01

    Full Text Available Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH, isolated systolic hypertension (ISH, isolated diastolic hypertension (IDH, and systolic-diastolic hypertension (SDH. Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5% and IDH (4.9% versus 4.7% were more prevalent among females, ISH (10.1% versus 6.2% was higher among males (P=0.048. Female subjects were more obese (P<0.0001 and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.

  20. Pulmonary Hypertension

    Science.gov (United States)

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

  1. Hormones and Hypertension

    Science.gov (United States)

    ... role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such as kidney ... the body can greatly improve or even cure secondary hypertension. Resources • Find-an-Endocrinologist: www.hormone.org or ...

  2. Pulmonary Hypertension in Scleroderma

    Science.gov (United States)

    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels of the lungs. If the high ... the right side of the heart. Patients with scleroderma are at increased risk for developing PH from ...

  3. Hypertension and Spina Bifida

    Science.gov (United States)

    SBA National Resource Center: 800-621-3141 Hypertension A disease that often goes undetected. What is hypertension? Hypertension, also called high blood pressure , is a condition in which the arteries of ...

  4. Intracranial Hypertension Research Foundation

    Science.gov (United States)

    ... PARTNERSHIPS Meet our Fundraising Partners Tweet Welcome Intracranial hypertension (IH) is the general term for the neurological ... high. (Old names for IH include Benign Intracranial Hypertension and Pseudotumor Cerebri). The Intracranial Hypertension Research Foundation ...

  5. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... What do I need to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and ... Should an HIV patient be tested for pulmonary hypertension? HIV patients know that medical supervision is critical ...

  6. Qualitative and quantitative radiation protection analysis of mucosa of ICR strained mice using selected herbal extracts such as GC-2112 from garlic (Allium sativum) and GX-2137 from ginseng (Panax sp.)

    International Nuclear Information System (INIS)

    Bunagan, J.B.

    2005-01-01

    Full text: Earlier reports showed that ginseng has significant radioprotective and stimulatory effect on the recovery of the lymphocytes and leukocytes. Using graded absorbed doses of radiation (1.5, 5, 20, 50 Gy) applied in ICR strain male white mice which was injected with GX-2137 from ginseng (Panax sp.) and GC-2112 from garlic (Allium sativum) was tested to prove some radioprotective efficiency. The herbal extracts were injected intraperitoneally and the experimental mice were sacrificed 2 and 48 hrs post-irradiation. Factors such as analyzing kinetics of critical tissue parameters (length of villi, the number of crypt and villi cells and cell density) and determining the Relative Protection Efficiencies (RPE) using quantitative histopathological techniques were used to quantify the radiation protection assay in the duodenum of ICR strain mice. Results showed that GC-2112 and GX-2137 protected the villi structures. After 2 hrs. post irradiation, tissue degeneration was evident. RPE values of significant radioprotection of the crypts is demonstrated at absorbed dose. It was found that some villi cells are even viable at non-physiologic dose of 50 Gy. (author)

  7. A replicating modified vaccinia tiantan strain expressing an avian-derived influenza H5N1 hemagglutinin induce broadly neutralizing antibodies and cross-clade protective immunity in mice.

    Directory of Open Access Journals (Sweden)

    Haixia Xiao

    Full Text Available To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT as a vaccine vector, we constructed MVTTHA-QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies (Nabs against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4. Neutralization tests (NT and Haemagglutination inhibition (HI antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.

  8. Neonatal hypertension.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2017-03-01

    Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

  9. A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice

    Science.gov (United States)

    Aiba, Yuji; Nakano, Yasuhiro; Koga, Yasuhiro; Takahashi, Kenji; Komatsu, Yasuhiko

    2015-01-01

    A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori,Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii,JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI. PMID:25771812

  10. A novel strain of Lactobacillus mucosae isolated from a Gaotian villager improves in vitro and in vivo antioxidant as well as biological properties in D-galactose-induced aging mice.

    Science.gov (United States)

    Yu, Xiaomin; Li, Shengjie; Yang, Dong; Qiu, Liang; Wu, Yaoping; Wang, Dengyuan; Shah, Nagendra P; Xu, Feng; Wei, Hua

    2016-02-01

    Twelve isolates isolated from the gastrointestinal tracts of Gaotian villagers in China, who had a lifespan of 92 yr, were examined for their antioxidants using free radical scavenging activity and 2,2-diphenyl-1-picrylhydrazyl. Three strains (i.e., Lactobacillus mucosae LMU1001, and Lactobacillus plantarum LPL0902 and LPL0302) were selected as candidates to prepare yogurt for testing their antioxidants in a model of d-galactose-induced aging mice, with vitamin C as a positive control. The results showed that L. mucosae LMU1001 was the best strain, which had similar in vivo antioxidant activity as vitamin C. A significant increase was found in the activities of glutathione peroxidase in serum and total superoxide dismutase in the liver, and a decrease in the level of malondialdehyde in serum. Regarding mRNA expression level detected quantitatively by real-time PCR, we observed that L. mucosae LMU1001 significantly upregulated antioxidant genes (i.e., MT1A and MT1M in HT-29 and Caco-2) and those genes (i.e., MT1, MT2, GPx1, and GPx2) in the intestinal tract of the model mice. Hence, this strain could be considered as a potential probiotic lactic acid bacterium for improving antioxidant levels in functional foods. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Elements determination of clinical relevance in biological tissues Dmd{sup mdx}/J dystrophic mice strains investigated by NAA; Determinacao de elementos de relevancia clinica em tecidos biologicos de camundongos distroficos Dmd{sup mdx}/J por AAN

    Energy Technology Data Exchange (ETDEWEB)

    Metairon, Sabrina

    2012-07-01

    In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMD{sup mdx}/J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (Sao Paulo, Brazil). The concentrations of these elements in biological tissues of Dmd{sup mdx}/J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

  12. Radiation-induced tumours in C57BLf/6JNrs[SPF] and C3Hf/HeMsNrs[SPF] strain male mice

    International Nuclear Information System (INIS)

    Kasuga, T.; Sado, T.; Noda, Y.; Terasima, T.; Kitagawa, T.

    1978-01-01

    Mice at the age of 12 weeks were irradiated with single graded doses of gamma rays delivered from caesium-137. The mice were kept in specific pathogen-free (SPF) conditions until death. In this communication, autopsy data from 385 males of C57BLf/6JNrs[SPF] and 278 males of C3Hf/HeMsNrs[SPF] mice are summarized. The median survival time of unirradiated control mice was 29 months for the C57BL and 25 months for the C3H mice respectively. The incidence of tumour-bearing mice in the control groups was 71.3% for the C57BL and 90.9% for the C3H mice. Major, spontaneous tumour types were reticular cell sarcoma (51.3%), liver tumour (8.8%), lung tumour (11.3%) for the C57BL, and liver tumour (84.6%), lung tumour (8.2%) and non-thymic lymphoma (3.6%) for the C3H mice. Miscellaneous tumours with a low incidence were vascular, bone, muscle, adrenal tumours and others. In the C57BL mice the incidence of reticular cell sarcoma declined gradually with increasing doses of radiation exposure from 0 to 800 R. Histological examination revealed that reticular cell sarcomas normally found in unirradiated C57BL mice originated from abdominal lymphatic tissues whereas lymphoblastic lymphoma in irradiated mice arose from thymus and/or submandibular lymph nodes. It is noteworthy that the peak incidence of thymoma (33.3%) was found after whole-body exposure up to 700 R. Myeloid leukaemia was also included although to a slight extent. The age at death with lymphoreticular tumours and myeloid leukaemias was shortened in a dose-dependent manner. In the C3H mice tumour induction by radiation was generally not remarkable. The incidence of myeloid leukaemia attained a peak (15%) at 200 R. A lowering of the age at death was found to be proportional to the dose delivered

  13. Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

    Science.gov (United States)

    Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

    2016-12-01

    Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet

    International Nuclear Information System (INIS)

    Tryndyak, Volodymyr P.; Latendresse, John R.; Montgomery, Beverly; Ross, Sharon A.; Beland, Frederick A.; Rusyn, Ivan; Pogribny, Igor P.

    2012-01-01

    MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. -- Highlights: ► Choline- and folate-deficiency induces a strain-specific fatty liver injury in mice. ► The extent of liver pathology was accompanied by the changes in microRNA expression. ► The levels of circulating microRNAs mirror the magnitude of

  15. Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: A comparative study using two strains of mice with different sensitivities to dioxin

    International Nuclear Information System (INIS)

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki

    2014-01-01

    We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2–20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J

  16. Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: A comparative study using two strains of mice with different sensitivities to dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki, E-mail: hyamada@phar.kyushu-u.ac.jp

    2014-08-01

    We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2–20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J

  17. Hypertension in women

    OpenAIRE

    Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

    2013-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestationa...

  18. Circulatory and Renal Consequences of Pregnancy in Diabetic NOD Mice

    Science.gov (United States)

    Burke, S.D.; Barrette, V.F.; David, S.; Khankin, E. V.; Adams, M.A.; Croy, B.A.

    2011-01-01

    Objectives Women with diabetes have elevated gestational risks for severe hemodynamic complications, including preeclampsia in mid- to late pregnancy. This study employed continuous, chronic radiotelemetry to compare the hemodynamic patterns in non-obese diabetic (NOD) mice who were overtly diabetic or normoglycemic throughout gestation. We hypothesized that overtly diabetic, pregnant NOD mice would develop gestational hypertension and provide understanding of mechanisms in progression of this pathology. Study Design Telemeter-implanted, age-matched NOD females with and without diabetes were assessed for six hemodynamic parameters (mean, systolic, diastolic, pulse pressures, heart rate and activity) prior to mating, over pregnancy and over a 72 hr post-partum interval. Urinalysis, serum biochemistry and renal histopathology were also conducted. Results Pregnant, normoglycemic NOD mice had a hemodynamic profile similar to other inbred strains, despite insulitis. This pattern was characterized by an interval of pre-implantation stability, post implantation decline in arterial pressure to mid gestation, and then a rebound to pre-pregnancy baseline during later gestation. Overtly diabetic NOD mice had a blood pressure profile that was normal until mid-gestation then become mildly hypotensive (−7mmHg, Ppost-partum (−10% pre-pregnancy pressure and HR, P<0.05). Conclusions Pregnancy accelerates circulatory and renal pathologies in overtly diabetic NOD mice and is characterized by depressed arterial pressure from mid-gestation and birth of growth 45 restricted offspring. PMID:22014504

  19. Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension.

    Science.gov (United States)

    Itani, Hana A; Dikalova, Anna E; McMaster, William G; Nazarewicz, Rafal R; Bikineyeva, Alfiya T; Harrison, David G; Dikalov, Sergey I

    2016-06-01

    Vascular superoxide (O˙2 (-)) and inflammation contribute to hypertension. The mitochondria are an important source of O˙2 (-); however, the regulation of mitochondrial O˙2 (-) and the antihypertensive potential of targeting the mitochondria remain poorly defined. Angiotensin II and inflammatory cytokines, such as interleukin 17A and tumor necrosis factor-α (TNFα) significantly contribute to hypertension. We hypothesized that angiotensin II and cytokines co-operatively induce cyclophilin D (CypD)-dependent mitochondrial O˙2 (-) production in hypertension. We tested whether CypD inhibition attenuates endothelial oxidative stress and reduces hypertension. CypD depletion in CypD(-/-) mice prevents overproduction of mitochondrial O˙2 (-) in angiotensin II-infused mice, attenuates hypertension by 20 mm Hg, and improves vascular relaxation compared with wild-type C57Bl/6J mice. Treatment of hypertensive mice with the specific CypD inhibitor Sanglifehrin A reduces blood pressure by 28 mm Hg, inhibits production of mitochondrial O˙2 (-) by 40%, and improves vascular relaxation. Angiotensin II-induced hypertension was associated with CypD redox activation by S-glutathionylation, and expression of the mitochondria-targeted H2O2 scavenger, catalase, abolished CypD S-glutathionylation, prevented stimulation mitochondrial O˙2 (-), and attenuated hypertension. The functional role of cytokine-angiotensin II interplay was confirmed by co-operative stimulation of mitochondrial O˙2 (-) by 3-fold in cultured endothelial cells and impairment of aortic relaxation incubated with combination of angiotensin II, interleukin 17A, and tumor necrosis factor-α which was prevented by CypD depletion or expression of mitochondria-targeted SOD2 and catalase. These data support a novel role of CypD in hypertension and demonstrate that targeting CypD decreases mitochondrial O˙2 (-), improves vascular relaxation, and reduces hypertension. © 2016 American Heart Association, Inc.

  20. Systolic hypertension in adult nigerians with hypertension

    International Nuclear Information System (INIS)

    Opadijo, O.G.; Salami, T.A.T.; Sanya, E.O.; Omotoso, A.B.O.

    2007-01-01

    To determine the prevalence of both systolic and diastolic hypertensions in relation to age and their impacts on target organ among adult Nigerians with hypertension. Newly diagnosed adult hypertensives, with blood pressure 140/90mm Hg, taken twice with mercury column sphygmomanometer at 3 weeks interval, were studied. The total number of hypertensive patients treated over this period was also taken into consideration. The newly diagnosed hypertensives were classified using JNC VI classification. The frequency of occurrence of target organ damage such as Left Ventricular Hypertrophy (LVH), heart failure, renal impairment etc. was charted according to systolic and or diastolic pressures. The occurrence of systolic or diastolic blood pressure was also related with the age of the patients. Blood metabolic parameters were compared in both systolic and diastolic blood pressures for their possible contributory role. Two thousand seven hundred and ninety-two adult hypertensive patients were managed over the study period. Of them, 218 (7.8%) were newly diagnosed and studied. There were 94 males and 124 females. Seventy-seven (35.3%) were aged 60 years and above with equal frequency in the gender. One hundred and seventy-eight (81.7%) cases had combined systolic and diastolic pressures. Twenty-nine (13.3%) patients had systolic hypertension. Twenty-five (86.2%) of these 29 were aged 50 years and above and 20 (69.0%) were aged 60 years and above. Eleven (5.0%) patients had isolated diastolic hypertension and they were all in the age bracket 40-49 years. Systolic blood pressure was found to be rising with advancing age while diastolic blood pressure peaked at mid 40's and declined. Target organ damage occurred more frequently with systolic hypertension and advancing age than with diastolic hypertension. Systolic hypertension occurred more frequently in this series of adult Nigerians with hypertension. It was higher with advancing age and associated with more target organ

  1. Initiation of protein synthesis by a labeled derivative of the Lactobacillus casei DN-114 001 strain during transit from the stomach to the cecum in mice harboring human microbiota.

    Science.gov (United States)

    Oozeer, R; Mater, D D G; Goupil-Feuillerat, N; Corthier, G

    2004-12-01

    Although studies on the survival of bacteria in the digestive tract have been reported in the literature, little data are available on the physiological adaptation of probiotics to the digestive environment. In previous work, a transcriptional fusion system (i.e., luciferase genes under the control of a deregulated promoter) was used to demonstrate that a derivative of the Lactobacillus casei DN-114 001 strain, ingested in a fermented milk and thus exhibiting initially a very weak metabolic activity, synthesized proteins de novo after its transit in the digestive tract of mice harboring human microbiota (known as human-microbiota-associated mice). With the same genetic system and animal model, we here investigate for the first time the ability of L. casei to reinitiate synthesis in the different digestive tract compartments. In this study, most ingested L. casei cells transited from the stomach to the duodenum-jejunum within 1 h postingestion. No luciferase activity was observed in these digestive tract compartments after the first hour. At later times, the bulk of bacteria had transited to the ileum and the cecum. Luciferase synthesis was detected between 1.5 and 2.0 h postingestion at the ileal level and from 1.5 h to at least 6.0 h postingestion in the cecum, where the activity remained at a maximum level. These results demonstrate that ingested L. casei (derivative of the DN-114 001 strain) administered via a fermented milk has already reinitiated protein synthesis when it reaches the ileal and cecal compartments.

  2. [Analgesia evoked by combined effect of corvitin and low-intensity microwaves on acupuncture points in mice of different genetic strains with somatic pain].

    Science.gov (United States)

    Hura, O V; Bahats'ka, O V; Lymans'kyĭ, Iu P

    2011-01-01

    The level of analgesia has been investigated in mice of two genotypes C57BL/6J Bl/6j and CBA/CaLac with the somatic pain caused by the formalin test after irradiation of acupuncture point E-36 by microwaves of low intensity (30-300 GHz, density of a stream of capacity of 3-10-9 B(T)/cm2) on a background entered corvitin (20 mg/kg). It is shown, that the action of these two factors causes significant analgesia with different levels: 43% in C57BL/6J Bl/6j mice and 33% in CBA/CaLac mice. The intensity of analgesia after action of microwaves and corvitin exceeds the level attained during separate use of these factors.

  3. Immunogenicity and protective effect of recombinant Brucella abortus Ndk (rNdk) against a virulent strain B. abortus 544 infection in BALB/c mice.

    Science.gov (United States)

    Hop, Huynh Tan; Simborio, Hannah Leah; Reyes, Alisha Wehdnesday Bernardo; Arayan, Lauren Togonon; Min, WonGi; Lee, Hu Jang; Kim, Dong Hee; Chang, Hong Hee; Kim, Suk

    2015-02-01

    In this study, we particularly evaluated the protective effect of recombinant protein encoded by Brucella abortus 544 ndk (nucleoside diphosphate kinase) gene against B. abortus infection in the BALB/c mice. Cloning and expression of B. abortus Ndk was accomplished by PCR amplification into a pMAL expression system, and purification of a recombinant Ndk (rNdk). As for the determination of IgG responses, rNdk induced vigorous IgG production, especially higher in IgG2a compared to IgG1 with titers of 5.2 and 4.8, respectively, whereas titers of these in mice immunized with MBP were 2.4 of IgG2a and 2.6 of IgG1. The analysis of cytokine has revealed that rNdk can strongly induce production of IFN-γ as well as proinflammatory cytokines (TNF, MCP1 and IL-6) but not much IL-10, suggesting rNdk elicited predominantly cell-mediated immune responses. Furthermore, the spleen proliferation and bacterial burden in the spleen of rNdk immunized mice were significantly lower than those of MBP-immunized mice against virulent B. abortus challenge (P abortus might be a useful candidate for subunit vaccine for brucellosis in animals. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Host subspecific viral strains in European house mice: Murine cytomegalovirus in the Eastern (Mus musculus musculus) and Western house mouse (Mus musculus domesticus).

    Science.gov (United States)

    Čížková, Dagmar; Baird, Stuart J E; Těšíková, Jana; Voigt, Sebastian; Ľudovít, Ďureje; Piálek, Jaroslav; Goüy de Bellocq, Joëlle

    2018-06-09

    Murine cytomegalovirus (MCMV) has been reported from house mice (Mus musculus) worldwide, but only recently from Eastern house mice (M. m. musculus), of particular interest because they form a semi-permeable species barrier in Europe with Western house mice, M. m. domesticus. Here we report genome sequences of EastMCMV (from Eastern mice), and set these in the context of MCMV genomes from genus Mus hosts. We show EastMCMV and WestMCMV are genetically distinct. Phylogeny splitting analyses show a genome wide (94%) pattern consistent with no West-East introgression, the major exception (3.8%) being a genome-terminal region of duplicated genes involved in host immune system evasion. As expected from its function, this is a region of maintenance of ancestral polymorphism: The lack of clear splitting signal cannot be interpreted as evidence of introgression. The EastMCMV genome sequences reported here can therefore serve as a well-described resource for exploration of murid MCMV diversity. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Prognostic Value of Echocardiography in Hypertensive Versus Nonhypertensive Participants From the General Population

    DEFF Research Database (Denmark)

    Modin, Daniel; Biering-Sørensen, Sofie Reumert; Mogelvang, Rasmus

    2018-01-01

    Hypertension may be the most significant cardiovascular risk factor. Few studies have assessed the prognostic value of echocardiography in hypertensive individuals. This study examines the incremental prognostic value of adding echocardiographic parameters to established risk factors in individuals...... of echocardiography in predicting cardiovascular outcomes in the general population is altered by hypertension. In hypertensive individuals, left ventricular mass index added incremental prognostic value in addition to established risk factors. In nonhypertensive individuals, global longitudinal strain added...

  6. Hypertensive retinopathy (image)

    Science.gov (United States)

    ... retina from high blood pressure is called hypertensive retinopathy. It occurs as the existing high blood pressure ... flame hemorrhages and cotton wool spots. As hypertensive retinopathy progresses, hard exudates can appear around the macula ...

  7. Hypertensive heart disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000163.htm Hypertensive heart disease To use the sharing features on this page, please enable JavaScript. Hypertensive heart disease refers to heart problems that occur because of ...

  8. Chronic Hypertension in Pregnancy

    Science.gov (United States)

    ... org/ by guest on June 19, 2018 Chronic Hypertension in Pregnancy Ellen W. Seely, MD; Cynthia Maxwell, ... M any women have been diag- nosed with hypertension (blood pressure Ͼ 140/ 90 mm Hg) when ...

  9. Conditional ablation of the prorenin receptor in nephron progenitor cells results in developmental programming of hypertension.

    Science.gov (United States)

    Song, Renfang; Kidd, Laura; Janssen, Adam; Yosypiv, Ihor V

    2018-04-01

    Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells (NPCs) of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump V-ATPase. Previously, we demonstrated that conditional ablation of the PRR in Six2 + NPCs in mice (Six2 PRR -/- ) causes early neonatal death. Here, we identified genes that are regulated by PRR in Six2 + NPCs FACS-isolated from Six2 PRR -/- and control kidneys on embryonic day E15.5 using whole-genome expression analysis. Seven genes with expression in CM cells previously shown to direct kidney development, including Notch1, β-catenin, Lef1, Lhx1, Jag1, and p53, were downregulated. The functional groups within the downregulated gene set included genes involved in embryonic and cellular development, renal regeneration, cellular assembly and organization, cell morphology, death and survival. Double-transgenic Six2 PRR -/- /BatGal + mice, a reporter strain for β-catenin transcriptional activity, showed decreased β-catenin activity in the UB in vivo. Reduced PRR gene dosage in heterozygous Six2 PRR +/- mice was associated with decreased glomerular number, segmental thickening of the glomerular basement membrane with focal podocyte foot process effacement, development of hypertension and increased soluble PRR (sPRR) levels in the urine at 2 months of age. Together, these data demonstrate that NPC PRR performs essential functions during nephrogenesis via control of hierarchy of genes that regulate critical cellular processes. Both reduced nephron endowment and augmented urine sPRR likely contribute to programming of hypertension in Six2 PRR +/- mice. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  10. Aspects of the granulomatous reaction in the liver of mice infected and reinfected with two different geographical strains of Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Pedro Raso

    1994-12-01

    Full Text Available In this study, which was undertaken in relation to the histopathologic behavior of two different strains (LE-Belo Horizonte, MG and SJ - São José dos Campos, SP in infections and reinfections (homologous or heterologous with Schistosoma mansoni, the authors confirmed a more accentuated pathogenicity of the SJ strain. All the reinfections showed the presence of typical granulomas of the acute phase, when performed either with the same strain (homologous or with a different strain (heterologous of the parasite of the primo infection. The possible mechanisms responsible for reactivation of the immunopathologic response in reinfections are discussed.No presente estudo, verificou-se o comportamento histopatológico das infecções e reinfecções, homólogas ou heterólogas, das cepas LE (Belo Horizonte, MG e SJ (São José dos Campos, SP de Schistosoma mansoni. Confirmou-se uma maior patogenicidade da cepa SJ de S. mansoni. As reinfecções, independentemente de terem sido feitas com a mesma cepa (homóloga ou cepa diferente da primo infecção (heteróloga do parasito, mostraram a presença de granulomas típicos da fase aguda. São discutidos os possíveis mecanismos responsáveis pela reagudização da resposta imunopatológica nas reinfecções.

  11. Maskeret hypertension i graviditeten

    DEFF Research Database (Denmark)

    Fischer, Margit Bistrup; Thingaard, Ebbe; Andersen, Anita Sylvest

    2018-01-01

    Hypertension during pregnancy is one of the leading causes of maternal and foetal morbidity and mortality. Monitoring of blood pressure is therefore an essential part of prenatal care. Masked hypertension, where blood pressure levels are elevated at home despite normal blood pressure levels...... monitored in a clinical setting, may lead to cardiovascular and obstetric complications equal to those of sustained hypertension. This article discusses masked hypertension and the need for further investigation of blood pressure monitoring during pregnancy....

  12. Maskeret hypertension i graviditeten

    DEFF Research Database (Denmark)

    Fischer, Margit Bistrup; Thingaard, Ebbe; Andersen, Anita Sylvest

    2018-01-01

    Hypertension during pregnancy is one of the leading causes of maternal and foetal morbidity and mortality. Monitoring of blood pressure is therefore an essential part of prenatal care. Masked hypertension, where blood pressure levels are elevated at home despite normal blood pressure levels monit...... monitored in a clinical setting, may lead to cardiovascular and obstetric complications equal to those of sustained hypertension. This article discusses masked hypertension and the need for further investigation of blood pressure monitoring during pregnancy....

  13. Hypertension after kidney transplantation

    NARCIS (Netherlands)

    Dobrowolski, L.C.

    2016-01-01

    Hypertension increases the cardiovascular risk in kidney transplant recipients (KTRs). In chapter 2 we found that hypertension was highly prevalent in adult (77.2%), paediatric (62.7%) and young adult (86.4%) KTRs. Transition from the paediatric to adult care did not affect hypertension and there

  14. Hypertension in pregnancy

    Directory of Open Access Journals (Sweden)

    Andrea Ungar

    2007-03-01

    Full Text Available Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories: chronic hypertension, pre-eclampsia/eclampsia, pre-eclampsia superimposed on chronic hypertension, and gestational hypertension. A relative paucity of investigative data, as well as the frequent difficulty in making an etiological diagnosis, may lead to problems in its management. This case report analyses current concepts regarding the hypertensive disorders of gestation, focusing on chronic hypertension. Chronic hypertension is defined as blood pressure exceeding 140/90 mmHg before pregnancy or before 20 weeks gestation. Hypertensive disorders in pregnancy may cause maternal and fetal morbidity and remain a leading source of maternal mortality. A prompt diagnosis is needed also because hypertension may be an indicator of pre-eclampsia, a condition which can evolve into serious complications. Maintaining blood pressure below 140/90 mmHg is recommended, although treatment should be determined on an individual basis. Many anti-hypertensive agents appear to be safe for use during pregnancy: methildopa has been the most studied of the anti-hypertensive drugs and has the best safety record. Labetalol, idralazine and nifedipine also have been found to be safe; ACE-inhibitors are absolutely contraindicated, because they are associated with intrauterine growth retardation.

  15. Genetik og hypertension

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tarnow, Lisa; Pedersen, Erling Bjerregaard

    2009-01-01

    Monogenic forms of hypertension are very rare, but have a well-characterized heredity. Primary hypertension is very common with a complex and polygenic heredity. Primary hypertension arises due to an interaction between multiple genetic and environmental factors. Its heredity is unknown, although...

  16. Milan hypertensive rat as a model for studying cation transport abnormality in genetic hypertension

    International Nuclear Information System (INIS)

    Ferrari, P.; Barber, B.R.; Torielli, L.; Ferrandi, M.; Salardi, S.; Bianchi, G.

    1987-01-01

    Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinary output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na+-K+ cotransport and passive permeability were faster. The differences in volume, sodium content, and Na+-K+ cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F1 (MHS X MNS) hybrids. Moreover, in normal segregating F2 hybrid populations there was a positive correlation between blood pressure and Na+-K+ cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus, erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension. 35 references

  17. Polyphenol Compounds of Mahkota Dewa (Phaleria macrocarpa[Scheff.] Boerl Up-regulated Caspase-3 and Apoptosis Index in Balb/c Strain Mice

    Directory of Open Access Journals (Sweden)

    Indranila KS

    2016-04-01

    Full Text Available Background: Polyphenol compounds of Mahkota Dewa (Phaleria macrocarpa[Scheff.] Boerl (PMD can potentially be used as ant cancer treatment by scavanging radical molecules. The effect in vivois still limited to Indonesia. Purpose: This research was aimed to validate the activity of PMD in increasingcaspase-3 expression and apoptosis in Balb/c mice, induced by Benzo(apyrene (BaP. Methods: A posttest control group was implemented and used by 40 Balb/c mice at the age of 1-2 weeks, with the body weight of 20-30 g. The tumor induction was administered to the mice using BaP. The animals were randomized into two groups called the control group and the PMD treatment group, the latter of which was given a dosage of 50mg. Lung tumor growth was assessed through surgery at week 8, 17, and 26. The results of caspase-3expression and apoptotic index from IHC-TUNEL staining were analyzed using Kruskal-Wallis, Mann-Whitney, One-way ANOVA, and Post hoc test LSD with significant levels of p<α (0,05.This research was approved by Ethical Clearance. Results: Oral administration of 50mg PMD significantly increased caspase-3 expression and apoptotic index in the treatment group animals at weeks 8, 17, and 26. Carcinogenesis incidence in the control group were respectively found at2,32±0,26 and 3,93±0,46 at weeks 8 and 26, while those of the treatment group were 1,88±0,38 and 0,88±0,22 (p=0,001. The apoptotic index in the control group was0,00±0,00 at 8 weeksand0,92+0,22at 26 weeks, whereas the indexes of the treatment group were 1,12±0,71 and 2,02±1,05 (p=0,001. In the control group, the caspase-3 expression at weeks 8 and 26 were 0,28±0,17 and 0,56±0,16, while those in the treatment group were 0,60±0,14 at week 8 and 2,52±0,33 at week 26 (p=0,001. Conclusion: The treatment of PMD effectively induced cell apoptosis in the Balb/c mice via up- regulation of the caspase-3 expression, thereby increasing the apoptotic index. This shows that PMD has anticancer

  18. Idiopathic portal hypertension

    International Nuclear Information System (INIS)

    Han, Tae Kyun; Ryu, Dae Sik; Kim, Heung Chul; Hur, Hun; Eom, Kyeung Tae; Namkung, Sook; Park, Man Soo; Hwang, Woo Chul; Lee, Kwan Seop

    1996-01-01

    To describe the radiologic findings of idiopathic portal hypertension and to find the points of differentiation between idiopathic portal hypertension and liver cirrhosis. Four portograms in five patients who for four years had suffered from pathologically confirmed idiopathic portal hypertension were retrospectively analyzed and compared with a portogram obtained from a control subject with liver cirrhosis. Portographic finding s of idiopathic portal hypertension were paucity of medium-sized portal branches, irregular and obtuse-angled division of peripheral branches, abrupt interruption and an avascular area beneath the liver margin. A portogram of idiopathic portal hypertension may be useful in differentiation this and liver cirrhosis

  19. SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

    Directory of Open Access Journals (Sweden)

    M. Yu. Yukina

    2016-01-01

    Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

  20. Role of the Immune System in Hypertension.

    Science.gov (United States)

    Rodriguez-Iturbe, Bernardo; Pons, Hector; Johnson, Richard J

    2017-07-01

    High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease. Copyright © 2017 the American Physiological Society.

  1. Phenotypic Characterization of a Novel Virulence-Factor Deletion Strain of Burkholderia mallei that Provides Partial Protection against Inhalational Glanders in Mice

    Science.gov (United States)

    2016-02-26

    Fort Detrick, MD, USA, 2 Telemedicine and Advanced Technology Research Center, Biotechnology HPC Software Applications Institute, United States Army...allelic exchange mutants, we grew the Bm cointegrate strain in yeast- extract tryptone (YT) broth medium and then serially diluted it onto YT agar...indicated. Cells were fixed with 4% paraformaldehyde and then blocked in PBS containing 0.25% saponin , 0.2% Bovine Serum Albumin (BSA) fraction V

  2. Sex differences in angiotensin II- induced hypertension

    Directory of Open Access Journals (Sweden)

    B. Xue

    2007-05-01

    Full Text Available Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG II-induced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen a receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

  3. Immunomorphologic Manifestations in Mice Liver Infected with Influenza A/H5N1, A/Goose/Krasnoozerskoye/627/05 Strain

    Directory of Open Access Journals (Sweden)

    Oxana V. Potapova

    2013-01-01

    Full Text Available Highly pathogenic avian influenza H5N1 (HPAI H5N1 viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6 and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase by Kupffer cells. Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.

  4. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain

    DEFF Research Database (Denmark)

    Vanwolleghem, Thomas; Bukh, Jens; Meuleman, Philip

    2008-01-01

    The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these Ig...... were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV...... infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve...

  5. Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance.

    Directory of Open Access Journals (Sweden)

    Wendy Marie Ingram

    Full Text Available Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response across T. gondii strains and the underlying mechanism for this pathogen-mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasite cysts or continuing brain inflammation.

  6. Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance.

    Science.gov (United States)

    Ingram, Wendy Marie; Goodrich, Leeanne M; Robey, Ellen A; Eisen, Michael B

    2013-01-01

    Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response across T. gondii strains and the underlying mechanism for this pathogen-mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasite cysts or continuing brain inflammation.

  7. Myocardial Deformation Measured by 3-Dimensional Speckle Tracking in Children and Adolescents With Systemic Arterial Hypertension.

    Science.gov (United States)

    Navarini, Susanne; Bellsham-Revell, Hannah; Chubb, Henry; Gu, Haotian; Sinha, Manish D; Simpson, John M

    2017-12-01

    Systemic arterial hypertension predisposes children to cardiovascular risk in childhood and adult life. Despite extensive study of left ventricular (LV) hypertrophy, detailed 3-dimensional strain analysis of cardiac function in hypertensive children has not been reported. The aim of this study was to evaluate LV mechanics (strain, twist, and torsion) in young patients with hypertension compared with a healthy control group and assess factors associated with functional measurements. Sixty-three patients (26 hypertension and 37 normotensive) were enrolled (mean age, 14.3 and 11.4 years; 54% men and 41% men, respectively). All children underwent clinical evaluation and echocardiographic examination, including 3-dimensional strain. There was no difference in LV volumes and ejection fraction between the groups. Myocardial deformation was significantly reduced in those with hypertension compared with controls. For hypertensive and normotensive groups, respectively, global longitudinal strain was -15.1±2.3 versus -18.5±1.9 ( P hypertensive and normotensive children, but children with hypertension had significantly lower strain indices. Whether reduced strain might predict future cardiovascular risk merits further longitudinal study. © 2017 American Heart Association, Inc.

  8. Noncirrhotic portal hypertension.

    Science.gov (United States)

    Da, Ben L; Koh, Christopher; Heller, Theo

    2018-05-01

    Noncirrhotic portal hypertension represents a heterogeneous group of liver disorders that is characterized by portal hypertension in the absence of cirrhosis. The purpose of this review is to serve as a guide on how to approach a patient with noncirrhotic portal hypertension with a focus on recent developments. Recent studies pertaining to noncirrhotic portal hypertension have investigated aetiological causes, mechanisms of disease, noninvasive diagnostic modalities, clinical characteristics in the paediatric population and novel treatment targets. Noncirrhotic portal hypertension is an underappreciated clinical entity that can be difficult to diagnosis without a healthy suspicion. Diagnosis then relies on a comprehensive understanding of the causes and clinical manifestations of this disease, as well as a careful interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play a significant role moving forward in this disease. Treatment in NCPH remains largely targeted at the individual sequalae of portal hypertension.

  9. Hypertension in Danish seafarers

    DEFF Research Database (Denmark)

    Tu, Mingshan; Jepsen, Jørgen Riis

    2016-01-01

    Background: Due to the high prevalence of arterial hypertension and its role in the development of athe- rosclerosis, myocardial infarction and stroke, hypertension is a major public health challenge worldwide. There is limited knowledge of the prevalence of hypertension among seafarers who......, however, are known to have an excess morbidity and mortality from these disorders. This article addresses the prevalence of hypertension among Danish seafarers and discusses potential risk factors for hypertension in maritime settings. Materials and methods: A representative sample of 629 Danish seafarers...... who had statutory medical examinations was studied from the beginning of October 2011 to the end of June 2012. The medical examination included measurements of blood pressure. The prevalence of hypertension in the study po- pulation was stratified by age, work place on board, smoking status, alcohol...

  10. Pediatric portal hypertension

    Science.gov (United States)

    Vogel, Clarissa Barbon

    2017-01-01

    Abstract: Pediatric portal hypertension management is a team approach between the patient, the patient's family, the primary caregiver, and specialty providers. Evidence-based practice guidelines have not been established in pediatrics. This article serves as a review for the primary care NP in the management of pediatric portal hypertension, discussing the etiology, pathophysiology, and clinical presentation of pediatric portal hypertension, diagnostic tests, and treatment and management options. PMID:28406835

  11. Hypertension og hyperlipidaemi

    DEFF Research Database (Denmark)

    Hansen, Henrik Steen; Larsen, Mogens Lytken

    2009-01-01

    Hypertension and hyperlipidemia are well-established and partially overlapping risk factors for cardiovascular disease. Analyses of cardiovascular morbidity in relationship to changes in blood pressure and in serum cholesterol levels have shown that combined reduction of both risk factors...... are important to achieve a reduction in morbidity. Statins have been shown to be effective in preventing both coronary and cerebrovascular events in both hypertensive and normotensive cases. Consequently, most recent guidelines recommend that statin treatment be considered in hypertensive patients aged less...

  12. Effect of aging and radiation in mice of different genotypes

    International Nuclear Information System (INIS)

    Storer, J.B.

    1976-01-01

    Data are presented on the life span of nine inbred strains and five hybrid strains of mice based on 400 mice of each sex for inbred and 200 mice of each sex for hybrid. Some of these mice were exposed when 120 days old to 250 R or 450 R of x radiation delivered at a dose rate of 60 R/min. Data on strain, sample size, and mean survival times are presented in tables

  13. 42. Hypertension: Morbidity review

    Directory of Open Access Journals (Sweden)

    Hamzullah khan

    2015-10-01

    Conclusions: hypertension is a major modifiable risk factor for coronary artery disease, stroke, eye abnormalities and end stage renal disease, which require proper counseling and management of patients.

  14. The new hypertension guidelines.

    Science.gov (United States)

    Stern, Ralph H

    2013-10-01

    The Canadian Hypertension Education Program (CHEP) has published guidelines annually since 2000. The CHEP guidelines are a model of concise, comprehensive, up-to-date, evidence-rated guidelines for physicians who diagnose and treat hypertension. The guidelines address measurement of blood pressure and the definition of hypertension, secondary hypertension evaluation and treatment, and blood pressure targets and medication choices in patients with and without compelling indications. This review describes CHEP's process for developing guidelines and provides an overview of the 2013 recommendations. ©2013 Wiley Periodicals, Inc.

  15. [Hypertension in women].

    Science.gov (United States)

    Tagle, Rodrigo; Tagle V, Rodrigo; Acevedo, Mónica; Valdés, Gloria

    2013-02-01

    The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.

  16. Identification of Immunodominant Responses to the Plasmodium falciparum Antigens PfUIS3, PfLSA1 and PfLSAP2 in Multiple Strains of Mice.

    Directory of Open Access Journals (Sweden)

    Rhea J Longley

    Full Text Available Malaria, caused by the Plasmodium parasite, remains a serious global public health concern. A vaccine could have a substantial impact on eliminating this disease, alongside other preventative measures. We recently described the development of three novel, viral vectored vaccines expressing either of the antigens PfUIS3, PfLSA1 and PfLSAP2. Each vaccination regimen provided high levels of protection against chimeric parasite challenge in a mouse model, largely dependent on CD8+ T cells. In this study we aimed to further characterize the induced cellular immune response to these vaccines. We utilized both the IFNγ enzyme-linked immunosorbent spot assay and intracellular cytokine staining to achieve this aim. We identified immunodominant peptide responses for CD4+ and CD8+ T cells for each of the antigens in BALB/c, C57BL/6 and HLA-A2 transgenic mice, creating a useful tool for researchers for subsequent study of these antigens. We also compared these immunodominant peptides with those generated from epitope prediction software, and found that only a small proportion of the large number of epitopes predicted by the software were identifiable experimentally. Furthermore, we characterized the polyfunctionality of the induced CD8+ T cell responses. These findings contribute to our understanding of the immunological mechanisms underlying these protective vaccines, and provide a useful basis for the assessment of these and related vaccines as clinical constructs.

  17. Anti-cholesterol activity in vivo test of multifunction herbs extract in the water using in vivo method in mice (Mus musculus L.) DDY-strain

    Science.gov (United States)

    Tristantini, Dewi; Christina, Diana

    2018-02-01

    Atherosclerosis is the hardening of the arteries due to cholesterol accumulation in the blood vessels. The occurrence of cardiovascular disease can be reduced by lowering cholesterol levels in the blood. Nevertheless, using some pharmaceutical synthetic medicine for lowering the cholesterol has several side effects that dangerous for human body. There are 3 plants, tanjung leaf (Mimusops elengi L.), star fruit leaf (Averrhoa carambola L.), and curcuma (Curcuma xanthorrhiza L.), which are combined empirically believed would serve as multifunction herbs. Tanjung leaf has been known to have antioxidant, anti-cholesterol, and anti-platelet activity, also star fruit leaf have anti-hyperglycemia activity. Furthermore, curcuma has been known as a hepatoprotection agent. In this study, the combination of all three simplicias were used as anti-cholesterol. Anti-cholesterol activity test by in vivo method using mice (Mus muculus L.) result in decreased cholesterol as much as 47% for 250 mL human dosage in 7 days. This performance equals to 73% of simvastatin activity in decreased cholesterol. In this study, we can conclude the multifunction herbs that were combination of tanjung (M. elengi) leaf, star fruit leaf (Averrhoa carambola L.), and curcuma (Curcuma xanthorrhiza L.) extract can be used as cholesterol decreasing medicine.

  18. Altered vasoactive balance in hypertension: A pharmacogenomic study

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef

    2006-01-01

    Roč. 24, č. S6 (2006), s. 24-24 ISSN 0263-6352. [Scientific Meeting of the International Society of Hypertension /21./. 15.10.2006-19.10.2006, Fukuoka] R&D Projects: GA MZd(CZ) NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : vasoactive balance * hypertension * recombinant inbred strains Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  19. Immunogenicity Evaluation of A Synthetic Peptide EgP-29aa134-142 from Echinococcus granulosus In BALB /c Strain Mice

    Directory of Open Access Journals (Sweden)

    Sh. Jafari

    2016-02-01

    Full Text Available Background: Cystic echinococcosis or hydatid disease is a widely endemic helminthic  zoonotic disease caused by infection with metacestodes the larval stage of the tapeworm Echinococcus granulosus. P-29, a 29-kDa antigen from E. granulosus, is a protoscolex specific component. The immunologic cross reactivity between P-29 and a major diagnostic antigen of E. granulosus (Ag5 indicated that P-29 might be another useful antigen of E. granulosus to be used in diagnosis or in multi epitope vaccines to prevent secondary echinococcosis. In this study, the peptide epitope regions after the identification and synthesis were evaluated in order to determine the effect of stimulating an immune response in a mouse model. Methods: In this study, the p29 antigen epitope regions of the parasite Echinococcus granulosus detected by the IEDB Bioinformatics software and a 8 amino acids sequence were synthesized. BALB/c mice were immunized subcutaneously three times with two weeks interval. Fourteen days after last immunization spleen tissues were extracted and splenocytes were cultured in presence of antigen for 72 hours. Supernatants were collected and used for cytokine assay by Quantikine  ELISA kit. Results: Sandwich ELISA results were analyzed and showed significant difference in IFN-γ but no significant differences observed in levels of two cytokines IL-4, IL-10, between immunized and control groups. Conclusion: This study has assessed the effect of synthetic peptide EgP-29aa134-142 on the immune response and our results showed that the peptide can increase IFN-γ and therefore induce activation of innate Immunity as well as CTL and Th1 response.

  20. Comportamento das cepas Y e Peruana do Trypanosoma cruzi no camundongo, após passagem em diferentes meios Behavior of the Y and Peruvian strains of Trypanasoma cruzi in mice, ofter passage through different media

    Directory of Open Access Journals (Sweden)

    Juracy B. Magalhães

    1985-03-01

    Nitrogen, passage through the insect vector and direct blood passage from mice to mice. The parameters considered for comparative study were as follows: parasitemia, mortality rate, maximum survival time, morphology of parasites in peripheral blood, tissue tropism and histopathological lesions. Each experimental group consisted of two sub-groups according to the inocula: 10.000 or 50.000 trypomastigotes. The basic characteristics of the strains remained unchanged. These were macrophagotropism, predominance of slender forms of the parasite in early infection and 100 per cent mortality rate in the acute phase of the infection. However, decrease in the virulence was observed when the culture forms were used or when the infection with low inoculum was used (10.00 forms. Therefore the main biological characteristics of the strains tended to remain the same, regardless of the conditions used for maintainance and cultivation.

  1. Therapeutic Exercise and Hypertension

    African Journals Online (AJOL)

    Nekky Umera

    patients but may not reduce the BP of normotensive individual. Exercise function ... and mortality in all age groups; it also creates major social, personal and financial ... drug therapy by as symptomatic hypertensive and high cost of drugs particularly in a ..... Events in hypertensive patients randomized to doxagosin versus.

  2. Noncirrotisk intrahepatisk portal hypertension

    DEFF Research Database (Denmark)

    Dam Fialla, Annette; Havelund, Troels

    2007-01-01

    Non-cirrhotic intrahepatic portal hypertension is characterized by portal hypertension in the absence of liver cirrhosis or portal vein thrombosis. The disease is common in the East and rarely seen in the West. Two cases with oesophageal varices are described. The histopathology is heterogeneous...... but includes vascular lesions and portal fibrosis. Patient management follows the current recommendations for variceal bleeding....

  3. Pulmonary Arterial Hypertension

    Science.gov (United States)

    ... heart). This type of pulmonary hypertension was called “secondary pulmonary hypertension” but is now referred to as PH, because the cause is known to be from lung disease, heart disease, or chronic thromboemboli (blood clots). Pulmonary Arterial Hypertension (PAH) used to be ...

  4. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Hypertension (High Blood Pressure) KidsHealth / For Teens / Hypertension (High Blood Pressure) What's ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

  5. Cervical Spondylosis and Hypertension

    Science.gov (United States)

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully with anterior cervical discectomy and fusion. Stimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation, and induce a sympathetic reflex to cause cervical vertigo and hypertension. In addition, chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms. Cervical spondylosis may be one of the causes of secondary hypertension. Early treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis. PMID:25761188

  6. Overweight, adipocytokines and hypertension

    DEFF Research Database (Denmark)

    Seven, Ekim; Husemoen, Lise L N; Wachtell, Kristian

    2014-01-01

    OBJECTIVE:: The adipocytokines, leptin, adiponectin, and interleukin-6, which stimulate liver C-reactive protein (CRP) production, are regarded as potential candidate intermediates between adipose tissue and overweight-induced hypertension. METHODS:: We examined the associations between leptin......, adiponectin, and CRP levels with both prevalent and 5-year incident hypertension (IHT) in a general population of Danish adults (n = 5868, 51.3% women, mean age 45.8 ± 7.9 years). RESULTS:: We recorded 2195 prevalent and 379 incident cases of hypertension. In models including leptin, CRP, adiponectin, sex.......023) in the fully adjusted model. The population attributable risk estimate of IHT owing to overweight was 31%. CONCLUSION:: Leptin, but not adiponectin or CRP, may play a mediating role in overweight-induced hypertension. However, as BMI was a strong independent predictor of hypertension, other factors than leptin...

  7. Hypertension in women.

    Science.gov (United States)

    Pimenta, Eduardo

    2012-02-01

    Hypertension is an important modifiable risk factor for cardiovascular (CV) morbidity and mortality, and a highly prevalent condition in both men and women. However, the prevalence of hypertension is predicted to increase more among women than men. Combined oral contraceptives (COCs) can induce hypertension in a small group of women and, increase CV risk especially among those with hypertension. Both COC-related increased CV risk and blood pressure (BP) returns to pretreatment levels by 3 months of its discontinuation. The effects of menopause and hormone replacement therapy (HRT) on BP are controversial, and COCs and HRT containing the new generation progestin drospirenone are preferred in women with established hypertension. Despite the high incidence of cancer in women, CV disease remains the major cause of death in women and comparable benefit of antihypertensive treatment have been demonstrated in both women and men.

  8. Overweight, adipocytokines and hypertension

    DEFF Research Database (Denmark)

    Seven, Ekim; Husemoen, Lise L N; Wachtell, Kristian

    2014-01-01

    OBJECTIVE: The adipocytokines, leptin, adiponectin, and interleukin-6, which stimulate liver C-reactive protein (CRP) production, are regarded as potential candidate intermediates between adipose tissue and overweight-induced hypertension. METHODS: We examined the associations between leptin......, adiponectin, and CRP levels with both prevalent and 5-year incident hypertension (IHT) in a general population of Danish adults (n = 5,868, 51.3% women, mean age 45.8 ± 7.9 years). RESULTS: We recorded 2195 prevalent and 379 incident cases of hypertension. In models including leptin, CRP, adiponectin, sex.......023) in the fully adjusted model. The population attributable risk estimate of IHT owing to overweight was 31%. CONCLUSION: Leptin, but not adiponectin or CRP, may play a mediating role in overweight-induced hypertension. However, as BMI was a strong independent predictor of hypertension, other factors than leptin...

  9. Influence of White-Coat Hypertension on Left Ventricular Deformation 2- and 3-Dimensional Speckle Tracking Study.

    Science.gov (United States)

    Tadic, Marijana; Cuspidi, Cesare; Ivanovic, Branislava; Ilic, Irena; Celic, Vera; Kocijancic, Vesna

    2016-03-01

    We sought to compare left ventricular deformation in subjects with white-coat hypertension to normotensive and sustained hypertensive patients. This cross-sectional study included 139 untreated subjects who underwent 24-hour ambulatory blood pressure monitoring and completed 2- and 3-dimensional examination. Two-dimensional left ventricular multilayer strain analysis was also performed. White-coat hypertension was diagnosed if clinical blood pressure was elevated and 24-hour blood pressure was normal. Our results showed that left ventricular longitudinal and circumferential strains gradually decreased from normotensive controls across subjects with white-coat hypertension to sustained hypertensive group. Two- and 3-dimensional left ventricular radial strain, as well as 3-dimensional area strain, was not different between groups. Two-dimensional left ventricular longitudinal and circumferential strains of subendocardial and mid-myocardial layers gradually decreased from normotensive control to sustained hypertensive group. Longitudinal and circumferential strains of subepicardial layer did not differ between the observed groups. We concluded that white-coat hypertension significantly affects left ventricular deformation assessed by 2-dimensional traditional strain, multilayer strain, and 3-dimensional strain. © 2016 American Heart Association, Inc.

  10. In Vivo Activities of Ceftolozane, a New Cephalosporin, with and without Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, Including Strains with Extended-Spectrum β-Lactamases, in the Thighs of Neutropenic Mice

    Science.gov (United States)

    Andes, D. R.

    2013-01-01

    Ceftolozane is a new cephalosporin with potent activity against Pseudomonas aeruginosa and Enterobacteriaceae. A neutropenic murine thigh infection model was used to determine which pharmacokinetic/pharmacodynamic index and magnitude drives the efficacy of ceftolozane with Gram-negative bacilli, to compare the rates of in vivo killing of P. aeruginosa by ceftolozane and ceftazidime, and to determine the impact of different ratios of ceftolozane plus tazobactam on Enterobacteriaceae containing extended-spectrum β-lactamases (ESBLs). Neutropenic mice had 106.2-7.1 CFU/thigh when treated with ceftolozane for 24 h with (i) various doses (3.12 to 1,600 mg/kg) and dosage intervals (3, 6, 12, and 24 h) against two Enterobacteriaceae strains, (ii) 0.39 to 800 mg/kg every 6 h for four Enterobacteriaceae and four P. aeruginosa strains, and (iii) 400 or 800 mg/kg with 2:1. 4:1, and 8:1 ratios of tazobactam against five Enterobacteriaceae strains with ESBLs. The pharmacokinetics of ceftolozane at 25, 100, and 400 mg/kg were linear with peak/dose values of 1.0 to 1.4 and half-lives of 12 to 14 min. T>MIC was the primary index driving efficacy. For stasis (1 log kill), T>MIC was 26.3% ± 2.1% (31.6% ± 1.6%) for wild-type Enterobacteriaceae, 31.1% ± 4.9% (34.8% ± 4.4%) for Enterobacteriaceae with ESBLs, and 24.0% ± 3.3% (31.5% ± 3.9%) for P. aeruginosa. At 200 mg/kg every 3 h, the rate of in vivo killing of P. aeruginosa was faster with ceftolozane than with ceftazidime (−0.34 to −0.41 log10 CFU/thigh/h versus −0.21 to −0.24 log10 CFU/thigh/h). The 2:1 ratio of ceftolozane with tazobactam was the most potent combination studied. The T>MIC required for ceftolozane is less than with other cephalosporins and may be due to more rapid killing. PMID:23274659

  11. TL transgenic mouse strains

    International Nuclear Information System (INIS)

    Obata, Y.; Matsudaira, Y.; Hasegawa, H.; Tamaki, H.; Takahashi, T.; Morita, A.; Kasai, K.

    1993-01-01

    As a result of abnormal development of the thymus of these mice, TCR αβ lineage of the T cell differentiation is disturbed and cells belonging to the TCR γδ CD4 - CD8 - double negative (DN) lineage become preponderant. The γδ DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, indicating that the γδ cells are incapable of participating in these reactions. Molecular and serological analyses of T-cell lymphomas reveal that they belong to the γδ lineage. Tg.Tla a -3-1 mice should be useful in defining the role of TL in normal and abnormal T cell differentiation as well as in the development of T-cell lymphomas, and further they should facilitate studies on the differentiation and function of γδ T cells. We isolated T3 b -TL gene from B6 mice and constructed a chimeric gene in which T3 b -TL is driven by the promoter of H-2K b . With the chimeric gene, two transgenic mouse strains, Tg. Con.3-1 and -2 have been derived in C3H background. Both strains express TL antigen in various tissues including skin. The skin graft of transgenic mice on C3H and (B6 X C3H)F 1 mice were rejected. In the mice which rejected the grafts, CD8 + TCRαβ cytotoxic T cells (CTL) against TL antigens were recognized. The recognition of TL by CTL did not require the antigen presentation by H-2 molecules. The results indicated that TL antigen in the skin becomes a transplantation antigen and behaves like a typical allogeneic MHC class I antigen. The facts that (B6 X C3H)F 1 mice rejected the skin expressing T3 b -TL antigen and induced CTL that killed TL + lymphomas of B6 origin revealed that TL antigen encoded by T3 b -TL is recognized as non-self in B6 mice. Experiments are now extended to analyze immune responses to TL antigen expressed on autochthonous T cell lymphomas. (J.P.N.)

  12. Action of 50 R X-ray doses on the breeding function of C3H strain mice - effect of splitting the dose, action of repeated irradiations on successive generations

    International Nuclear Information System (INIS)

    Alix, D.

    1965-01-01

    X-rays exposure effect was studied on C3H strain mice, at the standpoint of the effects produced on breeding function. The method used with this purpose was the following: single doses 20 - 30 - 40 and 50 R/dose, fractional doses: 50 R/total dose, divided in 2 - 5 - 10 or 25 irradiations distributed in one month duration. The offsprings were irradiated at the same doses than the parents, consanguinity being maintained. Statistical treatment of results was carried out, that led at the following conclusions: 1) Couples receiving single exposure of 50 R or two exposures of 25 R at one month interval give comparable results. Fractional doses do not involve the slightest diminution of X-rays effect. 2) 30 R exposure brings about a decrease in fertility, with an increase in abortions. Fertility of 20 R irradiated couples remains below controls. 3) After ten times 5 R and twenty-five 2 R, the number of abortions is the largest. Ovarian function is particularly sensitive to X-rays; one may think that twenty-five 2 R give injuries conditioning non-viability of conception products, smaller doses should produce mutations and yield births of altered genotype individuals. (author) [fr

  13. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension.

    Science.gov (United States)

    Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V

    2017-05-01

    Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 + T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 + T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1 -/- , lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4 + , CD8 + , or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 -/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 + but not CD8 + T cells restored the hypertensive phenotype in RAG1 -/- mice. Interestingly, RAG1 -/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 + cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

  14. Pulmonary hypertension CT imaging

    International Nuclear Information System (INIS)

    Nedevska, A.

    2013-01-01

    Full text: The right heart catheterization is the gold standard in the diagnosis and determines the severity of pulmonary hypertension. The significant technical progress of noninvasive diagnostic imaging methods significantly improves the pixel density and spatial resolution in the study of cardiovascular structures, thus changes their role and place in the overall diagnostic plan. Learning points: What is the etiology, clinical manifestation and general pathophysiological disorders in pulmonary hypertension. What are the established diagnostic methods in the diagnosis and follow-up of patients with pulmonary hypertension. What is the recommended protocol for CT scanning for patients with clinically suspected or documented pulmonary hypertension. What are the important diagnostic findings in CT scan of a patient with pulmonary hypertension. Discussion: The prospect of instantaneous complex - anatomical and functional cardiopulmonary and vascular diagnostics seems extremely attractive. The contrast enhanced multislice computed (CT ) and magnetic resonance imaging are very suitable methods for imaging the structures of the right heart, with the possibility of obtaining multiple projections and three-dimensional imaging reconstructions . There are specific morphological features that, if carefully analyzed, provide diagnostic information. Thus, it is possible to avoid or at least reduce the frequency of use of invasive diagnostic cardiac catheterization in patients with pulmonary hypertension. Conclusion: This review focuses on the use of contrast-enhanced CT for comprehensive evaluation of patients with pulmonary hypertension and presents the observed characteristic changes in the chest, lung parenchyma , the structures of the right half of the heart and pulmonary vessels

  15. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...

  16. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice....

  17. Hypertension and Cardiac Arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y H; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension (HTN) is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease (CAD), stroke, peripheral artery disease and chronic renal failure. Hypertensive heart disease can manifest as many types of cardiac arrhythmias, most commonly being atrial fibrillation......) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit of comprehensively reviewing the available evidence...

  18. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

  19. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Møller, Søren

    2004-01-01

    to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin......Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...... hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system...

  20. Secondary hypertension in adults.

    Science.gov (United States)

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-05-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. Copyright: © Singapore Medical Association.

  1. Pulmonary Hypertension Overview

    Science.gov (United States)

    ... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

  2. Hypertension and Anaesthesia

    African Journals Online (AJOL)

    worldwide, and is a major risk factor for coronary artery disease, myocardial ... pressure falls in different categories of systolic and diastolic pressure the higher ... Without this consensus, the management of the elderly hypertensive patient.

  3. Diabetes + Hypertension (comorbidity)

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This data set provides de-identified population data for diabetes and hypertension comorbidity prevalence in Allegheny County.

  4. Understanding idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Markey, Keira A; Mollan, Susan P; Jensen, Rigmor H

    2016-01-01

    Idiopathic intracranial hypertension is a disorder characterised by raised intracranial pressure that predominantly affects young, obese women. Pathogenesis has not been fully elucidated, but several causal factors have been proposed. Symptoms can include headaches, visual loss, pulsatile tinnitus...

  5. High Blood Pressure (Hypertension)

    Science.gov (United States)

    ... Print Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults has ... weight. How Will I Know if I Have High Blood Pressure? High blood pressure is a silent problem — you ...

  6. Hypertension and cardiac arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y.H.; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both...... supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia......, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society...

  7. Diabetes Mellitus and Hypertension

    OpenAIRE

    Tuğrul, Armağan

    2014-01-01

    Hypertension is a major worldwide health problem. Its prevalence is 1.5-2 times higher in diabetic population than that in non-diabetic individuals. Its pathogenesis depends on diabetic nephropathy in type 1, whereas may be multifactorial in type 2 diabetes mellitus. In diabetics, angiotensin converting enzyme inhibitors are most widely preferred in the treatment of hypertension because of their numerous desirable effects. In this article, the most recent data are presented on the relationshi...

  8. Hypertension og hjernen

    DEFF Research Database (Denmark)

    Christensen, Hanne; Strandgaard, Svend

    2009-01-01

    Hypertension is a major and modifiable risk factor of stroke and dementia. Hypertension causes remodelling of the cerebral resistance vessels, impairing their tolerance to very low blood pressure. In primary prevention of stroke, the effect of beta-blockers is inferior to other classes...... of antihypertensives. In secondary prevention of stroke, ACE-inhibitors and angiotensin blockers may be recommended as first choice drugs. Lowering of the blood pressure is, however, more important than the choice of drug. Udgivelsesdato: 2009-Jun-8...

  9. Cervical Spondylosis and Hypertension

    OpenAIRE

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully w...

  10. Thromboembolic chronicle pulmonary Hypertension

    International Nuclear Information System (INIS)

    Ovalle, Amador

    2003-01-01

    The thromboembolic chronicle pulmonary Hypertension, also well known as chronic lung thromboembolism not resolved; it is a form not very common of lung thromboembolism. Until very recently was considered a rare curiosity of autopsy, but as the methods of diagnoses have improved and our attitude has changed, the incidence of this nosological entity has experienced a notable increment, but the most excellent in this illness is maybe that it is a form of lung hypertension, potentially recoverable

  11. Renovascular hypertension: bibliographic review

    International Nuclear Information System (INIS)

    Cruz Guzman, Luis Fernando

    2011-01-01

    A review of the literature on the management of the renovascular disease is performed to provide better attention to patients. Renovascular hypertension is defined. The clinical implications and complications of the disease are determined. Pharmacological and surgical management are specified. Endovascular therapy has allowed to determine some indication in the management of hypertension renovascular. Instances where endovascular therapy has been beneficial are detailed. The new interventions for the management of renovascular disease are exposed [es

  12. Biology of portal hypertension.

    Science.gov (United States)

    McConnell, Matthew; Iwakiri, Yasuko

    2018-02-01

    Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

  13. Obligatory Role for B Cells in the Development of Angiotensin II-Dependent Hypertension.

    Science.gov (United States)

    Chan, Christopher T; Sobey, Christopher G; Lieu, Maggie; Ferens, Dorota; Kett, Michelle M; Diep, Henry; Kim, Hyun Ah; Krishnan, Shalini M; Lewis, Caitlin V; Salimova, Ekaterina; Tipping, Peter; Vinh, Antony; Samuel, Chrishan S; Peter, Karlheinz; Guzik, Tomasz J; Kyaw, Tin S; Toh, Ban-Hock; Bobik, Alexander; Drummond, Grant R

    2015-11-01

    Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R(-/-)) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R(-/-) (Δ30±4 mm Hg) relative to wild-type (Δ41±5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R(-/-) mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-β expression. BAFF-R(-/-) mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by ≈35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension. © 2015 American Heart Association, Inc.

  14. Knowledge and prevalence of risk factors for arterial hypertension ...

    African Journals Online (AJOL)

    Background: High job strain, mental stress, sedentary lifestyle, increase in BMI are among the factors associated with significantly higher incidence of hypertension. The job of bank employees is both sedentary in nature and accompanies high mental stress. The aim of this study is to assess the level of knowledge of risk ...

  15. [Epidemiologic and medical sociological aspects of hypertension].

    Science.gov (United States)

    Siegrist, J

    1995-10-01

    Cardiovascular diseases are a major determinant of overall and premature mortality in advanced and in rapidly developing societies. In view of their importance it is mandatory to identify underlying risk factors and to guide preventive and therapeutic actions accordingly. Hypertension is one of the most prevalent and well-established cardiovascular risk factors. This paper briefly summarizes some major determinants of high blood pressure from an epidemiologic and sociomedical point of view. Determinants include age, overweight, physical inactivity, salt and alcohol intake, family history of hypertension, race and socio-economic status. The complexity of these influences is discussed by pointing to interactions between genetic and socio-environmental influences, e.g. in the case of age, bodyweight and salt intake. Based on experimental animal research there is now solid evidence on direct links between psychosocial stress, patterns of neuroendocrine activation and elevation of blood pressure. Four theoretical concepts are described which identify conditions of chronic psychosocial vulnerability or protection in man, and their role in explaining the prevalence of hypertension in epidemiologic studies is discussed. The four concepts are labelled "socioemotional support", "lifestyle incongruity", "job strain" and "effort-reward-imbalance at work". Special emphasis is given to the two latter concepts in view of the potential role of occupational life in triggering high blood pressure during middle adulthood. For instance, Table 1 indicates that high job strain, i.e. high demands in combination with low control at work, is associated with a relative risk of 3 of being hypertensive, after adjusting for important confounders.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Pregnancy with Portal Hypertension

    Science.gov (United States)

    Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.

    2014-01-01

    Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. PMID:25755552

  17. Management of diabetic hypertensives

    Science.gov (United States)

    Ganesh, Jai; Viswanathan, Vijay

    2011-01-01

    Hypertension occurs twice as commonly in diabetics than in comparable nondiabetics. Patients with both disorders have a markedly higher risk for premature microvascular and macrovascular complications. Aggressive control of blood pressure (BP) reduces both micro- and macrovascular complications. In diabetic hypertensives, angiotensin converting enzyme inhibitors (ACEIs) are the first line in management of hypertension, and can be replaced by angiotensin II receptor blockers (ARBs) if patients are intolerant of them. Recent studies suggest ARBs to be on par with ACEI in reducing both macro- and microvascular risks. Adding both these agents may have a beneficial effect on proteinuria, but no extra macrovascular risk reduction. Thiazides can also be used as first line drugs, but are better used along with ACEI/ARBs. Beta-blockers [especially if the patient has coronary artery disease] and calcium channel blockers are used as second line add-on drugs. Multidrug regimens are commonly needed in diabetic hypertensives. Achieving the target BP of <130/80 is the priority rather than the drug combination used in order to arrest and prevent the progression of macro- and microvascular complications in diabetic hypertensives. PMID:22145142

  18. Hypertension in postmenopausal women: how to approach hypertension in menopause.

    Science.gov (United States)

    Modena, Maria Grazia

    2014-09-01

    During fertile life women are usually normo or hypotensive. Hypertension may appear during pregnancy and this represents a peculiar phenomenon increasing nowadays for delay time of pregnancy. Gestational hypertension appears partially similar to hypertension in the context of metabolic syndrome for a similar condition of increased waste circumference. Parity, for the same pathogenesis, has been reported to be associated to peri and postmenopausal hypertension, not confirmed by our study of parous women with transitional non persistent perimenopausal hypertension. Estrogen's deficiency inducing endothelial dysfunction and increased body mass index are the main cause for hypertension in this phase of life. For these reasons lifestyle modification, diet and endothelial active drugs represent the ideal treatment. Antioxidant agents may have a role in prevention and treatment of hypertension. In conclusion, hypertension in women represents a peculiar constellation of different biological and pathogenic factors, which need a specific gender related approach, independent from the male model.

  19. Knowledge and awareness of hypertension among patients with systemic hypertension.

    Science.gov (United States)

    Familoni, B. Oluranti; Ogun, S. Abayomi; Aina, A. Olutoyin

    2004-01-01

    BACKGROUND: In Nigeria, systemic hypertension is the commonest noncommunicable disease, and public awareness about hypertension and its determinants is poor. This study aims to assess the knowledge and level of awareness of the disease among hypertensive patients attending the medical outpatient clinic of Olabisi Onabanjo University Teaching Hospital (OOUTH). METHODOLOGY: Hypertensive patients who attended the medical outpatient clinic during the one-year study period and gave their consent were recruited into the study. Response to a questionnaire on various aspects of hypertension was analyzed using the STATA for Windows software. RESULTS: There were 254 hypertensive patients, of which 111 were males and 143 were females, giving a male: female ratio of 1:1.3. The mean age (SD) of the patients was 51 years +/- 12.2; 52.4% of the participants were aware that hypertension was the commonest noncommunicable disease in Nigeria. About one in 10 patients (11.4%) was aware that "nil symptom" is the commonest symptom of hypertension, while 37% were not aware that hypertension could cause renal failure. Only about one-third (35.4%) of the patients knew that hypertension should ideally be treated for life, while 58.3% believed that antihypertensive drugs should be used only when there are symptoms. The remaining 6.3% believed that the treatment of hypertension should be for periods ranging from two weeks to five years but not for life. CONCLUSION: This study has demonstrated inadequate knowledge of hypertension in patients with hypertension in our study population. Conscious efforts should be made and time set aside to health educate hypertensive patients. Organization of "hypertensive club or society" could be encouraged. These will reduce dissemination of false or inaccurate information by hypertensive patients to the public and its attendant dangers. PMID:15160976

  20. Oestrogen receptor alpha in pulmonary hypertension.

    Science.gov (United States)

    Wright, Audrey F; Ewart, Marie-Ann; Mair, Kirsty; Nilsen, Margaret; Dempsie, Yvonne; Loughlin, Lynn; Maclean, Margaret R

    2015-05-01

    Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  1. Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

    Science.gov (United States)

    Shih, Y-H; Tsai, S-F; Huang, S-H; Chiang, Y-T; Hughes, M W; Wu, S-Y; Lee, C-W; Yang, T-T; Kuo, Y-M

    2016-05-13

    Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice. Udgivelsesdato: 2009-Jun-15...

  3. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice Udgivelsesdato: 2009/6/15...

  4. Echocardiography in Arterial Hypertension.

    Science.gov (United States)

    de Simone, Giovanni; Mancusi, Costantino; Esposito, Roberta; De Luca, Nicola; Galderisi, Maurizio

    2018-05-02

    Hypertension is a condition characterized by pressure and/or volume overloads and echocardiography is helpful and feasible to understand hemodynamic mechanisms. Echocardiographic information is sometimes critical and susceptible of modifying decision making. In this review, we provide detailed descriptions of the parameters that can be derived from a standard transthoracic echocardiogram, including some more recent techniques. We will also explain how each parameter might have impact in the evaluation of the hypertensive patient and give indications on when to refer patients to echo-labs, which parameters are critical and which ones might be redundant, and how to use the information obtained in the report. Cardiac geometry, LV systolic and diastolic function, LV pump performance, output impedance and left atrial function are parameters that might be altered in arterial hypertension, but not necessarily doctors need the whole information for decision making. The critical measures are provided.

  5. [Hypertension in females].

    Science.gov (United States)

    Cífková, Renata

    2015-05-01

    Hypertension is the most common cardiovascular disorder affecting more males in younger age groups; in the age group of 45-64, it is equally frequent in both genders, it is more common in elderly females. Blood pressure increases more in females around the menopause. Use of hormonal replacement therapy is not associated with an BP increase but, because of increased risk of coronary events, stroke, and thromboembolic events, HRT is not re-commended in CVD prevention. There is a similar decrease in BP by antihypertensive drugs in both genders as well as benefit from antihypertensive treatment. Women report about a double rate of adverse events of antihypertensive drugs. Oral contraception use is associated with a mild BP increase in most women and development of overt hypertension in about 5 %. Pre-eclampsia is associated with increased risk of developing CVD later in life (more frequent development of hypertension, myocardial infarction, and stroke).

  6. Left ventricular functional, structural and energetic effects of normal aging: Comparison with hypertension.

    Directory of Open Access Journals (Sweden)

    Jehill D Parikh

    Full Text Available Both aging and hypertension are significant risk factors for heart failure in the elderly. The purpose of this study was to determine how aging, with and without hypertension, affects left ventricular function.Cross-sectional study of magnetic resonance imaging and 31P spectroscopy-based measurements of left ventricular structure, global function, strains, pulse wave velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated hypertensive patients (though no other cardiovascular disease or diabetes stratified into 3 age deciles from 50-79 years.Normal aging was associated with significant increases in systolic blood pressure, vascular stiffness, torsion, and impaired diastolic function (all P<0.05. Age-matched hypertension exacerbated the effects of aging on systolic pressure, and diastolic function. Hypertension alone, and not aging, was associated with increased left ventricular mass index, reduced energetic reserve, reduced longitudinal shortening and increased endocardial circumferential shortening (all P<0.05. Multiple linear regression analysis showed that these unique hypertensive features were significantly related to systolic blood pressure (P<0.05.1 Hypertension adds to the age-related changes in systolic blood pressure and diastolic function; 2 hypertension is uniquely associated with changes in several aspects of left ventricular structure, function, systolic strains, and energetics; and 3 these uniquely hypertensive-associated parameters are related to the level of systolic blood pressure and so are potentially modifiable.

  7. Peripheral adrenergic receptors in hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.; Insel, P. A.

    1990-01-01

    Increased sympathoadrenal activity appears to play an important role in the development or maintenance of elevated blood pressure in hypertensive patients and various animal models of hypertension. Alterations of adrenergic receptor number or responsiveness might contribute to this increased

  8. Radiation-induced renovascular hypertension

    International Nuclear Information System (INIS)

    Staab, G.E.; Tegtmeyer, C.J.; Constable, W.C.

    1976-01-01

    Radiation is known to produce changes in the small vessels and interstitium of the kidneys resulting in hypertension. Two cases of renal artery stenosis and resultant hypertension secondary to abdominal irradiation are reported and the literature is reviewed

  9. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  10. Knowing hypertension and diabetes

    DEFF Research Database (Denmark)

    Whyte, Susan Reynolds

    2015-01-01

    In Uganda, hypertension and diabetes have only recently been included in the health policy agenda. As they become treatable disorders, they take on more distinct contours in people's minds. This article relates knowledge about these two conditions to health institutions and technology...... for diagnosing and treating them. The response to the AIDS epidemic in Uganda provides an important context for, and contrast with, the emergence of hypertension and diabetes as social phenomena. Ethnographic fieldwork shows the interplay between experience of these conditions and the political economy...

  11. Idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne M; Jensen, Rigmor H

    2015-01-01

    AIMS: The aims of this article are to characterize the headache in idiopathic intracranial hypertension (IIH) and to field-test the ICHD diagnostic criteria for headache attributed to IIH. MATERIALS AND METHODS: We included 44 patients with new-onset IIH. Thirty-four patients with suspected but u...... tinnitus may suggest intracranial hypertension. Based on data from a well-defined IIH cohort, we propose a revision of the ICDH-3 beta diagnostic criteria with improved clinical applicability and increased sensitivity and specificity....

  12. Hypertension and renovascular disease

    DEFF Research Database (Denmark)

    Hasbak, P; Ibsen, H; Jensen, Lars Thorbjørn

    2002-01-01

    The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21%), nephr......The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21...

  13. Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

    OpenAIRE

    Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

    2003-01-01

    In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

  14. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease.

    Science.gov (United States)

    Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I

    2015-01-01

    Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production. © 2014 American Heart Association, Inc.

  15. Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of Centrally Mediated Mechanisms.

    Science.gov (United States)

    Sriramula, Srinivas; Lazartigues, Eric

    2017-12-01

    Hypertension is associated with increased activity of the kallikrein-kinin system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and inflammation. Despite evidence supporting a role for the B1R in blood pressure regulation, the mechanisms by which B1R could alter autonomic function and participate in the pathogenesis of hypertension remain unidentified. We sought to explore whether B1R-mediated inflammation contributes to hypertension and investigate the molecular mechanisms involved. In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate-salt model of neurogenic hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate-salt treatment in wild-type mice led to significant increases in B1R mRNA and protein levels and bradykinin levels, enhanced gene expression of carboxypeptidase N supporting an increase in the B1R ligand, associated with enhanced blood pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired baroreflex sensitivity, whereas these changes were blunted or prevented in B1R knockout mice. B1R stimulation was further shown to involve activation of the ASK1-JNK-ERK1/2 and NF-κB pathways in the brain. To dismiss potential developmental alterations in knockout mice, we further used B1R blockade selectively in the brain of wild-type mice. Supporting the central origin of this mechanism, intracerebroventricular infusion of a specific B1R antagonist, attenuated the deoxycorticosterone acetate-salt-induced increase in blood pressure in wild-type mice. Our data provide the first evidence of a central role for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone acetate-salt hypertension and offer novel insights into possible B1R-targeted therapies for the treatment of neurogenic hypertension. © 2017 American Heart Association, Inc.

  16. Hyperuricemia in Childhood Primary Hypertension

    OpenAIRE

    Feig, Daniel I.; Johnson, Richard J.

    2003-01-01

    Experimental animal models suggest that uric acid might have a pathogenic role in the early development of primary hypertension. We hypothesized that serum uric acid is correlated with blood pressure in children with new-onset, untreated, primary hypertension. We evaluated 125 consecutive children referred to the Baylor Pediatric Renal Program for evaluation of hypertension. None of the subjects had previously been evaluated or treated for hypertension. The children ranged in age from 6 to 18...

  17. Hypertension and experimental stroke therapies

    OpenAIRE

    O'Collins, Victoria E; Donnan, Geoffrey A; Macleod, Malcolm R; Howells, David W

    2013-01-01

    Hypertension is an established target for long-term stroke prevention but procedures for management of hypertension in acute stroke are less certain. Here, we analyze basic science data to examine the impact of hypertension on candidate stroke therapies and of anti-hypertensive treatments on stroke outcome. Methods: Data were pooled from 3,288 acute ischemic stroke experiments (47,899 animals) testing the effect of therapies on infarct size (published 1978–2010). Data were combined using meta...

  18. EMERGENCY STATES IN ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    M. A. Gurevich

    2014-01-01

    Full Text Available The article describes in detail potential emergency states in patients with different stages of arterial hypertension with special attention to diagnosis and rational management of hypertensive crisis. Differentiated approach to management of different forms of hypertensive crisis is specified.

  19. Primary lung hypertension in-patient with hypertension portal

    International Nuclear Information System (INIS)

    Restrepo Uribe; Villa Restrepo, Alfredo

    1990-01-01

    Thorax x-rays were reviewed in 18 patients with portal hypertension. In 28% of these we found radiologic signs of pulmonary hypertension of the precapillary type. The existing relation between primary pulmonary hypertension and portal hypertension has been established in different scientific papers. In the published series the incidence of primary pulmonary hypertension is less than the one of found in these patients the physiopathology of this association is reviewed, and as a hypothetic manner it is postulated the possible roll of the hypoxaemia of the residents, at the altitude of the Bogota city. (2.640 mts) as a helping factor in this phenomenon

  20. Reinfections with strains of Trypanosoma cruzi, of different biodemes as a factor of aggravation of myocarditis and myositis in mice Reinfecções com cepas do Trypanosoma cruzi de diferentes biodemas como fator agravante da miocardite e miosite em camundongos

    Directory of Open Access Journals (Sweden)

    Sonia Gumes Andrade

    2006-02-01

    Full Text Available Reinfections with Trypanosoma cruzi in patients from endemic areas have been claimed to be an aggravation factor of cardiac manifestations in Chagas' disease. In the present study, the influence of triple infections with strains of different biodemes, on cardiac and skeletal muscle lesions was experimentally tested. Fifty eight mice chronically infected with the Colombian strain (Biodeme Type III were successively reinfected as follows: 1st group - reinfected with 21 SF strain (Type II followed by Y strain (Type I ; 2nd - group reinfections with Y strain followed by 21SF strain. Isoenzyme analysis of parasites from hemocultures obtained from triple infected mice, revealed the patterns of three distinct zymodemes in the same animal. Each Trypanosoma cruzi strain was reisolated after four passages in mice on either the 7th, 14th or 30th day after inoculation with the blood of triple infected mice. Histopathology results demonstrated a significant exacerbation of cardiac and skeletal muscle inflammatory lesions, confirmed by morphometric evaluation, in mice with triple infection. No aggravation of parasitism was detected. The possibility of an enhancement of cellular response in the triple infected mice is suggested.Reinfecções pelo Trypanosoma cruzi em pacientes de áreas endêmicas têm sido mencionadas como fator agravante das manifestações cardíacas na doença de Chagas. No presente estudo, a influência da tríplice infecção com cepas de diferentes biodemas, sobre as lesões do miocárdio e de músculo esquelético foi investigada experimentalmente. Cinqüenta e oito camundongos cronicamente infectados com a cepa Colombiana do Trypanosoma cruzi (Biodema Tipo III foram sucessivamente reinoculadas como a seguir: 1º grupo - reinfectados com a cepa 21 SF (Tipo II seguido pela cepa Y (Tipo I; 2º grupo - reinfecção com a cepa Y seguida pela cepa 21SF. A análise isoenzimática dos parasitas das hemoculturas obtidas dos animais com tr

  1. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    Science.gov (United States)

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. © 2014 American Heart Association, Inc.

  2. IgG Receptor FcγRIIB Plays a Key Role in Obesity-Induced Hypertension

    Science.gov (United States)

    Sundgren, Nathan C.; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D.; Tanigaki, Keiji; Yuhanna, Ivan S.; Chambliss, Ken L.; Mineo, Chieko; Shaul, Philip W.

    2015-01-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB+/+ mice developed obesity-induced hypertension, FcγRIIB−/− mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet–fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. PMID:25368023

  3. Decoding white coat hypertension

    Science.gov (United States)

    Bloomfield, Dennis A; Park, Alex

    2017-01-01

    There is arguably no less understood or more intriguing problem in hypertension that the “white coat” condition, the standard concept of which is significantly blood pressure reading obtained by medical personnel of authoritative standing than that obtained by more junior and less authoritative personnel and by the patients themselves. Using hospital-initiated ambulatory blood pressure monitoring, the while effect manifests as initial and ending pressure elevations, and, in treated patients, a low daytime profile. The effect is essentially systolic. Pure diastolic white coat hypertension appears to be exceedingly rare. On the basis of the studies, we believe that the white coat phenomenon is a common, periodic, neuro-endocrine reflex conditioned by anticipation of having the blood pressure taken and the fear of what this measurement may indicate concerning future illness. It does not change with time, or with prolonged association with the physician, particularly with advancing years, it may be superimposed upon essential hypertension, and in patients receiving hypertensive medication, blunting of the nighttime dip, which occurs in about half the patients, may be a compensatory mechanisms, rather than an indication of cardiovascular risk. Rather than the blunted dip, the morning surge or the widened pulse pressure, cardiovascular risk appears to be related to elevation of the average night time pressure. PMID:28352632

  4. Angiography for renal hypertension

    International Nuclear Information System (INIS)

    Chuang, V.P.; Ernst, C.B.

    1985-01-01

    As angioplasty and operative techniques have become more precise and successful, so have evaluation techniques. Preoperative arteriography is indispensible for deciding on the appropriate treatment modality and the specifics of the procedure. Arteriography, therefore, remains the cornerstone in managing renovascular hypertension and renal arterial disease

  5. Children and Hypertension.

    Science.gov (United States)

    Carter, Denise

    1983-01-01

    Since children as young as seven years old can suffer from hypertension, all children should have blood pressure checked during physical examinations. Guidelines for testing children's blood pressure are presented along with suggestions about what schools and parents can do to help deal with the problem. (PP)

  6. Project "Hypertension Alert."

    Science.gov (United States)

    Sailors, Emma Lou

    1983-01-01

    "Hypertension Alert," a 1979-80 blood pressure screening-awareness project of the Yonkers, New York Public Schools, is described. Data is analyzed in tables for ethnic composition, and range of blood pressure readings for the high school, junior high school, and elementary school students tested. (Author/JMK)

  7. Hypertensive Heart Disease

    DEFF Research Database (Denmark)

    Wachtell, Kristian

    2011-01-01

    Abstract Hypertensive heart disease is prevalent and during the last decade it has been determined that patients with left ventricular (LV) hypertrophy have increased cardiovascular morbidity and mortality. However, many have doubted the effectiveness of LV mass assessment because it is difficult...

  8. What Is Pulmonary Hypertension?

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Pulmonary Hypertension - High Blood Pressure in the Heart-to-Lung System Updated:Jan ... Pressure" This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

  9. Hypertension og hjertet

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Andersen, Niels Holmark; Svendsen, Tage Lysbo

    2009-01-01

    of left ventricular mass is associated with substantial and significant reduction of cardiovascular morbidity and mortality. Hypertension is strongly associated with increased risk of subsequent heart failure. Meta analysis data suggests that reduction in blood pressure is also associated with very...

  10. Fermented milk for hypertension

    DEFF Research Database (Denmark)

    Usinger, Lotte; Reimer, Christina; Ibsen, Hans

    2012-01-01

    Fermented milk has been suggested to have a blood pressure lowering effect through increased content of proteins and peptides produced during the bacterial fermentation. Hypertension is one of the major risk factors for cardiovascular disease world wide and new blood pressure reducing lifestyle...

  11. Nitroglycerin kan give hypertension

    DEFF Research Database (Denmark)

    Mørup, Peter; Levinsen, Tine Holbæk; Hovind, Peter

    2011-01-01

    Hg. The conclusion was that her response was a paradoxical response to glycerylnitrate, orthostatism and a pathological response to massage of the carotid artery. This is the third reported case on paradoxical hypertension induced by glyceryl nitrates. It is speculated that dysfunction of the cerebral bloodflow...

  12. Hypertension, a health economics perspective.

    Science.gov (United States)

    Alcocer, Luis; Cueto, Liliana

    2008-06-01

    The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment.

  13. Pulmonary Hypertension and Pulmonary Vasodilators.

    Science.gov (United States)

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Wound Healing in Mac-1 Deficient Mice

    Science.gov (United States)

    2017-05-01

    Dentistry, University of Illinois at Chicago, Chicago, IL, USA. 2 Department of Defense Biotechnology High Performance Computing Software...study, we used a commercially available Mac-1 deficient strain to examine whether this deficit 5 extends to slightly smaller wounds and incisional...levels of Collagen I and Collagen III in wounds from the two strains of mice at any time point. Unwounded skin from both WT and Mac-1 -/- mice contained

  15. [Hypertension in polycystic ovary syndrome].

    Science.gov (United States)

    Ben Salem Hachmi, L; Ben Salem Hachmi, S; Bouzid, C; Younsi, N; Smida, H; Bouguerra, R; Ben Slama, C

    2006-01-01

    Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors. The aims of this study are to investigate the prevalence of hypertension in a female population with PCOS and to correlate hypertension with her clinical and hormonal profile. it is a transversal study of 79 PCOS patients with mean age of 25 +/- 7 years (range 13-44). PCOS diagnosis is made by Rotterdam consensus criteria's (2003). WHO definition of hypertension is used (BP 140/90 mmHg). Blood pressure is measured three times in each patient. Ovarian echography and biochemical assays (GnRH test, androgens, cholesterol, triglycerides, and oral glucose tolerance test) are made before the 5th day of the menstrual cycle. 12% of PCOS women have hypertension. Family history of hypertension is not a predictive factor of hypertension in our study. PCOS patients with hypertension are not significantly older than those without hypertension (28.4 +/- 6.5 vs. 25.2 +/- 7; p = 0.12). If compared to PCOS women without hypertension, those with hypertension have a significantly higher BMI (39.2 +/- 7 vs. 29.6; p = 0.0004). PCOS patients with and without hypertension do not differ significantly in their level of androgens and total cholesterol. Triglycerides level is higher in PCOS patients with hypertension (p = 0.06). In oral glucose tolerance test, areas under the curve of insulin and glucose are significantly higher in PCOS patients with hypertension (respectively p = 0.06 and 0.02). The area under the curve of LH during GnRH test is lower in PCOS patients with hypertension (p = 0.04).

  16. The evolving definition of systemic arterial hypertension.

    Science.gov (United States)

    Ram, C Venkata S; Giles, Thomas D

    2010-05-01

    Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

  17. Hepatic angiography: Portal hypertension

    International Nuclear Information System (INIS)

    Oliver, T.W. Jr.; Sones, P.J. Jr.

    1985-01-01

    Portal hypertension is usually a manifestation of underlying hepatic parenchymal disease, although it may be secondary to portal or hepatic venous thrombosis and rarely to hyperdynamic portal states. Portal hypertension may present as encephalopathy, ascites, jaundice, hepatic failure, or catastrophic upper gastrointestinal hemorrhage. Radiologic investigation should include indirect or direct measurements of portal pressure, assessment of portal venous perfusion, visualization of collaterals, and demonstration of arterial and venous anatomy for potential shunt procedure. Following survival of initial variceal bleeding, the most effective procedure to prevent recurrent hemorrhage is a shunt to decompress the varices. The decision whether to intervene medically or surgically during the acute hemorrhagic episode as well as the type of shunt used to prevent future hemorrhage is the subject of continuing controversy

  18. [Exercise in arterial hypertension].

    Science.gov (United States)

    Predel, Hans-Georg; Schramm, Thomas

    2006-09-01

    Regular endurance training has established itself as a major therapeutic principle in the specter of nonpharmacological measures in arterial hypertension. An initial medical check as well as an adequate technique, dosage and intensity of the prescribed exercise training are mandatory. With respect to the concomitant pharmacological treatment, it should be considered that the beneficial effects of lifestyle modification will not be counteracted by the chosen antihypertensive drug but, ideally, synergistically supported. Based on the individual clinical situation, principally all antihypertensive drugs recommended by the current European guidelines, may be prescribed as mono- or combination therapy.beta-receptor blockers are especially capable of controlling excessive exercise-induced blood pressure increase; however, they have metabolic and exercise physiological limitations. The neutrality concerning metabolic and exercise physiological parameters as well as the positive profile of side effects favor ACE inhibitors, long-acting calcium channel blockers and especially AT(1) antagonists in physically active hypertensive patients with concomitant metabolic syndrome.

  19. [Chronic hypertension and pregnancy].

    Science.gov (United States)

    Lecarpentier, Edouard; Tsatsaris, Vassili

    2012-09-01

    Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality and morbidity. The management of patients with chronic hypertension requires a multidisciplinary approach prior to conception, during pregnancy and post-partum. In the preconception period, fetotoxic agents should be discontinued. It is also essential to undertake a full cardiovascular examination which may, in some cases, question the possibility of pregnancy. During pregnancy, blood pressure should be monitored and controlled, but not necessarily returned to a normal value. Low blood pressure levels could indeed lead to placental hypoperfusion and fetal growth restriction. Close clinical, biological and ultrasound monitoring is recommended, even postpartum, since those patients are at higher risk for preeclampsia.

  20. Adrenal Mass Causing Secondary Hypertension.

    Science.gov (United States)

    Robinson, Darlene Y

    2015-11-01

    Most hypertensive patients have essential (primary) hypertension; only 5% to 10% have a secondary cause. Two clinical characteristics suggestive of secondary hypertension are early onset (hypertension (>180/110 mm Hg). When faced with these findings, clinicians should consider a secondary cause of hypertension. A 22-year-old woman being evaluated for asthma exacerbation in the emergency department was noted to have severe persistent hypertension. Additional evaluation revealed severe hypokalemia, metabolic alkalosis, and hypernatremia. The patient was admitted to the hospital for blood pressure management, electrolyte replacement, and further evaluation of presumed hyperaldosteronism. Diagnostic imaging revealed a large adrenal mass. Surgical resection was performed, leading to a diagnosis of hyperaldosteronism caused by adrenal carcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Secondary hypertension is far less common than essential hypertension; however, considering the large volume of patients seen in emergency departments, it is likely that some will have secondary hypertension. Emergency physicians should be aware of the clinical characteristics that suggest secondary hypertension so that the appropriate diagnostic and treatment pathways can be pursued. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Neurological disorders in hypertensive patients

    Directory of Open Access Journals (Sweden)

    N. V. Vakhnina

    2015-01-01

    Full Text Available Hypertension is one of the most common vascular diseases. The brain as target organs in hypertension is damaged more often and earlier. Neurological complications due to hypertension are frequently hyperdiagnosed in Russian neurological practice. Thus, headache, dizziness, impaired recall of recent events, nocturnal sleep disorders, and many other complaints in a hypertensive patient are usually regarded as a manifestation of dyscirculatory encephalopathy. At the same time headaches (tension headache and migraine in hypertensive patients are predominantly primary; headache associated with dramatic marked elevations in blood pressure is encountered in only a small number of patients. The role of cerebrovascular diseases in the development of dizziness in hypertensive patients is also overestimated. The vast majority of cases, patients with this complaint are in fact identified to have benign paroxysmal postural vertigo, Mеniеre’s disease, vestibular neuronitis, or vestibular migraine. Psychogenic disorders or multisensory insufficiency are generally responsible for non-systemic vertigo in hypertensive patients. Chronic cerebral circulatory insufficiency may cause non-systemic vertigo as a subjective equivalent of postural instability.Cognitive impairments (CIs are the most common and earliest manifestation of cerebrovascular lesion in hypertension. In most cases, CIs in hypertension were vascular and associated with cerebrovascular lesion due to lacunar infarcts and leukoaraiosis. However, mixed CIs frequently occur when hypertensive patients are also found to have signs of a degenerative disease, most commonly in Alzheimer’s disease.

  2. Epidemiology of hypertensive kidney disease.

    Science.gov (United States)

    Udani, Suneel; Lazich, Ivana; Bakris, George L

    2011-01-01

    The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD) attributable to hypertension continues to rise worldwide. Identifying the precise prevalence of CKD attributable to hypertension is difficult owing to the absence of uniform criteria to establish a diagnosis of hypertensive nephropathy. Despite the increasing prevalence of CKD-associated hypertension, awareness of hypertension among individuals with CKD remains suboptimal and rates of blood-pressure control remain poor. Targeted subgroups involved in studies of CKD seem to reach better rates of blood-pressure control, suggesting that this therapeutic goal can be achieved in patients with CKD. Elevated blood-pressure levels are associated with CKD progression. However, the optimal blood-pressure level and pharmacological agent remains unclear. Physicians treating patients with CKD must recognize the importance of maintaining optimal salt and volume balance to achieve blood-pressure goals. Furthermore, agents that modify the renin-angiotensin-aldosterone axis can be an important adjunct to therapy and physicians must monitor expected changes in serum creatinine and electrolyte levels after their administration. Hypertension remains a common factor complicating CKD. Future investigations identifying early signs of hypertension-related CKD, increasing awareness of the effects of hypertension in CKD and determining optimal therapeutic interventions might help reduce the incidence of hypertensive nephropathy.

  3. Angiography in portal hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Zeitler, E

    1982-04-05

    We report on the cooperative possibilities the radiologist has as to diagnosis and therapy of portal hypertension. The catheter angiography allows to make a differentiation between pre- and intrahepatic bloc and the localization of bleeding esophagus varices. Only after all endoscopic measures with sclerotherapy and Laser coagulation have failed, catheter angiography will be carried out as a therapeutic measure. The future development, however, will give the opportunity to a series of therapeutic attempts on the field of interventional radiology.

  4. Renal denervation and hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  5. Angiography in portal hypertension

    International Nuclear Information System (INIS)

    Zeitler, E.

    1982-01-01

    We report on the cooperative possibilities the radiologist has as to diagnosis and therapy of portal hypertension. The catheter angiography allows to make a differentiation between pre- and intrahepatic bloc and the localization of bleeding esophagus varices. Only after all endoscopic measures with sclerotherapy and Laser coagulation have failed, catheter angiography will be carried out as a therapeutic measure. The future development, however, will give the opportunity to a series of therapeutic attempts on the field of interventional radiology. (orig.) [de

  6. Managing hypertension by polyphenols.

    Science.gov (United States)

    Fernández-Arroyo, Salvador; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-06-01

    Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice. Georg Thieme Verlag KG Stuttgart · New York.

  7. [Resistant hypertension: An update].

    Science.gov (United States)

    Renna, N F

    2018-02-04

    An estimated 10% to 20% of hypertensive patients could be considered resistant to treatment (RH). These are patients who are not controlled using three drugs, at the maximum tolerated doses, including a diuretic, as well as those with high blood pressure controlled using four or more drugs. The term is used to identify patients that might benefit from special diagnostic and/or therapeutic consideration. The term 'refractory hypertension' has recently been proposed as a novel phenotype of antihypertensive failure. It refers to patients whose blood pressure cannot be controlled with maximum treatment. The first studies of this phenotype indicate that it is rare and affects less than 5% of patients with RH. Adherence to or compliance with medical treatment is key to defining resistant hypertension. Closer attention has been paid to clinical and experimental research since the first scientific statement for the diagnosis, assessment and treatment of RH from the American Heart Association, and in the European guidelines, was published in 2008. This review will set out the concepts relating to prevalence, prognosis and compliance and cover the latest developments on this subject. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    Science.gov (United States)

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  9. Hypertensive target organ damage in Ghanaian civil servants with hypertension.

    Directory of Open Access Journals (Sweden)

    Juliet Addo

    2009-08-01

    Full Text Available Low levels of detection, treatment and control of hypertension have repeatedly been reported from sub Saharan Africa, potentially increasing the likelihood of target organ damage.A cross-sectional study was conducted on 1015 urban civil servants aged > or = 25 years from seven central government ministries in Accra, Ghana. Participants diagnosed to have hypertension were examined for target organ involvement. Hypertensive target organ damage was defined as the detection of any of the following: left ventricular hypertrophy diagnosed by electrocardiogram, reduction in glomerular filtration rate, the presence of hypertensive retinopathy or a history of a stroke.Of the 219 hypertensive participants examined, 104 (47.5% had evidence of target organ damage. The presence of target organ damage was associated with higher systolic and diastolic blood pressure levels. The odds of developing hypertensive target organ damage was five to six times higher in participants with blood pressure (BP > or = 180/110 mmHg compared to those with BP < 140/90 mmHg, and there was a trend to higher odds of target organ damage with increasing BP (p = 0.001. Women had about lower odds of developing target organ damage compared to men.The high prevalence of target organ damage in this working population associated with increasing blood pressure, emphasises the need for hypertension control programs aimed at improving the detection of hypertension, and importantly addressing the issues inhibiting the effective treatment and control of people with hypertension in the population.

  10. Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

    1988-01-01

    Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

  11. [Control of hypertension in nursing homes].

    Science.gov (United States)

    Thomas, J M; Alvarez, W; Mulaj, M; De Breucker, S; Leeman, M; Pepersack, T

    2006-09-01

    In a cross sectional study we determined prevalence of hypertension among institutionalized old subjects. Prevalence of hypertension was 69%. Among detected hypertensive patients, 76% received an antihypertensive drug treatment. 61% of the declared hypertensive patients and 80% of the treated hypertensive patients had their blood pressure controlled. The general practitioners should better detect and treat this common geriatric problem associated with a high comorbidity.

  12. Taste and hypertension in humans

    DEFF Research Database (Denmark)

    Roura, Eugeni; Foster, Simon; Winklebach, Anja

    2016-01-01

    The association between salty taste and NaCl intake with hypertension is well-established, although it is far from completely understood. Other taste types such as sweet, umami or bitter have also been related to alterations in blood pressure. Here, we review the mutual relationship between taste...... and hypertension to identify potential avenues to better control blood pressure. This review focuses on published data involving humans, with the exception of a section on molecular mechanisms. There is compelling evidence to suggest that changes in salty taste sensitivity can be used to predict the onset...... of hypertension. This goes hand in hand with the medical concept of sodium sensitivity, which also increases with age, particularly in hypertensive patients. The association of hypertension with the loss of taste acuity less definitive with some data/conclusions masked by the use of anti-hypertensive drugs...

  13. Hypertension--forekomst og behandling

    DEFF Research Database (Denmark)

    Ibsen, Hans; Jørgensen, Torben; Jensen, Gorm B

    2009-01-01

    Hypertension is the most important modifiable risk factor for cardiovascular disease. However, less than half of all hypertensives have their blood pressure reduced to relevant goals. The prevalence of hypertension in Denmark was found to be between 26% and 40% of the adult population. Just over ...... half were aware of the diagnosis, but less than half were in treatment. Blood pressure control in patients who are undergoing treatment has improved during recent years, but there is still a gap to achievable control rates....

  14. Hypertension--forekomst og behandling

    DEFF Research Database (Denmark)

    Ibsen, Hans; Jørgensen, Torben; Jensen, Gorm B

    2009-01-01

    Hypertension is the most important modifiable risk factor for cardiovascular disease. However, less than half of all hypertensives have their blood pressure reduced to relevant goals. The prevalence of hypertension in Denmark was found to be between 26% and 40% of the adult population. Just over...... half were aware of the diagnosis, but less than half were in treatment. Blood pressure control in patients who are undergoing treatment has improved during recent years, but there is still a gap to achievable control rates....

  15. Hypertension og det metaboliske syndrom

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Jeppesen, Jørgen; Larsen, Mogens Lytken

    2009-01-01

    The metabolic syndrome is a relatively prevalent condition characterized by co-existence of several metabolic and cardiovascular risk factors including hypertension. Patients with hypertension have an increased risk of developing the metabolic syndrome which, in turn, increases the cardiovascular...... syndrome is of clinical importance as it makes the treating physician test for other elements of the syndrome in patients with one of the elements, e.g. hypertension. Udgivelsesdato: 2009-Jun...

  16. Hypertension og det metaboliske syndrom

    DEFF Research Database (Denmark)

    Olsen, Michael; Jeppesen, Jørgen; Larsen, Mogens

    2009-01-01

    The metabolic syndrome is a relatively prevalent condition characterized by co-existence of several metabolic and cardiovascular risk factors including hypertension. Patients with hypertension have an increased risk of developing the metabolic syndrome which, in turn, increases the cardiovascular...... syndrome is of clinical importance as it makes the treating physician test for other elements of the syndrome in patients with one of the elements, e.g. hypertension. Udgivelsesdato: 2009-Jun-15...

  17. [Hepatopulmonary syndrome and portopulmonary hypertension].

    Science.gov (United States)

    Marcu, Cristina; Schiffer, Eduardo; Aubert, John-David; Vionnet, Julien; Yerly, Patrick; Deltenre, Pierre; Marot, Astrid

    2017-08-30

    Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two frequent pulmonary complications of liver disease. Portal hypertension is a key element in the pathogenesis of both disorders, which are however distinct in terms of pathogenesis, diagnosis and treatment. HPS corresponds to an abnormal arterial oxygenation in relation with the development of intrapulmonary vascular dilatations. POPH is a pulmonary arterial hypertension in the setting of portal hypertension and elevated pulmonary vascular resistance. As both diseases are associated with an increased risk of morbidity and mortality, it is important to screen and evaluate the severity of these two disorders particularly in liver transplant candidates.

  18. Pulmonary hypertension in older adults.

    Science.gov (United States)

    McArdle, John R; Trow, Terence K; Lerz, Kathryn

    2007-12-01

    Pulmonary hypertension is a frequently encountered problem in older patients. True idiopathic pulmonary arterial hypertension can also be seen and requires careful exclusion in older patients. Institution of therapies must be tempered with an appreciation of individual comorbidities and functional limitations that may affect patients' ability to comply and benefit from the complex treatments available for pulmonary arterial hypertension. This article reviews the existing data on the various forms of pulmonary hypertension presenting in older patients and on appropriate therapy in this challenging population.

  19. ESSENTIAL ARTERIAL HYPERTENSION AND RISK FACTORS ASSOCIATED WITH HYPERTENSIVE NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Boban Milojković

    2014-12-01

    Full Text Available Arterial hypertension is a major risk factor that predisposes to cardiovascular disorders and is responsible for most of the morbidity and mortality in patients. Hypertension is closely associated with the kidney, because kidney disease can be both the cause and consequence of increased blood pressure. Elevation of blood pressure is a strong independent risk factor for hypertensive nephropathy and development of ESRD. The pathogenesis of ischemic hypertensive nephropathy (IHN is multifactoral, and in addition to blood pressure other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include obesity, smoking, male gender and other still unknown risk factors. The aim of this paper was to analyse the association between essential arterial hypertension and renal hypertensive disease and prevalence of other atherosclerotic risk factors in patients with developed hypertensive renal disease. In this prospective cross sectional study 283 patients of both genders with diagnosed essential hypertension and hypertensive renal disease were analysed. The anamnestic data related to age, duration of hypertension, history of smoking, presence of hypertensive retinopathy, hypertrophy of the left chamber and data about previous renal diseases were collected through conversation and medical documentation. The clinical examination comprise determination of blood pressure, body mass index (BMI, lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, serum urea and creatinine, urine, albumin and protein concentration. The total number of 283 patients (185 males and 98 females with HN was analyzed. The analysis revealed significantly higher proportion of males aged over 60 years with IHN. The mean age of examined hypertensive patients with IHN is 62.6±8.8 years with duration of hypertension 19.8±5.9 years. All examined patients had hypertensive retinopathy and

  20. Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Mancini, M.; Petretto, E.; Kleinert, C.; Scavone, A.; De, T.; Cook, S.; Šilhavý, Jan; Zídek, Václav; Pravenec, Michal; d´Amati, G.; Camici, P.G.

    2013-01-01

    Roč. 108, č. 1 (2013), s. 316 ISSN 0300-8428 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : arterial hypertension * coronary circulation * myocardial ischemia * spontaneously hypertensive rat * recombinant inbred strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.955, year: 2013

  1. Echocardiographic evaluation of the arterial stiffness in healthy subjects and hypertensive patients under 60 years

    International Nuclear Information System (INIS)

    Valiente Mustelier, Juan; Suarez Vazquez, Leisy; Cabrera Rego, Julio Oscar; Gandarilla Sarmientos, Julio Cesar

    2011-01-01

    We conducted a cross-sectional study that included 83 patients (healthy, n=43; hypertensive, n=40) assisted in the external consultation of the National Cardiology and Cardiovascular Surgery Institute, from April to October, 2009. We included clinical (age, sex, personal antecedents of smoking habit, obesity, hypercholesterolemia, arterial hypertension) and echocardiographic (diastolic function, arterial stiffness index [β], pressure strain elastic modulus [Ep], arterial compliance, local pulse wave velocity [LPWV]) variables

  2. A preliminary study on the pathogenicity of Bacillus licheniformis bacteria in immunodepressed mice

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Jensen, N.E.; Giese, Steen Bjørck

    1997-01-01

    The pathogenicity of 13 strains of Bacillus licheniformis was studied in immunodepressed mice. The strains had been isolated from cases of bovine abortions (n=5), bovine feedstuffs (n=3), soil (n=l), and grain products (n=2). The origin of two strains was unknown. Groups of 10 mice were inoculated...... intravenously with B. licheniformis bacteria at doses from...

  3. Evaluation and management of pediatric hypertensive crises: hypertensive urgency and hypertensive emergencies

    Directory of Open Access Journals (Sweden)

    Patel NH

    2012-11-01

    Full Text Available Nirali H Patel,1 Sarah K Romero,2 David C Kaelber31Division of Emergency Medicine, Akron Children's Hospital, Akron, OH, USA; 2Division of Emergency Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, USA; 3Departments of Information Services, Internal Medicine, Pediatrics, and Epidemiology and Biostatistics, The Center for Clinical Informatics Research and Education, The MetroHealth System and School of Medicine, Case Western Reserve University, Cleveland OH, USAAbstract: Hypertension (HTN in the pediatric population is estimated to have a world-wide prevalence of 2%-5%. As with adults, pediatric patients with HTN can present with hypertensive crises include hypertensive urgency and hypertensive emergencies. However, pediatric blood pressure problems have a greater chance of being from secondary causes of HTN, as opposed to primary HTN, than in adults. Thorough evaluation of a child with a hypertensive emergency includes accurate blood pressure readings, complete and focused symptom history, and appropriate past medical, surgical, and family history. Physical exam should include height, weight, four-limb blood pressures, a general overall examination and especially detailed cardiovascular and neurological examinations, including fundoscopic examination. Initial work-up should typically include electrocardiography, chest X-ray, serum chemistries, complete blood count, and urinalysis. Initial management of hypertensive emergencies generally includes the use of intravenous or oral antihypertensive medications, as well as appropriate, typically outpatient, follow-up. Emergency department goals for hypertensive crises are to (1 safely lower blood pressure, and (2 treat/minimize acute end organ damage, while (3 identifying underlying etiology. Intravenous antihypertensive medications are the treatment modality of choice for hypertensive emergencies with the goal of reducing systolic blood pressure by 25% of the original value over an 8

  4. Prevalence and persistence of masked hypertension in treated hypertensive patients

    NARCIS (Netherlands)

    Verberk, Willem J.; Thien, Theo; Kroon, Abraham A.; Lenders, Jacques W. M.; van Montfrans, Gert A.; Smit, Andries J.; de Leeuw, Peter W.

    2007-01-01

    Background: Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the

  5. Prevalence and persistence of masked hypertension in treated hypertensive patients.

    NARCIS (Netherlands)

    Verberk, W.J.; Thien, Th.; Kroon, A.A.; Lenders, J.W.M.; Montfrans, G.A. van; Smit, A.J.; Leeuw, P.W. de

    2007-01-01

    BACKGROUND: Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the

  6. Prevalence and persistence of masked hypertension in treated hypertensive patients

    NARCIS (Netherlands)

    Verberk, Willem J.; Thien, Theo; Kroon, Abraham A.; Lenders, Jacques W. M.; van Montfrans, Gert A.; Smit, Andries J.; de Leeuw, Peter W.

    2007-01-01

    BACKGROUND: Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the

  7. Dietary habits of hypertensive patients in a tertiary hypertension ...

    African Journals Online (AJOL)

    Introduction: The prescriptions regarding non-pharmacological care in the management of hypertension has been carefully defined by the various practice guidelines. However, there is paucity of data on dietary practices in our environment, therefore this study set out to determine the dietary practices of hypertensive ...

  8. Drug induced hypertension--An unappreciated cause of secondary hypertension.

    Science.gov (United States)

    Grossman, Alon; Messerli, Franz H; Grossman, Ehud

    2015-09-15

    Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Pre-Hypertension and Hypertension in Adolescence: How much ...

    African Journals Online (AJOL)

    Background: Hypertension is an important worldwide public-health challenge because of its high frequency and concomitant risks of cardiovascular and kidney disease. Previous studies have documented that hypertension may begin in adolescence, perhaps even in childhood. Objectives: This study set out to determine ...

  10. Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension

    DEFF Research Database (Denmark)

    Sällström, Johan; Peuckert, Christiane; Gao, Xiang

    2013-01-01

    Experimental hydronephrosis induced by partial ureteral obstruction at 3 wk of age causes hypertension and renal impairment in adult rats and mice. Signaling by Ephrin receptors (Eph) and their ligands (ephrins) importantly regulates embryonic development. Genetically modified mice, where...... the cytoplasmic domain of the EphA4 receptor has been substituted by enhanced green fluorescent protein (EphA4(gf/gf)), develop spontaneous hydronephrosis and provide a model for further studies of the disorder. The present study aimed to determine if animals with congenital hydronephrosis develop hypertension...... and renal injuries, similar to that of experimental hydronephrosis. Ultrasound and Doppler techniques were used to visualize renal impairment in the adult mice. Telemetric blood pressure measurements were performed in EphA4(gf/gf) mice and littermate controls (EphA4(+/+)) during normal (0.7% NaCl)- and high...

  11. Liquorice: a root cause of secondary hypertension

    OpenAIRE

    Varma, Ravi; Ross, Calum N.

    2017-01-01

    We describe a patient presenting with hypertension and hypokalaemia who was ultimately diagnosed with liquorice- induced pseudohyperaldosteronism. This rare cause of secondary hypertension illustrates the importance of a methodical approach to the assessment of hypertension.

  12. ORIGINAL ARTICLES Hypertension Guideline 2003 Update

    African Journals Online (AJOL)

    reduction of BP in the elderly and in those with severe hypertension should .... management of hypertension in adults by health care .... They may demonstrate postural and post- ..... Persons with severe hypertension fall into three categories.

  13. Genetics Home Reference: pulmonary arterial hypertension

    Science.gov (United States)

    ... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

  14. Isolated Systolic Hypertension: A Health Concern?

    Science.gov (United States)

    Isolated systolic hypertension: A health concern? Is having a high top number (systolic) blood pressure, but a normal bottom number (diastolic) ... mm Hg, you have a common type of high blood pressure called isolated systolic hypertension. Isolated systolic hypertension can ...

  15. Pharmacotherapy for mild hypertension

    Directory of Open Access Journals (Sweden)

    Diana Diao

    2012-01-01

    Full Text Available BACKGROUND: People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population. The benefits and harms of treating mild hypertension in primary prevention patients are not known at present. This review examines the existing randomized controlled trial (RCT evidence. OBJECTIVE: Primary objective: To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension (systolic blood pressure (BP 140-159 mmHg and/or diastolic BP 90-99 mmHg and without cardiovascular disease. METHODS: Search: We searched CENTRAL (2011, Issue 1, MEDLINE (1948 to May 2011, EMBASE (1980 to May 2011 and reference lists of articles. The Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE were searched for previous reviews and meta-analyses of anti-hypertensive drug treatment compared to placebo or no treatment trials up until the end of 2011. Selection criteria: RCTs of at least 1 year duration. Data collection and analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD, total cardiovascular events (CVS, and withdrawals due to adverse effects. MAIN RESULTS: Of 11 RCTs identified 4 were included in this review, with 8,912 participants. Treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15. In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57, stroke (RR 0.51, 95% CI 0.24, 1.08, or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32. Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95% CI 4.14, 5.57, ARR 9%. AUTHORS' CONCLUSIONS: Antihypertensive drugs used in the treatment of adults (primary prevention with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg have not been

  16. Nocturnal Hypertension: Neglected Issue in Comprehensive Hypertension Management

    Directory of Open Access Journals (Sweden)

    Andi Kristanto

    2016-09-01

    Full Text Available The body circardian rhythm affects blood pressure variability at day and night, therefore blood pressure at day and night might be different. Nocturnal hypertension is defined as increase of blood pressure >120/70mmHg at night, which is caused by disturbed circadian rhythm, and associated with higher cardiovascular and cerebrovascular events also mortality in hypertensive patients. Nocturnal hypertension and declining blood pressure pattern, can only be detected by continuous examination for 24 hours, also known as ambulatory blood pressure measurement (ABPM. Chronotherapy, has become a strategy for managing the hypertensive nocturnal patients, by taking hypertensive medication at night to obtain normal blood pressure decrease in accordance with the normal circadian rhythm and, improving blood pressure control.

  17. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Nielsen, Mette Lundgren; Pareek, Manan; Gerke, O

    2015-01-01

    We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population......, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed...

  18. Assessment of knowledge about hypertension

    Directory of Open Access Journals (Sweden)

    Paweł Węgorowski

    2017-07-01

    Patient knowledge about hypertension and its effects can affect the effectiveness of treatment. Medical education should be of paramount importance for medical staff, with particular attention to the self-control of blood pressure by patients. In summary, it is important to note that due to the high risk of complications, both treatment and prevention of hypertension are important.

  19. Resistant Hypertension and Cardiorenovascular Risk

    Directory of Open Access Journals (Sweden)

    Prkacin Ingrid

    2017-06-01

    Full Text Available Studies have documented independent contribution of sympathetic activation to the cardiovascular disease continuum. Hypertension is one of the leading modifiable factors. Most if not all the benefit of antihypertensive treatment depends on blood pressure lowering, regardless how it is obtained. Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of the concurrent use of three antihypertensive drugs of different classes. Ideally, one of the three drugs should be a diuretic, and all drugs should be prescribed at optimal dose amounts. Poor adherence to antihypertensive therapy, undiscovered secondary causes (e.g. obstructive sleep apnea, primary aldosteronism, renal artery stenosis, and lifestyle factors (e.g. obesity, excessive sodium intake, heavy alcohol intake, various drug interactions are the most common causes of resistant hypertension. Cardio(renovascular morbidity and mortality are significantly higher in resistant hypertensive than in general hypertensive population, as such patients are typically presented with a long-standing history of poorly controlled hypertension. Early diagnosis and treatment is needed to avoid further end-organ damage to prevent cardiorenovascular remodeling. Treatment strategy includes lifestyle changes, adding a mineralocorticoid receptor antagonist, treatment adherence in cardiovascular prevention and, in case of failure to control blood pressure, renal sympathetic denervation or baroreceptor activation therapy. The comparative outcomes in resistant hypertension deserve better understanding. In this review, the most current approaches to resistant hypertension and cardiovascular risk based on the available literature evidence will be discussed.

  20. Endocrine hypertension – Cushing's syndrome

    Science.gov (United States)

    Singh, Yashpal; Kotwal, Narendra; Menon, A. S.

    2011-01-01

    Hypertension is a major and frequent comorbid finding of Cushing's syndrome. This review discusses the etiology and pathophysiology of hypertension in Cushing's syndrome, while suggesting methods of management of this condition. It also provides an overview of diagnosis and management strategies in this disease. PMID:22145133

  1. The Immune System in Hypertension

    Science.gov (United States)

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  2. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development......Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

  3. Lysyl Oxidase Induces Vascular Oxidative Stress and Contributes to Arterial Stiffness and Abnormal Elastin Structure in Hypertension: Role of p38MAPK.

    Science.gov (United States)

    Martínez-Revelles, Sonia; García-Redondo, Ana B; Avendaño, María S; Varona, Saray; Palao, Teresa; Orriols, Mar; Roque, Fernanda R; Fortuño, Ana; Touyz, Rhian M; Martínez-González, Jose; Salaices, Mercedes; Rodríguez, Cristina; Briones, Ana M

    2017-09-01

    Vascular stiffness, structural elastin abnormalities, and increased oxidative stress are hallmarks of hypertension. Lysyl oxidase (LOX) is an elastin crosslinking enzyme that produces H 2 O 2 as a by-product. We addressed the interplay between LOX, oxidative stress, vessel stiffness, and elastin. Angiotensin II (Ang II)-infused hypertensive mice and spontaneously hypertensive rats (SHR) showed increased vascular LOX expression and stiffness and an abnormal elastin structure. Mice over-expressing LOX in vascular smooth muscle cells (TgLOX) exhibited similar mechanical and elastin alterations to those of hypertensive models. LOX inhibition with β-aminopropionitrile (BAPN) attenuated mechanical and elastin alterations in TgLOX mice, Ang II-infused mice, and SHR. Arteries from TgLOX mice, Ang II-infused mice, and/or SHR exhibited increased vascular H 2 O 2 and O 2 .- levels, NADPH oxidase activity, and/or mitochondrial dysfunction. BAPN prevented the higher oxidative stress in hypertensive models. Treatment of TgLOX and Ang II-infused mice and SHR with the mitochondrial-targeted superoxide dismutase mimetic mito-TEMPO, the antioxidant apocynin, or the H 2 O 2 scavenger polyethylene glycol-conjugated catalase (PEG-catalase) reduced oxidative stress, vascular stiffness, and elastin alterations. Vascular p38 mitogen-activated protein kinase (p38MAPK) activation was increased in Ang II-infused and TgLOX mice and this effect was prevented by BAPN, mito-TEMPO, or PEG-catalase. SB203580, the p38MAPK inhibitor, normalized vessel stiffness and elastin structure in TgLOX mice. We identify LOX as a novel source of vascular reactive oxygen species and a new pathway involved in vascular stiffness and elastin remodeling in hypertension. LOX up-regulation is associated with enhanced oxidative stress that promotes p38MAPK activation, elastin structural alterations, and vascular stiffness. This pathway contributes to vascular abnormalities in hypertension. Antioxid. Redox Signal. 27

  4. Dutch guideline for the management of hypertensive crisis -- 2010 revision

    NARCIS (Netherlands)

    van den Born, B. J. H.; Beutler, J. J.; Gaillard, C. A. J. M.; de Gooijer, A.; van den Meiracker, A. H.; Kroon, A. A.

    2011-01-01

    Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated

  5. Management of hypertension in pregnancy.

    Science.gov (United States)

    Chung, N A; Beevers, D G; Lip, G Y

    2001-01-01

    Hypertension is an important cause of both maternal and fetal morbidity and mortality in pregnant women. There are still no definitive guidelines as to when and how patients should be treated, but it is important that appropriate treatment is initiated early in patients at highest risk and they are closely monitored. Hypertension in pregnancy can be a difficult condition to diagnose and treat because of the numerous and differing classification systems that have been used in the past. One classification system, which accounts for the multisystem involvement which can occur in pre-eclampsia and eclampsia, divides hypertension in pregnancy into 3 main groups: pre-eclampsia, gestational hypertension and chronic hypertension. Little benefit to the fetus has been shown from treating gestational and chronic hypertension, but studies in this area have been small and would not have had the power to show a difference in outcome between treated and untreated groups. However, the reduction in morbidity and mortality in the treatment of pre-eclampsia is significant. Therefore, all pregnancies complicated by hypertension require monitoring to detect the possible onset of superimposed pre-eclampsia/eclampsia. Institutions should have a management strategy for those mothers with severe hypertension including a multidisciplinary approach, where the patient is to be monitored and which antihypertensive agents are to be used. It should not be forgotten that the definitive treatment for severe hypertension is delivery of the fetus despite risks to fetal morbidity and mortality. This will reduce blood pressure, but hypertension per se may still persist post partum requiring short term therapy.

  6. Central role for Melanocortin-4 receptors in offspring hypertension arising from maternal obesity

    NARCIS (Netherlands)

    Samuelsson, Anne Maj S; Mullier, Amandine; Maicas, Nuria; Oosterhuis, Nynke R.; Bae, Sung Eun; Novoselova, Tatiana V.; Chan, Li F.; Pombo, Joaquim M.; Taylor, Paul D.; Joles, Jaap A.; Coen, Clive W.; Balthasar, Nina; Poston, Lucilla

    2016-01-01

    Melanocortin-4 receptor (Mc4r)-expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they

  7. Cyclophilin B expression in renal proximal tubules of hypertensive rats.

    Science.gov (United States)

    Kainer, D B; Doris, P A

    2000-04-01

    Rat cyclophilin-like protein (Cy-LP) is a candidate hypertension gene initially identified by differential hybridization and implicated in renal mechanisms of salt retention and high blood pressure. We report the molecular characterization of rat cyclophilin B (CypB) and demonstrate, through sequence analysis and an allele-specific polymerase chain reaction primer assay, that CypB but not Cy-LP is expressed in rat kidney. CypB is an endoplasmic reticulum-localized prolyl-isomerase that interacts with elongation initiation factor 2-beta, an important regulator of protein translation and a central component of the endoplasmic reticulum stress response to hypoxia or ATP depletion. Active renal transport of sodium is increased in the spontaneously hypertensive rat (SHR), and there is evidence that this coincides with hypoxia and ATP depletion in the renal cortex. In the present studies we have examined expression of CypB in rat proximal tubules, which contributes to the increased renal sodium reabsorption in this model of hypertension. We report that CypB transcript abundance is significantly elevated in proximal convoluted tubules from SHR compared with the control Wistar-Kyoto strain. This upregulation occurs in weanling animals and precedes the development of hypertension, indicating that it is not a simple response to hypertension in SHR. Further, CypB expression is also higher in a proximal tubule cell line derived from SHR compared with a similar line derived from Wistar-Kyoto rats, indicating that this difference is genetically determined. No sequence differences were observed in the CypB cDNA from these 2 strains. These observations suggest that a genetically determined alteration in proximal tubules from SHR occurs that leads to increased expression of CypB. In view of evidence linking CypB to the regulation of elongation initiation factor-2, the upregulation of CypB may result from metabolic stress.

  8. Pulmonary arterial hypertension

    Science.gov (United States)

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  9. Hypertension in Patients with Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Vinicius Barbosa de; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade, E-mail: wolney@cardiol.br [Curso de Pós-Graduação em Ciências Cardiovasculares da Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2015-03-15

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

  10. Hypertension in Patients with Cancer

    International Nuclear Information System (INIS)

    Souza, Vinicius Barbosa de; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade

    2015-01-01

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality

  11. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  12. Does exercise pulmonary hypertension exist?

    Science.gov (United States)

    Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

    2016-09-01

    The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

  13. Interleukin-6 overexpression induces pulmonary hypertension.

    Science.gov (United States)

    Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

    2009-01-30

    Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.

  14. Masked Uncontrolled Hypertension in CKD.

    Science.gov (United States)

    Agarwal, Rajiv; Pappas, Maria K; Sinha, Arjun D

    2016-03-01

    Masked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75-78% (κ coefficient for agreement, 0.44-0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a κ coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90-110 mmHg group, 17% in the 110-119 mmHg group, 34% in the 120-129 mmHg group, and 66% in the 130-139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76-0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring. Copyright © 2016 by the American Society of Nephrology.

  15. Linkage disequilibrium in wild mice.

    Directory of Open Access Journals (Sweden)

    Cathy C Laurie

    2007-08-01

    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  16. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

    International Nuclear Information System (INIS)

    Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

  17. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Satwiko, Muhammad Gahan [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Ikeda, Koji [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Nakayama, Kazuhiko [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hocher, Berthold [Institute for Nutritional Science, University of Potsdam, Potsdam (Germany); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan)

    2015-09-25

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

  18. pre-hypertension and hypertension in apparently healthy ...

    African Journals Online (AJOL)

    user

    hypertension among urban adolescents in Calabar, south eastern Nigeria. This was a ... disease later in life but also to significantly increase .... beam balance is not available (Paynter and ..... keeping with work done among Nigerian School.

  19. Ethical Dilemmas when Diagnosing Hypertension

    Directory of Open Access Journals (Sweden)

    Sandra Santana López

    2012-12-01

    Full Text Available A review on the ethical dilemmas in the diagnosis of hypertension and some elements in the emergence of the bioethics concept was performed. Ethical conflicts that appear at each stage of diagnosis of hypertension: at the time of providing the information, at the point of indication and performance of diagnostic tests, when communicating the diagnosis and during subsequent decision making were identified. We conclude that technological development will introduce new ethical decisions in the diagnosis of hypertension that will increasingly involve the interests of society and create, in one way or another, ethical and moral conflict in the decision making process.

  20. [Hypertension in women after menopause].

    Science.gov (United States)

    Beaufils, Michel

    2006-06-01

    Menopause coincides with an increase in the incidence of hypertension in women. A direct role of estrogen deprivation in this increased blood pressure remains a topic of debate. Menopause probably accelerates the arterial changes related to aging. Hormone replacement therapy does not influence blood pressure significantly and is not contraindicated in hypertensive women. The effect of hormone replacement treatment on cardiovascular risk was recently the object of controversy. It does not increase risk except in cases of late treatment in older women who already have atherosclerosis. Hypertension management in women is otherwise similar to management in men.

  1. Hypertension--forekomst og behandling

    DEFF Research Database (Denmark)

    Ibsen, Hans; Jørgensen, Torben; Jensen, Gorm B

    2009-01-01

    Hypertension is the most important modifiable risk factor for cardiovascular disease. However, less than half of all hypertensives have their blood pressure reduced to relevant goals. The prevalence of hypertension in Denmark was found to be between 26% and 40% of the adult population. Just over...... half were aware of the diagnosis, but less than half were in treatment. Blood pressure control in patients who are undergoing treatment has improved during recent years, but there is still a gap to achievable control rates. Udgivelsesdato: 2009-Jun-8...

  2. [The magnetotherapy of hypertension patients].

    Science.gov (United States)

    Ivanov, S G; Smirnov, V V; Solov'eva, F V; Liashevskaia, S P; Selezneva, L Iu

    1990-01-01

    A study was made of the influence of the constant MKM2-1 magnets on patients suffering from essential hypertension. Continuous action of the magnetic field, created by such magnets, on the patients with stage II essential hypertension was noted to result in a decrease of arterial pressure without the occurrence of any side effects and in a simultaneous reduction of the scope of drug administration. Apart from that fact, magnetotherapy was discovered to produce a beneficial effect on the central hemodynamics and microcirculation. The use of the MKM2-1 magnets may be regarded as a feasible method of the treatment of essential hypertension patients at any medical institution.

  3. Definition and classification of pulmonary hypertension.

    Science.gov (United States)

    Humbert, Marc; Montani, David; Evgenov, Oleg V; Simonneau, Gérald

    2013-01-01

    Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure ≤15 mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases).

  4. [Diagnostic of secondary hypertension in clinical practice].

    Science.gov (United States)

    Somlóová, Z; Rosa, J; Petrák, O; Strauch, B; Zelinka, T; Holaj, R; Widimský, J

    2011-09-01

    Arterial hypertension is a common worldwide disease with a prevalence of approximately 26%. Secondary cause is known in 5-10% of patients with hypertension. We should think of secondary hypertension in all patients with resistant hypertension, in patients with sudden deterioration in the control of hypertension and in patients with laboratory and clinical signs of diseases associated with secondary hypertension. It is important to distinguish between secondary hypertension and pseudo-resistance (noncompliance to treatment, white coat syndrome). Secondary causes of hypertension can be divided into endocrine (primary aldosteronism, pheochromocytoma, hypercortisolism, hyperparathyreoidism), renal - renovascular and renal parenchymal hypertension, and other causes as sleep apnoe syndrome, hypertension in pregnancy, coarctation of the aorta and intracranial tumors.

  5. Job strain associated with increases in ambulatory blood and pulse pressure during and after work hours among female hotel room cleaners.

    Science.gov (United States)

    Feaster, Matt; Krause, Niklas

    2018-06-01

    Previously documented elevated hypertension rates among Las Vegas hotel room cleaners are hypothesized to be associated with job strain. Job strain was assessed by questionnaire. Ambulatory blood pressure (ABP) was recorded among 419 female cleaners from five hotels during 18 waking hours. Multiple linear regression models assessed associations of job strain with ABP and pulse pressure for 18-h, work hours, and after work hours. Higher job strain was associated with increased 18-h systolic ABP, after work hours systolic ABP, and ambulatory pulse pressure. Dependents at home but not social support at work attenuated effects. Among hypertensive workers, job strain effects were partially buffered by anti-hypertensive medication. High job strain is positively associated with blood pressure among female hotel workers suggesting potential for primary prevention at work. Work organizational changes, stress management, and active ABP surveillance and hypertension management should be considered for integrated intervention programs. © 2018 Wiley Periodicals, Inc.

  6. Definition and classification of hypertension: an update.

    Science.gov (United States)

    Giles, Thomas D; Materson, Barry J; Cohn, Jay N; Kostis, John B

    2009-11-01

    Since the publication of a paper by the American Society of Hypertension, Inc. Writing Group in 2003, some refinements have occurred in the definition of hypertension. Blood pressure is now recognized as a biomarker for hypertension, and a distinction is made between the various stages of hypertension and global cardiovascular risk. This paper discusses the logic underlying the refinements in the definition of hypertension. 2009 Wiley Periodical, Inc.

  7. Biomarkers in white-coat hypertension

    OpenAIRE

    Martin, Catherine Ann

    2017-01-01

    The introduction of ambulatory blood pressure monitoring in the 1960s provided new insights into the nature of high blood pressure disorders. Blood pressure is now categorised into four quadrants:normotension, masked hypertension, hypertension and white-coat hypertension. In white-coat hypertension blood pressure is elevated when taken at the doctor’s office but normal if taken outside the doctor’s office. Several controversies are associated with white-coat hypertension, which are discuss...

  8. Intracranial Hypertension: Medication and Surgery

    Science.gov (United States)

    ... fallen out of favor, unless there is a secondary inflammatory process caused by an underlying disease like ... have little effect on headaches caused by intracranial hypertension, they may temporarily affect the intensity of a ...

  9. Hypertension presenting early in pregnancy

    OpenAIRE

    Melvin, Audrey; Kinsley, Brendan

    2015-01-01

    Key Clinical Message Paraganglioma in pregnancy is an exceedingly rare and potentially life?threatening diagnosis. It is important that the clinicians consider secondary causes when women present with hypertension in early pregnancy.

  10. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    Facebook Twitter Instagram YouTube About PHA Contact Join Careers Store My Account Donate Patients About PH Diagnosis Treatments Newly ... areas © 2017 Pulmonary Hypertension Association. All Rights Reserved. Facebook Twitter Instagram YouTube

  11. Liver Hypertension: Treatment in Infancy !

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Liver Hypertension: Treatment in Infancy ! Liver Disease > Heart. No good non-invasive method. Repeated measurements problematic. Drug efficacy 50% at best. No predictors of response. We Need YOU !!

  12. [Menopause: Hypertension and vascular disease].

    Science.gov (United States)

    Zilberman, J M

    Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

    Directory of Open Access Journals (Sweden)

    T.R. Oliveira

    2009-09-01

    Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

  14. What is hypertension in diabetes?

    DEFF Research Database (Denmark)

    Hansen, K W; Poulsen, P L; Ebbehøj, E

    2001-01-01

    AIMS: To establish reference data for ambulatory blood pressure (AMBP) in normotensive, normoalbuminuric Type 1 diabetic patients and characterize the relation to clinic blood pressure (BP). To evaluate the statement of the third working party of the British Hypertension Society (BHS) that a target...... clinic BP in diabetes diabetic patients, who had never received anti-hypertensive drugs. Clinic BP was determined as the mean of at least three auscultatory...

  15. Radiological imaging in endocrine hypertension

    Directory of Open Access Journals (Sweden)

    Chandan J Das

    2011-01-01

    Full Text Available While different generations of assays have played important role in elucidating causes of different endocrine disorders, radiological techniques are instrumental in localizing the pathology. This statement cannot be truer in any disease entity other than endocrine hypertension. This review makes an effort to highlight the role of different radiological modalities, especially ultrasonography, computed tomography and magnetic resonance imaging, in the evaluation of different causes of endocrine hypertension.

  16. A focus on paediatric hypertension

    Directory of Open Access Journals (Sweden)

    Pier Paolo Bassareo

    2015-04-01

    Full Text Available Hypertension can begin early in childhood, as occasional increases in blood pressure or abnormal blood pressure responses to physical or emotional stress. High blood pressure in juvenile age is defined as a blood pressure repeatedly above the 95th percentile of specific nomograms. Its worldwide prevalence ranges from 1% to about 10%. The purpose of this paper is to perform an overview about characteristics, diagnosis, risk factors, therapy, and prognosis of paediatric hypertension.

  17. [Hypertension during pregnancy: Epidemiology, definition].

    Science.gov (United States)

    Fauvel, Jean-Pierre

    2016-01-01

    Hypertension in pregnancy has several forms that differ by their mechanisms and their consequences for mothers and fetus. Chronic hypertension is defined by SBP≥140mm Hg or DBP≥90mm Hg before pregnancy or before the 20th week of amenorrhea. Gestational hypertension is defined by SBP≥140mm Hg or DBP≥90mm Hg during or after the 20th week of amenorrhea. Preeclampsia is the occurrence of hypertension and proteinuria after 20weeks of amenorrhea. Severe preeclampsia is accompanied by clinical signs and symptoms indicating visceral pain. The HELLP syndrome is a severe preeclampsia accompanied by intravascular hemolysis and hepatic cytolysis. Eclampsia is characterized by seizures of the tonic-clonic type. A chronic hypertension is observed in 1-5% of pregnancies. Gestational hypertension without proteinuria appears in 5-6% of pregnancies. A preeclampsia develops in 1-2% of pregnancies, but much more frequently (up 34%) in the presence of risk factors. High blood pressure during pregnancy remains, by its complications, the leading cause of maternal morbidity and mortality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Renal sympathetic denervation in hypertension.

    Science.gov (United States)

    Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

    2011-11-01

    Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

  19. Hypertension and obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Phillips CL

    2013-05-01

    Full Text Available Craig L Phillips,1–3 Denise M O'Driscoll4,51Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, Australia; 2National Health and Medical Research Council Center for Integrated Research and Understanding of Sleep, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; 3Discipline of Sleep Medicine, Sydney Medical School, University of Sydney, Sydney, Australia; 4Monash Lung and Sleep, Monash Medical Centre, Monash University, Melbourne, Australia; 5Department of Medicine, Southern Clinical School, Monash University, Melbourne, AustraliaAbstract: Obstructive sleep apnea (OSA is increasingly being recognized as a major health burden with strong focus on the associated cardiovascular risk. Studies from the last two decades have provided strong evidence for a causal role of OSA in the development of systemic hypertension. The acute physiological changes that occur during apnea promote nocturnal hypertension and may lead to the development of sustained daytime hypertension via the pathways of sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction. This review will focus on the acute hemodynamic disturbances and associated intermittent hypoxia that characterize OSA and the potential pathophysiological mechanisms responsible for the development of hypertension in OSA. In addition the epidemiology of OSA and hypertension, as well as the role of treatment of OSA, in improving blood pressure control will be examined.Keywords: obstructive sleep apnea, hypertension, intermittent hypoxia, ambulatory blood pressure, sympathetic activation

  20. Efficacy and Safety of Platelet Glycoprotein Receptor Blockade in Aged and Comorbid Mice With Acute Experimental Stroke.

    Science.gov (United States)

    Kraft, Peter; Schuhmann, Michael K; Fluri, Felix; Lorenz, Kristina; Zernecke, Alma; Stoll, Guido; Nieswandt, Bernhard; Kleinschnitz, Christoph

    2015-12-01

    Despite the medical and socioeconomic effect of ischemic stroke and extensive preclinical research, treatment options for ischemic stroke are limited. We recently identified and characterized essential steps of thrombus formation in stroke and demonstrated that inhibition of the platelet glycoprotein (GP) receptors Ib and VI, but not IIb/IIIa, protects young and healthy mice from ischemic neurodegeneration. Whether these findings translate to the clinic remains unclear. Considering that the typical stroke patient is elderly with comorbidity, we aimed to analyze the efficacy and safety of novel preclinical antithrombotics in adult and comorbid mice with acute experimental stroke. We subjected adult, healthy, atherosclerotic (Ldlr(-/-)), diabetic (streptozotocin treated), and hypertensive (RenTgMK) mice to a 60-minute transient middle cerebral artery occlusion. Animals were pretreated with anti-GPVI antibodies or treated 1 hour after stroke induction with anti-GPIb or anti-GPIIb/IIIa antigen-binding fragments, respectively. Isotype treatment served as control. Twenty-four hours after transient middle cerebral artery occlusion, we visually assessed the intracerebral hemorrhage rate and measured infarct volumes (using 2,3,5-triphenyltetrazolium chloride-stained brain slices) and functional outcome (using Bederson and grip-test scores). GPIb and GPVI inhibition protected the mice from ischemic stroke without increasing bleeding complications. In contrast, GPIIb/IIIa inhibition was not protective but increased the intracerebral hemorrhage rate. Inhibition of early steps of thrombus formation protects adult and comorbid mice from ischemic stroke. The use of clinically meaningful mouse strains might improve the translation of preclinical stroke research to the clinic. © 2015 American Heart Association, Inc.

  1. Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

    Directory of Open Access Journals (Sweden)

    Pei-Rong Wang

    2015-03-01

    Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

  2. Hypertensive thalamic hemorrhage

    International Nuclear Information System (INIS)

    Munaka, Masahiro; Nishikawa, Michio; Hirai, Osamu; Kaneko, Takaaki; Watanabe, Syu; Fukuma, Jun; Handa, Hajime

    1988-01-01

    In the past six years, we have had experience with 40 patients with hypertensive thalamic hemorrhages, as verified by CT scan at our hospital within 24 hours. These patients were classified into the following three groups according to the location of the bleeding point and the size of the hematoma: (1) anteromedial (4 cases), (2) posterolateral (16 cases), and (3) massive (20 cases). The (1) and (2) hematomas were small (less than 3 cm in diameter), while those in (3) were large (more than 3 cm in diameter). Twenty cases (50% of all the thalamic hematomas) were small hematomas. The characteristic clinical symptoms of the anteromedial type were a mild disturbance of consciousness and thalamic dementia, while those of the posterolateral type were motor and sensory disturbance, and thalamic aphasia, respectively. Twenty cases (50%) were large hematomas. The clinical symptoms of these cases were mainly consciousness disturbance; 7 of them expired. Based on this experience, it may be considered that the patients whose hematoma size was larger than 3 cm had a poor prognosis and that the patients with the posterolateral type had a poor functional diagnosis. (author)

  3. Paranormal healing and hypertension

    Science.gov (United States)

    Beutler, Jaap J; Attevelt, Johannes T M; Schouten, Sybo A; Faber, Joop A J; Mees, Evert J Dorhout; Geijskes, Gijsbert G

    1988-01-01

    A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37), and no paranormal healing (controls; n=38). Healing at a distance and no paranormal healing were investigated double blind. Systolic and diastolic blood pressures were significantly reduced in all three groups at week 15 (mean reduction (95% confidence interval) 17·1 (14·0 to 20·2)/8·3 (6·6 to 10·0) mm Hg). Only the successive reductions in diastolic blood pressures among the groups from week to week were significantly different. Each week diastolic pressure was consistently lower (average 1·9 mm Hg) after healing at a distance compared with control, but on paired comparison these differences were not significant. Probably week to week variations among the groups accounted for any differences noted. In this study no treatment was consistently better than another and the data cannot therefore be taken as evidence of a paranormal effect on blood pressure. Probably the fall in blood pressure in all three groups either was caused by the psychosocial approach or was a placebo effect of the trial itself. PMID:3134082

  4. Melatonin, mitochondria and hypertension.

    Science.gov (United States)

    Baltatu, Ovidiu C; Amaral, Fernanda G; Campos, Luciana A; Cipolla-Neto, Jose

    2017-11-01

    Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin-angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin-angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.

  5. Voluntary Wheel Running in Mice.

    Science.gov (United States)

    Goh, Jorming; Ladiges, Warren

    2015-12-02

    Voluntary wheel running in the mouse is used to assess physical performance and endurance and to model exercise training as a way to enhance health. Wheel running is a voluntary activity in contrast to other experimental exercise models in mice, which rely on aversive stimuli to force active movement. This protocol consists of allowing mice to run freely on the open surface of a slanted, plastic saucer-shaped wheel placed inside a standard mouse cage. Rotations are electronically transmitted to a USB hub so that frequency and rate of running can be captured via a software program for data storage and analysis for variable time periods. Mice are individually housed so that accurate recordings can be made for each animal. Factors such as mouse strain, gender, age, and individual motivation, which affect running activity, must be considered in the design of experiments using voluntary wheel running. Copyright © 2015 John Wiley & Sons, Inc.

  6. Occupational Stress and Hypertension among Railway Loco Pilots and Section Controllers

    OpenAIRE

    Jayakumar, Devasigamoney

    2017-01-01

    Introduction: A cross-sectional study on occupational stress was conducted on loco pilots in 2008, in view of loco pilots being one of the high strain jobs in Indian Railways. Subsequently, a comparative cross-sectional study on occupational stress was conducted among section controllers in 2011, which is another high strain job of Indian Railways. Objective: The studies were conducted to analyze and compare occupational stress and hypertension. Setting and Design: A cross-sectional study on ...

  7. Increased extracellular volume and altered mechanics are associated with LVH in hypertensive heart disease, not hypertension alone.

    Science.gov (United States)

    Kuruvilla, Sujith; Janardhanan, Rajesh; Antkowiak, Patrick; Keeley, Ellen C; Adenaw, Nebiyu; Brooks, Jeremy; Epstein, Frederick H; Kramer, Christopher M; Salerno, Michael

    2015-02-01

    The goal of this study was to assess the relationship among extracellular volume (ECV), native T1, and systolic strain in hypertensive patients with left ventricular hypertrophy (HTN LVH), hypertensive patients without LVH (HTN non-LVH), and normotensive controls. Diffuse myocardial fibrosis in HTN LVH patients, as reflected by increased ECV and native T1, may be an underlying mechanism contributing to increased cardiovascular risk compared with HTN non-LVH subjects and controls. Furthermore, increased diffuse fibrosis in HTN LVH subjects may be associated with reduced peak systolic and early diastolic strain rate compared with the other 2 groups. T1 mapping was performed in 20 HTN LVH (mean age, 55 ± 11 years), 23 HTN non-LVH (mean age, 61 ± 12 years), and 22 control subjects (mean age, 54 ± 7 years) on a Siemens 1.5-T Avanto (Siemens Healthcare, Erlangen, Germany) using a previously validated modified look-locker inversion-recovery pulse sequence. T1 was measured pre-contrast and 10, 15, and 20 min after injection of 0.15 mmol/kg gadopentetate dimeglumine, and the mean ECV and native T1 were determined for each subject. Measurement of circumferential strain parameters were performed using cine displacement encoding with stimulated echoes. HTN LVH subjects had higher native T1 compared with controls (p < 0.05). HTN LVH subjects had higher ECV compared with HTN non-LVH subjects and controls (p < 0.05). Peak systolic circumferential strain and early diastolic strain rates were reduced in HTN LVH subjects compared with HTN non-LVH subjects and controls (p < 0.05). Increased levels of ECV and native T1 were associated with reduced peak systolic and early diastolic circumferential strain rate across all subjects. HTN LVH patients had higher ECV, longer native T1 and associated reduction in peak systolic circumferential strain, and early diastolic strain rate compared with HTN non-LVH and control subjects. Measurement of ECV and native T1 provide a noninvasive

  8. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall

    2000-06-01

    Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

  9. Inherent and antigen-induced airway hyperreactivity in NC mice

    Directory of Open Access Journals (Sweden)

    Tetsuto Kobayashi

    1999-01-01

    Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sen