WorldWideScience

Sample records for mice significant differences

  1. Manipulation of Ovarian Function Significantly Influenced Sarcopenia in Postreproductive-Age Mice

    Directory of Open Access Journals (Sweden)

    Rhett L. Peterson

    2016-01-01

    Full Text Available Previously, transplantation of ovaries from young cycling mice into old postreproductive-age mice increased life span. We anticipated that the same factors that increased life span could also influence health span. Female CBA/J mice received new (60 d ovaries at 12 and 17 months of age and were evaluated at 16 and 25 months of age, respectively. There were no significant differences in body weight among any age or treatment group. The percentage of fat mass was significantly increased at 13 and 16 months of age but was reduced by ovarian transplantation in 16-month-old mice. The percentages of lean body mass and total body water were significantly reduced in 13-month-old control mice but were restored in 16- and 25-month-old recipient mice by ovarian transplantation to the levels found in six-month-old control mice. In summary, we have shown that skeletal muscle mass, which is negatively influenced by aging, can be positively influenced or restored by reestablishment of active ovarian function in aged female mice. These findings provide strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.

  2. Paintings discrimination by mice: Different strategies for different paintings.

    Science.gov (United States)

    Watanabe, Shigeru

    2017-09-01

    C57BL/6 mice were trained on simultaneous discrimination of paintings with multiple exemplars, using an operant chamber with a touch screen. The number of exemplars was successively increased up to six. Those mice trained in Kandinsky/Mondrian discrimination showed improved learning and generalization, whereas those trained in Picasso/Renoir discrimination showed no improvements in learning or generalization. These results suggest category-like discrimination in the Kandinsky/Mondrian task, but item-to-item discrimination in the Picasso/Renoir task. Mice maintained their discriminative behavior in a pixelization test with various paintings; however, mice in the Picasso/Renoir task showed poor performance in a test that employed scrambling processing. These results do not indicate that discrimination strategy for any Kandinsky/Mondrian combinations differed from that for any Picasso/Monet combinations but suggest the mice employed different strategies of discrimination tasks depending upon stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Biodistribution of Different Sized Nanodiamonds in Mice.

    Science.gov (United States)

    Purtov, Konstantin; Petunin, Alexey; Inzhevatkin, Evgeny; Burov, Andrey; Ronzhin, Nikita; Puzyr, Alexey; Bondar, Vladimir

    2015-02-01

    The particle size is one of critical parameters influencing the biodistribution of detonation nanodiamonds (DND) after their administration into the body. As DNDs are prone to aggregation, the difference between their sizes in aqueous and physiological solutions has to be taken into account. Radioactive I125-BSA molecules were covalently immobilized on DNDs divided in three fractions of different average size. The DND-BSAI125 conjugates were intravenously administrated into adult mice and the particle allocation in the animal's organs and blood was evaluated based on the radioactivity distribution. We conclude that most of the conjugates were taken from the bloodstream and trapped in the liver and spleen. The short-term distribution pattern for all DNDs was similar regardless of size and practically unchanged with time. No significant clearance of the particles was observed for 4 h, but the presence of DNDs was detected in the blood. It was found that the largest particles tend to accumulate more into the liver as compared to the smaller ones. However, the size effect was not well pronounced for the studied size range.

  4. Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

    Science.gov (United States)

    Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

    2017-04-01

    Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

  5. Virulence differences among Francisella tularensis subsp. tularensis clades in mice.

    Directory of Open Access Journals (Sweden)

    Claudia R Molins

    Full Text Available Francisella tularensis subspecies tularensis (type A and holarctica (type B are of clinical importance in causing tularemia. Molecular typing methods have further separated type A strains into three genetically distinct clades, A1a, A1b and A2. Epidemiological analyses of human infections in the United States suggest that A1b infections are associated with a significantly higher mortality rate as compared to infections caused by A1a, A2 and type B. To determine if genetic differences as defined by molecular typing directly correlate with differences in virulence, A1a, A1b, A2 and type B strains were compared in C57BL/6 mice. Here we demonstrate significant differences between survival curves for infections caused by A1b versus A1a, A2 and type B, with A1b infected mice dying earlier than mice infected with A1a, A2 or type B; these results were conserved among multiple strains. Differences were also detected among type A clades as well as between type A clades and type B with respect to bacterial burdens, and gross anatomy in infected mice. Our results indicate that clades defined within F. tularensis subsp. tularensis by molecular typing methods correlate with virulence differences, with A1b strains more virulent than A1a, A2 and type B strains. These findings indicate type A strains are not equivalent with respect to virulence and have important implications for public health as well as basic research programs.

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

    Science.gov (United States)

    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.

  7. Testing the Difference of Correlated Agreement Coefficients for Statistical Significance

    Science.gov (United States)

    Gwet, Kilem L.

    2016-01-01

    This article addresses the problem of testing the difference between two correlated agreement coefficients for statistical significance. A number of authors have proposed methods for testing the difference between two correlated kappa coefficients, which require either the use of resampling methods or the use of advanced statistical modeling…

  8. Apoptosis of bone marrow leukemia cells in mice after low dose radiation at different time

    International Nuclear Information System (INIS)

    Li Guangyu; Yu Mingming; Li Xianjun; Liu Zhixiang

    2007-01-01

    Objective: To investigate the apoptosis of bone marrow leukemia cell in mice after low dose radiation (LDR) at different time and the experimental basis for LDR auxiliary therapy on leukemia. Methods: WEHI-3 cells were injected into BALB/c mice through tail veins to make an experimental mice model of myelornonocytic leukemia. 60 leukemia mice models were divided half-and half. 30 mice models in experimental group were irradiated with LDR of 75mGy at the same time while the others 30 in the control group were not. 6 mice models with LDR and 6 mice models without LDR would be killed at the time the 1st day, the 2nd day, the 3rd day, the 5th day- and the l0th day after LDR in order to extract bone marrow samples. The apoptosis percentage of leukemia cells in bone marrow was examined. Results: The apoptosis percentage of leukemia cells in experimental group was increasing after LDR and went to top on the 2nd day and the 3rd day. The apoptosis percentage of leukemia cells was remarkably different between experimental and control group, all P<0.05. Conclusion: LDR could significantly increase the apoptosis percentage of bone marrow leukemia cells in mice. Its mechanism is remarkably different in kill and wound of big dose radiation to tumour cells. It is probably related to of the increase immune exciting response as to promote some cytokine secretion, in leukemia mice. (authors)

  9. [Changes and significance of peripheral blood platelet count in tumor shrinkage induced by a low dose of CTX in T739 mice].

    Science.gov (United States)

    Li, Mo-lin; Jia, Yu-jie; Jiang, Miao-na; Shu, Xiao-hong; Li, Chuan-gang

    2008-06-01

    To establish a mouse model for BTT739 tumor-bearing mice cured by a low dose of cyclophosphamide (CTX). And then to observe the dynamic changes and significance of peripheral blood counts especially blood platelet count during tumor shrinkage induced by a low dose of CTX in T739 mice. Mouse bladder carcinoma tissues were inoculated subcutaneously into T739 mice. Seven days later, different doses of CTX or the same volume of NS were administered intraperitoneally to treat these tumor-bearing T739 mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of CTX that could cure most of these tumor-bearing mice. Then another 12 tumor-bearing mice were randomly divided into 15 mg/kg CTX treatment group and control group. Blood samples were obtained from orbital venous sinus on different times after CTX treatment. Complete blood counts were performed and the relationship between peripheral blood platelet counts and tumor shrinkage was analyzed. Within 2 weeks after CTX treatment, the speed of tumor shrinkage had a positive relationship with the dose of CTX used; but the survival rate of the tumor-bearing mice had a negative relationship with the dose of CTX used in 2 months after CTX treatment. 15 mg/kg CTX could cure most of the tumor bearing mice, while it had no remarkably inhibitive effects on peripheral blood cells. The perpherial platelet count increased to (1483.4+/-184.4)x10(9)/L in mice 6 h after CTX treatment. There was significant difference compared with that in mice of control group (1086.6+/-81.0)x10(9)/L (P0.05). CTX 15 mg/kg could cure most of bladder tumor-bearing T739 mice. The transient increase of the peripheral platelet count in 6 h after CTX treatment may relate to the antitumor effects of CTX.

  10. Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

    Science.gov (United States)

    Liu, Peng; Xing, Bo; Chu, Zheng; Liu, Fei; Lei, Gang; Zhu, Li; Gao, Ya; Chen, Teng; Dang, Yong-Hui

    2017-07-01

    Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Test for the statistical significance of differences between ROC curves

    International Nuclear Information System (INIS)

    Metz, C.E.; Kronman, H.B.

    1979-01-01

    A test for the statistical significance of observed differences between two measured Receiver Operating Characteristic (ROC) curves has been designed and evaluated. The set of observer response data for each ROC curve is assumed to be independent and to arise from a ROC curve having a form which, in the absence of statistical fluctuations in the response data, graphs as a straight line on double normal-deviate axes. To test the significance of an apparent difference between two measured ROC curves, maximum likelihood estimates of the two parameters of each curve and the associated parameter variances and covariance are calculated from the corresponding set of observer response data. An approximate Chi-square statistic with two degrees of freedom is then constructed from the differences between the parameters estimated for each ROC curve and from the variances and covariances of these estimates. This statistic is known to be truly Chi-square distributed only in the limit of large numbers of trials in the observer performance experiments. Performance of the statistic for data arising from a limited number of experimental trials was evaluated. Independent sets of rating scale data arising from the same underlying ROC curve were paired, and the fraction of differences found (falsely) significant was compared to the significance level, α, used with the test. Although test performance was found to be somewhat dependent on both the number of trials in the data and the position of the underlying ROC curve in the ROC space, the results for various significance levels showed the test to be reliable under practical experimental conditions

  12. Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

    Science.gov (United States)

    Shang, Xueliang; Shang, Yingchun; Fu, Jingxuan; Zhang, Tao

    2017-08-01

    The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

  13. One arm exercise induces significant interarm diastolic blood pressure difference.

    Science.gov (United States)

    Hong, Dezhi; Wang, Jiwei; Su, Hai; Xu, Jingsong; Liu, Yanna; Peng, Qiang; Wang, Lijuan

    2011-06-01

    This study is designed to investigate the inducing effect of one arm exercise on interarm difference (IAD) in the blood pressure (BP). Fifty healthy young participants were included in the study. Three-minute exercises of the right arm elbow flexion and extension were performed. The bilateral brachial BP was simultaneously measured with two automatic BP measurement devices before (basic) and immediately 0, 5, 10, 15, 20, and 30 min after exercise. The absolute difference in the systolic BP (SBP) and diastolic BP (DBP) between the left and right BP of at least 10 mmHg was recognized as sIAD and dIAD. The baseline data of the SBP and DBP in left and right arms revealed no significant difference (SBP: 110 ± 10 vs. 111 ± 11 mmHg; DBP: 66 ± 8 vs. 66 ± 9 mmHg, both not significant). The prevalence of dIAD was 2% at the baseline. However, this prevalence increased to 80% at 0 min, as right arm exercise induced the right DBP decrease and left DBP increase, and then the prevalence decreased gradually within a 30-min recovery period. The prevalence of sIAD was zero at the baseline and the maximal prevalence was 8% during the 20-min postexercise period. One arm exercise can lead to a significant IAD in DBP. Any arm exercise should be avoided before BP measurement.

  14. Sex differences in complex regional pain syndrome type I (CRPS-I) in mice.

    Science.gov (United States)

    Tang, Chaoliang; Li, Juan; Tai, Wai Lydia; Yao, Weifeng; Zhao, Bo; Hong, Junmou; Shi, Si; Wang, Song; Xia, Zhongyuan

    2017-01-01

    Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I. Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines. Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion. Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.

  15. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin

    2009-01-01

    The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At.......The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At....

  16. Significance of perfectionism in understanding different forms of insomnia

    Directory of Open Access Journals (Sweden)

    Totić-Poznanović Sanja

    2012-01-01

    Full Text Available Introduction. Studies consistently show a connection between perfectionism as a multidimensional construct with various psychological and psychopathological states and characteristics. However, studies that analyze the connection between this concept and sleep disturbances, especially modalities of insomnia, are rare. Objective. The aim of this study was to examine whether dimensions of perfectionism can explain different forms of insomnia; difficulties initiating sleep (insomnia early, difficulties during the sleep (insomnia middle, waking in early hours of the morning (insomnia late and dissatisfaction with sleep quality (subjective insomnia. Methods. The sample consisted of 254 students of the School of Medicine in Belgrade. Predictive significance of nine perfectionism dimensions, measured by Frost’s and Hewitt’s and Flett’s scales of multi-dimensional perfectionism, related to four modalities of insomnia, measured by a structured questionnaire, was analyzed by multiple linear regression method. Results. Perfectionism dimensions are significant predictors of each of the tested forms of insomnia. Doubt about actions significantly predicts initial insomnia; to other-oriented perfectionism in the negative pole and socially prescribed perfectionism underlie the difficulties during the sleep, while organization and parental criticism underlie late insomnia. Significant predictors of subjective insomnia are personal standards and organization and to other-oriented perfectionism on the negative pole. Three of nine analyzed dimensions were not confirmed as significant; concern over mistakes, parental expectations and self-oriented perfectionism. Conclusion. Various aspects of perfectionism can be considered as a vulnerability factor for understanding some forms of insomnia. Out of all forms of insomnia tested, perfectionism as the personality trait proved to be the most significant for understanding subjective insomnia.

  17. Middle age has a significant impact on gene expression during skin wound healing in male mice.

    Science.gov (United States)

    Yanai, Hagai; Lumenta, David Benjamin; Vierlinger, Klemens; Hofner, Manuela; Kitzinger, Hugo-Benito; Kamolz, Lars-Peter; Nöhammer, Christa; Chilosi, Marco; Fraifeld, Vadim E

    2016-08-01

    The vast majority of research on the impact of age on skin wound healing (WH) compares old animals to young ones. The middle age is often ignored in biogerontological research despite the fact that many functions that decline in an age-dependent manner have starting points in mid-life. With this in mind, we examined gene expression patterns during skin WH in late middle-aged versus young adult male mice, using the head and back punch models. The rationale behind this study was that the impact of age would first be detectable at the transcriptional level. We pinpointed several pathways which were over-activated in the middle-aged mice, both in the intact skin and during WH. Among them were various metabolic, immune-inflammatory and growth-promoting pathways. These transcriptional changes were much more pronounced in the head than in the back. In summary, the middle age has a significant impact on gene expression in intact and healing skin. It seems that the head punch model is more sensitive to the effect of age than the back model, and we suggest that it should be more widely applied in aging research on wound healing.

  18. Explanation of significant differences for the TNX groundwater operable unit

    International Nuclear Information System (INIS)

    Palmer, E.R.

    1997-01-01

    This Explanation of Significant Differences (ESD) is being issued by the Department of Energy (DOE), the lead agency for the Savannah River Site (SRS), with concurrence by the Environmental Protection Agency-Region IV (EPA) and South Carolina Department of Health and Environmental Control (SCDHEC) to announce changes in the interim remediation strategy selected for the TNX Groundwater Operable Unit. The TNX Area is located adjacent to the Savannah River in the southwestern portion of SRS. The remedy selected in the Interim Record of Decision (IROD) to achieve the interim action goals was the Hybrid Groundwater Corrective Action (HGCA). The HGCA consisted of a recirculation well system and an air stripper with a series of groundwater extraction wells. The original remediation strategy needs to be modified because the recirculation well system was determined to be ineffective in this area due to geological factors and the nature of the contamination

  19. Effect of Different Starvation Levels on Cognitive Ability in Mice

    Science.gov (United States)

    Li, Xiaobing; Zhi, Guoguo; Yu, Yi; Cai, Lingyu; Li, Peng; Zhang, Danhua; Bao, Shuting; Hu, Wenlong; Shen, Haiyan; Song, Fujuan

    2018-01-01

    Objective: To study the effect of different starvation levels on cognitive ability in mice. Method: Mice were randomly divided into four groups: normal group, dieting group A, dieting group B, dieting group C. The mice of normal group were given normal feeding amount, the rest of groups were given 3/4 of normal feeding amount, 2/4 of normal feeding amount and 1/4 of normal feeding amount. After feeding mice four days, the weight was observed and T-maze experiment, Morris water maze test, open field test and Serum Catalase activity were detected. Result: Compared with the normal group, the correct rate of the intervention group in the T-maze experiment was decreased and dieting group A> dieting group B> dieting group C. In the Morris water maze test, Compared with the normal group, the correct rate of the intervention group was increased. Among these three intervention groups, dieting group A had the highest correct rate and the difference of dieting group B and dieting group C were similar. In the open field test, Compared with the normal group, the exploration rate of the surrounding environment in the intervention group was increased. In the Serum Catalase test, Compared with the normal group, the activities of serum peroxidase in the intervention groups were decreased and dieting group A> dieting group B> dieting group C. Conclusion: A certain level of starvation could affect the cognitive ability of mice. In a certain range, the level of starvation is inversely proportional to cognitive ability in mice.

  20. Sex differences in insulin resistance in GABAB1 knockout mice.

    Science.gov (United States)

    Bonaventura, M M; Rodriguez, D; Ferreira, M L; Crivello, M; Repetto, E M; Bettler, B; Libertun, C; Lux-Lantos, V A

    2013-02-27

    We have previously demonstrated that the absence of functional GABA B receptors (GABABRs) disturbs glucose homeostasis in GABAB1KO mice. The aim of this work was to extend our studies of these alterations in GABAB1KO mice and investigate the sexual differences therein. Male and female, GABAB1KO and WT mice were used. Glucose and insulin tolerance tests (GTT and ITT), and insulin and glucagon secretion tests (IST and GST) were performed. Blood glucose, serum insulin and hyperglycemic hormones were determined, and HOMA-IR calculated. Skeletal muscle insulin receptor β subunit (IRβ), insulin receptor substrates 1/2 (IRS1, IRS2) and hexokinase-II levels were determined by Western blot. Skeletal muscle insulin sensitivity was assessed by in vivo insulin-induced Akt phosphorylation (Western blot). Food intake and hypothalamic NPY mRNA expression (by qPCR) were also evaluated. Fasted insulin and HOMA-IR were augmented in GABAB1KO males, with no alterations in females. Areas under the curve (AUC) for GTT and ITT were increased in GABAB1KO mice of both genders, indicating compromised insulin sensitivity. No genotype differences were observed in IST, GST or in IRβ, IRS1, IRS2 and hexokinase-II expression. Akt activation was severely impaired in GABAB1KO males while no alterations were observed in females. GABAB1KO mice showed increased food intake and NPY expression. Glucose metabolism and energy balance disruptions were more pronounced in GABAB1KO males, which develop peripheral insulin resistance probably due to augmented insulin secretion. Metabolic alterations in females were milder and possibly due to previously described reproductive disorders, such as persistent estrus. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

    Science.gov (United States)

    Chen, Xia; Sun, Chang-Kai; Han, Guo-Zhu; Peng, Jin-Yong; Li, Ying; Liu, Yan-Xia; Lv, Yuan-Yuan; Liu, Ke-Xin; Zhou, Qin; Sun, Hui-Jun

    2009-04-21

    To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

  2. Lack of significant metabolic abnormalities in mice with liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1.

    LENUS (Irish Health Repository)

    Lavery, Gareth G

    2012-07-01

    Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA

  3. Different perception levels of histamine-induced itch sensation in young adult mice.

    Science.gov (United States)

    Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

    2018-05-01

    Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Parent socialization effects in different cultures: significance of directive parenting.

    Science.gov (United States)

    Sorkhabi, Nadia

    2012-06-01

    In this article, the controversy of divergent findings in research on parental socialization effects in different cultures is addressed. Three explanations intended to address divergent findings of socialization effects in different cultures, as advanced by researchers who emphasize cultural differences, are discussed. These include cultural differences in socialization values and goals of parents, parental emotional and cognitive characteristics associated with parenting styles, and adolescents' interpretations or evaluations of their parents' parenting styles. The empirical evidence for and against each of these arguments is examined and an alternative paradigm for understanding and empirical study of developmental outcomes associated with parenting styles in different cultures is suggested. Baumrind's directive parenting style is presented as an alternative to the authoritarian parenting style in understanding the positive developmental effects associated with "strict" parenting in cultures said to have a collectivist orientation. Directions for research on the three explanations are mentioned.

  5. Renal Proteome in Mice with Different Susceptibilities to Fluorosis

    Science.gov (United States)

    Peres-Buzalaf, Camila; Salvato, Fernanda; Labate, Carlos Alberto; Everett, Eric T.; Whitford, Gary Milton; Buzalaf, Marília Afonso Rabelo

    2013-01-01

    A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis due to their genetic backgrounds. They also differ with respect to several features of fluoride (F) metabolism and metabolic handling of water. This study was done to determine whether differences in F metabolism could be explained by diversities in the profile of protein expression in kidneys. Weanling, male A/J mice (susceptible to dental fluorosis, n = 18) and 129P3/J mice (resistant, n = 18) were housed in pairs and assigned to three groups given low-F food and drinking water containing 0, 10 or 50 ppm [F] for 7 weeks. Renal proteome profiles were examined using 2D-PAGE and LC-MS/MS. Quantitative intensity analysis detected between A/J and 129P3/J strains 122, 126 and 134 spots differentially expressed in the groups receiving 0, 10 and 50 ppmF, respectively. From these, 25, 30 and 32, respectively, were successfully identified. Most of the proteins were related to metabolic and cellular processes, followed by response to stimuli, development and regulation of cellular processes. In F-treated groups, PDZK-1, a protein involved in the regulation of renal tubular reabsorption capacity was down-modulated in the kidney of 129P3/J mice. A/J and 129P3/J mice exhibited 11 and 3 exclusive proteins, respectively, regardless of F exposure. In conclusion, proteomic analysis was able to identify proteins potentially involved in metabolic handling of F and water that are differentially expressed or even not expressed in the strains evaluated. This can contribute to understanding the molecular mechanisms underlying genetic susceptibility to dental fluorosis, by indicating key-proteins that should be better addressed in future studies. PMID:23308176

  6. Sex differences in obesity development in pair-fed neuronal lipoprotein lipase deficient mice

    Directory of Open Access Journals (Sweden)

    Hong Wang

    2016-10-01

    pair-fed female NEXLPL−/− mice. ERα mRNA levels were not significantly modified in other brain regions examined, nor in the hypothalamus of male NEXLPL−/− mice compared to control mice. Conclusions: These results suggest that the mechanism underlying ERα regulation of body weight interacts with the LPL-dependent lipid processing in the hypothalamus in a sex specific way. ERα could provide the link between brain lipid sensing and sex differences in obesity development. This study has the potential important clinical implication to provide better management for women who suffer from obesity and obesity-related co-morbidities. Keywords: Lipoprotein lipase, Pair feeding, Sex-differences, Estrogen receptor, Obesity

  7. Prognostic significance of between-arm blood pressure differences.

    Science.gov (United States)

    Agarwal, Rajiv; Bunaye, Zerihun; Bekele, Dagim M

    2008-03-01

    Blood pressure (BP) recordings often differ between arms, but the extent to which these differences are reproducible and whether the differences have prognostic importance is unknown. We enrolled 421 consecutive patients from a medicine and a renal clinic at a veterans' hospital. Three BP recordings were obtained in each arm using an oscillometric device in a sequential manner and repeated in 1 week. Patients were followed for all-cause mortality arm had 5.1-mm Hg higher systolic BP that attenuated by approximately 2.2 mm Hg a week later. Systolic BP dropped 6.9 mm Hg over 1 week and by an additional 5.3 mm Hg in patients with chronic kidney disease. Accounting for the visit and arm effect improved the reproducibility of the BP measurements. The intraclass correlation coefficient was 0.74, which improved to 0.88 after accounting for visit and 0.93 after accounting for arm. The crude mortality rate was 6.33 per 100 patient-years. Every 10-mm Hg difference in systolic BP between the arms conferred a mortality hazard of 1.24 (95% CI: 1.01 to 1.52) after adjusting for average systolic BP and chronic kidney disease. BP differences between arms are reproducible and carry prognostic information. Patients should have evaluation of BP in both arms at the screening visit.

  8. Numerical variation of cell lysosomes of the proximal convoluted tubules of mice Kidneys submitted to different X-ray doses

    International Nuclear Information System (INIS)

    Silva Lapa, R. de C.R. da; Pacheco, I.P.; Segreto, C.

    1984-01-01

    The number of cell lysosomes of the proximal convoluted tubules of mice Kidneys (Mus musculus) before and after whole-body irradiation with different X-ray doses is confronted. The mice were sacrificed after 72 hours and the cortex fragments were conduct to electron microscopy. A statistically significant numerical reduction of the lysosomas was observed in 72 hours. (M.A.C.) [pt

  9. Conducting tests for statistically significant differences using forest inventory data

    Science.gov (United States)

    James A. Westfall; Scott A. Pugh; John W. Coulston

    2013-01-01

    Many forest inventory and monitoring programs are based on a sample of ground plots from which estimates of forest resources are derived. In addition to evaluating metrics such as number of trees or amount of cubic wood volume, it is often desirable to make comparisons between resource attributes. To properly conduct statistical tests for differences, it is imperative...

  10. Significance of perfectionism in understanding different forms of insomnia

    OpenAIRE

    Totić-Poznanović Sanja; Šaula-Marojević Biljana; Zebić Mirjana

    2012-01-01

    Introduction. Studies consistently show a connection between perfectionism as a multidimensional construct with various psychological and psychopathological states and characteristics. However, studies that analyze the connection between this concept and sleep disturbances, especially modalities of insomnia, are rare. Objective. The aim of this study was to examine whether dimensions of perfectionism can explain different forms of insomnia; difficulties initiating sleep (insomnia early)...

  11. [Neonatal Semax and saline injections induce open-field behavior changes in mice of different genotypes].

    Science.gov (United States)

    Shilova, O B; Markina, N V; Perepelkina, O V; Gichenok, I V; Korochkin, L I; Poletaeva, I I

    2004-01-01

    DBA/2, CBA mice, and their F1 hybrids (first series) and 101/HY and C3H mice (second series) were injected as neonates (2-7 days of life) with Semax (sc., 7 microg per animal). Semax is a peptide analogue of ACHT4-10 fragment which is resistant to degradation. The common feature of remote effects of both Semax and saline injections was the set of changes in the open-field behavior in adult (2.5- to 3-month-old) animals as compared to intact mice. Unexpectedly, the neonatal saline injections induced many changes in adult behavior, part of these effects being genotype-dependent. The most conspicuous shifts (genotype-dependent increase or decline) in freezing, grooming and rearing scores were displayed by DBA/2 and C3H mice, whereas the hole-poke frequencies were significantly changed in CBA and C3H mice. Squares crossed in the center of arena and rearing number were significantly increased in saline group of DBA/2 mice, whereas in Semax-injected DBA/2 group they were approximately equal to the level of intact mice. This means that the remote effects of noxious stimulation (injections of saline) were in some ways "compensated" as the result of concomitant peptide effect. At the same time, the numbers of freezing and grooming episodes were also increased in these groups. Because exploratory behavior and manifestations of anxiety increased or decreased simultaneously, it proves to be difficult to ascribe these changes to behavioral modulation along the "novelty seeking--anxiety" axis. In mice of other genotypes, changes in the same indices of the open-field behavior were revealed, but these changes were different in their direction. It was suggested that the complex patterns of postnatal behavior was the result of neonatal injections modulating subsequent brain development.

  12. Significant Differences in Nurses’ Knowledge of Basic Wound Management

    DEFF Research Database (Denmark)

    Zarchi, Kian; Latif, Seemab; Haugaard, Vibeke B

    2014-01-01

    Wounds represent a growing healthcare problem due to an aging population. Nurses play a key role in wound management and their theoretical understanding of basic wound management may be expected to influence the quality of wound therapy fundamentally. In this study, we evaluated the level...... of knowledge of wound management in 136 Danish nurses working in 3 different settings: advanced wound care clinics, home care and general hospital departments. We found that hospital nurses had less theoretical knowledge than home care nurses and nurses working at advanced wound care clinics. We also found...... of wound management in Denmark and suggests how improvements might be achieved....

  13. Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.

    Directory of Open Access Journals (Sweden)

    Yusuke Echigoya

    Full Text Available Duchenne muscular dystrophy (DMD, one of the most common and lethal genetic disorders, and the mdx mouse myopathies are caused by a lack of dystrophin protein. These dystrophic muscles contain sporadic clusters of dystrophin-expressing revertant fibers (RFs, as detected by immunohistochemistry. RFs are known to arise from muscle precursor cells with spontaneous exon skipping (alternative splicing and clonally expand in size with increasing age through the process of muscle degeneration/regeneration. The expansion of revertant clusters is thought to represent the cumulative history of muscle regeneration and proliferation of such precursor cells. However, the precise mechanisms by which RFs arise and expand are poorly understood. Here, to test the effects of mutation types and aging on RF expansion and muscle regeneration, we examined the number of RFs in mdx mice (containing a nonsense mutation in exon 23 and mdx52 mice (containing deletion mutation of exon 52 with the same C57BL/6 background at 2, 6, 12, and 18months of age. Mdx mice displayed a significantly higher number of RFs compared to mdx52 mice in all age groups, suggesting that revertant fiber expansion largely depends on the type of mutation and/or location in the gene. A significant increase in the expression and clustering levels of RFs was found beginning at 6months of age in mdx mice compared with mdx52 mice. In contrast to the significant expansion of RFs with increasing age, the number of centrally nucleated fibers and embryonic myosin heavy chain-positive fibers (indicative of cumulative and current muscle regeneration, respectively decreased with age in both mouse strains. These results suggest that mutation types and aging differently affect revertant fiber expansion in mdx and mdx52 mice.

  14. Gender differences in cocaine pharmacokinetics in CF-1 mice.

    Science.gov (United States)

    Visalli, Thomas; Turkall, Rita; Abdel-Rahman, Mohamed S

    2005-01-15

    Hepatocellular damage is thought to occur as a result of cytochrome P450-mediated oxidation of cocaine to norcocaine (NC), a precursor of the hepatotoxic nitrosonium ion. However, this damage occurs only in male mice, with females exhibiting minimal biochemical and histological signs of hepatocellular stress. The objective of this study was to determine the plasma time course and tissue disposition of cocaine and its metabolites to further investigate the role that metabolism may play in the gender difference observed. Male and female CF-1 mice were orally administered 20mg/kg cocaine hydrochloride once daily for 7 days. Blood samples were withdrawn at various time points post-injection and analyzed for cocaine and its metabolites benzoylecgonine (BE), norcocaine, ecgonine methyl ester (EME), and ecgonine (E). In addition, tissue concentrations of cocaine and its metabolites were determined in liver, heart, brain, and kidney tissue. The results demonstrated that the plasma elimination half-life of cocaine is nearly three times longer in males versus females. Non-hepatotoxic hydrolysis metabolites BE, EME, and E were higher in female tissues while norcocaine was detected in tissues of male animals only. This study revealed that differences in cocaine pharmacokinetics and the resultant differences in the biodisposition of cocaine and its metabolites in tissues contribute to the mechanism of gender difference seen in cocaine hepatotoxicity.

  15. Sensitivity to immunodepressant action of cyclophosphamide: analysis of interstrain differences in mice.

    Science.gov (United States)

    Pevnitsky, L A; Telegin LYu; Zhirnov, G F; Mazurov, A V; Viktorov, V V

    1985-01-01

    In one of our previous studies (Pevnitsky et al., Bull. exp. Biol. Med., 83, 438-440, 1977), we have found significant differences between various strains of mice in the sensitivity to immunodepressant action of cyclophosphamide (CP). The degree of these differences was not determined by the level of their immune response which indicates that the cause of the interstrain differences lies in a specific reaction of mice to the immunodepressant. The main parameters of CP effect which may be responsible for variable sensitivity to the immunodepressant action in vivo were studied in several murine strains (Balb/cJLacSto, CBA/CaLacSto, and DBA/2JSto): (1) rate of the preparation activation in liver microsomes; (2) pharmacokinetics of NBP-metabolites in the blood serum; (3) immunodepressant action of the in vivo activated CP; (4) sensitivity of immunocompetent target cells to activated CP effect. It was found that DBA/2 mice are the most sensitive to CP in vivo. The level of "active" CP in their blood serum is higher than in BALB/c mice. Besides, they are characterized by a higher sensitivity of immunocompetent cells compared to BALB/c and CBA mice.

  16. Naloxone effects on behavior of inbred mice with different response to emotional stress in open field test.

    Science.gov (United States)

    Nadorova, A V; Kozlovskaja, M M; Seredenin, S B

    2009-10-01

    Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and C57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and C57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in C57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in C57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Proteomic study on gender differences in aging kidney of mice

    Directory of Open Access Journals (Sweden)

    Cristobal Susana

    2009-04-01

    Full Text Available Abstract Background This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS. Results This proteomic analysis detected age-related changes in protein expression in 55 protein-spots, corresponding to 22 spots in males and 33 spots in females. We found a protein expression signature (PES of aging composed by 8 spots, common for both genders. The identified proteins indicated increases in oxidative and proteolytic proteins and decreases in glycolytic proteins, and antioxidant enzymes. Conclusion Our results provide insights into the gender differences associated to the decline of kidney function in aging. Thus, we show that proteomics can provide valuable information on age-related changes in expression levels of proteins and related modifications. This pilot study is still far from providing candidates for aging-biomarkers. However, we suggest that the analysis of these proteins could suggest mechanisms of cellular aging in kidney, and improve the kidney selection for transplantation.

  19. 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

  20. 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

  1. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    Science.gov (United States)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

  2. Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

    Directory of Open Access Journals (Sweden)

    Ingemar Björkhem

    2013-09-01

    Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

  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. Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

    Science.gov (United States)

    Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

    2017-12-01

    We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

  5. Different histopathological subtypes of Hodgkin lymphoma show significantly different levels of FDG uptake

    DEFF Research Database (Denmark)

    Hutchings, Martin; Loft, Annika; Hansen, Mads

    2006-01-01

    ) patients, 20.8 g/ml in 11 mixed cellularity (MC) patients, and 19.5 g/ml in four patients with unclassified classical HL (CHL-NOS), (ANOVA, p = 0.011). Out of 780 sites (600 lymph node regions plus 180 organs), 208 sites were found to be affected with HL. Mean SUV(max) was 8.3 g/ml in the 12 sites with NLP......, 11.2 g/ml in the 147 sites affected with NS, 14.6 g/ml in the 36 sites with MC, and 13.1 g/ml in the 13 sites with CHL-NOS (ANOVA, p = 0.002). There is a significant difference in FDG/glucose uptake between the different histopathological subtypes of HL....

  6. Tularemia induces different biochemical responses in BALB/c mice and common voles

    Directory of Open Access Journals (Sweden)

    Vitula Frantisek

    2009-06-01

    Full Text Available Abstract Background Both BALB/c mice and common voles (Microtus arvalis are considered highly susceptible to tularemia. However, the common vole is reported to harbour Francisella tularensis in European habitats as well as to survive longer with chronic shedding of the bacterium. The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection. Methods Rodents were evaluated for differences in the total antioxidant capacity derived from low-molecular-weight antioxidants, biochemistry including lipid metabolism, tissue bacterial burdens and histopathology following experimental intraperitoneal infection with 160 colony forming units (CFU pro toto. Results Bacterial burdens in common voles started to develop later post-exposure and amounted to lower levels than in BALB/c mice. Elevation of liver function enzymes was more pronounced in mice than common voles and there were marked differences in lipid metabolism in the course of tularemia in these two species. Hypertriglyceridemia and hypercholesterolemia developed in mice, while physiologically higher levels of triglycerides and cholesterol showed a decreasing tendency in common voles. On the other hand, the total plasma antioxidant capacity gradually dropped to 81.5% in mice on day 5 post-infection, while it increased to 130% on day 6 post-infection in common voles. Significant correlations between tissue bacterial burdens and several biochemical parameters were found. Conclusion As differences in lipid metabolism and the total antioxidant capacity of highly susceptible rodent species were demonstrated, the role of triglycerides, cholesterol and antioxidants in tularemic sepsis should be further investigated.

  7. [Different aluminum adjuvants significantly enhances the effect of immunization on Brucella Omp31].

    Science.gov (United States)

    Qing, Rui; Xiang, Qingke; Liu, Zhongqi; Xiao, Fei; Yang, Fan

    2018-02-01

    Objective To investigate the effect of aluminum phosphate (AP) and aluminum hydroxide (AH) as adjuvants on Brucella outer membrane protein 31 (Omp31) in inducing humoral and cellular immune responses and immune protection. Methods AP and AH adjuvants were prepared and separately mixed with Brucella Omp31 protein to measure the adsorption rates. The AP- and AH-absorbed Omp31 protein were intraperitoneally injected into BLAB/c mice at 0, 2, and 4 weeks, and meanwhile, unabsorbed Omp31 protein and PBS were used as controls. The levels of serum IgG, IgG1, IgG2a and genital tract secretion sIgA were determined by ELISA at 0, 2, 4 and 6 weeks. Spleen cells were collected for culture at 6 weeks, and the cells were stimulated by Omp31 for 48 hours followed by the analysis of IFN-γ and IL-10 levels in the supernatants by ELISA, and the determination of lymphocyte proliferation by CCK-8 assay. The mice were challenged with Brucella at 6 weeks, and bacterial content in spleen tissue was determined 1 and 2 weeks later. Results AP and AH could absorb over 70% and 85% of the Omp31 protein, respectively, for solutions at all the tested concentrations. ELISA suggested that serum IgG, IgG1, IgG2a and genital tract sIgA levels peaked 2 weeks after the last immunization for both AP and AH groups, and antibody level was higher in the AP and AH groups than the control groups, and higher in the AH group than in the AP group. CCK-8 assay showed that the proliferating rate of lymphocytes induced by the AH group was significantly higher than that by the AP group, and the AH group also showed significantly higher IFN-γ level in the supernatant than the AP group, but no significant difference in IL-10 level. The AH group had remarkably lower bacterial load in the spleen than the AP group 2 weeks after challenged by Brucella 16M strain. Conclusion Both AP and AH adjuvants effectively enhanced immunogenicity and immune protection of the Brucella Omp31 protein, and AH was superior to AP in

  8. Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences.

    Science.gov (United States)

    Philips, Mari-Anne; Abramov, Urho; Lilleväli, Kersti; Luuk, Hendrik; Kurrikoff, Kaido; Raud, Sirli; Plaas, Mario; Innos, Jürgen; Puussaar, Triinu; Kõks, Sulev; Vasar, Eero

    2010-02-11

    Myg1 (Melanocyte proliferating gene 1) is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization. In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. To study the effects of Myg1 loss-of-function, we created Myg1-deficient (-/-) mice by displacing the entire coding sequence of the gene. Initial phenotyping, covering a multitude of behavioural, cognitive, neurological, physiological and stress-related responses, revealed that homozygous Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1 (-/-) mice showed an inconsistent pattern of altered anxiety-like behaviour in different tests. The plus-maze and social interaction tests revealed that male Myg1 (-/-) mice were significantly less anxious than their wild-type littermates; female (-/-) mice showed increased anxiety in the locomotor activity arena. Restraint-stress significantly reduced the expression of the Myg1 gene in the prefrontal cortex of female wild-type mice and restrained female (-/-) mice showed a blunted corticosterone response, suggesting involvement of Myg1 in stress-induced responses. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice. Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences.

  9. Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

    Directory of Open Access Journals (Sweden)

    Xin Qiao

    2017-09-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

  10. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  11. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  12. Galectins expressed differently in genetically susceptible C57BL/6 and resistant BALB/c mice during acute ocular Toxoplasma gondii infection.

    Science.gov (United States)

    Chen, S-J; Zhang, Y-X; Huang, S-G; Lu, F-L

    2017-07-01

    Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin-receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.

  13. Differences in Susceptibility of Inbred Mice to Bacillus anthracis

    Science.gov (United States)

    1985-04-26

    dilutions of the mixture were prepared and injected into A/J and CBA/J mice via the tail vein, as described by Ezzell et al. (9). Five mice per strain were...xylazine (Rompun, Miles Laboratories, Shawnee, Kansas) in 50 pl, and were dissected iwnmediately. Gross pathological changes were noted, heart blood and...anthracis; a histopathological study of skin lesions produced by B. anthracis in susceptible and resistant animal species. J. Infect. Dis. 80:1-13. 9. Ezzell

  14. [Genetic differences in mice in the sensitivity to the immunodepressive action of alkylating agents].

    Science.gov (United States)

    Kim, N I; Telegin, L Iu; Pevnitskiĭ, L A

    1983-04-01

    The immunodepressant action of cyclophosphamide, thiophosphamide and sarcolysine was examined in experimental primary immune response in mice of different lines immunized with sheep red blood cells. DBA/2 and C3H/Sn mice were marked by the highest sensitivity to the immunodepressant action of the alkylating agents. BALB/c mice were relatively resistant to the immunodepressant action. Possible reasons for the interspecific differences found are discussed.

  15. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

    2016-01-01

    Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

  16. Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

    Directory of Open Access Journals (Sweden)

    Sanne Terryn

    2016-08-01

    Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

  17. A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice.

    Science.gov (United States)

    Tagliamonte, Maria; Petrizzo, Annacarmen; Napolitano, Maria; Luciano, Antonio; Rea, Domenica; Barbieri, Antonio; Arra, Claudio; Maiolino, Piera; Tornesello, Marialina; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

    2016-02-24

    The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. In the present study, the counterbalance effect of a novel metronomic chemotherapy protocol on such an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy consisted of a novel multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4(+) T cell reduction and CD8(+) T cell increase. Furthermore, a significant reduction in the percentage of both CD25(+)FoxP3(+) and CD25(+)CD127(low) regulatory T cell population was found both in the spleens and in the tumor lesions. Finally, the metronomic chemotherapy induced an intrinsic CD8(+) T cell response specific to B16 naturally expressed Trp2 TAA. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment. Consequently, the intrinsic anti-tumor T cell immunity could exert its function, targeting specific TAA and significantly containing tumor growth. Overall, the results show that this represents a promising adjuvant approach to significantly enhance efficacy of intrinsic or vaccine-elicited tumor-specific cellular immunity.

  18. The concentration of fear: mice's behavioural and physiological stress responses to different degrees of predation risk

    Science.gov (United States)

    Sánchez-González, Beatriz; Planillo, Aimara; Navarro-Castilla, Álvaro; Barja, Isabel

    2018-02-01

    Predation is an unavoidable and dangerous fact in the lifetime of prey animals and some sign of the proximity of a predator may be enough to trigger a response in the prey. We investigated whether different degrees of predation risk by red foxes ( Vulpes vulpes) evoke behavioural and physiological stress responses in wood mice ( Apodemus sylvaticus) . We examined the variation in mice responses due to individual factors (sex and reproductive status) and related them to the concentration of the volatile compounds from fox faeces over time. In our experiment, we introduced predation cues into four plots, each subjected to a different concentration treatment (0, 10, 50 and 100% concentration of fresh faeces of red fox), based on the following outline: initial odourless phase 0, phase1 in which predation treatment was renewed daily, and phase 2 in which we renewed the treatment only on the first day. Wood mice were live trapped during all three phases and the physiological response was measured non-invasively by analysing faecal corticosterone metabolites (FCM) in freshly collected faeces. Data were analysed by Generalized Linear Mixed Models. Overall, males were trapped less often than females, and reproductively active individuals from both sexes avoided traps more than non-reproductively active individuals, especially in medium- and high- concentration plots. Variations in FCM concentrations were explained by plot, the interaction between plot and treatment phase, and the interaction between the treatment phase and the reproductive status. During phase 1, we detected a significant rise in FCM levels that increased with predator faecal odour concentration. Additionally, reproductively active individuals showed a strong physiological response during both phases 1 and 2 in all plots, except the control plot. Our results indicated that wood mice are able to discriminate different degrees of predation risk, which allows them to trigger gradual changes in their

  19. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

    Directory of Open Access Journals (Sweden)

    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  20. Temporal stability of novelty exploration in mice exposed to different open field tests.

    Science.gov (United States)

    Kalueff, Allan V; Keisala, Tiina; Minasyan, Anna; Kuuslahti, Marianne; Tuohimaa, Pentti

    2006-03-01

    We investigated behavioural activity and temporal distribution (patterning) of mouse exploration in different open field (OF) arenas. Mice of 129S1 (S1) strain were subjected in parallel to three different OF arenas (Experiment 1), two different OF arenas in two trials (Experiment 2) or two trials of the same OF test (Experiment 3). Overall, mice demonstrated a high degree of similarity in the temporal profile of novelty-induced horizontal and vertical exploration (regardless of the size, colour and shape of the OF), which remained stable in subsequent OF exposures. In Experiments 4 and 5, we tested F1 hybrid mice (BALB/c-S1; NMRI-S1), and Vitamin D receptor knockout mice (generated on S1 genetic background), again showing strikingly similar temporal patterns of their OF exploration, despite marked behavioural strain differences in anxiety and activity. These results suggest that mice are characterised by stability of temporal organization of their exploration in different OF novelty situations.

  1. Are voluntary wheel running and open-field behavior correlated in mice? Different answers from comparative and artificial selection approaches.

    Science.gov (United States)

    Careau, Vincent; Bininda-Emonds, Olaf R P; Ordonez, Genesis; Garland, Theodore

    2012-09-01

    Voluntary wheel running and open-field behavior are probably the two most widely used measures of locomotion in laboratory rodents. We tested whether these two behaviors are correlated in mice using two approaches: the phylogenetic comparative method using inbred strains of mice and an ongoing artificial selection experiment on voluntary wheel running. After taking into account the measurement error and phylogenetic relationships among inbred strains, we obtained a significant positive correlation between distance run on wheels and distance moved in the open-field for both sexes. Thigmotaxis was negatively correlated with distance run on wheels in females but not in males. By contrast, mice from four replicate lines bred for high wheel running did not differ in either distance covered or thigmotaxis in the open field as compared with mice from four non-selected control lines. Overall, results obtained in the selection experiment were generally opposite to those observed among inbred strains. Possible reasons for this discrepancy are discussed.

  2. Radioprotective effect of RSP-CM on mice irradiated with different doses

    International Nuclear Information System (INIS)

    Zhang Xia; Yang Rujun; Zhang Xin; Yang Yunfang; Jin Zhijun; Xiang Yingsong

    2000-01-01

    Objective: To investigate the radioprotective effects of cytokines on hematopoietic impairment of irradiated mice. Methods: Using RSP-CM and LP3-CM respectively originated GM-CSF and G-CSF to treat ICR mice irradiated with different doses of 60 Co γ-rays. The 30-day survival rate of mice, the mean survival days of dead mice were determined and the numbers of peripheral white blood cells and BMC of part of the mice were counted. At the same time, GM clonogenic activity of BM was assayed. Results:RSP-CM could effectively raise 30-day survival rate of mice irradiated with 7.5 Gy. However, LP3-CM had no obvious effect. Judging from the comparative survival ratio, only the RSP-CM treated group showed protective effect on the 8.0 Gy -irradiated mice. The 8.5 Gy-irradiated mice all died within 30 days, indicating that GM-CSF had weak effect on higher dose-irradiated mice. Conclusion: GM-CSF can stimulate the hematopoietic system of irradiated mice, and has dose-effect and time-effect relations. M-CSF used singly has no obvious effect

  3. Report 10. Cooperative immune responses of different generations of mice

    International Nuclear Information System (INIS)

    Savtsova, Z.D.; Kovbasyuk, S.A.; Yudina, O.Yu.; Zaritskaya, M.Yu.; Voejkova, I.M.; Orlovskij, A.A.; Indyk, V.M.; Serkiz, Ya.I.

    1991-01-01

    The immune status of mice has been assessed by the whole complex of data. The permanent action of low-level radiation has been shown to suppress considerably the rate of reactions of the delayed-type hypersensitivity and graft-versus host disease, as well as NK and specific cytolytic T-lymphocyte activity. The dynamics of accumulation and the levels of antibodies in the serum, lung and trachea extracts are virtually invariable. The resistance of experimental animals to influenza is lower than that of non-irradiated mice of the same line and age. The data obtained indicate that the immune disturbances revealed are connected not only with the alteration of lymphoid cell populations, but also with the alteration of the immune regulation mechanisms

  4. 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.

  5. Environmental Challenges and Physiological Solutions: Comparative Energetic Daily Rhythms of Field Mice Populations from Different Ecosystems

    Science.gov (United States)

    Scantlebury, Michael; Haim, Abraham

    2012-01-01

    Daily and seasonal variations in physiological characteristics of mammals can be considered adaptations to temporal habitat variables. Across different ecosystems, physiological adjustments are expected to be sensitive to different environmental signals such as changes in photoperiod, temperature or water and food availability; the relative importance of a particular signal being dependent on the ecosystem in question. Energy intake, oxygen consumption (VO2) and body temperature (Tb) daily rhythms were compared between two populations of the broad-toothed field mouse Apodemus mystacinus, one from a Mediterranean and another from a sub-Alpine ecosystem. Mice were acclimated to short-day (SD) ‘winter’ and long-day (LD) ‘summer’ photoperiods under different levels of salinity simulating osmotic challenges. Mediterranean mice had higher VO2 values than sub-Alpine mice. In addition, mice exposed to short days had higher VO2 values when given water with a high salinity compared with mice exposed to long days. By comparison, across both populations, increasing salinity resulted in a decreased Tb in SD- but not in LD-mice. Thus, SD-mice may conserve energy by decreasing Tb during (‘winter’) conditions which are expected to be cool, whereas LD-mice might do the opposite and maintain a higher Tb during (‘summer’) conditions which are expected to be warm. LD-mice behaved to reduce energy expenditure, which might be considered a useful trait during ‘summer’ conditions. Overall, increasing salinity was a clear signal for Mediterranean-mice with resultant effects on VO2 and Tb daily rhythms but had less of an effect on sub-Alpine mice, which were more responsive to changes in photoperiod. Results provide an insight into how different populations respond physiologically to various environmental challenges. PMID:23251469

  6. Individual Differences in Behavioural Reaction to a Changing Environment in Mice and Rats

    NARCIS (Netherlands)

    Benus, R.F.; Koolhaas, J.M.; Oortmerssen, G.A. van

    1987-01-01

    Aggressive and non-aggressive male mice differ in their reaction to a changing social environment. In order to investigate if this differentiation holds also for non-social situations male mice are trained in a standard maze task, whereafter a change (extramaze and intramaze, respectively) is

  7. Phenolic Compositions and Antioxidant Activities Differ Significantly among Sorghum Grains with Different Applications

    Directory of Open Access Journals (Sweden)

    Shuyu Shen

    2018-05-01

    Full Text Available Sorghum grains with different applications had different phenolic profiles, which were corresponded to various antioxidant capacities. In this study, total phenolic, proanthocyanidins and flavonoids contents, as well as contents of individual phenolic compounds from sorghum grains with various applications were determined, and their antioxidant capacities were evaluated. Total phenolic contents (TPC and total proanthocyanidins contents (TPAC showed strong correlation with antioxidant activities (r > 0.95, p < 0.01. Hongyingzi (S-1, one of the brewing sorghums, showed the highest level of TPC and TPAC, while white grain sorghum (S-8 had the lowest. Except for black grain sorghum (S-7, that contained the highest contents of ferulic acid, brewing sorghum grains contained the higher contents of the most individual phenolic compounds, especially the variety S-1. The correlation among individual phenolic compounds and antioxidant activities indicated that the free forms of protocatechuic acid (r = 0.982 of FRAPassay, p < 0.01 and taxifolin (r = 0.826 of FRAP assay, p < 0.01 may be the main functional compounds. These results indicate that brewing sorghum grains can also be utilized as effective materials for functional foods.

  8. Differences in the acute intestinal syndrome after partial and total abdominal irradiation in mice

    International Nuclear Information System (INIS)

    Dewit, L.; Oussoren, Y.; Bartelink, H.; Stewart, F.A.

    1985-01-01

    The acute intestinal syndrome in mice was analysed after partial (PAI) and total abdominal irradiation (TAI). The LDsub(50/15) was significantly higher after PAI (16.3 Gy) than after TAI(14.3 Gy). The dose-response curve for maximal weight loss also showed a shift of 1.8-2 Gy to higher doses after PAI compared with TAI. The X-ray survival curve for duodenal crypt cells was shifted by only 0.6 Gy for PAI and TAI. In order to assess the possible role of radiation-induced leucopenia and the influence of irradiating the spleen (shielded with PAI), lethality, weight loss and blood leucocyte counts were compared after PAI and TAI in splenectomized and non-splenectomized mice. No major difference in leucopenia was found between the different treatment groups, whereas the differences in lethality and weight loss between PAI and TAI remained the same. Shielding the spleen in the partial abdominal field therefore did not contribute to the difference in LDsub(50/15). These findings imply that the increased LDsub(50/15) after PAI compared with TAI was mainly due to shielding of a small part of the bowel (about 13 per cent of the abdominal area). (author)

  9. Selection for high and low oxygen consumption-induced differences in maintenance energy requirements of mice.

    Science.gov (United States)

    Darhan, Hongyu; Kikusato, Motoi; Toyomizu, Masaaki; Roh, Sang-Gun; Katoh, Kazuo; Sato, Masahiro; Suzuki, Keiichi

    2017-07-01

    Maintenance energy requirements (MER) of mice selected for high (H) or low (L) oxygen consumption (OC) were compared. Forty-four mice from H and L OC lines were weaned at 3 weeks and divided into four experimental groups: group A were sacrificed at 4 weeks; group B were fed ad libitum, and groups C and D were fed 2.8 and 2.4 g/day, respectively, from 4 to 8 weeks of age. Groups B-D were sacrificed at 8 weeks. Chemical components were estimated for all groups. MER was estimated using a model that partitioned metabolizable energy intake into that used for maintenance, and protein and fat deposition. The feed conversion ratio for the B group was significantly higher in the H than in the L line. Feed intake for metabolic energy content per metabolic body size was significantly also higher in the H line, whereas accumulated energy content per metabolic body size was significantly higher in the L line. MER of the H line was greater than that of the L line (P < 0.10). These results suggest that selection for H or L OC produced differences in chemical components, feed efficiency, and MER between the H and L lines. © 2016 Japanese Society of Animal Science.

  10. A different role of angiotensin II type 1a receptor in the development and hypertrophy of plantaris muscle in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Ogawa, Masahito; Watanabe, Ryo; Isobe, Mitsuaki

    2016-02-01

    The role of angiotensin II type 1 (AT1) receptors in muscle development and hypertrophy remains unclear. This study was designed to reveal the effects that a loss of AT1 receptors has on skeletal muscle development and hypertrophy in mice. Eight-week-old male AT1a receptor knockout (AT1a(-/-)) mice were used for this experiment. The plantaris muscle to body weight ratio, muscle fiber cross-sectional area, and number of muscle fibers of AT1a(-/-) mice was significantly greater than wild type (WT) mice in the non-intervention condition. Next, the functional overload (OL) model was used to induce plantaris muscle hypertrophy by surgically removing the two triceps muscles consisting of the calf, soleus, and gastrocnemius muscles in mice. After 14 days of OL intervention, the plantaris muscle weight, the amount of fiber, and the fiber area increased. However, the magnitude of the increment of plantaris weight was not different between the two strains. Agtr1a mRNA expression did not change after OL in WT muscle. Actually, the Agt mRNA expression level of WT-OL was lower than WT-Control (C) muscle. An atrophy-related gene, atrogin-1 mRNA expression levels of AT1a(-/-)-C, WT-OL, and AT1a(-/-)-OL muscle were lower than that of WT-C muscle. Our findings suggest that AT1 receptor contributes to plantaris muscle development via atrogin-1 in mice.

  11. 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.

  12. 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

  13. Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice

    NARCIS (Netherlands)

    Leenaars, P.P.A.M.; Koedam, M.A.; Wester, P.W.; Baumans, V.; Claassen, E.; Hendriksen, C.F.M.

    1998-01-01

    We evaluated the side effects induced by injection of Freund's adjuvant (FA) and alternative adjuvants combined with different antigens. Rabbits and mice were injected subcutaneously, intramuscularly (rabbits) and intraperitoneally (mice) with different adjuvants (FA, Specol, RIBI, TiterMax,

  14. Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

    Science.gov (United States)

    Schmitt, Ulrich; Hiemke, Christoph; Fahrenholz, Falk; Schroeder, Anja

    2006-12-15

    Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

  15. Multivariate Analysis of Variance: Finding significant growth in mice with craniofacial dysmorphology caused by the Crouzon mutation

    DEFF Research Database (Denmark)

    Thorup, Signe Strann; Ólafsdóttir, Hildur; Darvann, Tron Andre

    2010-01-01

    Crouzon syndrome is characterized by growth disturbances caused by premature fusion of the cranial growth zones. A mouse model with mutation Fgfr2C342Y, equivalent to the most common Crouzon syndrome mutation (henceforth called the Crouzon mouse model), has a phenotype showing many parallels to t...... used micro-CT scans of 4-week-old mice (N=5) and 6-week-old mice (N=10) with Crouzon syndrome (Fgfr2 C342Y/+) were compared to control groups of 4-week-old wild-type mice (N=5) and 6-week-old wild-type mice (N=10), respectively....

  16. 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

  17. 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.

  18. Differences in the immunologic reactivity of mice treated with UVB or methoxsalen plus UVA radiation

    International Nuclear Information System (INIS)

    Kripke, M.L.; Morison, W.L.; Parrish, J.A.

    1981-01-01

    Skin tumors induced in mice by chronic exposure to UVB radiation are often highly antigenic and regress when transplanted into normal syngeneic animals, but grow progressively in immunosuppressed mice. Exposure of mice to subtumorigenic doses of UVB radiation can abolish this immunologic rejection phenomenon. In this study, we have investigated the effects of treatment with 8-methoxypsoralen plus UVA radiation (PUVA) on the rejection of antigenic UVB-induced tumors. PUVA treatment, with either topical or systemic administration of the psoralen, did not alter the normal process of rejection of UVB-induced tumors. Mice treated with both minimally and markedly phototoxic doses of PUVA rejected tumors with a frequency similar to that seen in untreated animals, although these tumors grew progressively in UVB-irradiated mice. These results indicate that the effects of PUVA treatment differ from those of UVB irradiation in that PUVA treatment does not alter the immunologic rejection of UVB-induced tumors

  19. Differences between seizure-prone and non-seizure-prone mice with regard to glutamate and GABA receptor binding in the hippocampus and other regions of the brain

    DEFF Research Database (Denmark)

    Frandsen, A; Belhage, B; Schousboe, A

    1987-01-01

    Quisqualate-preferring glutamate receptors were determined in membranes from frontal cortex, occipital cortex, hippocampus and cerebellum, from seizure-prone DBA/2J BOM and seizure-resistant C57/BL mice. The animals were studied 21, 27 and 40 days postnatally, i.e., before, during and after the age...... at which DBA mice are most susceptible to seizures. Radio-binding assays were performed using [3H]AMPA in the presence of 100 nM glutamate. Except for the occipital cortex, where no significant differences between the two strains were observed, all areas of the brain of DBA mice exhibited significantly (P...... less than 0.001, t test) higher AMPA binding than the corresponding areas of C57/BL mice at 27 days of age. At pre- and post-susceptible ages, the two strains showed no significant differences in the hippocampus and occipital cortex. A significant difference was observed, however, in the frontal cortex...

  20. Cell kinetics of Ehrlich ascites carcinoma transplanted in mice with different degrees of tumor resistance

    International Nuclear Information System (INIS)

    Brandt, K.L.B.

    1974-01-01

    Cell proliferation kinetics of Ehrlich ascites carcinoma grown in two strains of mice with different degrees of resistance to this tumor were examined. In the first portion of the study, growth of Ehrlich ascites carcinoma in nonresistant Swiss (Iowa) and slightly resistant CF1 mice was examined by measuring animal weight gain and host survival time after intraperitoneal injection of tumor cells. Since it appeared that CF1 mice were inherently more resistant than Swiss mice to the Ehrlich carcinoma, the second part of this investigation involved attempts to immunize CF1 mice against the tumor. Subcutaneous injections of Ehrlich cells previously exposed in vitro to 5000 R of 250 kVp x rays were utilized. One immunizing inoculation of lethally irradiated tumor cells afforded protection against an intraperitoneal challenge of 40 thousand Ehrlich cells. By varying the number and timing of immunizing inoculations it was possible to induce different degrees of tumor resistance in these mice. The most effective immunizing procedure utilized multiple inoculations of lethally irradiated tumor cells (LITC), followed by challenges with viable tumor cells (less than 1 million) which were rejected. These mice could then resist challenge inocula of 4 million viable tumor cells. In a few animals the immunizing procedures were ineffective; these animals, when challenged, developed even larger tumors than control mice. Tumor cell proliferation kinetics in these animals as well as in mice that were rejecting the tumor were examined in the third phase of the project. A shortening of the cell cycle was observed in almost all LITC-treated mice, whether tumor growth was eventually inhibited or stimulated. Decreased duration of the DNA-synthesis phase (S) of the tumor cell cycle was also a consistent finding. The role of the immune response in stimulating mitosis as well as in killing foreign cells was discussed. (U.S.)

  1. Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice

    Directory of Open Access Journals (Sweden)

    Qingtao Liu

    2016-11-01

    Full Text Available H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06 virus was highly pathogenic for mice, with a 50% mouse lethal dose of 102.83 50% egg infectious dose, whereas the A/duck/Nanjing/01/1999 (NJ01 virus was low pathogenic for mice, with a 50% mouse lethal dose of >106.81 50% egg infectious dose. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only twelve different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.

  2. Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

    Science.gov (United States)

    Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

    2016-10-15

    Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Miettinen, Hanna, E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, P.O. Box 95, FI-70701 Kuopio (Finland); Sankari, Satu, E-mail: satu.sankari@helsinki.fi [Central Laboratory of the Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014 University of Helsinki (Finland); Hegde, Nagabhooshan [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Lindén, Jere, E-mail: jere.linden@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland)

    2012-07-15

    The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance.

  4. Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

    International Nuclear Information System (INIS)

    Pohjanvirta, Raimo; Miettinen, Hanna; Sankari, Satu; Hegde, Nagabhooshan; Lindén, Jere

    2012-01-01

    The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD 50 for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance.

  5. Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Milton Levin

    2008-12-01

    Full Text Available The immunotoxic potential of domoic acid (DA, a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 µg/g b.w. and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 µM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr, a significant decrease in neutrophil phagocytosis (24-hr, a significant decrease in monocyte phagocytosis (48-hr, and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr. In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 µM. B- and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 µM, and significantly decreased at 100 µM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species.

  6. Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

    Science.gov (United States)

    Beery, Annaliese K.; Christensen, Jennifer D; Lee, Nicole S.; Blandino, Katrina L.

    2018-01-01

    Social behavior is often described as a unified concept, but highly social (group-living) species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex) during extended choice tests, although short-term preferences are not known. Mice (Mus musculus) are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT) typically used in mice (short, no direct contact), and the partner preference test (PPT) used in voles (long, direct contact). A subset of voles also underwent a PPT using barriers (long, no direct contact). In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of selective social

  7. Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

    Directory of Open Access Journals (Sweden)

    Annaliese K. Beery

    2018-03-01

    Full Text Available Social behavior is often described as a unified concept, but highly social (group-living species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex during extended choice tests, although short-term preferences are not known. Mice (Mus musculus are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT typically used in mice (short, no direct contact, and the partner preference test (PPT used in voles (long, direct contact. A subset of voles also underwent a PPT using barriers (long, no direct contact. In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of

  8. The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

    Directory of Open Access Journals (Sweden)

    Jingsheng Liang

    2015-01-01

    Full Text Available We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine mutation in human cardiac troponin I (cTnI on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV and right (RV ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

  9. Genetic differences between two substrains of NZB mice.

    Science.gov (United States)

    Oikawa, T; Katoh, H; Shoji, Y; Esaki, K; Ishikawa, M; Yuhki, N; Kuzumaki, N; Tateno, M; Yoshiki, T

    1985-02-01

    We have compared the NZB/B1NJ (/NJ) and NZB/B1Pt (/Pt) mouse substrains with respect to a number of immunological and biochemical polymorphisms. In agreement with earlier findings by other workers, we detected histocompatibility antigen difference(s) between the two substrains. Serological analysis indicated that /NJ and /Pt expressed the same allotypes of H-2, Thy-1 and Lyt-1 antigens, while they differed for the Lyt-2 antigen. Amongst 15 biochemical polymorphisms, which we assayed, /NJ and /Pt differed for four, namely Pep-3, Mup-1, Gpd-1 and Hbb. In addition, the two NZB substrains differed for the Hc marker (haemolytic complement).

  10. 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

  11. The Effect of Different Photoperiods in Circadian Rhythms of Per3 Knockout Mice

    Directory of Open Access Journals (Sweden)

    D. S. Pereira

    2014-01-01

    Full Text Available The aim of this study was to analyse the circadian behavioural responses of mice carrying a functional knockout of the Per3 gene (Per3−/− to different light : dark (L : D cycles. Male adult wild-type (WT and Per3−/− mice were kept under 12-hour light : 12-hour dark conditions (12L : 12D and then transferred to either a short or long photoperiod and subsequently released into total darkness. All mice were exposed to both conditions, and behavioural activity data were acquired through running wheel activity and analysed for circadian characteristics during these conditions. We observed that, during the transition from 12L : 12D to 16L : 8D, Per3−/− mice take approximately one additional day to synchronise to the new L : D cycle compared to WT mice. Under these long photoperiod conditions, Per3−/− mice were more active in the light phase. Our results suggest that Per3−/− mice are less sensitive to light. The data presented here provides further evidence that Per3 is involved in the suppression of behavioural activity in direct response to light.

  12. Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.

    Directory of Open Access Journals (Sweden)

    Emilie Lyne Saussereau

    Full Text Available BACKGROUND: Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF. Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE in CF mice must be well characterized for correct interpretation. METHODS: We performed V(TE measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice. RESULTS: We determined the typical V(TE values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(- solution was considered to indicate a normal response. CONCLUSIONS: These data will make it possible to interpret changes in nasal V(TE in mouse models of CF, in future preclinical studies.

  13. Species-relevant inescapable stress differently influences memory consolidation and retrieval of mice in a spatial radial arm maze.

    Science.gov (United States)

    Janitzky, K; Schwegler, H; Kröber, A; Roskoden, T; Yanagawa, Y; Linke, R

    2011-05-16

    Stress affects learning and there are both facilitating and impairing actions of stressors on memory processes. Here we investigated the influence of acute exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethological relevant stressor for rodents, on spatial memory formation and performance in a radial arm maze (RAM) task and studied TMT effects on corticosterone levels in GAD67-GFP knock-in mice and their wildtype littermates. Our results suggest that predator odor-exposure differently affects consolidation and retrieval of memory in a hippocampus-dependent spatial learning task in adult male mice, independently from their genotypes. Acute TMT-stress before retrieval facilitates performance, whereas repeated TMT-stress during consolidation exerts no influence. Additionally, we found genotype specific effects of TMT on corticosterone release. While TMT-stress tend to result in increased corticosterone release in wildtypes there was a significant decrease in transgenic mice. Taken together, these findings indicate that biologically significant predator odor-induced stress can have different actions on the strength of spatial memory formation depending on the timing with regard to memory phases. Furthermore, we suppose an impact of GABAergic mechanisms on HPA-stress axis activation to TMT resulting in absent peripheral corticosterone release of GAD67-GFP mice. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. The influence of enriched environment on spatial memory in Swiss mice of different ages

    Directory of Open Access Journals (Sweden)

    Alessandra Fernandes Druzian

    2015-08-01

    Full Text Available The objective of this study was to evaluate the influence of enriched environment on spatial memory acquisition in mice of three different age groups. Weanling, young, and young adult female Swiss mice were housed in a standard control or enriched environment for 50 days, and their spatial memory was tested with the Morris Water Maze. We did not observe an experimental effect for spatial memory acquisition, and there was neither an effect of time of analysis nor an interaction between experimental group and time of analysis. Regarding effects of experimental group and training day in relation to latency in finding the hidden platform, we did find an effect in the experimental young adult mice group (p = 0.027, but there was no interaction between these factors in all three groups. Based on these findings environmental enrichment did not enhance spatial memory acquisition in female Swiss mice in the tested age groups.

  15. Sex differences in the effects of adolescent social deprivation on alcohol consumption in μ-opioid receptor knockout mice.

    Science.gov (United States)

    Moriya, Yuki; Kasahara, Yoshiyuki; Hall, F Scott; Sakakibara, Yasufumi; Uhl, George R; Tomita, Hiroaki; Sora, Ichiro

    2015-04-01

    Evidence based on clinical and experimental animal studies indicates that adolescent social deprivation influences alcohol consumption in a sex-dependent manner, perhaps by influencing stress responses. However, the mechanisms underlying the interaction between these phenomena remain to be elucidated. Since the μ-opioid receptor (MOP) has been reported to have key roles in social stress responses as well as the reinforcing/addictive effects of ethanol, MOP is a candidate molecule that may link adolescent social deprivation and subsequent alterations in alcohol consumption. To evaluate the involvement of MOP and social isolation-induced changes in alcohol consumption, as well as the effect of sex differences on responses to social isolation, alcohol consumption was assessed using a two-bottle home-cage consumption procedure (8 % ethanol vs. water) in MOP knockout (MOP-KO) and wild type (WT) mice of both sexes exposed to adolescent social deprivation or reared socially. Isolation rearing had no effects upon alcohol consumption of WT mice, whereas it significantly altered alcohol consumption in both male and female MOP-KO mice. Interestingly, social isolation affected ethanol consumption differently in male and female mice. Ethanol consumption was increased in male MOP-KO mice, but decreased in female MOP-KO mice, by isolation rearing. These results indicate that disturbances of MOP function influence the effects of isolation rearing on ethanol consumption in a sex-dependent manner. Consequently, this suggests the possibility that genetic variation that influences MOP function may have differential roles in alcoholism in men and women, and alcoholism treatments that target MOP function may be differentially effective in males and females.

  16. High-intensity interval training (swimming) significantly improves the adverse metabolism and comorbidities in diet-induced obese mice.

    Science.gov (United States)

    Motta, Victor F; Aguila, Marcia B; Mandarim-DE-Lacerda, Carlos A

    2016-05-01

    Controlling obesity and other comorbidities in the population is a challenge in modern society. High-intensity interval training (HIIT) combines short periods of high-intensity exercise with long recovery periods or a low-intensity exercise. The aim was to assess the impact of HIIT in the context of diet-induced obesity in the animal model. C57BL/6 mice were fed one of the two diets: standard chow (lean group [LE]) or a high-fat diet (obese group [OB]). After twelve weeks, the animals were divided into non-trained groups (LE-NT and OB-NT) and trained groups (LE-T and OB-T), and began an exercise protocol. For biochemical analysis of inflammatory and lipid profile, we used a colorimetric enzymatic method and an automatic spectrophotometer. One-way ANOVA was used for statistical analysis of the experimental groups with Holm-Sidak post-hoc Test. Two-way ANOVA analyzed the interactions between diet and HIIT protocol. HIIT leads to significant reductions in body mass, blood glucose, glucose tolerance and hepatic lipid profile in T-groups compared to NT-groups. HIIT was able to reduce plasma levels of inflammatory cytokines. Additionally, HIIT improves the insulin immunodensity in the islets, reduces the adiposity and the hepatic steatosis in the T-groups. HIIT improves beta-oxidation and peroxisome proliferator-activated receptor (PPAR)-alpha and reduces lipogenesis and PPAR-gamma levels in the liver. In skeletal muscle, HIIT improves PPAR-alpha and glucose transporter-4 and reduces PPAR-gamma levels. HIIT leads to attenuate the adverse effects caused by a chronic ingestion of a high-fat diet.

  17. Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor-Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products.

    Science.gov (United States)

    Kristofikova, Zdena; Ricny, Jan; Sirova, Jana; Ripova, Daniela; Lubitz, Irit; Schnaider-Beeri, Michal

    2015-08-01

    It has been suggested that advanced glycation end (AGE) products, via cognate receptor activation, are implicated in several diseases, including Alzheimer's disease. The NMDA receptor-nitric oxide pathway appears to be influenced by AGE products and involved in the pathogenesis of this type of dementia. In this study, C57BL/6J (WT) and transgenic (Tg2576) mice expressing human mutant amyloid precursor protein were kept on prolonged (8 months) diets containing regular or high amounts of AGE products. After the decapitation of 11-months old mice, brain tissue analyses were performed [expressions of the NR1, NR2A and NR2B subunits of NMDA receptors, activities of neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS)]. Moreover, levels of malondialdehyde and of human amyloid β 1-42 were estimated. We found increased activity of nNOS in WT mice maintained on a high compared to regular AGE diet; however, no similar differences were found in Tg2576 mice. In addition, we observed an increase in NR1 expression in Tg2576 compared to WT mice, both kept on a diet high in AGE products. Correlation analyses performed on mice kept on the regular AGE diet supported close links between particular subunits (NR2A-NR2B, in WT as well as in Tg2576 mice), between subunits and synthase (NR2A/NR2B-nNOS, only in WT mice) or between particular synthases (nNOS-iNOS, only in WT). Correlation analysis also revealed differences between WT mice kept on both diets (changed correlations between NR2A/NR2B-nNOS, between nNOS-eNOS and between eNOS-iNOS). Malondialdehyde levels were increased in both Tg2576 groups when compared to the corresponding WT mice, but no effects of the diets were observed. Analogously, no significant effects of diets were found in the levels of soluble or insoluble amyloid β 1-42 in Tg2576 mice. Our results demonstrate that prolonged ingestion of AGE products can influence the NMDA receptor-nitric oxide pathway in the brain and that only WT mice

  18. Liver proteome of mice with different genetic susceptibilities to the effects of fluoride

    Directory of Open Access Journals (Sweden)

    Zohaib Nisar KHAN

    Full Text Available ABSTRACT A/J and 129P3/J mice strains have been widely studied over the last few years because they respond quite differently to fluoride (F exposure. 129P3/J mice are remarkably resistant to the development of dental fluorosis, despite excreting less F in urine and having higher circulating F levels. These two strains also present different characteristics regardless of F exposure. Objective In this study, we investigated the differential pattern of protein expression in the liver of these mice to provide insights on why they have different responses to F. Material and Methods Weanling male A/J and 129P3/J mice (n=10 from each strain were pared and housed in metabolic cages with ad libitum access to low-F food and deionized water for 42 days. Liver proteome profiles were examined using nLC-MS/MS. Protein function was classified by GO biological process (Cluego v2.0.7 + Clupedia v1.0.8 and protein-protein interaction network was constructed (PSICQUIC, Cytoscape. Results Most proteins with fold change were increased in A/J mice. The functional category with the highest percentage of altered genes was oxidation-reduction process (20%. Subnetwork analysis revealed that proteins with fold change interacted with Disks large homolog 4 and Calcium-activated potassium channel subunit alpha-1. A/J mice had an increase in proteins related to energy flux and oxidative stress. Conclusion This could be a possible explanation for the high susceptibility of these mice to the effects of F, since the exposure also induces oxidative stress.

  19. The analgesic effect of different antidepressants combined with aspirin on thermally induced pain in Albino mice

    Directory of Open Access Journals (Sweden)

    Abdalla S. Elhwuegi

    2012-04-01

    Full Text Available Background:Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice.Methods:Different groups of six animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg, imipramine (2.5, 7.5, 15 or 30 mg/kg, fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg, mirtazapine (1.25, 2.5, or 5 mg/kg and a combination of a fixed dose of aspirin (100 mg/kg with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT of the lowest dose (by 23% and the highest dose (by 20%. The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively.Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug.

  20. Estimating significances of differences between slopes: A new methodology and software

    Directory of Open Access Journals (Sweden)

    Vasco M. N. C. S. Vieira

    2013-09-01

    Full Text Available Determining the significance of slope differences is a common requirement in studies of self-thinning, ontogeny and sexual dimorphism, among others. This has long been carried out testing for the overlap of the bootstrapped 95% confidence intervals of the slopes. However, the numerical random re-sampling with repetition favours the occurrence of re-combinations yielding largely diverging slopes, widening the confidence intervals and thus increasing the chances of overlooking significant differences. To overcome this problem a permutation test simulating the null hypothesis of no differences between slopes is proposed. This new methodology, when applied both to artificial and factual data, showed an enhanced ability to differentiate slopes.

  1. Clinical significance of changes of serum osteocalcin (BGP) levels in subjects of different age-groups

    International Nuclear Information System (INIS)

    Jiang Lihua; Zhang Jin; Han Cuihua; Ouyang Qiaohong

    2006-01-01

    Objective: To investigate the changes of serum BGP levels in different age-groups. Methods: Serum BGP levels were determined with RIA in 306 subjects of different age-groups. Results: The serum BGP levels were highest in subjects of the pre-adolescent group (age5-15, n=60, vs other groups, all P 50, n=80, P<0.001). Levels in the middle age group were the lowest and were significantly lower than those in the old age group (P<0.001). No sex related differences were observed in the pre-adolescent and middle age groups, but in the youth group, serum BGP levels were significantly higher in the males than those in the females (P<0.05). However, in the old age group, the reverse was true i.e. values being significantly higher in the females (vs males, P<0.01). Conclusion: Serum BGP levels varied greatly among the different age groups. (authors)

  2. The Ability of Different Imputation Methods to Preserve the Significant Genes and Pathways in Cancer

    Directory of Open Access Journals (Sweden)

    Rosa Aghdam

    2017-12-01

    Full Text Available Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM method was applied to detect the significant genes in rectal and lung cancers to showcase the utility of imputation approaches in preserving significant genes. To determine the impact of different imputation methods on the identification of important genes, the chi-squared test was used to compare the proportions of overlaps between significant genes detected from original data and those detected from the imputed datasets. Additionally, the significant genes are tested for their enrichment in important pathways, using the ConsensusPathDB. Our results showed that almost all the significant genes and pathways of the original dataset can be detected in all imputed datasets, indicating that there is no significant difference in the performance of various imputation methods tested. The source code and selected datasets are available on http://profiles.bs.ipm.ir/softwares/imputation_methods/.

  3. The Ability of Different Imputation Methods to Preserve the Significant Genes and Pathways in Cancer.

    Science.gov (United States)

    Aghdam, Rosa; Baghfalaki, Taban; Khosravi, Pegah; Saberi Ansari, Elnaz

    2017-12-01

    Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM) method was applied to detect the significant genes in rectal and lung cancers to showcase the utility of imputation approaches in preserving significant genes. To determine the impact of different imputation methods on the identification of important genes, the chi-squared test was used to compare the proportions of overlaps between significant genes detected from original data and those detected from the imputed datasets. Additionally, the significant genes are tested for their enrichment in important pathways, using the ConsensusPathDB. Our results showed that almost all the significant genes and pathways of the original dataset can be detected in all imputed datasets, indicating that there is no significant difference in the performance of various imputation methods tested. The source code and selected datasets are available on http://profiles.bs.ipm.ir/softwares/imputation_methods/. Copyright © 2017. Production and hosting by Elsevier B.V.

  4. Biographical Narratives of Encounter: The Significance of Mobility and Emplacement in Shaping Attitudes towards Difference

    Science.gov (United States)

    Sadgrove, Joanna

    2014-01-01

    This paper is located within work in urban studies about the significance of contact with difference as a means for reducing prejudice and achieving social change. Recent approaches, influenced by theories of affect, have emphasised non-conscious everyday negotiations of difference in the city. In this paper it is argued that such approaches lose sight of the significance of the subject: of the reflective judgements of ‘others’ made by individuals; of our ability to make decisions around the control of our feelings and identifications; and of the significance of personal pasts and collective histories in shaping the ways we perceive and react to encounters. Rather, this paper uses a biographical approach focusing on interviewees’ narratives of encounter. Through its attention to processes of mobility and emplacement, it contributes to debates about when contact with difference matters by highlighting the importance of everyday social normativities in the production of moral dispositions. PMID:26300566

  5. Potential Causes of Significant Inventory Differences at Bulk Handling Facilities and the Importance of Inventory Difference Action Levels

    International Nuclear Information System (INIS)

    Homer, Alan; O’Hagan, Brendan

    2015-01-01

    Accountancy for nuclear material can be split into two categories. Firstly, where possible, accountancy should be in terms of items that can be transferred as discrete packages and their contents fixed at the time of their creation. All items must remain accounted for at all times, and a single missing item is considered significant. Secondly, where nuclear material is unconstrained, for example in a reprocessing plant where it can change form, there is an uncertainty that relates to the amount of material present in any location. Cumulatively, these uncertainties can be summed and provide a context for any estimate of material in a process. Any apparent loss or gain between what has been physically measured within a facility during its physical inventory take and what is reported within its nuclear material accounts is known as an inventory difference. The cumulative measurement uncertainties can be used to set an action level for the inventory difference so that if an inventory difference is observed outside of such action levels, the difference is classified as significant and an investigation to find the root cause(s) is required. The purpose of this paper is to explore the potential causes of significant inventory differences and to provide a framework within which an inventory difference investigation can be carried out.

  6. Immunomodulatory activities of different solvent extracts from Tricholoma matsutake (S. Ito et S. Imai) singer (higher basidiomycetes) on normal mice.

    Science.gov (United States)

    Yin, Xiulian; You, Qinghong; Jiang, Zhonghai

    2012-01-01

    The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.

  7. Differences in ultrasonic vocalizations between wild and laboratory California mice (Peromyscus californicus.

    Directory of Open Access Journals (Sweden)

    Matina C Kalcounis-Rueppell

    Full Text Available BACKGROUND: Ultrasonic vocalizations (USVs emitted by muroid rodents, including laboratory mice and rats, are used as phenotypic markers in behavioral assays and biomedical research. Interpretation of these USVs depends on understanding the significance of USV production by rodents in the wild. However, there has never been a study of muroid rodent ultrasound function in the wild and comparisons of USVs produced by wild and laboratory rodents are lacking to date. Here, we report the first comparison of wild and captive rodent USVs recorded from the same species, Peromyscus californicus. METHODOLOGY AND PRINCIPAL FINDINGS: We used standard ultrasound recording techniques to measure USVs from California mice in the laboratory (Peromyscus Genetic Stock Center, SC, USA and the wild (Hastings Natural History Reserve, CA, USA. To determine which California mouse in the wild was vocalizing, we used a remote sensing method that used a 12-microphone acoustic localization array coupled with automated radio telemetry of all resident Peromyscus californicus in the area of the acoustic localization array. California mice in the laboratory and the wild produced the same types of USV motifs. However, wild California mice produced USVs that were 2-8 kHz higher in median frequency and significantly more variable in frequency than laboratory California mice. SIGNIFICANCE: The similarity in overall form of USVs from wild and laboratory California mice demonstrates that production of USVs by captive Peromyscus is not an artifact of captivity. Our study validates the widespread use of USVs in laboratory rodents as behavioral indicators but highlights that particular characteristics of laboratory USVs may not reflect natural conditions.

  8. Effect of three different cultivars of Lepidium meyenii (Maca on learning and depression in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Gonzales Gustavo F

    2006-06-01

    Full Text Available Abstract Background Lepidium meyenii Walp. (Brassicaceae, known as Maca, is a Peruvian hypocotyl growing exclusively between 4000 and 4500 m altitude in the central Peruvian Andes, particularly in Junin plateau and is used traditionally to enhance fertility. Maca is a cultivated plant and different cultivars are described according to the color of the hypocotyls. Methods The study aimed to elucidate the effect of Yellow, Red and Black Maca on cognitive function and depression in ovariectomized (OVX mice. In all experiments OVX mice were treated during 21 days and divided in four groups: control group, Yellow Maca, Red Maca and Black Maca. Latent learning was assessed using the water finding task and the antidepressant activity of the three varieties of Maca was evaluated using the forced swimming test. Animals were sacrificed at the end of each treatment and the uterus were excised and weighed. Results Black Maca was the variety that showed the best response in the water finding task, particularly in the trained mice. The three varieties were effective to reduce finding latency in non trained and trained mice (P Conclusion Black Maca appeared to have more beneficial effects on latent learning in OVX mice; meanwhile, all varieties of Maca showed antidepressant activity.

  9. [Distributions of H3K27me3 and its modification enzymes in different tissues of mice].

    Science.gov (United States)

    Wang, Yuying; Wang, Xinli; Zhang, Ran; Zhang, Zhiyan; Wang, Yu; Yang, Bo; Wang, Guanjie; Zhang, Xin; Ma, Fuhao; Xu, Hongye; Wu, Xiaohui; Zhang, Feng; Li, Qing

    2017-11-01

    Objective To investigate the levels of trimethylated histone 3 at lysine residue 27 (H3K27me3) and its modification enzymes Zeste gene enhancer homolog 2 (EZH2), lysine-specific demethylase 6B (Kdm6B/JMJD3) and lysine-specific demethylase 6A (Kdm6A/UTX) in tissues and organs of 7-day and 2-month postnatal mice. Methods Immunohistochemistry was used to detect the expressions of H3K27me3 and its modification enzymes EZH2, JMJD3 and UTX in the brain, salivary glands, back fat, thymus, lung, heart, stomach, intestines, liver, testes, and skin of 7-day and 2-month mice. Real-time quantitative PCR was used to confirm the results. The relationships between H3K27me3 and its modification enzymes were analyzed statistically. Results Immunohistochemistry showed H3K27me3 persistently present in all examined tissues of 7-day and 2-month mice. EZH2 was persistently expressed in the brain, heart, liver, and skin of 7-day and 2-month mice, but only expressed in the salivary glands, adipose tissues, thymus, lung, intestines, and testes of 2-month mice. JMJD3 was expressed in the brain, salivary glands, adipose tissues, lung, heart, stomach, intestines, testes, skin of 7-day mice, but was not expressed in the lung, adipose tissues and stomach of 2-month mice. UTX was expressed in the brain, salivary glands, adipose tissues, lung, heart, testes, skin of 7-day mice, but only expressed in the testes of 2-month mice. Most mRNA of H3K27 modification enzymes were moderately or highly expressed as their immunohistochemical results were positive. Conclusion There was H3K27me3 persistently present in the all examined tissues at different stages. EZH2 was mostly expressed in the brain, salivary glands, adipose tissues, thymus, lung, heart, intestines, liver, testes and skin of 2-month-old mice. JMJD3 and UTX were mostly expressed in the brain, salivary glands, adipose tissues, lung, heart, skin and testes of 7-day-old mice. No significant association was found between the distribution of H3K

  10. CAST/EiJ and C57BL/6J Mice Differ in Their Oral and Postoral Attraction to Glucose and Fructose.

    Science.gov (United States)

    Sclafani, Anthony; Vural, Austin S; Ackroff, Karen

    2017-03-01

    A recent study indicated that CAST/EiJ and C57BL/6J mice differ in their taste preferences for maltodextrin but display similar sucrose preferences. The present study revealed strain differences in preferences for the constituent sugars of sucrose. Whereas B6 mice preferred 8% glucose to 8% fructose in 2-day tests, the CAST mice preferred fructose to glucose. These preferences emerged with repeated testing which suggested post-oral influences. In a second experiment, 2-day choice tests were conducted with the sugars versus a sucralose + saccharin (SS) mixture which is highly preferred in brief access tests. B6 mice strongly preferred glucose but not fructose to the non-nutritive SS whereas CAST mice preferred SS to both glucose and fructose even when food restricted. This implied that CAST mice are insensitive to the postoral appetite stimulating actions of the 2 sugars. A third experiment revealed, however, that intragastric glucose and fructose infusions conditioned significant but mild flavor preferences in CAST mice, whereas in B6 mice glucose conditioned a robust preference but fructose was ineffective. Thus, unlike other mouse strains and rats, glucose is not more reinforcing than fructose in CAST mice. Their oral preference for fructose over glucose may be related to a subsensitive maltodextrin receptor or glucose-specific receptor which is stimulated by glucose but not fructose. The failure of CAST mice to prefer glucose to a non-nutritive sweetener distinguishes this strain from other mouse strains and rats. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. The Effects of Different Doses of Curcuma longa Aqueous Extract on Memory Retention and Retrieval in Male Mice

    Directory of Open Access Journals (Sweden)

    2016-12-01

    Full Text Available Background and Objectives: Curcumin belongs to ginger family, which is used as food and drug from ancient times. Different studies have shown beneficial effects of curcumin on peptic ulcer, rheumatoid arthritis, asthma, and various types of cancer. In this study, the effect of different doses of Curcuma longa aqueous extract on memory retention and retrieval of mice, was investigated using passive avoidance apparatus. Methods: Mice were divided into 6 groups of 8 each for memory retention test and 6 groups of 8 each for memory retrieval test {experimental groups receiving the extract intraperitoneally at doses of 100, 200, 400, 800mg/kg, blank group, and control group}. In memory retention test, the curcumin extract was administered immediately after electric shock, while in the memory retrieval test, it was administered 24 h after receiving electric shock. To compare the complete stepping in the experiment days, One-way ANOVA and post-test LSD were used. The level of significance was considered p<0.05. Results: In this study, curcuma longa aqueous extract significantly increased memory retention and retrieval on the 4th day compared to blank and control groups. The best response for memory retention was obtained at the dose of 100mg/kg and for memory retrieval at the dose of 200mg/kg. Conclusion: According to the results of this study, it seems that Curcuma longa aqueous extract improves memory retention and retrieval in healthy mice.  

  12. Influence of different types of bedding materials on immune response and serum biochemical profile of caged mice

    Directory of Open Access Journals (Sweden)

    Vijayakumar . R

    Full Text Available Contact bedding material is an important environmental factor and welfare creator for laboratory mice. It can alter important physiological process and create potential chance for experimental variation which puts hurdle for comparability. The present experiment was conducted to assess the possible impact of different types of bedding material viz CPS, NWS and PH with fifty one albino mice for a period of fifteen weeks in Laboratory Animal Facility. It was observed that local immunity in mice was enhanced in NWS. During in vitro immune assays, mice from NWS showed higher OD value for reactive oxygen radical, produced more NO2 and higher stimulation index i.e. 0.71 ± 0.01, 30.67 ± 0.88 μM and 7.90 ± 0.17, respectively than PH (0.23 ± 0.01, 17.0 ± 1.15 μM and 6.33 ± 0.21 and CPS (0.33 ± 0.03, 15.67 ± 1.20 μM and 6.46 ± 0.27. There was no influence of bedding type on systemic response. Reduced glutathione value in liver was higher in NWS than PH and CPS i.e. 8.54 ± 0.2, 7.09 ± 0.18 and 6.96 ± 0.14 μmole/ gm of tissue. But heart reduced glutathione showed no variation among different types of bedding materials. Serum analysis showed significantly (p<0.05 higher total protein and albumin value for enriched groups. But globulin value was not significantly differing for enriched and non-enriched groups. [Veterinary World 2010; 3(9.000: 417-420

  13. Biomechanical adaptations of mice cortical bone submitted to three different exercise modalities

    Science.gov (United States)

    Frajacomo, Fernando Tadeu Trevisan; Falcai, Maurício José; Fernandes, Cleverson Rodrigues; Shimano, Antonio Carlos; Garcia, Sérgio Britto

    2013-01-01

    Objective To compare the adaptive effects of three non-weight bearing exercise on bone mechanical properties. Methods 24 male Balb/c mice (22-25g), were randomly divided into four groups (n=6): sedentary group (S); swimming group (N) which performed sessions five times per week for 60 min progressively; resistance group (R), which performed climbing exercise with progressive load, three times per week; and combined group (C), which performed the same protocols aforementioned being three times a week according to N protocol and two times a week the R protocol during eight weeks. Biomechanical tests, load until failure and stiffness evaluation of shinbone was performed after animals have been sacrificed. Results Stiffness values were statistically higher only in the isolated modalities groups (N and R, 41.68 ± 10.43 and 41.21 ± 11.38 N/mm, respectively) compared with the S group (28.48 ± 7.34 N/mm). However, taking into consideration the final body mass, relative values, there was no difference in the biomechanical tests among the groups. Conclusion Data from the present investigation demonstrated a favorable influence of muscle contraction in lower impact isolated exercise modalities on absolute stiffness values, i.e.groups N and R, whereas the combined group (C) did not present any statistical significant difference compared to sedentary group. Level of Evidence II, Prospective Comparative Study. PMID:24453691

  14. Substrains of Inbred Mice Differ in Their Physical Activity as a Behavior

    Directory of Open Access Journals (Sweden)

    Dario Coletti

    2013-01-01

    Full Text Available Recent studies strengthen the belief that physical activity as a behavior has a genetic basis. Screening wheel-running behavior in inbred mouse strains highlighted differences among strains, showing that even very limited genetic differences deeply affect mouse behavior. We extended this observation to substrains of the same inbred mouse strain, that is, BALB/c mice. We found that only a minority of the population of one of these substrains, the BALB/c J, performs spontaneous physical activity. In addition, the runners of this substrain cover a significantly smaller distance than the average runners of two other substrains, namely, the BALB/c ByJ and the BALB/c AnNCrl. The latter shows a striking level of voluntary activity, with the average distance run/day reaching up to about 12 kilometers. These runners are not outstanders, but they represent the majority of the population, with important scientific and economic fallouts to be taken into account during experimental planning. Spontaneous activity persists in pathological conditions, such as cancer-associated cachexia. This important amount of physical activity results in a minor muscle adaptation to endurance exercise over a three-week period; indeed, only a nonsignificant increase in NADH transferase+ fibers occurs in this time frame.

  15. Experimental immunologically mediated aplastic anemia (AA) in H-2k identical, Mls (M) locus different mice

    Energy Technology Data Exchange (ETDEWEB)

    Knospe, W.H.; Steinberg, D.; Speck, B.

    1983-07-01

    Immunologically mediated aplastic anemia (AA) was experimentally induced in mice by injecting 10(7) lymph node cells (LNC) from donor mice of one inbred strain to another H-2k identical but Mls mismatched strain previously given 600 rad total body gamma irradiation (TBI). AA developed after 2 weeks to 6 months in selected strain combinations used and usually 60 to 90% of the mice died. Clinical signs of graft-versus-host disease did not occur and splenic atrophy rather than splenomegaly was the rule. Histologically these mice had a lesion of the hematopoietic microenvironment characterized by sinusoidal injury and stromal necrosis. Others have demonstrated injury to hematopoietic stem cells. C3H/He LNC induced AA whereas C3H/HeJ LNC failed to induce AA. The C3H/HeJ strain carries a macrophage defect and these results suggest that a macrophage-like cell may be a mediator of immunological injury in this experimental model. Although all strain combinations evaluated were H-2k identical and Mls mismatched, certain Mls combinations resulted in AA and identical Mls mismatched but different strains did not. Both strong (Mlsd) and weak (Mlsc) stimulating LNC induce AA but simple Mls differences do not explain the AA as similar Mls combinations but different strain combinations fail to induce AA.

  16. The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy.

    Science.gov (United States)

    Löscher, Wolfgang; Ferland, Russell J; Ferraro, Thomas N

    2017-08-01

    It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals' performance in behavioral tests that often accompany acute and chronic seizure testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Significance analysis of the regional differences on icing time of water onto fire protective clothing

    Science.gov (United States)

    Zhao, L. Z.; Jing, L. S.; Zhang, X. Z.; Xia, J. J.; Chen, Y.; Chen, T.; Hu, C.; Bao, Z. M.; Fu, X. C.; Wang, R. J.; Wang, Y.; Wang, Y. J.

    2017-09-01

    The object of this work was to determine the icing temperature in icing experiment. Firstly, a questionnaire investigation was carried out on 38 fire detachments in different regions. These Statistical percentage results were divided into northern east group and northern west group. Secondly, a significance analysis between these two results was made using Mann-Whitney U test. Then the icing temperature was determined in different regions. Thirdly, the icing experiment was made in the environment of -20°C in Daxing’an Mountain. The anti-icing effect of new fire protective clothing was verified in this icing.

  18. THE IMPORTANCE OF ‘SIGNIFICANT OTHERS’ IN BRIDGING THE GAPS BETWEEN DIFFERENT READING CONTEXTS

    Directory of Open Access Journals (Sweden)

    Anna-Karin Svensson

    2018-04-01

    Full Text Available The current research is an in-depth study of four pre-service teachers’ own experience of reading in various contexts and for different reasons. The aim is to analyse what has been significant regarding reading in a life history perspective by the use of narratives. A socio-cultural perspective on reading is used as analysis tool. The over-arching result from analysing pre-service teachers’ narratives is that reading is a relational process regardless of the context reading takes place in. The emerging themes allow a deeper understanding on critical aspects for developing reading in various contexts and at different levels. Significant others seem important in every reading practice, from new readers in primary school to pre-service teachers’ reading at university level. The narratives reveal a need for bridging the gaps that arise between the reading practices in the various contexts that students meet in school and university.

  19. Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

    Directory of Open Access Journals (Sweden)

    Catherine L Townsend

    2016-09-01

    Full Text Available Antibody variable regions are composed of a heavy and a light chain and in humans there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain CDR-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 - light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains, and probed the Protein Data Bank (PDB to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda and heavy chain gene rearrangements are correlated within donors, but can differ between donors. This indicates that TdT may work with differing efficiencies between different people, but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  20. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    Science.gov (United States)

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  1. Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

    Directory of Open Access Journals (Sweden)

    Moens Ugo

    2007-11-01

    Full Text Available Abstract Background The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. Methods We performed primary SHIRPA observations during background breeding into the C57BL/6 background and assessed the behaviour of the background-bred animals on the elevated plus maze and in the light-dark test. Our results were analyzed using Chi-square tests and homo- and heteroscedatic T-tests. Results Female transgenic mice displayed increased amounts of head dips and open arm time on the maze, compared to littermate controls. In addition, they also explored further into the open arm on the elevated plus maze and were less active in the closed arm compared to littermate controls. Male transgenic mice displayed no differences in anxiety, but their locomotor activity increased compared to non-transgenic littermates. Conclusion Our results revealed anxiety-related traits and locomotor differences between transgenic mice expressing constitutive active MAPKAPK5 and control littermates.

  2. Magnetic resonance imaging detects significant sex differences in human myocardial strain

    Directory of Open Access Journals (Sweden)

    Reynolds Lina M

    2011-08-01

    Full Text Available Abstract Background The pathophysiology responsible for the significant outcome disparities between men and women with cardiac disease is largely unknown. Further investigation into basic cardiac physiological differences between the sexes is needed. This study utilized magnetic resonance imaging (MRI-based multiparametric strain analysis to search for sex-based differences in regional myocardial contractile function. Methods End-systolic strain (circumferential, longitudinal, and radial was interpolated from MRI-based radiofrequency tissue tagging grid point displacements in each of 60 normal adult volunteers (32 females. Results The average global left ventricular (LV strain among normal female volunteers (n = 32 was significantly larger in absolute value (functionally better than in normal male volunteers (n = 28 in both the circumferential direction (Male/Female = -0.19 ± 0.02 vs. -0.21 ± 0.02; p = 0.025 and longitudinal direction (Male/Female = -0.14 ± 0.03 vs. -0.16 ± 0.02; p = 0.007. Conclusions The finding of significantly larger circumferential and longitudinal LV strain among normal female volunteers suggests that baseline contractile differences between the sexes may contribute to the well-recognized divergence in cardiovascular disease outcomes. Further work is needed in order to determine the pathologic changes that occur in LV strain between women and men with the onset of cardiovascular disease.

  3. Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

    Energy Technology Data Exchange (ETDEWEB)

    Crabbe, Rory A. [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada); Hill, Kathleen A., E-mail: khill22@uwo.ca [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada)

    2010-09-10

    Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

  4. Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

    International Nuclear Information System (INIS)

    Crabbe, Rory A.; Hill, Kathleen A.

    2010-01-01

    Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

  5. Significant interarm blood pressure difference predicts cardiovascular risk in hypertensive patients: CoCoNet study.

    Science.gov (United States)

    Kim, Su-A; Kim, Jang Young; Park, Jeong Bae

    2016-06-01

    There has been a rising interest in interarm blood pressure difference (IAD), due to its relationship with peripheral arterial disease and its possible relationship with cardiovascular disease. This study aimed to characterize hypertensive patients with a significant IAD in relation to cardiovascular risk. A total of 3699 patients (mean age, 61 ± 11 years) were prospectively enrolled in the study. Blood pressure (BP) was measured simultaneously in both arms 3 times using an automated cuff-oscillometric device. IAD was defined as the absolute difference in averaged BPs between the left and right arm, and an IAD ≥ 10 mm Hg was considered to be significant. The Framingham risk score was used to calculate the 10-year cardiovascular risk. The mean systolic IAD (sIAD) was 4.3 ± 4.1 mm Hg, and 285 (7.7%) patients showed significant sIAD. Patients with significant sIAD showed larger body mass index (P < 0.001), greater systolic BP (P = 0.050), more coronary artery disease (relative risk = 1.356, P = 0.034), and more cerebrovascular disease (relative risk = 1.521, P = 0.072). The mean 10-year cardiovascular risk was 9.3 ± 7.7%. By multiple regression, sIAD was significantly but weakly correlated with the 10-year cardiovascular risk (β = 0.135, P = 0.008). Patients with significant sIAD showed a higher prevalence of coronary artery disease, as well as an increase in 10-year cardiovascular risk. Therefore, accurate measurements of sIAD may serve as a simple and cost-effective tool for predicting cardiovascular risk in clinical settings.

  6. Significant interarm blood pressure difference predicts cardiovascular risk in hypertensive patients

    Science.gov (United States)

    Kim, Su-A; Kim, Jang Young; Park, Jeong Bae

    2016-01-01

    Abstract There has been a rising interest in interarm blood pressure difference (IAD), due to its relationship with peripheral arterial disease and its possible relationship with cardiovascular disease. This study aimed to characterize hypertensive patients with a significant IAD in relation to cardiovascular risk. A total of 3699 patients (mean age, 61 ± 11 years) were prospectively enrolled in the study. Blood pressure (BP) was measured simultaneously in both arms 3 times using an automated cuff-oscillometric device. IAD was defined as the absolute difference in averaged BPs between the left and right arm, and an IAD ≥ 10 mm Hg was considered to be significant. The Framingham risk score was used to calculate the 10-year cardiovascular risk. The mean systolic IAD (sIAD) was 4.3 ± 4.1 mm Hg, and 285 (7.7%) patients showed significant sIAD. Patients with significant sIAD showed larger body mass index (P < 0.001), greater systolic BP (P = 0.050), more coronary artery disease (relative risk = 1.356, P = 0.034), and more cerebrovascular disease (relative risk = 1.521, P = 0.072). The mean 10-year cardiovascular risk was 9.3 ± 7.7%. By multiple regression, sIAD was significantly but weakly correlated with the 10-year cardiovascular risk (β = 0.135, P = 0.008). Patients with significant sIAD showed a higher prevalence of coronary artery disease, as well as an increase in 10-year cardiovascular risk. Therefore, accurate measurements of sIAD may serve as a simple and cost-effective tool for predicting cardiovascular risk in clinical settings. PMID:27310982

  7. Gender differences in cerebral metabolism for color processing in mice: A PET/MRI Study.

    Science.gov (United States)

    Njemanze, Philip C; Kranz, Mathias; Amend, Mario; Hauser, Jens; Wehrl, Hans; Brust, Peter

    2017-01-01

    Color processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women. The present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition. PET revealed a reverse pattern relative to dark condition compared to previous human studies: Male mice presented with left visual cortex dominance for blue through the right eye, while female mice presented with right visual cortex dominance for blue through the left eye. We applied statistical parametric mapping (SPM) to examine gender differences in activated architectonic areas within the orbital and medial prefrontal cortex and related cortical and sub-cortical areas that lead to the striatum, medial thalamus and other brain areas. The metabolic connectivity of the orbital and medial prefrontal cortex evoked by blue stimulation spread through a wide range of brain structures implicated in viscerosensory and visceromotor systems in the left intra-hemispheric regions in male, but in the right-to-left inter-hemispheric regions in female mice. Color functional ocular dominance plasticity was noted in the right eye in male mice but in the left eye in female mice. This study of color processing in an animal model could be applied in the study of the role of gender differences in brain disease.

  8. 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.

  9. 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.

  10. Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

    International Nuclear Information System (INIS)

    Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel; Sánchez-Gutiérrez, Manuel; Piña-Guzmán, Belem; Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo; Quintanilla-Vega, Betzabet

    2014-01-01

    Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

  11. Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Urióstegui-Acosta, Mayrut; Hernández-Ochoa, Isabel [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Sánchez-Gutiérrez, Manuel [Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Hidalgo (Mexico); Piña-Guzmán, Belem [Instituto Politécnico Nacional-UPIBI, D.F. (Mexico); Rafael-Vázquez, Leticia; Solís-Heredia, M.J.; Martínez-Aguilar, Gerardo [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico); Quintanilla-Vega, Betzabet, E-mail: mquintan@cinvestav.mx [Departamento de Toxicología, CINVESTAV-IPN, D.F. (Mexico)

    2014-09-15

    Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to

  12. Further characterization of benzodiazepine receptor differences in long-sleep and short-sleep mice

    International Nuclear Information System (INIS)

    Marley, R.J.; Stinchcomb, A.; Wehner, J.M.

    1988-01-01

    Molecular and conformational characteristics of benzodiazepine (BZ) receptors in cortex and cerebellum from long-sleep and mice were investigated using heat inactivation and beta-carboline competition techniques. To investigate differences in the allosteric coupling between GABA and BZ receptors, the protection of BZ receptors from heat inactivation, by GABA, was also evaluated. The two genotypes do not differ in the affinity or number of BZ receptors in the cortex or cerebellum. They do, however, appear to differ in the molecular structure and/or regulation of the conformational state of the receptor in the cortex, as indicated by a greater sensitivity of LS mice to both heat inactivation and beta-carboline competition of 3 H-flunitrazepam (FNZ) binding in this region. Evidence for differences in the nature of coupling between GABA and BZ receptors is provided by the finding in that in both regions, GABA protected BZ receptors from inactivation to a greater degree in LS mice. The relationship between these differences and the multiplicity of expression of BZ receptors is discussed

  13. Effect of anti-gut inflammatory agent on insulin resistance and lipid profile of mice fed different diets

    NARCIS (Netherlands)

    Wang, Zheng; Bao, Zhijun

    Purpose: To further explore the effect of 5-aminosalicylic acid (5-ASA) treatment on lipid levels in mice fed different diets. Methods: Groups of 9 - 10 mice each were randomly assigned to 6 different diets, low-fat diet (LFD) with or without 5-ASA, high-fat diet (HFD) with or without 5-ASA, and

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Using the Bootstrap Method for a Statistical Significance Test of Differences between Summary Histograms

    Science.gov (United States)

    Xu, Kuan-Man

    2006-01-01

    A new method is proposed to compare statistical differences between summary histograms, which are the histograms summed over a large ensemble of individual histograms. It consists of choosing a distance statistic for measuring the difference between summary histograms and using a bootstrap procedure to calculate the statistical significance level. Bootstrapping is an approach to statistical inference that makes few assumptions about the underlying probability distribution that describes the data. Three distance statistics are compared in this study. They are the Euclidean distance, the Jeffries-Matusita distance and the Kuiper distance. The data used in testing the bootstrap method are satellite measurements of cloud systems called cloud objects. Each cloud object is defined as a contiguous region/patch composed of individual footprints or fields of view. A histogram of measured values over footprints is generated for each parameter of each cloud object and then summary histograms are accumulated over all individual histograms in a given cloud-object size category. The results of statistical hypothesis tests using all three distances as test statistics are generally similar, indicating the validity of the proposed method. The Euclidean distance is determined to be most suitable after comparing the statistical tests of several parameters with distinct probability distributions among three cloud-object size categories. Impacts on the statistical significance levels resulting from differences in the total lengths of satellite footprint data between two size categories are also discussed.

  16. Two distinct groups within the Bacillus subtilis group display significantly different spore heat resistance properties.

    Science.gov (United States)

    Berendsen, Erwin M; Zwietering, Marcel H; Kuipers, Oscar P; Wells-Bennik, Marjon H J

    2015-02-01

    The survival of bacterial spores after heat treatment and the subsequent germination and outgrowth in a food product can lead to spoilage of the food product and economical losses. Prediction of time-temperature conditions that lead to sufficient inactivation requires access to detailed spore thermal inactivation kinetics of relevant model strains. In this study, the thermal inactivation kinetics of spores of fourteen strains belonging to the Bacillus subtilis group were determined in detail, using both batch heating in capillary tubes and continuous flow heating in a micro heater. The inactivation data were fitted using a log linear model. Based on the spore heat resistance data, two distinct groups (p subtilis group could be identified. One group of strains had spores with an average D120 °C of 0.33 s, while the spores of the other group displayed significantly higher heat resistances, with an average D120 °C of 45.7 s. When comparing spore inactivation data obtained using batch- and continuous flow heating, the z-values were significantly different, hence extrapolation from one system to the other was not justified. This study clearly shows that heat resistances of spores from different strains in the B. subtilis group can vary greatly. Strains can be separated into two groups, to which different spore heat inactivation kinetics apply. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

    Science.gov (United States)

    Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

    2002-11-01

    Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P Defibrotide plus rhG-CSF resulted in a significant increase (P Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed progenitor cells. These data might have relevant implications for autologous and allogeneic anticancer therapy in humans.

  18. Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Alexandra Wagnerova

    2017-01-01

    Full Text Available Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male were divided into three groups for each sex. The first group received pure water (CTRL. The other two groups received 1.5% dextran sulfate sodium (DSS to induce colitis from which one group was treated with resveratrol (DSS + RSV. Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

  19. Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

    Science.gov (United States)

    Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

    2017-06-01

    Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Significant clinical differences in primary hyperparathyroidism between patients with and those without concomitant thyroid disease

    International Nuclear Information System (INIS)

    Masatsugu, Toshihiro; Kuroki, Syoji; Tanaka, Masao

    2005-01-01

    We evaluated the differences in diagnosis and treatment for primary hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid disease. One hundred and ten patients with pHPT underwent parathyroid localization and thyroid examination by ultrasonography (US) and sestamibi scintigraphy (MIBI). The clinical and biochemical findings, parathyroid localization, and operations performed were compared in 49 patients without thyroid disease and 61 patients with thyroid disease. Asymptomatic hypercalcemia was significantly more prevalent in patients with concomitant thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P<0.01). The mean serum calcium was significantly higher and the inorganic phosphate level was significantly lower in patients without concomitant thyroid disease than in those with concomitant thyroid disease (P<0.05, P<0.01, respectively). The pathologic parathyroid gland was identified significantly more often in patients without concomitant thyroid disease than in those with concomitant thyroid disease both by US and MIBI (P<0.05). Unilateral exploration was performed more often in patients without thyroid disease than in those with thyroid disease (P<0.01). Primary hyperparathyroidism was diagnosed at an earlier stage in patients with concomitant thyroid disease. Thyroid disease concomitant with pHPT influenced parathyroid localization as well as the indication for minimally invasive parathyroidectomy. (author)

  1. Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Ehteda, Anahid; Galettis, Peter; Pillai, Krishna; Morris, David L

    2013-01-01

    Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated. Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone. The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment

  2. Small airway function changes and its clinical significance of asthma patients in different clinical phases

    Directory of Open Access Journals (Sweden)

    Yan-Hui Zhou

    2016-11-01

    Full Text Available Objective: To observe the small airways function changes of asthmatic patients in different clinical phases and to discuss its clinical significance. Methods: A total of 127 patients diagnosed as asthma were selected randomly and pulmonary function (PF of them was determined by conventional method. Then they were divided into A, B and C group based on PF results. All 34 patients in A group suffered from acute asthma attack for the first time. All 93 patients in B group had been diagnosed as asthma but in remission phase. C Group was regarded as Control group with 20 healthy volunteers. Then FEV1, FEF50%, FEF75% levels of patients in each group were analyzed, and ΔFEV1, ΔFEF75% and ΔFEF50% levels of patients in each group were compared after bronchial dilation test. Results: It was found that most patients in group A and B had abnormal small airways function, and their small airways function was significantly different compared with that of group C (P<0.01. In addition, except for group C, ΔFEF75%,ΔFEF50% levels in A and B group were improved more significantly than ΔFEV1 levels (P<0.01. Conclusions: Asthma patients in acute phase all have abnormal small airways function. Most asthma patients in remission phase also have abnormal small airways function. After bronchial dilation test, whether patients in acute phase or in remission phase, major and small airways function of them are improved, but improvement of small airways function is weaker than that of major airways. This indicates that asthma respiratory tract symptoms in different phases exists all the time and so therapeutic process is needed to perform step by step.

  3. Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

    Science.gov (United States)

    Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

    2018-03-01

    Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. Factors correlating with significant differences between X-ray structures of myoglobin

    International Nuclear Information System (INIS)

    Rashin, Alexander A.; Domagalski, Marcin J.; Zimmermann, Michael T.; Minor, Wladek; Chruszcz, Maksymilian; Jernigan, Robert L.

    2014-01-01

    Conformational differences between myoglobin structures are studied. Most structural differences in whale myoglobin beyond the uncertainty threshold can be correlated with a few specific structural factors. There are always exceptions and a search for additional factors is needed. The results might have serious implications for biological insights from conformational differences. Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horse and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are very similar to the cluster of horse structures, which all have a similar GH-loop distortion apparently owing to intermolecular crystal lattice hydrogen bonds to the GH loop from residues near the distal histidine His64. The variations of the GH-loop coordinates in the whale structures are likely to be owing to the observed alternative intermolecular crystal lattice bond, with the change to the GH loop distorting bonds correlated with the binding of specific ‘unusual’ ligands. Such an alternative intermolecular bond is not observed in horse myoglobins, obliterating any correlation with the ligands. Intermolecular bonds do not usually cause significant coordinate differences and cannot be validated as their universal cause. Most of the native-like whale myoglobin structure outliers can be correlated with a few specific factors. However, these factors do not always lead to coordinate differences beyond the previously determined uncertainty

  5. Factors correlating with significant differences between X-ray structures of myoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Rashin, Alexander A., E-mail: alexander-rashin@hotmail.com [BioChemComp Inc., 543 Sagamore Avenue, Teaneck, NJ 07666 (United States); Iowa State University, 112 Office and Lab Bldg, Ames, IA 50011-3020 (United States); Domagalski, Marcin J. [University of Virginia, 1340 Jefferson Park Avenue, Jordan Hall, Room 4223, Charlottesville, VA 22908 (United States); Zimmermann, Michael T. [Iowa State University, 112 Office and Lab Bldg, Ames, IA 50011-3020 (United States); Minor, Wladek [University of Virginia, 1340 Jefferson Park Avenue, Jordan Hall, Room 4223, Charlottesville, VA 22908 (United States); Chruszcz, Maksymilian [University of Virginia, 1340 Jefferson Park Avenue, Jordan Hall, Room 4223, Charlottesville, VA 22908 (United States); University of South Carolina, 631 Sumter Street, Columbia, SC 29208 (United States); Jernigan, Robert L. [Iowa State University, 112 Office and Lab Bldg, Ames, IA 50011-3020 (United States); BioChemComp Inc., 543 Sagamore Avenue, Teaneck, NJ 07666 (United States)

    2014-02-01

    Conformational differences between myoglobin structures are studied. Most structural differences in whale myoglobin beyond the uncertainty threshold can be correlated with a few specific structural factors. There are always exceptions and a search for additional factors is needed. The results might have serious implications for biological insights from conformational differences. Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horse and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are very similar to the cluster of horse structures, which all have a similar GH-loop distortion apparently owing to intermolecular crystal lattice hydrogen bonds to the GH loop from residues near the distal histidine His64. The variations of the GH-loop coordinates in the whale structures are likely to be owing to the observed alternative intermolecular crystal lattice bond, with the change to the GH loop distorting bonds correlated with the binding of specific ‘unusual’ ligands. Such an alternative intermolecular bond is not observed in horse myoglobins, obliterating any correlation with the ligands. Intermolecular bonds do not usually cause significant coordinate differences and cannot be validated as their universal cause. Most of the native-like whale myoglobin structure outliers can be correlated with a few specific factors. However, these factors do not always lead to coordinate differences beyond the previously determined uncertainty

  6. Process of Judging Significant Modifications for Different Transportation Systems compared to the Approach for Nuclear Installations

    Directory of Open Access Journals (Sweden)

    Nicolas Petrek

    2015-12-01

    Full Text Available The implementation of the CSM regulation by the European Commission in 2009 which harmonizes the risk assessment process and introduces a rather new concept of judging changes within the European railway industry. This circumstance has risen the question how other technology sectors handle the aspect of modifications and alterations. The paper discusses the approaches for judging the significance of modifications within the three transport sectors of European railways, aviation and maritime transportation and the procedure which is used in the area of nuclear safety. We will outline the similarities and differences between these four methods and discuss the underlying reasons. Finally, we will take into account the role of the European legislator and the fundamental idea of a harmonization of the different approaches.

  7. Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure.

    Science.gov (United States)

    Zhang, Lu; Zhang, Zhenzhen; Wang, Feng; Tian, Xiuzhi; Ji, Pengyun; Liu, Guoshi

    2017-10-02

    Embryo implantation is crucial for animal reproduction. Unsuccessful embryo implantation leads to pregnancy failure, especially in human-assisted conception. Environmental factors have a profound impact on embryo implantation. Because people are being exposed to more light at night, the influence of long-term light exposure on embryo implantation should be explored. The effects of long photoperiodic exposure and melatonin on embryo implantation and offspring growth were examined. Long photoperiodic exposure (18:6 h light:dark) was selected to resemble light pollution. Melatonin (10 -2 , 10 -3 , 10 -4 , 10 -5  M) was added to the drinking water of mice starting at Day 1 (vaginal plugs) until delivery. Melatonin treatment (10 -4 ,10 -5  M) significantly increased litter sizes compared to untreated controls (12.9 ± 0.40 and 12.2 ± 1.01 vs. 11.5 ± 0.43; P melatonin (10 -4  M) was selected for further investigation. No remarkable differences were found between melatonin-treated mice and controls in terms of the pups' birth weights, weaning survival rates, and weaning weights. Long photoperiodic exposure significantly reduced the number of implantation sites in treated mice compared to controls (light/dark, 12/12 h), and melatonin rescued this negative effect. Mechanistic studies revealed that melatonin enhanced the serum 17β-estradiol (E 2 ) levels in the pregnant mice and upregulated the expression of the receptors MT1 and MT2 and p53 in uterine tissue. All of these factors may contribute to the beneficial effects of melatonin on embryo implantation in mice. Melatonin treatment was associated with beneficial effects in pregnant mice, especially those subjected to long photoperiodic exposure. This was achieved by enhanced embryo implantation. At the molecular level, melatonin administration probably increases the E 2 level during pregnancy and upregulates p53 expression by activating MT1/2 in the uterus. All of the changes may improve the

  8. An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice.

    Science.gov (United States)

    Wijayatunga, Nadeeja N; Pahlavani, Mandana; Kalupahana, Nishan S; Kottapalli, Kameswara Rao; Gunaratne, Preethi H; Coarfa, Cristian; Ramalingam, Latha; Moustaid-Moussa, Naima

    2018-02-06

    Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.

  9. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    Science.gov (United States)

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Super-resolution structure of DNA significantly differs in buccal cells of controls and Alzheimer's patients.

    Science.gov (United States)

    Garcia, Angeles; Huang, David; Righolt, Amanda; Righolt, Christiaan; Kalaw, Maria Carmela; Mathur, Shubha; McAvoy, Elizabeth; Anderson, James; Luedke, Angela; Itorralba, Justine; Mai, Sabine

    2017-09-01

    The advent of super-resolution microscopy allowed for new insights into cellular and physiological processes of normal and diseased cells. In this study, we report for the first time on the super-resolved DNA structure of buccal cells from patients with Alzheimer's disease (AD) versus age- and gender-matched healthy, non-caregiver controls. In this super-resolution study cohort of 74 participants, buccal cells were collected and their spatial DNA organization in the nucleus examined by 3D Structured Illumination Microscopy (3D-SIM). Quantitation of the super-resolution DNA structure revealed that the nuclear super-resolution DNA structure of individuals with AD significantly differs from that of their controls (p structure of AD significantly differs in mild, moderate, and severe disease with respect to the DNA-containing and DNA-free/poor spaces. We conclude that whole genome remodeling is a feature of buccal cells in AD. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  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. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Nóra Kutszegi

    Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

  13. The distribution of 14C-chitosan by different molecular weight in mice

    International Nuclear Information System (INIS)

    Kim, Kwang Yoon; Kim, Young Ho; Bom, Hee Seung; Kim, Ji Yeul; Kim, Hee Kyung; Roh, Young Bok; Nishimura, Yoshikazu

    1998-01-01

    Chitosan is a nontoxic natural chealtor which was made by chitin, and reduced a contamination of radiostrontium in animals. In this experiment, a different molecular weight of C-14 chitosan was intravenously administered to mice, and then the distribution of C-14 chitosan in the body was observed. Male mice (8 to 10 weeks, body weight of 30 to 35g) of ICR strain were used. C-14 chitosan, mice was sacrificed at the 6th hour, 1st, 3rd, 5th, and 7th day. Beta radioactivities in the blood, liver, kidney, liver, muscle, testis, and urine was measured using a liquid scintillation analyzer. Most of the C-14 chitosan was excreted through urine within 6 hours. Biodistribution of C-14 chitosan was similar despite the difference of molecular weight. Higher distributions of radioactivities were found in the liver, kidney, spleen. The relative concentration in tissue increased for the 6 hours and then decreased. In conclusion, most of C-14 chitosan was excreted through urine despite the difference of molecular weight. and, low molecular weight of C-14 chitosan showed higher distribution than high molecular weight of C-14 chitosan in tissues

  14. Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

    NARCIS (Netherlands)

    Barends, M.; de Rond, L. G. H.; Dormans, J.; van Oosten, M.; Boelen, A.; Neijens, H. J.; Osterhaus, A. D. M. E.; Kimman, T. G.

    2004-01-01

    Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response,

  15. Intrapartum caesarean rates differ significantly between ethnic groups--relationship to induction.

    LENUS (Irish Health Repository)

    Ismail, Khadijah I

    2012-01-31

    OBJECTIVE: Given international variation in obstetric practices and outcomes, comparison of labour outcomes in different ethnic groups could provide important information regarding the underlying reasons for rising caesarean delivery rates. Increasing numbers of women from Eastern European countries are now delivering in Irish maternity hospitals. We compared labour outcomes between Irish and Eastern European (EE) women in a large tertiary referral center. STUDY DESIGN: This was a prospective consecutive cohort study encompassing a single calendar year. The cohort comprised 5550 Irish and 867 EE women delivered in a single institution in 2009. Women who had multiple pregnancies, breech presentation, and elective or pre-labour caesarean sections (CS) were excluded. Data obtained from birth registers included maternal age, nationality, parity, gestation, onset of labour, mode of delivery and birth weight. RESULTS: The overall intrapartum CS rate was 11.4% and was significantly higher in Irish compared to EE women (11.8% vs. 8.8%; p=0.008). The proportion of primiparas was lower in Irish compared to EE women (44.8% vs. 63.6%; p<0.0001). The intrapartum CS rate was almost doubled in Irish compared to EE primiparas (20.7% vs. 11.0%; p<0.0001). Analysis of primiparas according to labour onset revealed a higher intrapartum CS rate in Irish primiparas in both spontaneous (13.5% vs. 7.2%; p<0.0001) and induced labour (29.5% vs. 19.3%; p=0.005). Irish women were older with 19.7% of primiparas aged more than 35, compared to 1.6% of EE women (p<0.0001). The primigravid CS rate in Irish women was significantly higher in women aged 35 years or older compared women aged less than 35 (30.6% vs. 18.3%; p<0.0001) consistent in both spontaneous and induced labour. The primiparous induction rate was 45.4% in Irish women compared to 32% in EE women, and more Irish women were induced before 41 weeks gestation. CONCLUSION: The results highlight that primigravid intrapartum CS rates were

  16. Significant differences in parameters of glucose metabolism in children of hypertensive and normotensive parents.

    Science.gov (United States)

    Gryko, Anna; Głowińska-Olszewska, Barbara; Płudowska, Katarzyna; Smithson, W Henry; Owłasiuk, Anna; Żelazowska-Rutkowska, Beata; Wojtkielewicz, Katarzyna; Milewski, Robert; Chlabicz, Sławomir

    2017-01-01

    In the recent years, alterations in the carbohydrate metabolism, including insulin resistance, are considered as risk factors in the development of hypertension and its complications in young age. Hypertension is associated with significant cardiovascular morbidity and mortality. The onset of pathology responsible for the development of hypertension, as well as levels of biomarkers specific for early stages of atherosclerosis are poorly understood. To compare a group of children whose parents have a history of hypertension (study group) with a group of children with normotensive parents (reference group), with consideration of typical risk factors for atherosclerosis, parameters of lipid and carbohydrate metabolism, anthropometric data and new biomarkers of early cardiovascular disease (hsCRP, adiponectin, sICAM-1). The study population consists of 84 children. Of these, 40 children (mean age 13.6±2.7 years) had a parental history of hypertension, and 44 aged 13.1±3.7 yrs were children of normotensive parents. Anthropometric measurements were taken, and measurements of blood pressure, lipid profile, glucose and insulin levels were carried out. The insulin resistance index (HOMA IR) was calculated. Levels of hsCRP, soluble cell adhesion molecules (sICAM) and adiponectin were measured. There were no statistically significant differences in anthropometric parameters (body mass, SDS BMI, skin folds) between groups. Values of systolic blood pressure were statistically significantly higher in the study group (Me 108 vs. 100 mmHg, p= 0.031), as were glycaemia (Me 80 vs. 67 mg/dl pchildren of hypertensive parents) (Me 1.68 vs. 0.80 mmol/l × mU/l, p=0.007). Lower adiponectin levels (Me 13959.45 vs. 16822 ng/ml, p=0.020) were found in children with a family history of hypertension. No significant differences were found in the levels of sICAM, hsCRP, and parameters of lipid metabolism. Family history of hypertension is correlated with higher values of systolic blood

  17. Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

    Science.gov (United States)

    Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

    2018-05-17

    Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  18. Difference in Perseverative Errors during a Visual Attention Task with Auditory Distractors in Alpha-9 Nicotinic Receptor Subunit Wild Type and Knock-Out Mice.

    Science.gov (United States)

    Jorratt, Pascal; Delano, Paul H; Delgado, Carolina; Dagnino-Subiabre, Alexies; Terreros, Gonzalo

    2017-01-01

    The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through olivocochlear (OC) neurons. Medial OC neurons make cholinergic synapses with outer hair cells (OHCs) through nicotinic receptors constituted by α9 and α10 subunits. One of the physiological functions of the α9 nicotinic receptor subunit (α9-nAChR) is the suppression of auditory distractors during selective attention to visual stimuli. In a recent study we demonstrated that the behavioral performance of alpha-9 nicotinic receptor knock-out (KO) mice is altered during selective attention to visual stimuli with auditory distractors since they made less correct responses and more omissions than wild type (WT) mice. As the inhibition of the behavioral responses to irrelevant stimuli is an important mechanism of the selective attention processes, behavioral errors are relevant measures that can reflect altered inhibitory control. Errors produced during a cued attention task can be classified as premature, target and perseverative errors. Perseverative responses can be considered as an inability to inhibit the repetition of an action already planned, while premature responses can be considered as an index of the ability to wait or retain an action. Here, we studied premature, target and perseverative errors during a visual attention task with auditory distractors in WT and KO mice. We found that α9-KO mice make fewer perseverative errors with longer latencies than WT mice in the presence of auditory distractors. In addition, although we found no significant difference in the number of target error between genotypes, KO mice made more short-latency target errors than WT mice during the presentation of auditory distractors. The fewer perseverative error made by α9-KO mice could be explained by a reduced motivation for reward and an increased impulsivity during decision making with auditory distraction in KO mice.

  19. Difference in Perseverative Errors during a Visual Attention Task with Auditory Distractors in Alpha-9 Nicotinic Receptor Subunit Wild Type and Knock-Out Mice

    Directory of Open Access Journals (Sweden)

    Pascal Jorratt

    2017-11-01

    Full Text Available The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through olivocochlear (OC neurons. Medial OC neurons make cholinergic synapses with outer hair cells (OHCs through nicotinic receptors constituted by α9 and α10 subunits. One of the physiological functions of the α9 nicotinic receptor subunit (α9-nAChR is the suppression of auditory distractors during selective attention to visual stimuli. In a recent study we demonstrated that the behavioral performance of alpha-9 nicotinic receptor knock-out (KO mice is altered during selective attention to visual stimuli with auditory distractors since they made less correct responses and more omissions than wild type (WT mice. As the inhibition of the behavioral responses to irrelevant stimuli is an important mechanism of the selective attention processes, behavioral errors are relevant measures that can reflect altered inhibitory control. Errors produced during a cued attention task can be classified as premature, target and perseverative errors. Perseverative responses can be considered as an inability to inhibit the repetition of an action already planned, while premature responses can be considered as an index of the ability to wait or retain an action. Here, we studied premature, target and perseverative errors during a visual attention task with auditory distractors in WT and KO mice. We found that α9-KO mice make fewer perseverative errors with longer latencies than WT mice in the presence of auditory distractors. In addition, although we found no significant difference in the number of target error between genotypes, KO mice made more short-latency target errors than WT mice during the presentation of auditory distractors. The fewer perseverative error made by α9-KO mice could be explained by a reduced motivation for reward and an increased impulsivity during decision making with auditory distraction in KO mice.

  20. Over-Expression of Porcine Myostatin Missense Mutant Leads to A Gender Difference in Skeletal Muscle Growth between Transgenic Male and Female Mice.

    Science.gov (United States)

    Ma, Dezun; Gao, Pengfei; Qian, Lili; Wang, Qingqing; Cai, Chunbo; Jiang, Shengwang; Xiao, Gaojun; Cui, Wentao

    2015-08-24

    Myostatin, a transforming growth factor-β family member, is a negative regulator of skeletal muscle development and growth. Piedmontese cattle breeds have a missense mutation, which results in a cysteine to tyrosine substitution in the mature myostatin protein (C313Y). This loss-of-function mutation in myostatin results in a double-muscled phenotype in cattle. Myostatin propeptide is an inhibitor of myostatin activity and is considered a potential agent to stimulate muscle growth in livestock. In this study, we generated transgenic mice overexpressing porcine myostatin missense mutant (pmMS), C313Y, and wild-type porcine myostatin propeptide (ppMS), respectively, to examine their effects on muscle growth in mice. Enhanced muscle growth was observed in both pmMS and ppMS transgenic female mice and also in ppMS transgenic male mice. However, there was no enhanced muscle growth observed in pmMS transgenic male mice. To explore why there is such a big difference in muscle growth between pmMS and ppMS transgenic male mice, the expression level of androgen receptor (AR) mutant AR45 was measured by Western blot. Results indicated that AR45 expression significantly increased in pmMS transgenic male mice while it decreased dramatically in ppMS transgenic male mice. Our data demonstrate that both pmMS and ppMS act as myostatin inhibitors in the regulation of muscle growth, but the effect of pmMS in male mice is reversed by an increased AR45 expression. These results provide useful insight and basic theory to future studies on improving pork quality by genetically manipulating myostatin expression or by regulating myostatin activity.

  1. Differences in muscarinic acetylcholine receptor subtypes in the central nervous system of long sleep and short sleep mice

    International Nuclear Information System (INIS)

    Watson, M.; Ming, X.; McArdle, J.J.

    1989-01-01

    Differences in voluntary ethanol consumption have been noted in various inbred strains of mice and pharmacogenetic approaches have been used to study the mechanisms of action of many drugs such as ethanol. Long-sleep (LS) and short-sleep (SS) mice, selectively bred for differences in ethanol induced narcosis, provide a method by which a relationship between the differential responsiveness of these geno-types and muscarinic acetylcholine receptors (mAChR) may be evaluated. Sleep times after injection of 3ml ethanol/kg (i.p.) verified the higher sensitivity of LS vs. SS. Mean body weights of LS (26.5g) vs. SS (22g) were also significantly (p 3 H](-) quinuclidinylbenzilate ([ 3 H](-)QNB), a specific but nonsubtype selective mAChR antagonist, [ 3 H]pirenzepine ([ 3 H]PZ), a specific M1 mAChR antagonist and [ 3 H]11-2-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido (2,3-b) (1,4) benzodiazepine-6-one, ([ 3 H]AF-DX 116), an M2 selective antagonist were performed to determine mAChR affinity (K d ) and density (B max ) in CNS regions such as the cerebral cortex, hippocampus, corpus striatum and other areas. Significantly lower (30-40%) [ 3 H](-)QNB binding suggests that SS have fewer mAChR's than LS in many areas. These differences may relate to their differential ethanol sensitivity

  2. Nestin-Cre Mice Are Affected by Hypopituitarism, Which Is Not Due to Significant Activity of the Transgene in the Pituitary Gland

    Science.gov (United States)

    Galichet, Christophe; Lovell-Badge, Robin; Rizzoti, Karine

    2010-01-01

    Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS) enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP). Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report. PMID:20625432

  3. Analysis of mortality from different causes of death in mice exposed to fast neutrons

    International Nuclear Information System (INIS)

    Coppola, M.; Covelli, V.; Di Majo, V.

    1985-01-01

    The results of a further analysis of data obtained from a large experiment carried out at the Laboratory of Pathology of CRE Casaccia on mice irradiated with neutrons and with X-rays at different ages are reported. In particular, the attention is focused on the possible relationship of the life-span shortening observed in irradiated animals with the different causes of death. In the case of young adult mice, data have been separately analysed for tumour free and tumour bearing mice, and showed that a marked life-span shortening is associated with incidence and rate of radiation induced neoplasms. In addition the occurrence of solid tumours, evaluated as age adjusted final incidences, indicated a sharp increase already at very low doses of neutrons while for X-rays this phenomenon was essentially confined in the range of 3 to 6 Gy. From these data the possibility of evaluating neutron RBE at low doses, as well as the implications for quality factors, are discussed

  4. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars.

    Science.gov (United States)

    Lin, Hong; Rao, Jun; Shi, Jianxin; Hu, Chaoyang; Cheng, Fang; Wilson, Zoe A; Zhang, Dabing; Quan, Sheng

    2014-09-01

    Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean seeds are a rich and important resource for proteins and oils. While "omics" studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especially in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield. © 2014 Institute of Botany, Chinese Academy of Sciences.

  5. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars

    Institute of Scientific and Technical Information of China (English)

    Hong Lin; Jun Rao; Jianxin Shi; Chaoyang Hu; Fang Cheng; Zoe AWilson; Dabing Zhang; Sheng Quan

    2014-01-01

    Soybean [Glycine max (L.) Merr.] is one of the world’s major crops, and soybean seeds are a rich and important resource for proteins and oils. While “omics”studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especial y in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetical y related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

  6. Functional significance of genetically different symbiotic algae Symbiodinium in a coral reef symbiosis.

    Science.gov (United States)

    Loram, J E; Trapido-Rosenthal, H G; Douglas, A E

    2007-11-01

    The giant sea anemone Condylactis gigantea associates with members of two clades of the dinoflagellate alga Symbiodinium, either singly or in mixed infection, as revealed by clade-specific quantitative polymerase chain reaction of large subunit ribosomal DNA. To explore the functional significance of this molecular variation, the fate of photosynthetically fixed carbon was investigated by (14)C radiotracer experiments. Symbioses with algae of clades A and B released ca. 30-40% of fixed carbon to the animal tissues. Incorporation into the lipid fraction and the low molecular weight fraction dominated by amino acids was significantly higher in symbioses with algae of clade A than of clade B, suggesting that the genetically different algae in C. gigantea are not functionally equivalent. Symbioses with mixed infections yielded intermediate values, such that this functional trait of the symbiosis can be predicted from the traits of the contributing algae. Coral and sea anemone symbioses with Symbiodinium break down at elevated temperature, a process known as 'coral bleaching'. The functional response of the C. gigantea symbiosis to heat stress varied between the algae of clades A and B, with particularly depressed incorporation of photosynthetic carbon into lipid of the clade B algae, which are more susceptible to high temperature than the algae of clade A. This study provides a first exploration of how the core symbiotic function of photosynthate transfer to the host varies with the genotype of Symbiodinium, an algal symbiont which underpins corals and, hence, coral reef ecosystems.

  7. MR first pass perfusion of benign and malignant cardiac tumours - significant differences and diagnostic accuracy

    International Nuclear Information System (INIS)

    Bauner, K.U.; Picciolo, M.; Theisen, D.; Sandner, T.A.; Reiser, M.F.; Huber, A.M.; Sourbron, S.; Schmitz, C.

    2012-01-01

    To determine the diagnostic value of magnetic resonance (MR) first pass perfusion in the differentiation of benign and malignant cardiac tumours. 24 patients with cardiac tumours (11 malignant, histopathological correlation present in all cases) were examined using MRI. In addition to morphological sequences a saturation-recovery T1w-GRE technique was implemented for tumour perfusion. The maximum relative signal enhancement (RSE[%]) and the slope of the RSE t -curve (slopeRSE[%/s]) of tumour tissue were assessed. A t-test was used to identify significant differences between benign and malignant tumours. Sensitivities and specificities were calculated for detection of malignant lesions and were compared with the sensitivity and specificity based on solely morphological image assessment. The RSE and slopeRSE of malignant cardiac tumours were significantly higher compared with benign lesions (p < 0.001 and p < 0.001). The calculated sensitivities and specificities of RSE and slopeRSE for identification of malignant lesions were 100% and 84.6% and 100% and 92.3%, respectively with cut-off values of 80% and 6%/s. The sensitivity and specificity for identification of malignant lesions on the basis of morphological imaging alone were 90.9% and 69.2%. With first pass perfusion, malignant cardiac masses can be identified with higher sensitivity and specificity compared with morphological image assessment alone. (orig.)

  8. Sex differences in the activity of mice: modulation by postnatal gonadal hormones.

    Science.gov (United States)

    Broida, J; Svare, B

    1984-03-01

    A series of six experiments was performed to examine the influence of postnatal-gonadal-hormone exposure on home-cage activity in Rockland-Swiss albino mice. Intact females were more active than their male counterparts and gonadectomy in adulthood, while reducing levels of the behavior in both sexes, did not eliminate the gender difference. Males that were castrated on the day of birth were more active than animals castrated 5, 10, or 25 days later. Also, females treated with testosterone propionate on the day of birth were less active than oil-treated controls and females exposed to the steroid 10 days after birth. Thus, perinatal exposure to gonadal hormones suppresses adult levels of home-cage activity in mice.

  9. 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.

  10. Statistically significant faunal differences among Middle Ordovician age, Chickamauga Group bryozoan bioherms, central Alabama

    Energy Technology Data Exchange (ETDEWEB)

    Crow, C.J.

    1985-01-01

    Middle Ordovician age Chickamauga Group carbonates crop out along the Birmingham and Murphrees Valley anticlines in central Alabama. The macrofossil contents on exposed surfaces of seven bioherms have been counted to determine their various paleontologic characteristics. Twelve groups of organisms are present in these bioherms. Dominant organisms include bryozoans, algae, brachiopods, sponges, pelmatozoans, stromatoporoids and corals. Minor accessory fauna include predators, scavengers and grazers such as gastropods, ostracods, trilobites, cephalopods and pelecypods. Vertical and horizontal niche zonation has been detected for some of the bioherm dwelling fauna. No one bioherm of those studied exhibits all 12 groups of organisms; rather, individual bioherms display various subsets of the total diversity. Statistical treatment (G-test) of the diversity data indicates a lack of statistical homogeneity of the bioherms, both within and between localities. Between-locality population heterogeneity can be ascribed to differences in biologic responses to such gross environmental factors as water depth and clarity, and energy levels. At any one locality, gross aspects of the paleoenvironments are assumed to have been more uniform. Significant differences among bioherms at any one locality may have resulted from patchy distribution of species populations, differential preservation and other factors.

  11. Clinical Significance and Characteristic Clinical Differences of Cytolytic Vaginosis in Recurrent Vulvovaginitis.

    Science.gov (United States)

    Yang, Shuhua; Zhang, Yuexiang; Liu, Ying; Wang, Jianhong; Chen, Shuqin; Li, Shuxia

    2017-01-01

    The study aimed to evaluate whether cytolytic vaginosis (CV) has important clinical implications for recurrent vulvovaginitis and to identify clinical differences between CV and vulvovaginal candidosis (VVC). Medical histories, physical examinations and laboratory findings were used to diagnose and assess the prevalence rates of various vulvovaginal infections among 536 women with recurrent vulvovaginitis. Chi-square and Fisher exact tests were used to compare age, menstrual cycle phase at episode onset, symptoms/signs of infection and discharge characteristics between CV and VVC with single infection. Among the 484 women with a single-infection recurrent vulvovaginitis, the prevalence of CV (n = 143; 26.7%) was second only to VVC (n = 196; 36.6%). CV symptoms occurred predominantly during the ovulatory and luteal phases. Meanwhile, VVC episodes were not concentrated premenstrually, but rather occurred throughout the menstrual cycle. Significant differences were found in the vaginal pH, discharge characteristics and frequency of inflammatory symptoms between the 2 groups. CV is clinically important, because it is a common cause of recurrent vulvovaginitis. To distinguish CV from VVC, gynecologists should consider the patient's medical history, physical and laboratory findings, vaginal pH and vaginal discharge characteristics. © 2016 S. Karger AG, Basel.

  12. Significant profile differences among male and female adventure tourists in Pretoria, South Africa

    Directory of Open Access Journals (Sweden)

    Melissa Jeanette Lötter

    2014-01-01

    Full Text Available Different adventure activities/experiences evolve because individuals, their motives, behaviours, and experiences differ and change over time. This notion illustrates the broad nature of adventure tourism and its links with other forms of tourism. In turn, adventure tourism companies are compelled to promote/sell an array of activities/experiences to a diverse range of markets as novel and exclusive experiences to facilitate the growth of adventure holidays (Swarbrooke et al., 2003. To assist adventure tourism companies in achieving effective marketing strategies, the study’s objective is to identify significant sociopsychological profile differences among male and female adventure tourists in Pretoria, South Africa. Furthermore, to facilitate the comparison of adventure tourists’ profiles, an equal number of respondents were male (117 and female (117, which provided a 93.6% response rate. In comparison to female respondents, male respondents prefer winter as a season to participate in hard/high-risk adventure activities when they are with or without their family, and they participate in adventure activities for travelling and socialising purposes. Whereas, female respondents predominantly regard scuba-diving, abseiling, and helicopter flights as a hard/high-risk adventure activity, although these activities are generally regarded by the overall sample as being soft/low-risk adventure activities. Furthermore, even though females’ participation in adventure activities is sponsored, they did not participate or only participated in adventure activities once over the past year due to fear/risk and/or lack of skill. This study established that there is a need to further research adventure tourists’ profiles before it could be equally accepted and interpreted.

  13. Response pattern's of immunoglobulins evaluation in different lineages of mice infected with T. cruzi

    International Nuclear Information System (INIS)

    Silva, Andreia dos Santos

    2006-01-01

    The present work has employed different mice lineages (A/J, C57BL/6, B6AF1, BXA1 and BXA2) that were challenged with different doses of T. cruzi. The objective was to evaluate the pattern of immunoglobulins response presented by resistant and susceptible mice to T. cruzi as well as the lineages developed from the matting between them. So that evaluation was done by using lineages serums' sample, analyzed by ELISA's method. In agreement with the results observed all the lineages presented higher response to IgG2a and IgG2b, if compared with the titles to IgG1. IgG1 immunoglobulins involve a type Th2 pattern response which expressed allergic immunological responses, while IgG2 involves a pattern response Th1 that expresses cellular immunological response. The different lineages used in this research also presented different immunological response pattern by the infection with T. cruzi. Mice of the lineage C57BL/6 are resistant to the infection, while the animals of the lineage A/J are susceptible. The animals of the lineage B6AF1 are more resistant to the infection than their original parental C57BL/6. The immunological response developed by hybrid mice present traces of both susceptible and resistant parental A/J and C57BL/6, respectively. The animals of the lineage BXA1 can be considered resistant to the infection, but they don't present the same control as that presented by those of the lineages B6AF1 and C57BL/6. The animals of the lineage BXA2 can be considered susceptible to the infection, but they can control it for a long period, surviving like this, longer than the animals of the lineage A/J. In addition it was observed that the IgG2b immunoglobulins are very important to the resistance of mice to T. cruzi infection. (author)

  14. Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice.

    Science.gov (United States)

    Tirelli, E; Witkin, J M

    1994-10-01

    Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.

  15. Oral challenges with four apple cultivars result in significant differences in oral allergy symptoms.

    Science.gov (United States)

    Nybom, Hilde; Cervin-Hoberg, Charlotte; Andersson, Morgan

    2013-01-01

    We analyzed the hypoallergenic potential of a recently bred apple selection with unusually low content of Mal d 1, using an oral challenge model with three additional apple cultivars for comparison. Sixty-six birch pollen-allergic individuals with a history of oral allergy syndrome after apple intake were subjected to a double-blind oral provocation with two apple cultivars (B:0654 and 'Discovery'). Thirteen also tested two other apple cultivars ('Ingrid Marie' and 'Gloster'). Three doses were given consecutively, 30 min apart: 10 g without peel, and 10 and 50 g with peel. A final assessment was conducted 30 min after the last intake. Oral symptoms were graded from 0 to 5. Total oral symptom score (TOS) included all scores for each cultivar at all time points. B:0654 induced significantly higher TOS than 'Discovery' when tested by 66 individuals, in spite of its lower Mal d 1 content. TOS values were higher in females and increased with increasing age of the individuals when challenged with 'Discovery'. Among the 13 individuals who tested all four cultivars, B:0654 produced a higher score after the second dose compared to 'Ingrid Marie'. This was also the case after the third dose compared to 'Ingrid Marie' and 'Gloster', and again 30 min after the last intake compared to each of the other three cultivars, as well as a higher TOS compared to each of the other three cultivars (all p safe and well tolerated, and produced significant differences among the apple cultivars. Contrary to expectations, B:0654 was less well tolerated than the other three cultivars. Copyright © 2013 S. Karger AG, Basel.

  16. Cost Minimization Analysis of Different Strategies of Management of Clinically Significant Scorpion Envenomation Among Pediatric Patients.

    Science.gov (United States)

    Sinha, Madhumita; Quan, Dan; McDonald, Fred W; Valdez, André

    2016-12-01

    Scorpion antivenom was recently approved for use in patients with clinically significant scorpion envenomation in the United States; no formal economic analysis on its impact on cost of management has been performed. Three different strategies of management of scorpion envenomation with systemic neurotoxic symptoms in children were compared for cost minimization from a societal perspective. In strategy I, patients were managed with supportive care only without antivenom. In strategy II, an aggressive strategy of full-dose antivenom (initial dose of 3 vials with the use of additional vials administered 1 vial at a time) was considered. In strategy III, a single-vial serial antivenom dosing strategy titrated to clinical response was considered. Clinical probabilities for the different strategies were obtained from retrospective review of medical records of patients with scorpion envenomation over a 10-year period at our institution. Baseline cost values were obtained from patient reimbursement data from our institution. In baseline analysis, strategy I of supportive care only with no antivenom was least costly at US $3466.50/patient. Strategy III of single-vial serial dosing was intermediate but less expensive than strategy II of full-dose antivenom, with an incremental cost of US $3171.08 per patient. In a 1-way sensitivity analysis, at a threshold antivenom cost of US $1577.87, strategy III of single-vial serial dosing became the least costly strategy. For children with scorpion envenomation, use of a management strategy based on serial dosing of antivenom titrated to clinical response is less costly than a strategy of initial use of full-dose antivenom.

  17. Lactobacillus casei Zhang and vitamin K2 prevent intestinal tumorigenesis in mice via adiponectin-elevated different signaling pathways.

    Science.gov (United States)

    Zhang, Yong; Ma, Chen; Zhao, Jie; Xu, Haiyan; Hou, Qiangchuan; Zhang, Heping

    2017-04-11

    The incidence of colon cancer has increased considerably and the intestinal microbiota participate in the development of colon cancer. We showed that the L. casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated intestinal tumor burden in mice. This was associated with increased serum adiponectin levels in both treatments. But osteocalcin level was only increased by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF-κB) and intestinal Claudin15/Chloride intracellular channel 4(CLIC4)/Transforming Growth Factor Beta(TGF-β) signaling, while the vitamin K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK signaling pathway. Fecal DNA sequencing by the Pacbio RSII method revealed there was significantly lower Helicobacter apodemus, Helicobacter mesocricetorum, Allobaculum stercoricanis and Adlercreutzia equolifaciens following both interventions compared to the model group. Moreover, different caecum acetic acid and butyric acid levels and enrichment of other specific microbes also determined the activity of the different regulatory pathways. Together these data show that L. casei Zhang and Vitamin K2 can suppress gut risk microbes and promote beneficial microbial metabolites to reduce colonic tumor development in mice.

  18. Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity.

    Science.gov (United States)

    Spruiell, Krisstonia; Gyamfi, Afua A; Yeyeodu, Susan T; Richardson, Ricardo M; Gonzalez, Frank J; Gyamfi, Maxwell A

    2015-09-01

    Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor α, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. U.S. Government work not protected by U.S. copyright.

  19. TNF-α in CRPS and 'normal' trauma--significant differences between tissue and serum.

    Science.gov (United States)

    Krämer, Heidrun H; Eberle, Tatiana; Uçeyler, Nurcan; Wagner, Ina; Klonschinsky, Thomas; Müller, Lars P; Sommer, Claudia; Birklein, Frank

    2011-02-01

    Posttraumatic TNF-alpha signaling may be one of the factors responsible for pain and hyperalgesia in complex regional pain syndromes (CRPS). In order to further specify the role of TNF-alpha we investigated tissue (skin) and serum concentrations in three different patient groups: patients with osteoarthritis and planned surgery, with acute traumatic upper limb bone fracture waiting for surgery, and with CRPS I. Thirty patients (10 in each group) were recruited. Mean CRPS duration was 36.1 ± 8.1 weeks (range 8- 90 weeks). Skin punch biopsies were taken at the beginning of the surgery in osteoarthritis and fracture patients and from the affected side in CRPS patients. Blood samples were taken before the respective procedures. Skin and serum TNF-alpha levels were quantified by ELISA. Compared to patients with osteoarthritis, skin TNF-alpha was significantly elevated in CRPS (pCRPS patients was higher than in patients with acute bone fracture (pCRPS, and lower in fracture patients (pCRPS patients. This increase persists for months after limb trauma and may offer the opportunity for targeted treatment. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  20. Scratch deformation behavior of thermoplastic materials with significant differences in ductility

    International Nuclear Information System (INIS)

    Hadal, R.S.; Misra, R.D.K.

    2005-01-01

    A comparative study of the scratch deformation behavior of neat ethylene-propylene copolymers and polypropylene with significant differences in ductility is made by combining morphological examination by electron microscopy and scratch deformation parameters by atomic force microscopy. Also, the deformation behavior during scratch tests is examined for their respective long and short chain polymers. The ability of polymeric materials to resist scratch deformation under identical scratch test conditions follows the sequence (from maximum resistance to minimum resistance): short chain polypropylene > long chain polypropylene > short chain ethylene-propylene > long chain ethylene-propylene. The scratch tracks in ethylene-propylene copolymers were characterized by a consecutive parabolic pattern containing voids, while polypropylenes exhibited zig-zag periodic scratch tracks. The greater plastic flow in ethylene-propylene copolymers is encouraged by the high ductility of the copolymer and the ability to nucleate microvoids. The quasi-static periodic scratch tracks are a consequence of sequential accumulation and release of tangential force and represents the stick-slip process. The susceptibility to scratch deformation is discussed in terms of modulus, elastic recovery, scratch hardness, and entanglement density of polymeric materials. A higher effective entanglement density and percentage crystallinity of short chain polymers is helpful in enhancing scratch resistance as compared to their respective long chain polymers

  1. No gender differences in prognosis and preventive treatment in patients with AMI without significant stenoses

    DEFF Research Database (Denmark)

    Hansen, Kim; Hvelplund, Anders; Abildstrøm, Steen Zabell

    2011-01-01

    : By compiling data from Danish registries, we identified 20,800 patients hospitalized with AMI during 2005-2007. We included the 834 women and 761 men without significant stenoses on CAG who were discharged and alive after 60 days. Main outcome measures: All-cause mortality, recurrent AMI, and redeeming...... a prescription for a lipid-lowering drug, beta-blocker, clopidogrel, or aspirin within 60 days of discharge. Results: During follow-up, 97 women and 60 men died, resulting in a crude female/male hazard ratio (HR) of 1.51 (95% CI 1.09-2.08). After adjustment for age, time-period, and comorbidity, the gender...... difference was attenuated (HR 1.22, 95% CI 0.86-1.72). AMI recurrence was experienced by 28 women and 29 men with a female/male HR 0.88 (95% CI 0.52-1.48). After multivariable adjustment results were similar (HR 0.84, 95% CI 0.50-1.43). More women than men redeemed a prescription for lipid-lowering drugs...

  2. Flow cytometry analysis reveals different activation profiles of thrombin- or TRAP-stimulated platelets in db/db mice. The regulatory role of PAR-3.

    Science.gov (United States)

    Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Przygodzki, Tomasz; Watala, Cezary

    2017-06-01

    Recent studies have shown that it may be the concentration of thrombin, which is discriminative in determining of the mechanism of platelet activation via protease activated receptors (PARs). Whether the observed phenomenon of differentiated responses of mouse platelets to various thrombin concentrations in non-diabetic db/+ and diabetic db/db mice depends upon the concerted action of various PARs, remains to be established. We found elevated reactivity of platelets, as well as the enhanced PAR-3 expression in response to both the used concentrations of AYPGKF in db/db mice, as compared to db/+ heterozygotes. At low concentration of thrombin platelets from diabetic mice demonstrated hyperreactivity, reflected by higher expression of PAR-3. For higher thrombin concentration, blood platelets from db/db mice appeared hyporeactive, compared to db/+ animals, while no significant differences in PAR-3 expression were observed between diabetic and non-diabetic mice. The novel and previously unreported finding resulting from our study is that the increased expression of PAR-3 in response to either TRAP for PAR-4 or low thrombin (when PAR-4 is not the efficient thrombin receptor) may be one of the key events contributing to higher reactivity of platelets in db/db mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Mutation-related differences in exploratory, spatial and depressive-like behavior in pcd and Lurcher cerebellar mutant mice

    Directory of Open Access Journals (Sweden)

    Jan eTuma

    2015-05-01

    Full Text Available The cerebellum is not only essential for motor coordination but is also involved in cognitive and affective processes. These functions of the cerebellum and mechanisms of their disorders in cerebellar injury are not completely understood. There is a wide spectrum of cerebellar mutant mice which are used as models of hereditary cerebellar degenerations. Nevertheless, they differ in pathogenesis of manifestation of the particular mutation and also in the strain background. The aim of this work was to compare spatial navigation, learning and memory in pcd and Lurcher mice, two of the most frequently used cerebellar mutants. The mice were tested in the open field for exploration behavior, in the Morris water maze with visible as well as reversal hidden platform tasks and in the forced swimming test for motivation assessment. Lurcher mice showed different space exploration activity in the open field and a lower tendency to depressive-like behavior in the forced swimming test compared with pcd mice. Severe deficit of spatial navigation was shown in both cerebellar mutants. However, the overall performance of Lurcher mice was better than that of pcd mutants. Lurcher mice showed the ability of visual guidance despite difficulties with the direct swim towards a goal. In the probe trial test, Lurcher mice preferred the visible platform rather than the more recent localization of the hidden goal.

  4. Biochemical responses to dietary α-linolenic acid restriction proceed differently among brain regions in mice.

    Science.gov (United States)

    Miyazawa, Daisuke; Yasui, Yuko; Yamada, Kazuyo; Ohara, Naoki; Okuyama, Harumi

    2011-08-01

    Previously, we noted that the dietary restriction of α-linolenic acid (ALA, n-3) for 4 weeks after weaning brought about significant decreases in the BDNF content and p38 MAPK activity in the striatum of mice, but not in the other regions of the brain, compared with an ALA- and linoleic acid (LNA, n-6)-adequate diet. In this study, we examined whether a prolonged dietary manipulation induces biochemical changes in other regions of the brain as well. Mice were fed a safflower oil (SAF) diet (ALA-restricted, LNA-adequate) or a perilla oil (PER) diet (containing adequate amounts of ALA and LNA) for 8 weeks from weaning. The docosahexaenoic acid (DHA, 22:6n-3) contents and p38 MAPK activities in the cerebral cortex, striatum and hippocampus were significantly lower in the SAF group. The BDNF contents and protein kinase C (PKC) activities in the cerebral cortex as well as in the striatum, but not in the hippocampus, were significantly lower in the SAF group. These data indicate that the biochemical changes induced by the dietary restriction of ALA have a time lag in the striatum and cortex, suggesting that the signal is transmitted through decreased p38 MAPK activity and BDNF content and ultimately decreased PKC activity.

  5. 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.

  6. Herpes simplex virus ophthalmic disease induced using two different methods of mice inoculation

    Directory of Open Access Journals (Sweden)

    Sílvia Regina Ferreira Gonçalves Pereira

    Full Text Available Two different procedures for inoculation of HSV on corneas of BALB/c mice were evaluated. The first was by the use of HSV suspensions directly on the corneas and the other was after corneal scarification. Animals by this later method presented greater morbidity and mortality than those of first group, suggesting that inoculation of HSV without scarification of the cornea should be the method of choice for the study of HSV ophthalmic infection. This model showed also be an efficient experimental system to testing antiviral drugs.

  7. Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.

    Science.gov (United States)

    Thompson, Zoe; Argueta, Donovan; Garland, Theodore; DiPatrizio, Nicholas

    2017-03-01

    The endocannabinoid system serves many physiological roles, including in the regulation of energy balance, food reward, and voluntary locomotion. Signaling at the cannabinoid type 1 receptor has been specifically implicated in motivation for rodent voluntary exercise on wheels. We studied four replicate lines of high runner (HR) mice that have been selectively bred for 81 generations based on average number of wheel revolutions on days five and six of a six-day period of wheel access. Four additional replicate lines are bred without regard to wheel running, and serve as controls (C) for random genetic effects that may cause divergence among lines. On average, mice from HR lines voluntarily run on wheels three times more than C mice on a daily basis. We tested the general hypothesis that circulating levels of endocannabinoids (i.e., 2-arachidonoylglycerol [2-AG] and anandamide [AEA]) differ between HR and C mice in a sex-specific manner. Fifty male and 50 female mice were allowed access to wheels for six days, while another 50 males and 50 females were kept without access to wheels (half HR, half C for all groups). Blood was collected by cardiac puncture during the time of peak running on the sixth night of wheel access or no wheel access, and later analyzed for 2-AG and AEA content by ultra-performance liquid chromatography coupled to tandem mass spectrometry. We observed a significant three-way interaction among sex, linetype, and wheel access for 2-AG concentrations, with females generally having lower levels than males and wheel access lowering 2-AG levels in some but not all subgroups. The number of wheel revolutions in the minutes or hours immediately prior to sampling did not quantitatively predict plasma 2-AG levels within groups. We also observed a trend for a linetype-by-wheel access interaction for AEA levels, with wheel access lowering plasma concentrations of AEA in HR mice, while raising them in C mice. In addition, females tended to have higher AEA

  8. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice

    OpenAIRE

    Almind, Katrine; Manieri, Monia; Sivitz, William I.; Cinti, Saverio; Kahn, C. Ronald

    2007-01-01

    C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle ...

  9. Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences.

    Science.gov (United States)

    de Fiebre, Nancyellen C; Sumien, Nathalie; Forster, Michael J; de Fiebre, Christopher M

    2006-09-01

    Two tests often used in aging research, the elevated path test and the Morris water maze test, were examined for their application to the study of brain aging in a large sample of C57BL/6JNia mice. Specifically, these studies assessed: (1) sensitivity to age and the degree of interrelatedness among different behavioral measures derived from these tests, (2) the effect of age on variation in the measurements, and (3) the reliability of individual differences in performance on the tests. Both tests detected age-related deficits in group performance that occurred independently of each other. However, analysis of data obtained on the Morris water maze test revealed three relatively independent components of cognitive performance. Performance in initial acquisition of spatial learning in the Morris maze was not highly correlated with performance during reversal learning (when mice were required to learn a new spatial location), whereas performance in both of those phases was independent of spatial performance assessed during a single probe trial administered at the end of acquisition training. Moreover, impaired performance during initial acquisition could be detected at an earlier age than impairments in reversal learning. There were modest but significant age-related increases in the variance of both elevated path test scores and in several measures of learning in the Morris maze test. Analysis of test scores of mice across repeated testing sessions confirmed reliability of the measurements obtained for cognitive and psychomotor function. Power calculations confirmed that there are sufficiently large age-related differences in elevated path test performance, relative to within age variability, to render this test useful for studies into the ability of an intervention to prevent or reverse age-related deficits in psychomotor performance. Power calculations indicated a need for larger sample sizes for detection of intervention effects on cognitive components of the

  10. Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to {gamma} Rays

    Energy Technology Data Exchange (ETDEWEB)

    Trani, Daniela [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht (Netherlands); Moon, Bo-Hyun [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Kallakury, Bhaskar; Hartmann, Dan P. [Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Datta, Kamal [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Fornace, Albert J., E-mail: af294@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia)

    2013-01-01

    Purpose: The purpose of the present study was to assess the effect of 1 and 5 Gy radiation doses and to investigate the interplay of gender and radiation with regard to intestinal tumorigenesis in an adenomatous polyposis coli (APC) mutant mouse model. Methods and Materials: Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of {gamma} rays and euthanized when most of the treated mice became moribund. Small and large intestines were processed to determine tumor burden, distribution, and grade. Expression of proliferation marker Ki-67 and estrogen receptor (ER)-{alpha} were also assessed by immunohistochemistry. Results: We observed that, with both 1 Gy and 5 Gy of {gamma} rays, females displayed reduced susceptibility to radiation-induced intestinal tumorigenesis compared with males. As for radiation effect on small intestinal tumor progression, although no substantial differences were found in the relative frequency and degree of dysplasia of adenomas in irradiated animals compared with controls, invasive carcinomas were found in 1-Gy- and 5-Gy-irradiated animals. Radiation exposure was also shown to induce an increase in protein levels of proliferation marker Ki-67 and sex-hormone receptor ER-{alpha} in both non tumor mucosa and intestinal tumors from irradiated male mice. Conclusions: We observed important sex-dependent differences in susceptibility to radiation-induced intestinal tumorigenesis in Apc1638N/+ mutants. Furthermore, our data provide evidence that exposure to radiation doses as low as 1 Gy can induce a significant increase in intestinal tumor multiplicity as well as enhance tumor progression in vivo.

  11. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

    Science.gov (United States)

    Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

    2015-01-01

    Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

  12. Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury.

    Science.gov (United States)

    Shimizu, Nobutaka; Doyal, Mark F; Goins, William F; Kadekawa, Katsumi; Wada, Naoki; Kanai, Anthony J; de Groat, William C; Hirayama, Akihide; Uemura, Hirotsugu; Glorioso, Joseph C; Yoshimura, Naoki

    2017-11-19

    Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRG) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. The number of CMV promoter vector-labeled neurons was not altered after SCI. The number of CGRP and TRPV1 promoter vector-labeled neurons was significantly increased whereas the number of NF200 vector-labeled neurons was decreased in L6 DRG after SCI. The median size of CGRP promoter-labeled C-fiber neurons was increased from 247.0 in SI mice to 271.3μm 2 in SCI mice whereas the median cell size of TRPV1 promoter vector-labeled neurons was decreased from 245.2 in SI mice to 216.5μm 2 in SCI mice. CGRP and TRPV1 mRNA levels of laser-captured bladder afferent neurons labeled with Fast Blue were significantly increased in SCI mice compared to SI mice. Thus, using a novel HSV vector-mediated neuronal labeling technique, we found that SCI induces expansion of the CGRP- and TRPV1-expressing C-fiber cell population, which could contribute to C-fiber afferent hyperexcitability and NDO after SCI. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. The relationship between the population size and the postirradiation mortality of mice with respect to individual differences in stress reactivity

    International Nuclear Information System (INIS)

    Pospisil, M.; Pipalova, I.; Netikova, J.

    1976-01-01

    Differences in radiosensitivity, expressed by the death rate up to the 30th day after irradiation by single whole-body exposures in the region of LD 50 , were followed in mice caged in groups by five, 15 and 25 individuals. No marked differences in the whole-group mortality of differently sized collectives were detected. Preirradiation as well as postirradiation leucocyte counts (after a sublethal irradiation) exhibit, however, differences, which correspond to an assumed different degree of the adrenocortical activity in differently sized collectives. Also the follow-up of the stress reactivity of the animals by measuring the Na/K ratio in 24-hour-samples of urine prior to irradiation demonstrated marked differences between the groups with low number and high number of animals in a cage. By correlating values of this indirect indicator of the adrenocortical activity with manifestations of the individual radiosensitivity it was found that the extremely hyporeactive animals (belonging to groups with five animals per cage) and the extremely hyperreactive ones (belonging to groups with 25 animals per cage) exhibit a markedly higher mortality. The absence of differences in the whole-group mortality of differently sized collectives can be explained by the existence of nonlinear 'U'-shaped relations between the adrenocortical activity and the individuals' radiosensitivity. The results support the conception on the unfavorable prognostic significance of unbalanced reactions of homeostatic functions of system regulation under conditions of radiation syndrome. (orig.) [de

  14. Faculty Decisions on Serials Subscriptions Differ Significantly from Decisions Predicted by a Bibliometric Tool.

    Directory of Open Access Journals (Sweden)

    Sue F. Phelps

    2016-03-01

    of the faculty choices. The p-value for this relationship was less than 0.0001, also indicating that the result was not by chance. A quadratic model plotted alongside the previous linear model follows a similar pattern. The p-value of the comparison is 0.0002, which indicates the quadratic model’s fit cannot be explained by random chance. Main Results – The authors point out three outstanding findings. First, the match rate between faculty valuations and bibliometric scores for serials is 65%. This exceeds the 50% rate that would indicate random association, but also indicates a statistically significant difference between faculty and bibliometric valuations. Secondly, the match rate with the bibliometric scores for titles that faculty chose to keep (73% was higher than those they chose to cancel (54%. Thirdly, the match rate increased with higher bibliometric scores. Conclusions – Though the authors identify only a modest degree of similarity between faculty and bibliometric valuations of serials, it is noted that there is more agreement in the higher valued serials than the lower valued serials. With that in mind, librarians might focus faculty review on the lower scoring titles in the future, taking into consideration that unique faculty interests may drive selection at that level and would need to be balanced with the mission of the library.

  15. AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging.

    Science.gov (United States)

    Ordoñez-Gutierrez, Lara; Fernandez-Perez, Ivan; Herrera, Jose Luis; Anton, Marta; Benito-Cuesta, Irene; Wandosell, Francisco

    2016-09-06

    Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, AβPP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the AβPP/PS1 transgenic line, which was found to be ten-fold higher in 15-month-old females. Amyloid-β accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.

  16. Significant regional differences in Denmark in outcome after cochlear implants in children

    DEFF Research Database (Denmark)

    Percy-Smith, Lone; Busch, Georg Walter; Sandahl, Minna

    2012-01-01

    The objectives of the present study were to study regional differences in outcome for a paediatric cochlear implant (CI) population after the introduction of universal neonatal hearing screening (UNHS) and bilateral implantation in Denmark....

  17. The differences between emission, waste, and a good, and their significance to waste management policy

    International Nuclear Information System (INIS)

    Holm-Mueller, K.

    1994-01-01

    This paper defines the transportability of solid waste as its major difference compared to emissions. Several specific possibilities for politics dealing with the problems of solid waste are deduced from this characteristic. The difference between solid waste and good lies in the valuation of objects. As is shown the negative valuation of waste has a great influence on the effect of possible politics derived in part one of this paper. (orig.) [de

  18. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice.

    Science.gov (United States)

    Almind, Katrine; Manieri, Monia; Sivitz, William I; Cinti, Saverio; Kahn, C Ronald

    2007-02-13

    C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a beta3-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice.

  19. Diurnal-and sex-related difference of metallothionein expression in mice

    Directory of Open Access Journals (Sweden)

    Zhang Dan

    2012-07-01

    Full Text Available Abstract Background Metallothionein (MT is a small, cysteine-rich, metal-binding protein that plays an important role in protecting against toxicity of heavy metal and chemicals. This study was aimed to define diurnal and sex variation of MT in mice. Methods Adult mice were maintained in light- and temperature-controlled facilities for 2 weeks with light on at 8:00 and light off at 20:00. The blood, liver, and kidneys were collected every 4 h during the 24 h period. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis and MT protein was determined by western blot and the Cd/hemoglobin assay. Results The diurnal variations in mRNA levels of MT-1 and MT-2in liver were dramatic, up to a 40-foldpeak/trough ratio. MT mRNA levels in kidneys and blood also showed diurnal variation, up to 5-fold peak/trough ratio. The diurnal variation of MT mRNAs resembled the clock gene albumin site D-binding protein (Dbp, and was anti-phase to the clock gene Brain and Muscle ARNT-like Protein 1 (Bmal1 in liver and kidneys. The peaks of MT mRNA levels were higher in females than in males. Hepatic MT protein followed a similar pattern, with about a 3-fold difference. Conclusion MT mRNA levels and protein showed diurnal- and sex-variation in liver, kidney, and blood of mice, which could impact the body defense against toxic stimuli.

  20. Field Dependence/Independence Cognitive Styles: Are They Significant at Different Levels of Vocabulary Knowledge?

    Science.gov (United States)

    Rostampour, Mohammad; Niroomand, Seyyedeh Mitra

    2014-01-01

    Cognitive styles influence the performance of language learners and can predict their success in the process of language learning. Considering field dependence/independence cognitive styles, this study aims at determining if they are significant in English vocabulary knowledge. A number of EFL university students took part in the study. The…

  1. [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.

  2. [Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy].

    Science.gov (United States)

    Firstova, Iu Iu; Dolotov, O V; Kondrakhin, e A; Dubynina, E V; Grivennikov, I A; Kovalev, G I

    2009-01-01

    The influence of subchronic administration of nootropic drugs (piracetam, phenotropil, meclophenoxate, pantocalcine, semax, nooglutil) on the brain-derived neurotrophic factor (BDNF) content in hippocampal and cortical tissues in mice with different exploratory behavior--high efficacy (HE) against low efficacy (LE)--in cross-maze test has been studied. The initial BDNF concentration in hippocamp (but not in cortex) of control HE mice was higher than that in LE mice (LE, 0.091 +/- 0.005 pg/microg; HE, 0.177 +/- 0.005 pg/microg; p nootrope effects, at least partially, via increase in hippocampal BDNF level, which is achieved only under conditions of cognitive deficiency.

  3. What Makes Your Writing Style Unique? Significant Differences Between Two Famous Romanian Orators

    NARCIS (Netherlands)

    Dascalu, Mihai; Gifu, Daniela; Trausan-Matu, Stefan

    2016-01-01

    This paper introduces a novel, in-depth approach of analyzing the differences in writing style between two famous Romanian orators, based on automated textual complexity indices for Romanian language. The considered authors are: (a) Mihai Eminescu, Romania’s national poet and a

  4. Do Age and Sex of School Students Make Significant Difference in Their Multiple Intelligences?

    Science.gov (United States)

    Ravi, R.; Vedapriya, S. Gethsi

    2009-01-01

    Multiple Intelligences are a new educational theory proposed by Howard Gardner in 1983. Multiple intelligences describe an array of different kinds of intelligences exhibited by human beings. This theory consists of verbal-linguistic, logical and mathematics, visual and spatial, bodily kinesthetic, musical-rhythmic, intrapersonal, interpersonal,…

  5. Assay of serum ferritin by two different radioimmunometric methods and its clinical significance

    International Nuclear Information System (INIS)

    Kaltwasser, J.P.; Werner, E.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Frankfurt am Main

    1977-01-01

    Serum ferritin was measured by two different radioimmunometric methods a) the Addison assay, b) a commercial radioimmunoassay. Iron storage in the body was determined using 59 Fe. A dose correlation was found between serum ferritin and iron storage in the body. (AJ) [de

  6. Conventions of Courtship: Gender and Race Differences in the Significance of Dating Rituals

    Science.gov (United States)

    Jackson, Pamela Braboy; Kleiner, Sibyl; Geist, Claudia; Cebulko, Kara

    2011-01-01

    Dating rituals include dating--courtship methods that are regularly enacted. This study explores gender and race differences in the relative importance placed on certain symbolic activities previously identified by the dating literature as constituting such rituals. Using information collected from a racially diverse sample of college students (N…

  7. Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

    Science.gov (United States)

    Jafari, M R; Zarrindast, M R; Djahanguiri, B

    2004-10-01

    Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

  8. The minute virus of mice exploits different endocytic pathways for cellular uptake

    Energy Technology Data Exchange (ETDEWEB)

    Garcin, Pierre O.; Panté, Nelly, E-mail: pante@zoology.ubc.ca

    2015-08-15

    The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake.

  9. Radiation genetic injury and metabolic difference of tritiated thymidine in testis of young and adult mice

    Energy Technology Data Exchange (ETDEWEB)

    Mingyue, Lun; Shoupeng, Zhu

    1990-04-01

    The radiogenetoxicological effects on the adult testis and the metabolic difference of tritiated thymidine between the testis of young and adult BALB/C mice were studied. When 0.037 MBq/g.b.w. of tritiated thymidine was given i.v. to mice, the initial burden of tritium in the adult was larger than that of tritium in the young. But the retention of tritium in testis of the young gradually become larger than that of tritium in the adult with the passing time. Tritiated thymidine which was incorporated into DNA of the male germ cell nuclei damaged the genetic materials and caused the rising of the rates of the dominant lethal and the dominant mutation which produced skeletal abnomalities in the offspring. The relationship between the dominant lethal mutation index (Y) and the injected activity of tritiated thymidine (I, MBq/g.b.w.) is described by Y = 74.13 + 80.20 I (r = 0.95). The relationship between the incidence of the dominant skeletal mutation in the offspring (B) and the injected activity is B = 0.16 + 0.079 I ( r = 0.85).

  10. Radiation genetic injury and metabolic difference of tritiated thymidine in testis of young and adult mice

    International Nuclear Information System (INIS)

    Lun Mingyue; Zhu Shoupeng.

    1990-01-01

    The radiogenetoxicological effects on the adult testis and the metabolic difference of tritiated thymidine between the testis of young and adult BALB/C mice were studied. When 0.037 MBq/g.b.w. of tritiated thymidine was given i.v. to mice, the initial burden of tritium in the adult was larger than that of tritium in the young. But the retention of tritium in testis of the young gradually become larger than that of tritium in the adult with the passing time. Tritiated thymidine which was incorporated into DNA of the male germ cell nuclei damaged the genetic materials and caused the rising of the rates of the dominant lethal and the dominant mutation which produced skeletal abnomalities in the offspring. The relationship between the dominant lethal mutation index (Y) and the injected activity of tritiated thymidine (I, MBq/g.b.w.) is described by Y = 74.13 + 80.20 I (r = 0.95). The relationship between the incidence of the dominant skeletal mutation in the offspring (B) and the injected activity is B = 0.16 + 0.079 I ( r = 0.85)

  11. Benzophenone guttiferone A from Garcinia achachairu Rusby (Clusiaceae presents genotoxic effects in different cells of mice.

    Directory of Open Access Journals (Sweden)

    Peterson Menezes Terrazas

    Full Text Available Benzophenones from natural sources and those of synthetic analogues present several reports of potent biological properties, and Guttiferone A represents a promising medicinal natural compound with analgesic and gastroprotective profiles. Considering that there are no reports that assess the genetic toxicity of Guttiferone A, the present study was undertaken to investigate the genotoxic potential of this benzophenone isolated from seeds of Garcinia achachairu in terms of DNA damage in different cells of Swiss albino mice using the comet assay, and its clastogenic/aneugenic effects in bone marrow cells in vivo by the micronucleus test. Cytotoxicity was assessed by scoring polychromatic (PCE and normochromatic (NCE erythrocytes ratio. Guttiferone A was administered by oral gavage at doses of 15, 30 and 60 mg/kg. The results showed that Guttiferone A produced genotoxic effects in leukocytes, liver, bone marrow, brain and testicle cells and clastogenic/aneugenic effects in bone marrow erythrocytes of mice. The PCE/NCE ratio indicated no cytotoxicity. Since guttiferone A is harmful to the genetic material we suggest caution in its use by humans.

  12. [Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

    Science.gov (United States)

    Ma, Yi-Ran; Ren, Si-Hua; He, Yu-Xin; Wang, Lin-Lin; Jin, Li; Hao, Yi-Wen

    2012-10-01

    This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.

  13. The minute virus of mice exploits different endocytic pathways for cellular uptake

    International Nuclear Information System (INIS)

    Garcin, Pierre O.; Panté, Nelly

    2015-01-01

    The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake

  14. The significance of different diacylgycerol synthesis pathways on plant oil composition and bioengineering

    Directory of Open Access Journals (Sweden)

    Philip David Bates

    2012-07-01

    Full Text Available The unique properties of vegetable oils from different plants utilized for food, industrial feedstocks, and fuel is dependent on the fatty acid (FA composition of triacylglycerol (TAG. Plants can use two main pathways to produce diacylglycerol (DAG, the immediate precursor molecule to TAG synthesis: 1 De novo DAG synthesis, and 2 conversion of the membrane lipid phosphatidylcholine (PC to DAG. The FA esterified to PC are also the substrate for FA modification (e.g. desaturation, hydroxylation, etc., such that the FA composition of PC-derived DAG can be substantially different than that of de novo DAG. Since DAG provides two of the three FA in TAG, the relative flux of TAG synthesis from de novo DAG or PC-derived DAG can greatly affect the final oil FA composition. Here we review how the fluxes through these two alternate pathways of DAG/TAG synthesis are determined and present evidence that suggests which pathway is utilized in different plants. Additionally, we present examples of how the endogenous DAG synthesis pathway in a transgenic host plant can produce bottlenecks for engineering of plant oil FA composition, and discuss alternative strategies to overcome these bottlenecks to produce crop plants with designer vegetable oil compositions.

  15. 'It's Made a Huge Difference': Recognition, Rights and the Personal Significance of Civil Partnership

    OpenAIRE

    Beccy Shipman; Carol Smart

    2007-01-01

    In this paper we map briefly some of the arguments around the meaning and significance of the introduction of Civil Partnership in England and Wales, and in this way show how contested these meanings are with some groups profoundly against this legal reform and others supporting it, but for a mixture of reasons. We then turn to our empirical data based on interviews with same-sex couples to explore the extent to which these arguments and issues are part of the everyday decision making process...

  16. Significant Differences Characterise the Correlation Coefficients between Biocide and Antibiotic Susceptibility Profiles in Staphylococcus aureus.

    Science.gov (United States)

    Oggioni, Marco R; Coelho, Joana Rosado; Furi, Leonardo; Knight, Daniel R; Viti, Carlo; Orefici, Graziella; Martinez, Jose-Luis; Freitas, Ana Teresa; Coque, Teresa M; Morrissey, Ian

    2015-01-01

    There is a growing concern by regulatory authorities for the selection of antibiotic resistance caused by the use of biocidal products. We aimed to complete the detailed information on large surveys by investigating the relationship between biocide and antibiotic susceptibility profiles of a large number of Staphylococcus aureus isolates using four biocides and antibiotics commonly used in clinical practice. The minimal inhibitory concentration (MIC) for most clinically-relevant antibiotics was determined according to the standardized methodology for over 1600 clinical S. aureus isolates and compared to susceptibility profiles of benzalkonium chloride, chlorhexidine, triclosan, and sodium hypochlorite. The relationship between antibiotic and biocide susceptibility profiles was evaluated using non-linear correlations. The main outcome evidenced was an absence of any strong or moderate statistically significant correlation when susceptibilities of either triclosan or sodium hypochlorite were compared for any of the tested antibiotics. On the other hand, correlation coefficients for MICs of benzalkonium chloride and chlorhexidine were calculated above 0.4 for susceptibility to quinolones, beta-lactams, and also macrolides. Our data do not support any selective pressure for association between biocides and antibiotics resistance and furthermore do not allow for a defined risk evaluation for some of the compounds. Importantly, our data clearly indicate that there does not involve any risk of selection for antibiotic resistance for the compounds triclosan and sodium hypochlorite. These data hence infer that biocide selection for antibiotic resistance has had so far a less significant impact than feared.

  17. Postexercise Glycogen Recovery and Exercise Performance is Not Significantly Different Between Fast Food and Sport Supplements.

    Science.gov (United States)

    Cramer, Michael J; Dumke, Charles L; Hailes, Walter S; Cuddy, John S; Ruby, Brent C

    2015-10-01

    A variety of dietary choices are marketed to enhance glycogen recovery after physical activity. Past research informs recommendations regarding the timing, dose, and nutrient compositions to facilitate glycogen recovery. This study examined the effects of isoenergetic sport supplements (SS) vs. fast food (FF) on glycogen recovery and exercise performance. Eleven males completed two experimental trials in a randomized, counterbalanced order. Each trial included a 90-min glycogen depletion ride followed by a 4-hr recovery period. Absolute amounts of macronutrients (1.54 ± 0.27 g·kg-1 carbohydrate, 0.24 ± 0.04 g·kg fat-1, and 0.18 ±0.03g·kg protein-1) as either SS or FF were provided at 0 and 2 hr. Muscle biopsies were collected from the vastus lateralis at 0 and 4 hr post exercise. Blood samples were analyzed at 0, 30, 60, 120, 150, 180, and 240 min post exercise for insulin and glucose, with blood lipids analyzed at 0 and 240 min. A 20k time-trial (TT) was completed following the final muscle biopsy. There were no differences in the blood glucose and insulin responses. Similarly, rates of glycogen recovery were not different across the diets (6.9 ± 1.7 and 7.9 ± 2.4 mmol·kg wet weight- 1·hr-1 for SS and FF, respectively). There was also no difference across the diets for TT performance (34.1 ± 1.8 and 34.3 ± 1.7 min for SS and FF, respectively. These data indicate that short-term food options to initiate glycogen resynthesis can include dietary options not typically marketed as sports nutrition products such as fast food menu items.

  18. Different extraction pretreatments significantly change the flavonoid contents of Scutellaria baicalensis

    Science.gov (United States)

    Yu, Chunhao; Qu, Fengyun; Mao, Yanyong; Li, Dong; Zhen, Zhong; Nass, Rachael; Calway, Tyler; Wang, Yunwei; Yuan, Chun-Su; Wang, Chong-Zhi

    2014-01-01

    Context Scutellaria baicalensis is one of the most commonly used medicinal herbs, especially in traditional Chinese medicine. However, compared to many pharmacological studies of this botanical, much less attention has been paid to the quality control of the herb’s pretreatment prior to extract preparation, an issue that may affect therapeutic outcomes. Objective The current study was designed to evaluate whether different pretreatment conditions change the contents of its four major flavonoids in the herb, i.e., two glycosides (baicalin and wogonoside) and two aglycons (baicalein and wogonin). Materials and methods An HPLC assay was used to quantify the contents of these four flavonoids. The composition changes of four flavonoids by different pretreatment conditions including solvent, treatment time, temperature, pH value, and herb/solvent ratio were evaluated. Results After selection of the first order time-curve kinetics, our data showed that at 50°C, 1:5 herb/water (in w/v) ratio and pH 6.67 yielded an optimal conversion rate from flavonoid glycosides to their aglycons. In this optimized condition, the contents of baicalin and wogonoside were decreased to 1/70 and 1/13, while baicalein and wogonin were increased 3.5 and 3.1 folds, respectively, compared to untreated herb. Discussion and conclusion The markedly variable conversion rates by different pretreatment conditions complicated the quality control of this herb, mainly due to the high amount of endogenous enzymes of S. baicalensis. Optimal pretreatment conditions obtained from this study could be used obtain the highest level of desired constituents to achieve better pharmacological effects. PMID:23738852

  19. Null hypothesis significance tests. A mix-up of two different theories

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg

    2015-01-01

    criticisms raised against NHST. As practiced, NHST has been characterized as a ‘null ritual’ that is overused and too often misapplied and misinterpreted. NHST is in fact a patchwork of two fundamentally different classical statistical testing models, often blended with some wishful quasi......-Bayesian interpretations. This is undoubtedly a major reason why NHST is very often misunderstood. But NHST also has intrinsic logical problems and the epistemic range of the information provided by such tests is much more limited than most researchers recognize. In this article we introduce to the scientometric community...

  20. Biomedical research in france and brazil: an analysis of significant differences and ethical issues

    OpenAIRE

    Hervé Moizan

    2016-01-01

    At first sight, Brazil and France seem pretty distant from one another, but on the map, they are not separated by the Atlantic Ocean, but by the Oyapock River, located between the state of Amapa and French Guiana (French overseas department), creating a 730 km long international border. If the distance does exist, it is very different when we finely analyze some similarities in the field of biomedical research. France is the biggest country of Western Europe and covers 1/5 of the European ...

  1. Thermodynamic study of three pharmacologically significant drugs: Density, viscosity, and refractive index measurements at different temperatures

    International Nuclear Information System (INIS)

    Iqbal, Muhammad Javed; Chaudhry, Mansoora Ahmed

    2009-01-01

    Measurements of density, viscosity, and refractive index of three pharmacologically significant drugs, i.e. diclofenac sodium, cetrizine, and doxycycline have been carried in aqueous medium at T = (293.15 to 313.15) K. An automated vibrating-tube densimeter, viscometer, and refractometer are used in a concentration range from (7.5) . 10 -3 to 25 . 10 -3 ) mol . kg -1 . The precise density results are used to evaluate the apparent molar volume, partial molar volume, thermal expansion coefficient, partial molar expansivity, and the Hepler's constant. Viscosity results are used to calculate the Jones-Dole viscosity B-coefficient, free energy of activation of the solute and solvent, activation enthalpy, and activation entropy. The molar refractive indices of the drug solutions can be employed to calculate molar refraction. It is inferred from these results that the above mentioned drugs act as structure-making compounds due to hydrophobic hydration of the molecules in the drugs

  2. Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adolescents

    DEFF Research Database (Denmark)

    Bisgaard, Amalie; Sørensen, Kaspar; Johannsen, Trine Holm

    2014-01-01

    children (21%) had levels below detection limit of assay. Baseline levels of FGF21 showed positive correlation with triglycerides, but no significant correlations were found between FGF21-concentration and body mass index (BMI), DXA-derived fat percentage, LDL- HDL- and non-HDL cholesterol, leptin......INTRODUCTION: Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor with effect on glucose and lipid metabolism, and shown to be elevated in diseases related to metabolic syndrome. Due to the increasing frequency of metabolic syndrome in the pediatric population, and as FGF21 studies...... in children are limited, we investigated baseline serum levels of FGF21 in healthy children during an oral glucose tolerance test. METHODS: A total of 179 children and adolescents from the COPENHAGEN Puberty Study were included. An OGTT with glucose and insulin measurements, a dual energy X-ray absorptiometry...

  3. Harvesting yeast (Saccharomyces cerevisiae) at different physiological phases significantly affects its functionality in bread dough fermentation.

    Science.gov (United States)

    Rezaei, Mohammad N; Dornez, Emmie; Jacobs, Pieter; Parsi, Anali; Verstrepen, Kevin J; Courtin, Christophe M

    2014-05-01

    Fermentation of sugars into CO2, ethanol and secondary metabolites by baker's yeast (Saccharomyces cerevisiae) during bread making leads to leavening of dough and changes in dough rheology. The aim of this study was to increase our understanding of the impact of yeast on dough related aspects by investigating the effect of harvesting yeast at seven different points of the growth profile on its fermentation performance, metabolite production, and the effect on critical dough fermentation parameters, such as gas retention potential. The yeast cells harvested during the diauxic shift and post-diauxic growth phase showed a higher fermentation rate and, consequently, higher maximum dough height than yeast cells harvested in the exponential or stationary growth phase. The results further demonstrate that the onset of CO2 loss from fermenting dough is correlated with the fermentation rate of yeast, but not with the amount of CO2 that accumulated up to the onset point. Analysis of the yeast metabolites produced in dough yielded a possible explanation for this observation, as they are produced in different levels depending on physiological phase and in concentrations that can influence dough matrix properties. Together, our results demonstrate a strong effect of yeast physiology at the time of harvest on subsequent dough fermentation performance, and hint at an important role of yeast metabolites on the subsequent gas holding capacity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Thermodynamic study of three pharmacologically significant drugs: Density, viscosity, and refractive index measurements at different temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Iqbal, Muhammad Javed [Department of Chemistry, Quaid-i-Azam University, Islamabad 45320 (Pakistan)], E-mail: mjiqauchem@yahoo.com; Chaudhry, Mansoora Ahmed [Department of Chemistry, Quaid-i-Azam University, Islamabad 45320 (Pakistan)

    2009-02-15

    Measurements of density, viscosity, and refractive index of three pharmacologically significant drugs, i.e. diclofenac sodium, cetrizine, and doxycycline have been carried in aqueous medium at T = (293.15 to 313.15) K. An automated vibrating-tube densimeter, viscometer, and refractometer are used in a concentration range from (7.5) . 10{sup -3} to 25 . 10{sup -3}) mol . kg{sup -1}. The precise density results are used to evaluate the apparent molar volume, partial molar volume, thermal expansion coefficient, partial molar expansivity, and the Hepler's constant. Viscosity results are used to calculate the Jones-Dole viscosity B-coefficient, free energy of activation of the solute and solvent, activation enthalpy, and activation entropy. The molar refractive indices of the drug solutions can be employed to calculate molar refraction. It is inferred from these results that the above mentioned drugs act as structure-making compounds due to hydrophobic hydration of the molecules in the drugs.

  5. Antimicrobial Resistance Patterns in Women with Positive Urine Culture: Does Menopausal Status Make a Significant Difference?

    Directory of Open Access Journals (Sweden)

    Pawel Miotla

    2017-01-01

    Full Text Available Aim. Urinary tract infection (UTI is considered one of the most common bacterial infections in women. The aim of this study was to investigate the types of uropathogens present, as well as the degree of antimicrobial drug resistance seen among premenopausal (n=2748 and postmenopausal (n=1705 women with uncomplicated UTI. Methods. Urinary samples (n=4453 collected from women with UTI were analyzed in terms of uropathogens present. These were considered as positive if bacterial growth was ≥105 colony forming units (CFUs/mL. Susceptibility and resistance testing for commonly used antibiotics was subsequently assessed. Results. The most common uropathogens cultured from urine samples were Escherichia coli (65.5%, followed by Enterococcus faecalis (12.2%, Klebsiella pneumoniae (4.7%, and Proteus mirabilis (4.2%. The resistance to ampicillin exceeded 40%, independently of menopausal status. Of note, resistance to ciprofloxacin exceeded 25% among postmenopausal patients. Moreover, resistance of all uropathogens to commonly used antimicrobials was significantly higher in postmenopausal women. Conclusion. Due to the high resistance rate, ampicillin, ciprofloxacin, and the trimethoprim/sulfamethoxazole combination should be avoided in treating postmenopausal women affected by UTI without being indicated by initial urine culture report. Finally, cephalexin and cefuroxime are promising alternatives as initial treatment in postmenopausal women.

  6. Effects of different levels of food restriction on passive-avoidance memory and the expression of synapsin I in young mice.

    Science.gov (United States)

    Deng, L; Wu, Z-N; Han, P-Z

    2009-01-01

    The present study investigated the effects of food restriction (FR) on memory and the expression of synapsin I in the brain of young mice. The results showed that 20% FR did not retard the body weight gain of mice, while the 60% and 80% FR reduced the mice's body weight. The memory after 24 hr of learning was not changed by FR, whereas long-term memory was improved significantly in 20% FR mice. In addition, 60% and 80% FR did not impair the mice's memory. The transcriptional expression of synapsin I in mice brain was up-regulated by 20% FR, and down-regulated by 60% and 80% FR.

  7. Bile ductal injury and ductular reaction are frequent phenomena with different significance in autoimmune hepatitis.

    Science.gov (United States)

    Verdonk, Robert C; Lozano, Mallaki F; van den Berg, Aad P; Gouw, Annette S H

    2016-09-01

    The significance of bile duct injury and ductular reaction in biopsies from autoimmune hepatitis patients is not clear. We aim to establish the prevalence and clinical relevance of both phenomena in autoimmune hepatitis. Cases of newly diagnosed, untreated autoimmune hepatitis without overlap syndrome were selected. Pretreatment and follow up biopsies were scored for inflammation, fibrosis, bile ductal injury and ductular reaction. Thirty-five cases were studied of whom 14 cases had follow up biopsies. Bile duct injury was present in 29 cases (83%), mostly in a PBC-like pattern and was not correlated with demographical or laboratory findings. Ductular reaction, observed in 25 of 35 cases (71%) using conventional histology and in 30 of 32 cases (94%) using immunohistochemistry, was correlated with portal and lobular inflammation, interface hepatitis and centrilobular necrosis as well as bile duct injury and fibrosis. In 11 of 14 cases (79%) ductular reaction remained present on post-treatment biopsy whereas bile duct injury persisted in six of 14 (43%) of cases. Bile duct injury and ductular reaction are very common in newly diagnosed autoimmune hepatitis and cannot be predicted biochemically. Bile duct injury may subside in the majority of treated AIH cases while DR tends to persist during follow up. These findings show that the two phenomena are part of the spectrum of AIH with dissimilar responses to treatment and do not necessarily point towards an overlap syndrome. Persistence of ductular reaction after treatment supports the notion that it represents a regenerative response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Different reasons for one significant choice: Factors influencing homeschooling choice in Israel

    Science.gov (United States)

    Guterman, Oz; Neuman, Ari

    2017-06-01

    Homeschooling is an alternative to conventional education in many countries all over the world, though legal regulations vary. This article examines why parents opt for homeschooling. The large body of research on the topic (especially from the United States) points to a variety of reasons for making the choice to homeschool. The most common reasons are of a pedagogical nature, but in many cases they are also family-related. What has not yet been investigated in depth is the relationship between the different reasons for choosing homeschooling and the way in which homeschooling is practised. There is also a lack of research on the relationship between the reasons for choosing homeschooling and the parents' personalities, educational background and attitudes towards both homeschooling in particular and the education system in general. Using a mixed methods design in order to examine these relationships, the authors of this article questioned 62 homeschooling families in Israel. The findings indicate that some parents chose to homeschool for pedagogical reasons only and others for both pedagogical and family-related reasons. Furthermore, the latter group held more positive views of the effect of homeschooling on children - and the mothers in that group, on average, were more educated compared with those who cited pedagogical reasons alone. The reasons for choosing homeschooling were also found to be associated with the character of the homeschooling practice, with families whose reasons were pedagogical only devoting more hours, on average, specifically to studying.

  9. Genetic differences in hemoglobin function between highland and lowland deer mice

    DEFF Research Database (Denmark)

    Storz, Jay F.; Runck, Amy M.; Moriyama, Hideaki

    2010-01-01

    In high-altitude vertebrates, adaptive changes in blood–O2 affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O2 affinity and/or responsiveness to allosteric effectors that modulate Hb–O2 affinity. This mode of genotypic specialization is considered typical...... of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O2 affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal....... The results of a combined genetic and proteomic analysis revealed that deer mice harbor a high level of Hb isoform diversity that is attributable to allelic polymorphism at two tandemly duplicated -globin genes and two tandemly duplicated β-globin genes. This high level of isoHb diversity translates...

  10. Biomedical research in france and brazil: an analysis of significant differences and ethical issues

    Directory of Open Access Journals (Sweden)

    Hervé Moizan

    2016-06-01

    Full Text Available At first sight, Brazil and France seem pretty distant from one another, but on the map, they are not separated by the Atlantic Ocean, but by the Oyapock River, located between the state of Amapa and French Guiana (French overseas department, creating a 730 km long international border. If the distance does exist, it is very different when we finely analyze some similarities in the field of biomedical research. France is the biggest country of Western Europe and covers 1/5 of the European Union. Apart from Metropolitan France, the country contains overseas territories, remnants of its colonial past. Over the centuries, France has known several political systems, from Ancient History to the current Republic. According to Ernest Renan, the French nation is more an ideology than a reality, primarily based on “the desire of living together and the wish to highlight our legacy”(1. The tragic attacks of November 2015 and all the reactions over the next days illustrate this. Brazil, discovered by the Portuguese explorer Pedro Alvares during the 16th century, is established on half of South America and is about 16 times bigger than France. This giant does not look to the past but is always moving forward. The concept of nation is really strong throughout the country, as shown by the enthusiasm of soccer players wearing the national auriverde jersey and the National Team supporters. Furthermore, they possess a strong culture of entrepreneurship defined by Stefan Zweig as the legacy of the early colonial era(2. Biomedical research is a human activity which aims to give expected solutions, and sometimes unexpected ones too, to a major and insoluble problem at a given time. This research is based on knowledge and will question it with a scientific approach, spread between what is known today and what will be known tomorrow. Ideally, the point of getting new knowledge is to improve a group of people or the entire population’s health. The researcher is a

  11. [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.

  12. Birth defects and aplastic anemia: differences in polycyclic hydrocarbon toxicity associated with the Ah locus. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Nebert, D.W.; Levitt, R.C.; Jensen, N.M.; Lambert, G.H.; Felton, J.S.

    1977-01-01

    The balance between cytochrome(s) P/sub 1/-450 and other forms of P-450 in the liver, and probably many nonhepatic tissues as well, appears to be important in the toxicity, carcinogenicity, mutagenicity, and teratogenicity of numerous compounds. Thus, allelic differences in a single gene--the Ah locus-- can have profound effects on the susceptibility of mice to drug toxicity and cancer. There is evidence for the Ah lous in the human. Striking increases in the incidence of stillborns, reorptions,and malformations caused by 3-methylcholanthrene or 7,12-dimethylbenz(a)anthracene were observed in the aromatic hydrocarbon responsive C57BL/6N,C3H/HeN, and BALB/cAnN inbred strains, compared with the genetically nonresponsive AKR/N. These data suggest that an association exists between the Ah locus and teratogenesis. Although numerous teratogenic differences among inbred mouse strains have been previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance, on the basis of known differences in polycyclic hydrocarbon metabolism regulated by the Ah locus.

  13. The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes.

    Science.gov (United States)

    Fu, Changhui; Liu, Tianlong; Li, Linlin; Liu, Huiyu; Chen, Dong; Tang, Fangqiong

    2013-03-01

    Mesoporous silica nanoparticles (MSNs) are emerging as one of the promising nanomaterials for biomedical applications, but the nanomaterials-body interaction exposed by different administration routes remained poorly understood. In the present study, a systematic investigation of the absorption, distribution, excretion and toxicity of silica nanoparticles (SNs) with the average size of 110 nm after four different exposure routes including intravenous, hypodermic, intramuscular injection and oral administration to mice were achieved. The results showed that a fraction of the SNs administrated by the intramuscular and hypodermic injection could cross different biological barriers into the liver but with a low absorption rate. Exposing by oral administration, SNs were absorbed into the intestinal tract and persisted in the liver. And SNs administrated by intravenous injection were mainly present in the liver and spleen. In addition, SNs could cause inflammatory response around the injection sites after intramuscular and hypodermic injection. It was also found that SNs were mainly excreted through urine and feces after different exposure routes. This study will be helpful for selecting the appropriate exposed routes for the development of nanomaterials-based drug delivery system for biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Differences in peripheral sensory input to the olfactory bulb between male and female mice

    Science.gov (United States)

    Kass, Marley D.; Czarnecki, Lindsey A.; Moberly, Andrew H.; McGann, John P.

    2017-04-01

    Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

  15. Gender differences in locomotor and stereotypic behavior associated with l-carnitine treatment in mice.

    Science.gov (United States)

    Benvenga, Salvatore; Itri, Elenora; Hauser, Peter; De Tolla, Louis; Yu, Sui-Foh; Testa, Giuseppe; Pappalardo, Maria Angela; Trimarchi, Francesco; Amato, Antonino

    2011-02-01

    The carnitines exert neuroprotective and neuromodulatory actions, and carnitine supplementation increases locomotor activity (LMA) in experimental animals. We measured 13 indexes of LMA and 3 indexes of stereotypic activity (STA) in adult male and female caged mice. In a randomized 4-week trial, 10 males and 10 females received 50 mg/kg body weight PO l-carnitine, and another 10 males and 10 females received placebo. Compared with placebo-treated females, placebo-treated males had a greater number of stereotypies (NSTs), stereotypy counts (STCs), stereotypy time (STT), and right front time (RFT), but smaller total distance traveled (TDT), margin distance (MD), number of vertical movements (NVMs), and left rear time (LRT). Compared with placebo-treated males, carnitine-treated males had greater horizontal activity (HA), movement time (MT), NVM, STT, TDT, STC, MD, LRT, and clockwise revolutions (CRs), but smaller left front time (LFT) and RFT. Compared with placebo-treated females, carnitine-treated females had greater NST, STC, STT, LFT, and RFT, but smaller NM, HA, NVM, VA, MT, anticlockwise revolutions (ACRs), CR, TDT, and MD; right rear time (RRT) remained statistically insignificant across all comparisons. In summary, l-carnitine caused gender differences to persist for STC, diminish for NST and STT, disappear for LRT and NVM, change in the opposite direction for TDT and MD, appear de novo for HA, VA, NM, MT, and LFT, and remain absent for RRT and ACR. Some indexes of LMA and STA are sexually dimorphic in adult mice, and l-carnitine differentially maintains, diminishes/cancels, inverts, or creates the sexual dimorphism of particular indexes. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  16. Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

    Science.gov (United States)

    Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

    2015-03-01

    Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. © 2014 International Society for Neurochemistry.

  17. Differences in basal and stress-induced HPA regulation of wild house mice selected for high and low aggression

    NARCIS (Netherlands)

    Veenema, AH; Meijer, OC; de Kloet, ER; Koolhaas, JM; Bohus, BG; Meijer, Onno C.; Koolhaas, J M

    Male wild house mice, selected for short (SAL) and long (LAL) attack latency, show distinctly different behavioral strategies in coping with environmental challenges. In this study, we tested the hypothesis that this difference in coping style is associated with a differential stress responsiveness

  18. 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

  19. Effect of different stressors on voluntary ethanol intake in ethanol-dependent and nondependent C57BL/6J mice.

    Science.gov (United States)

    Lopez, Marcelo F; Anderson, Rachel I; Becker, Howard C

    2016-03-01

    Several animal models have evaluated the effect of stress on voluntary ethanol intake with mixed results. The experiments reported here examined the effects of different stressors on voluntary ethanol consumption in dependent and nondependent adult male C57BL/6J mice. In Experiment 1, restraint, forced swim, and social defeat stress procedures all tended to reduce ethanol intake in nondependent mice regardless of whether the stress experience occurred 1 h or 4 h prior to ethanol access. The reduction in ethanol consumption was most robust following restraint stress. Experiment 2 examined the effects of forced swim stress and social defeat stress on drinking in a dependence model that involved repeated cycles of chronic intermittent ethanol (CIE) exposure. Repeated exposure to forced swim stress prior to intervening test drinking periods that followed repeated cycles of CIE exposure further increased ethanol consumption in CIE-exposed mice while not altering intake in nondependent mice. In contrast, repeated exposure to the social defeat stressor in a similar manner reduced ethanol consumption in CIE-exposed mice while not altering drinking in nondependent mice. Results from Experiment 3 confirmed this selective effect of forced swim stress increasing ethanol consumption in mice with a history of CIE exposure, and also demonstrated that enhanced drinking is only observed when the forced swim stressor is administered during each test drinking week, but not if it is applied only during the final test week. Collectively, these studies point to a unique interaction between repeated stress experience and CIE exposure, and also suggest that such an effect depends on the nature of the stressor. Future studies will need to further explore the generalizability of these results, as well as mechanisms underlying the ability of forced swim stress to selectively further enhance ethanol consumption in dependent (CIE-exposed) mice but not alter intake in nondependent animals

  20. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    International Nuclear Information System (INIS)

    Abasolo, Ibane; Pujal, Judit; Navarro, Pilar; Rabanal, Rosa M.; Serafin, Anna; Millan, Olga; Real, Francisco X.

    2009-01-01

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  1. Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.

    Directory of Open Access Journals (Sweden)

    Elizabeth Osterndorff-Kahanek

    Full Text Available Chronically available alcohol escalates drinking in mice and a single injection of the immune activator lipopolysaccharide can mimic this effect and result in a persistent increase in alcohol consumption. We hypothesized that chronic alcohol drinking and lipopolysaccharide injections will produce some similar molecular changes that play a role in regulation of alcohol intake. We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes among four groups of animals, three consuming alcohol (vs water in different consumption tests and one injected with lipopolysaccharide (vs. vehicle. The three tests of alcohol consumption are the continuous chronic two bottle choice (Chronic, two bottle choice available every other day (Chronic Intermittent and limited access to one bottle of ethanol (Drinking in the Dark. Gene expression changes were more numerous and marked in liver than in prefrontal cortex for the alcohol treatments and similar in the two tissues for lipopolysaccharide. Many of the changes were unique to each treatment, but there was significant overlap in prefrontal cortex for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide and in liver all pairs showed overlap. In silico cell-type analysis indicated that lipopolysaccharide had strongest effects on brain microglia and liver Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine-related (PPP1R1B, DRD1, DRD2, FOSB, PDNY network that was highly over-represented in the Chronic Intermittent group, with several genes from the network being also regulated in the Chronic and lipopolysaccharide (but not Drinking in the Dark groups. Liver showed a CYP and GST centered metabolic network shared in part by all four treatments. We demonstrate common consequences of chronic alcohol

  2. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Abasolo, Ibane [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Pujal, Judit; Navarro, Pilar [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Rabanal, Rosa M.; Serafin, Anna [Universitat Autonoma de Barcelona, Departament de Medicina i Cirurgia Animals, Barcelona (Spain); Millan, Olga [Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Real, Francisco X. [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid (Spain)

    2009-07-15

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  3. Characterisation of innate lymphoid cell populations at different sites in mice with defective T cell immunity [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Emma E. Dutton

    2018-03-01

    Full Text Available Background: Innate lymphoid cells (ILCs have now been identified within most tissues of the body and current evidence indicates that this family of cells play a fundamental role in maintaining tissue homeostasis. However, few studies have compared the ILC populations between several tissues. Methods: We sought to generate a comprehensive characterisation of the ILC populations in different tissues of C57BL/6 WT and genetically modified mice targeting costimulatory pathways, using transcription factor expression to define specific groups. Results: Consistent with studies individually describing the ILC composition in different tissues, our analysis revealed different ILC groups dominate the ILC population in different tissues. Additionally, we observed a population of  IL-7Rα+Id2+ cells lacking expression of lineage markers but also lacking expression of GATA-3, RORgt or T-bet. This population was most evident in ear skin where it outnumbered the defined ILC groups, however, further experiments demonstrated that detection of these cells was influenced by how the tissue was digested, raising concerns as to its real nature. Since both ILC2 and ILC3 express ICOS, we then investigated the requirement for ICOS:ICOSL interactions in the homeostasis of ILC populations at these sites. Surprisingly, no significant differences were detected in the number of ILC1, ILC2 or ILC3 between WT and ICOSL-/- mice in any tissue, indicating that this pathway is not required for ILC homeostasis at these sites. These data were compared with CD80-/-CD86-/- mice given evidence of CD28 expression by some ILC and ILC crosstalk with activated T cells. Notably, the absence of CD28 ligands resulted in a significant increase in ILC2 and ILC3 numbers in the intestine. Conclusions: Together, these data provide new insight into ILC composition in different tissues in both WT and genetically modified mice where key costimulatory pathways are genetically deleted, providing a

  4. 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,

  5. Deletion of hepatic FoxO1/3/4 genes in mice significantly impacts on glucose metabolism through downregulation of gluconeogenesis and upregulation of glycolysis.

    Directory of Open Access Journals (Sweden)

    Xiwen Xiong

    Full Text Available Forkhead transcription factors FoxO1/3/4 have pleiotrophic functions including anti-oxidative stress and metabolism. With regard to glucose metabolism, most studies have been focused on FoxO1. To further investigate their hepatic functions, we generated liver-specific FoxO1/3/4 knockout mice (LTKO and examined their collective impacts on glucose homeostasis under physiological and pathological conditions. As compared to wild-type mice, LTKO mice had lower blood glucose levels under both fasting and non-fasting conditions and they manifested better glucose and pyruvate tolerance on regular chow diet. After challenged by a high-fat diet, wild-type mice developed type 2 diabetes, but LTKO mice remained euglycemic and insulin-sensitive. To understand the underlying mechanisms, we examined the roles of SIRT6 (Sirtuin 6 and Gck (glucokinase in the FoxO-mediated glucose metabolism. Interestingly, ectopic expression of SIRT6 in the liver only reduced gluconeogenesis in wild-type but not LTKO mice whereas knockdown of Gck caused glucose intolerance in both wild-type and LTKO mice. The data suggest that both decreased gluconeogenesis and increased glycolysis may contribute to the overall glucose phenotype in the LTKO mice. Collectively, FoxO1/3/4 transcription factors play important roles in hepatic glucose homeostasis.

  6. Protective Effect of Different Anti-Rabies Virus VHH Constructs against Rabies Disease in Mice

    Science.gov (United States)

    Terryn, Sanne; Francart, Aurélie; Lamoral, Sophie; Hultberg, Anna; Rommelaere, Heidi; Wittelsberger, Angela; Callewaert, Filip; Stohr, Thomas; Meerschaert, Kris; Ottevaere, Ingrid; Stortelers, Catelijne; Vanlandschoot, Peter; Kalai, Michael; Van Gucht, Steven

    2014-01-01

    Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable

  7. Global Gene Expression Differences in Joints of Mice with Divergent Post Traumatic Osteoarthritis Phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Kibui, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-07-28

    Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation which prompts pain, stiffness and swelling. Contributing factors include age, genetics, obesity, injury and overuse of joints. OA is defined by an acute phase and a chronic phase whereby inflammation and degeneration of articular cartilage and other tissues is followed by joint pain and limited mobility. Patients remain asymptomatic until substantial joint damage has occurred and therefore rely on long term surgical joint replacement and pain management as their sole treatment options. For this reason, there is an increasing need to identify early stage osteoarthritis biomarkers. Our study aimed to identify and characterize gene expression variances in 3 different mouse strains (STR/ort, C57BL/6 and MRL/MpJ) with different susceptibility to post traumatic osteoarthritis (PTOA). Through RNA sequence analysis of whole knee joint RNA, we identified differentially expressed genes associated with the initial stages of PTOA in relation to mice with divergent phenotypes. These results will help elucidate potential mechanisms responsible for PTOA outcomes.

  8. Effect of whole body neutron irradiation on certain enzyme activities in different brain areas in mice

    International Nuclear Information System (INIS)

    Kotb, M.A.; Ashour, A.M.; El-Bassiouni, E.A.

    1994-01-01

    Male swiss albino mice were exposed to whole-body irradiation by fast neutrons of 14 MeV average energy. Two single doses of 0.08 sievert and 0.16 sievert were used, corresponding to fluences of 1.27 X 10 8 and 2.54 X 10 8 n/cm 2 respectively. Two enzymes were assessed in different layers of the cerebrum and cerebellum of mouse brain. Changes in the activities of acid phosphatase (ACP) and succinic dehydrogenase (SDH) were taken to measure alterations in lysosomal and mitochondrial functions respectively. The degrees of lysosomal affection in different layers of the cerebrum were not uniform, while changes in A activity were very prominent in certain layers (e.g. external pyramidal layer, polymorphous cells layer and white matter), they were practically absent in others (e.g. internal pyramidal layer). Stronger effect was noted in the tissue layers of the cerebellum. The activity of SDH decreased as result of fast neutron irradiation. The response was more apparent for this enzyme than for ACP. This indicates more liability for a decrease in energy metabolism with consequent effect on behavioural and physiological functions under central nervous system control. 4 figs., 4 tabs

  9. Kinetics of EGFR expression during fractionated irradiation varies between different human squamous cell carcinoma lines in nude mice

    International Nuclear Information System (INIS)

    Eicheler, Wolfgang; Krause, Mechthild; Hessel, Franziska; Zips, Daniel; Baumann, Michael

    2005-01-01

    Background and purpose: Preclinical and clinical data indicate that high pretherapeutic EGFR expression is associated with poor local tumour control, possibly caused by a high repopulation rate of clonogenic cells during radiotherapy in these tumours. Previous data reported from our laboratory showed a correlation between EGFR expression and acceleration of repopulation in poorly differentiated FaDu human squamous cell carcinoma (SCC) during fractionated irradiation. To test whether this is a general phenomenon, two further SCC were investigated in the present study. Patients and methods: GL and UT-SCC-14, two moderately well differentiated and keratinising hSCC, were grown as xenografts in nude mice. Functional data on the repopulation kinetics during fractionated irradiation for these tumour models have been previously determined. The expression of EGFR during fractionation was analysed by immunohistochemistry. Endpoints were the membrane-staining score and the proportion of EGFR-positive cells (EGFR labelling index). Results: Different kinetics of EGFR expression during fractionated RT were found. In UT-SCC-14, EGFR staining score and labelling index increased significantly during radiotherapy. In GL SCC, the EGFR expression was unchanged. Both tumours are characterized by a small but significant repopulation rate during radiotherapy. Conclusions: The expression of EGFR may change significantly during fractionated irradiation. No clear correlation between EGFR expression and the repopulation kinetics of clonogenic tumour cells during fractionated irradiation was found. The changes in EGFR expression during irradiation warrant further investigation on their prognostic implications and on their importance for therapeutic interventions

  10. Species differences in methanol and formic acid pharmacokinetics in mice, rabbits and primates

    International Nuclear Information System (INIS)

    Sweeting, J. Nicole; Siu, Michelle; McCallum, Gordon P.; Miller, Lutfiya; Wells, Peter G.

    2010-01-01

    Methanol (MeOH) is metabolized primarily by alcohol dehydrogenase in humans, but by catalase in rodents, with species variations in the pharmacokinetics of its formic acid (FA) metabolite. The teratogenic potential of MeOH in humans is unknown, and its teratogenicity in rodents may not accurately reflect human developmental risk due to differential species metabolism, as for some other teratogens. To determine if human MeOH metabolism might be better reflected in rabbits than rodents, the plasma pharmacokinetics of MeOH and FA were compared in male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys over time (24, 48 and 6 h, respectively) following a single intraperitoneal injection of 0.5 or 2 g/kg MeOH or its saline vehicle. Following the high dose, MeOH exhibited saturated elimination kinetics in all 3 species, with similar peak concentrations and a 2.5-fold higher clearance in mice than rabbits. FA accumulation within 6 h in primates was 5-fold and 43-fold higher than in rabbits and mice respectively, with accumulation being 10-fold higher in rabbits than mice. Over 48 h, FA accumulation was nearly 5-fold higher in rabbits than mice. Low-dose MeOH in mice and rabbits resulted in similarly saturated MeOH elimination in both species, but with approximately 2-fold higher clearance rates in mice. FA accumulation was 3.8-fold higher in rabbits than mice. Rabbits more closely than mice reflected primates for in vivo MeOH metabolism, and particularly FA accumulation, suggesting that developmental studies in rabbits may be useful for assessing potential human teratological risk.

  11. Non-invasive prediction of hemodynamically significant coronary artery stenoses by contrast density difference in coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Hell, Michaela M., E-mail: michaela.hell@uk-erlangen.de [Department of Cardiology, University of Erlangen (Germany); Dey, Damini [Department of Biomedical Sciences, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Taper Building, Room A238, 8700 Beverly Boulevard, Los Angeles, CA 90048 (United States); Marwan, Mohamed; Achenbach, Stephan; Schmid, Jasmin; Schuhbaeck, Annika [Department of Cardiology, University of Erlangen (Germany)

    2015-08-15

    Highlights: • Overestimation of coronary lesions by coronary computed tomography angiography and subsequent unnecessary invasive coronary angiography and revascularization is a concern. • Differences in plaque characteristics and contrast density difference between hemodynamically significant and non-significant stenoses, as defined by invasive fractional flow reserve, were assessed. • At a threshold of ≥24%, contrast density difference predicted hemodynamically significant lesions with a specificity of 75%, sensitivity of 33%, PPV of 35% and NPV of 73%. • The determination of contrast density difference required less time than transluminal attenuation gradient measurement. - Abstract: Objectives: Coronary computed tomography angiography (CTA) allows the detection of obstructive coronary artery disease. However, its ability to predict the hemodynamic significance of stenoses is limited. We assessed differences in plaque characteristics and contrast density difference between hemodynamically significant and non-significant stenoses, as defined by invasive fractional flow reserve (FFR). Methods: Lesion characteristics of 59 consecutive patients (72 lesions) in whom invasive FFR was performed in at least one coronary artery with moderate to high-grade stenoses in coronary CTA were evaluated by two experienced readers. Coronary CTA data sets were acquired on a second-generation dual-source CT scanner using retrospectively ECG-gated spiral acquisition or prospectively ECG-triggered axial acquisition mode. Plaque volume and composition (non-calcified, calcified), remodeling index as well as contrast density difference (defined as the percentage decline in luminal CT attenuation/cross-sectional area over the lesion) were assessed using a semi-automatic software tool (Autoplaq). Additionally, the transluminal attenuation gradient (defined as the linear regression coefficient between intraluminal CT attenuation and length from the ostium) was determined

  12. Cytokine gene expression and pathology in mice experimentally infected with different isolates of Trypanosoma evansi.

    Science.gov (United States)

    Krishnamoorthy, P; Sengupta, P P; Das, Sangita; Ligi, M; Shome, B R; Rahman, H

    2016-11-01

    Aim of the present study was to assess the cytokine gene expression in liver, kidney and spleen and histopathological changes in mice infected with buffalo and dog isolates of Trypanosoma evansi. Forty-four Swiss albino mice was divided into eleven groups of four mice each and injected subcutaneously with 1 × 10 5 trypanosomes of buffalo and dog isolate to twenty mice each, four mice served as control. Mice were examined for clinical signs, blood smear for trypanosome counts. Blood for PCR, liver, kidney, spleen, heart, lung, testis and abdominal muscle for histopathology and liver, kidney, spleen for cytokine gene expression studies, were collected. Mice showed dullness, lethargy, hunched back, sluggish movements on D4 and D5 in buffalo and dog isolate, respectively. Parasite count in blood varied between the two isolates of T. evansi. By PCR, trypanosome DNA was detected on D1 and D2 for buffalo and dog isolate, respectively. Splenomegaly was observed in mice infected with buffalo isolate but not with dog isolate. Histopathological changes were observed in liver, kidney, spleen and heart of mice but no changes in testis and abdominal muscles. Blood vessels of liver, heart, lung showed presence of trypanosomes in mice infected with buffalo isolate but not for dog isolate. Cytokine gene expression of IL-2, IL-4, IL-6, IL-12, TNF-α and IFN-γ increased in liver, kidney and spleen in both these isolates. However, the buffalo isolate exhibited pronounced increase in cytokine gene expression when compare to dog isolate of T. evansi. Anti-inflammatory cytokine gene IL-10 showed 50-60 and 10-20 folds increment in buffalo and dog isolates, respectively. This is the first report of IL-4, IL-6, IL-10 and IL-12 cytokine changes in mice infected with T. evansi. A variation in pathogenicity between buffalo and dog isolates was recorded indicating buffalo isolate of T. evansi remained more pathogenic in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice.

    Science.gov (United States)

    Ponzoni, L; Moretti, M; Sala, M; Fasoli, F; Mucchietto, V; Lucini, V; Cannazza, G; Gallesi, G; Castellana, C N; Clementi, F; Zoli, M; Gotti, C; Braida, D

    2015-10-01

    Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks. One hour after the last session, half of the animals were sacrificed for neurochemical analysis, and the others underwent mecamylamine-precipitated or spontaneous withdrawal for the purposes of behavioural analysis. Chronic intermittent non-contingent, second-hand exposure to cigarette smoke or e-cig vapour led to similar brain cotinine and nicotine levels, similar urine cotinine levels and the similar up-regulation of α4β2 nicotinic acetylcholine receptors in different brain areas, but had different effects on body weight, food intake, and the signs of mecamylamine-precipitated and spontaneous withdrawal episodic memory and emotional responses. The findings of this study demonstrate for the first time that e-cig vapour induces addiction-related neurochemical, physiological and behavioural alterations. The fact that inhaled cigarette smoke and e-cig vapour have partially different dependence-related effects indicates that compounds other than nicotine contribute to tobacco dependence. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  14. Effect of Different Thermal Neutron Fluxes on Blood of Male Mice

    International Nuclear Information System (INIS)

    Abd El-Latif, A.A.; Saeid, Kh. S.; Abd El-Latif, A.A.; Emara, N.M.; Emara, N.M.

    2010-01-01

    This work deals with the exposing of male mice to different fluxes of thermal neutron .Investigation has been performed by calculating of thermal neutron fluxes(0.27x10 8 N/cm 2 . 1h , 0.54x10 8 N/cm 2 . 1h, 1.08x10 8 N/cm 2 . 1h, 2.16x10 8 N/cm 2 . 3h and 4.32x10 8 N/cm 2 . 6h) which emitted from neutron irradiation cell with source Ra - Be (α,n) have activity 3 m. Ci made by leybold(55930) . The number and differential leucocytes counts types of white blood cells in million per cubic millimeter (W. B. Cs. mm -3 ) ,the number of platelets mm -3 ,the number of red blood cells in million per cubic millimeter (R. B. Cs. mm -3 ), the hemoglobin in Blood (mg/dl), the lymphocytes ,and the eosiniphil leucocytes in blood decrease with increasing thermal neutron fluxes. But neutrophile and monocytes in blood increase with increasing the thermal neutron fluxes

  15. Inulin with different degrees of polymerization modulates composition of intestinal microbiota in mice.

    Science.gov (United States)

    Zhu, Limeng; Qin, Song; Zhai, Shixiang; Gao, Yonglin; Li, Lili

    2017-05-01

    The study aimed to analyze the global influences of dietary inulin with different degrees of polymerization (DP) on intestinal microbial communities. Six-week-old male C57BL/6J mice were treated with fructo-oligosaccharides and inulin for 6 weeks. Fecal samples were obtained at time point 0 and 6th week. 16S rRNA sequence analysis was used to measure intestinal microbiota performed on the Illumina MiSeq platform. Influences of dietary inulin on intestinal microbiota were more complex effects than bifidogenic effects, relative abundance of butyrate-producing bacteria increased after interventions. Akkermansia muciniphila, belonging to mucin-degrading species, became a dominant species in Verrucomicrobia phylum after treatment with fructo-oligosaccharides and inulin. Modulation effects of intestinal microbiota were positively correlated with DP. Lower DP interventions exhibited better effects than higher DP treatment on stimulation of probiotics. We hypothesized that Akkermansia muciniphila played an important role on maintaining balance between mucin and short chain fatty acids. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Early differences in metabolic flexibility between obesity-resistant and obesity-prone mice

    Czech Academy of Sciences Publication Activity Database

    Bardová, Kristina; Horáková, Olga; Janovská, Petra; Hansíková, Jana; Kůs, Vladimír; van Schothorst, E. M.; Hoevenaars, F.P.M.; Uil, M.; Hensler, Michal; Keijer, J.; Kopecký, Jan

    2016-01-01

    Roč. 124, May (2016), s. 163-170 ISSN 0300-9084 R&D Projects: GA MŠk(CZ) 7E10059; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : indirect calorimetry * glucose tolerance * weaning * C57BL/6J mice * A/J mice * metabolic flexibility Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.112, year: 2016

  17. Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Lee, Gwang-Hee [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Kim, Dong-Wan, E-mail: dwkim1@korea.ac.kr [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of)

    2016-10-15

    Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies

  18. Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice

    Directory of Open Access Journals (Sweden)

    Bing-Ying Ho

    2012-10-01

    Full Text Available The in vitro and in vivo bioactivities of silibinin (SB, paclitaxel (PTX and SB and PTX in combination (SB+PTX against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value<1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1 and N-cadherin expression, inhibition of matrix metalloprotease (MMP-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL−COX−2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL−COX−2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer.

  19. Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice

    NARCIS (Netherlands)

    Fiebig, A.; Loof, T.G.; Babbar, A.; Itzeg, A.; Koehorst, J.J.; Schaap, P.J.; Nitsche-Schmitz, D.P.

    2015-01-01

    Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to

  20. Effects of Differing Response-Force Requirements on Food-Maintained Responding in C57BL/6J Mice

    Science.gov (United States)

    Zarcone, Troy J.; Chen, Rong; Fowler, Stephen C.

    2009-01-01

    The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all…

  1. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  2. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    International Nuclear Information System (INIS)

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-01-01

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

  3. Gender Differences in Response to Prolonged Every-Other-Day Feeding on the Proliferation and Apoptosis of Hepatocytes in Mice.

    Science.gov (United States)

    Piotrowska, Katarzyna; Tarnowski, Maciej; Zgutka, Katarzyna; Pawlik, Andrzej

    2016-03-19

    Intermittent fasting decreases glucose and insulin levels and increases insulin sensitivity and lifespan. Decreased food intake influences the liver. Previous studies have shown gender differences in response to various types of caloric restriction, including every-other-day (EOD) feeding, in humans and rodents. Our goal was to show the influence of prolonged EOD feeding on the morphology, proliferation and apoptosis of livers from male and female mice. After nine months of an EOD diet, the livers from male and female mice were collected. We examined their morphology on histological slides using the Hematoxilin and Eosine (H_E) method and Hoechst staining of cell nuclei to evaluate the nuclear area of hepatocytes. We also evaluated the expression of mRNA for proto-oncogens, pro-survival proteins and apoptotic markers using Real Time Polimerase Chain Reaction (PCR). We noted increased lipid content in the livers of EOD fed female mice. EOD feeding lead to a decrease of proliferation and apoptosis in the livers of female and male mice, which suggest that tissue maintenance occurred during EOD feeding. Our experiment revealed sex-specific expression of mRNA for proto-oncogenes and pro-survival and pro-apoptotic genes in mice as well as sex-specific responses to the EOD treatment.

  4. Gender Differences in Response to Prolonged Every-Other-Day Feeding on the Proliferation and Apoptosis of Hepatocytes in Mice

    Directory of Open Access Journals (Sweden)

    Katarzyna Piotrowska

    2016-03-01

    Full Text Available Intermittent fasting decreases glucose and insulin levels and increases insulin sensitivity and lifespan. Decreased food intake influences the liver. Previous studies have shown gender differences in response to various types of caloric restriction, including every-other-day (EOD feeding, in humans and rodents. Our goal was to show the influence of prolonged EOD feeding on the morphology, proliferation and apoptosis of livers from male and female mice. After nine months of an EOD diet, the livers from male and female mice were collected. We examined their morphology on histological slides using the Hematoxilin and Eosine (H_E method and Hoechst staining of cell nuclei to evaluate the nuclear area of hepatocytes. We also evaluated the expression of mRNA for proto-oncogens, pro-survival proteins and apoptotic markers using Real Time Polimerase Chain Reaction (PCR. We noted increased lipid content in the livers of EOD fed female mice. EOD feeding lead to a decrease of proliferation and apoptosis in the livers of female and male mice, which suggest that tissue maintenance occurred during EOD feeding. Our experiment revealed sex-specific expression of mRNA for proto-oncogenes and pro-survival and pro-apoptotic genes in mice as well as sex-specific responses to the EOD treatment.

  5. Experimental Tityus serrulatus scorpion envenomation: age- and sex-related differences in symptoms and mortality in mice

    Directory of Open Access Journals (Sweden)

    Pucca MB

    2011-01-01

    Full Text Available Among the various methods for evaluating animal venom toxicity, the calculation of the median lethal dose (LD50 is the most widely used. Although different protocols can be used to calculate the LD50, the source of the venom and the method of extraction, as well as the strain, age, and sex of the animal model employed, should be taken into consideration. The objective of the present study was to evaluate the influence of sex and age on the toxicity of Tityus serrulatus scorpion venom in Swiss mice. Although the symptoms of envenomation were similar in male and female animals, female mice proved to be more resistant to the venom. In females, age had no impact on the susceptibility to scorpion envenomation. Male mice were more sensitive to T. serrulatus venom. Moreover, in males, age was an important parameter since sensitivity to the venom increased with age.

  6. Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes.

    Science.gov (United States)

    Chen, Xuqi; Wang, Lixin; Loh, Dawn H; Colwell, Christopher S; Taché, Yvette; Reue, Karen; Arnold, Arthur P

    2015-09-01

    We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5months); food intake was measured second-by-second for 7days starting 5weeks later, and body weight and composition were measured for 22weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice - including relationship of sex differences

    International Nuclear Information System (INIS)

    Ogawa, Rei; Mizuno, Hiroshi; Watanabe, Atsushi; Migita, Makoto; Hyakusoku, Hiko; Shimada, Takashi

    2004-01-01

    We have previously demonstrated that adipose-derived stromal cells (ASCs) as well as bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. Both types are considered to include mesenchymal stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have also previously reported the plasticity of BSCs and ASCs. In this study, we focused on adipogenic differentiation in vitro by ASCs harvested from GFP transgenic mice. Moreover, preadipocytes and mature adipocytes were harvested at the same time, and the cells were cultured to compare them with ASCs. Inguinal fat pads from GFP transgenic mice were used for the isolation of ASCs, preadipocytes, and mature adipocytes. After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks. Adipogenic differentiation of ASCs was assessed by Oil Red O staining and the expression of the adipocyte specific peroxisome proliferative activated receptor γ2 (PPAR-γ2) gene. These ASCs stained positively, and expression of PPAR-γ2 was detected. Moreover, we also tried to characterize the influence of sex differences on the adipogenic differentiation of ASCs harvested from both male and female mice. This was assessed by the expression levels of the PPAR-γ2 gene using real-time PCR. The results showed that the expression levels of ASCs harvested from female mice were a maximum of 2.89 times greater than those harvested from male mice. This suggests that the adipogenic differentiation of ASCs is closely related to sex differences

  8. Postnatal mandible growth in wild and laboratory mice: Differences revealed from bone remodeling patterns and geometric morphometrics.

    Science.gov (United States)

    Martínez-Vargas, Jessica; Muñoz-Muñoz, Francesc; Martinez-Maza, Cayetana; Molinero, Amalia; Ventura, Jacint

    2017-08-01

    Comparative information on the variation in the temporospatial patterning of mandible growth in wild and laboratory mice during early postnatal ontogeny is scarce but important to understand variation among wild rodent populations. Here, we compare mandible growth between two ontogenetic series from the second to the eighth week of postnatal life, corresponding to two different groups of mice reared under the same conditions: the classical inbred strain C57BL/6J, and Mus musculus domesticus. We characterize the ontogenetic patterns of bone remodeling of the mandibles belonging to these laboratory and wild mice by analyzing bone surface, as well as examine their ontogenetic form changes and bimodular organization using geometric morphometrics. Through ontogeny, the two mouse groups display similar directions of mandible growth, according to the temporospatial distribution of bone remodeling fields. The allometric shape variation of the mandibles of these mice entails the relative enlargement of the ascending ramus. The organization of the mandible into two modules is confirmed in both groups during the last postnatal weeks. However, especially after weaning, the mandibles of wild and laboratory mice differ in the timing and localization of several remodeling fields, in addition to exhibiting different patterns of shape variation and differences in size. The stimulation of dentary bone growth derived from the harder post-weaning diet might account for some features of postnatal mandible growth common to both groups. Nonetheless, a large component of the postnatal growth of the mouse mandible appears to be driven by the inherent genetic programs, which might explain between-group differences. © 2017 Wiley Periodicals, Inc.

  9. Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR knockout mice: implications on anti-glucagon therapies for diabetes

    Directory of Open Access Journals (Sweden)

    Molloy Mark P

    2011-06-01

    Full Text Available Abstract Background Glucagon is an important hormone in the regulation of glucose homeostasis, particularly in the maintenance of euglycemia and prevention of hypoglycemia. In type 2 Diabetes Mellitus (T2DM, glucagon levels are elevated in both the fasted and postprandial states, which contributes to inappropriate hyperglycemia through excessive hepatic glucose production. Efforts to discover and evaluate glucagon receptor antagonists for the treatment of T2DM have been ongoing for approximately two decades, with the challenge being to identify an agent with appropriate pharmaceutical properties and efficacy relative to potential side effects. We sought to determine the hepatic & systemic consequence of full glucagon receptor antagonism through the study of the glucagon receptor knock-out mouse (Gcgr-/- compared to wild-type littermates. Results Liver transcriptomics was performed using Affymetric expression array profiling, and liver proteomics was performed by iTRAQ global protein analysis. To complement the transcriptomic and proteomic analyses, we also conducted metabolite profiling (~200 analytes using mass spectrometry in plasma. Overall, there was excellent concordance (R = 0.88 for changes associated with receptor knock-out between the transcript and protein analysis. Pathway analysis tools were used to map the metabolic processes in liver altered by glucagon receptor ablation, the most notable being significant down-regulation of gluconeogenesis, amino acid catabolism, and fatty acid oxidation processes, with significant up-regulation of glycolysis, fatty acid synthesis, and cholesterol biosynthetic processes. These changes at the level of the liver were manifested through an altered plasma metabolite profile in the receptor knock-out mice, e.g. decreased glucose and glucose-derived metabolites, and increased amino acids, cholesterol, and bile acid levels. Conclusions In sum, the results of this study suggest that the complete ablation

  10. Effect of Different Concentrations of Melatonin on Live Births Resulting from the Transfer of Two-Cell Embryos of NMRI Mice

    Directory of Open Access Journals (Sweden)

    Mahdi Saadati

    2014-12-01

    .47%, respectively. No infant was born at the concentrations of 1 µM and 100 nM of melatonin . The highest rate of live births was obtained at the concentration of 100 µM and showed a significant difference with the control group (p ≤ 0.01. There was no significant difference in live births at the concentration of 10 µm and control group.   Conclusion : The results of this study indicated that subcutaneous injection of melatonin improves the two-cell mouse embryo growth and post implantation development of mice.

  11. Prenatal lipopolysaccharide exposure affects sexual dimorphism in different germlines of mice with a depressive phenotype.

    Science.gov (United States)

    Reis-Silva, Thiago M; Cohn, Daniel W H; Sandini, Thaísa M; Udo, Mariana S B; Teodorov, Elizabeth; Bernardi, Maria Martha

    2016-03-15

    The objective of the present study was to investigate whether prenatal lipopolysaccharide (LPS) administration modifies the expression of depressive and non-depressive-like behavior in male and female mice across two generations. The sexual dimorphism of these mice was also examined in the open-field test. Male and female mice of the parental (F0) generation were selected for depressive- or non-depressive-like behavioral profiles using the tail suspension test (TST). Animals with similar profiles were matched for further mating. On gestation day (GD) 15, pregnant F0 mice received LPS (100μg/kg, i.p.) and were allowed to nurture their offspring freely. Adult male and female of the F1 generation were then selected according to behavioral profiles and observed in the open field. Male and female mice of the two behavioral profiles were then mated to obtain the F2 generation. Adults from the F2 generation were also behaviorally phenotyped, and open field behavior was assessed. Male mice that were selected for depressive- and non-depressive-like behaviors and treated or not with LPS in the parental generation exhibited similar proportions of behavioral profiles in both filial lines, but LPS exposure increased the number of depressive-like behavior. An effect of gender was observed in the F1 and F2 generations, in which male mice were more sensitive to the intergenerational effects of LPS in the TST. These data indicate that prenatal LPS exposure on GD15 in the F0 generation influenced the transmission of depressive- and non-depressive-like behavior across filial lines, with sexual dimorphism between phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Different behavioral effect dose–response profiles in mice exposed to two-carbon chlorinated hydrocarbons: Influence of structural and physical properties

    International Nuclear Information System (INIS)

    Umezu, Toyoshi; Shibata, Yasuyuki

    2014-01-01

    The present study aimed to clarify whether dose–response profiles of acute behavioral effects of 1,2-dichloroethane (DCE), 1,1,1-trichloroethane (TCE), trichloroethylene (TRIC), and tetrachloroethylene (PERC) differ. A test battery involving 6 behavioral endpoints was applied to evaluate the effects of DCE, TCE, TRIC, and PERC in male ICR strain mice under the same experimental conditions. The behavioral effect dose–response profiles of these compounds differed. Regression analysis was used to evaluate the relationship between the dose–response profiles and structural and physical properties of the compounds. Dose–response profile differences correlated significantly with differences in specific structural and physical properties. These results suggest that differences in specific structural and physical properties of DCE, TCE, TRIC, and PERC are responsible for differences in behavioral effects that lead to a variety of dose–response profiles. - Highlights: • We examine effects of 4 chlorinated hydrocarbons on 6 behavioral endpoints in mice. • The behavioral effect dose–response profiles for the 4 compounds are different. • We utilize regression analysis to clarify probable causes of the different profiles. • The compound's physicochemical properties probably produce the different profiles

  13. Different behavioral effect dose–response profiles in mice exposed to two-carbon chlorinated hydrocarbons: Influence of structural and physical properties

    Energy Technology Data Exchange (ETDEWEB)

    Umezu, Toyoshi, E-mail: umechan2@nies.go.jp; Shibata, Yasuyuki, E-mail: yshibata@nies.go.jp

    2014-09-01

    The present study aimed to clarify whether dose–response profiles of acute behavioral effects of 1,2-dichloroethane (DCE), 1,1,1-trichloroethane (TCE), trichloroethylene (TRIC), and tetrachloroethylene (PERC) differ. A test battery involving 6 behavioral endpoints was applied to evaluate the effects of DCE, TCE, TRIC, and PERC in male ICR strain mice under the same experimental conditions. The behavioral effect dose–response profiles of these compounds differed. Regression analysis was used to evaluate the relationship between the dose–response profiles and structural and physical properties of the compounds. Dose–response profile differences correlated significantly with differences in specific structural and physical properties. These results suggest that differences in specific structural and physical properties of DCE, TCE, TRIC, and PERC are responsible for differences in behavioral effects that lead to a variety of dose–response profiles. - Highlights: • We examine effects of 4 chlorinated hydrocarbons on 6 behavioral endpoints in mice. • The behavioral effect dose–response profiles for the 4 compounds are different. • We utilize regression analysis to clarify probable causes of the different profiles. • The compound's physicochemical properties probably produce the different profiles.

  14. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

    Science.gov (United States)

    Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi; Tanaka, Teruyuki

    2018-01-01

    Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

  15. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

    Directory of Open Access Journals (Sweden)

    Kosuke Okuda

    Full Text Available Mutations in the Cyclin-dependent kinase-like 5 (CDKL5 gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be

  16. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory

    Science.gov (United States)

    Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi

    2018-01-01

    Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

  17. Comparative Anti-Diabetic Evaluation of Different Parts of Himalrandia tetrasperma in Alloxan Induced Diabetic in Mice

    International Nuclear Information System (INIS)

    Ajaib, M.

    2016-01-01

    The present experiments were designed to investigate the acute effects of methanolic extracts of various parts of H. tetrasperma in diabetic mice. The basic phyto-chemical study showed the occurrence of alkaloids, saponins, flavonoids and tannins as main phyto-constituents in the methanolic extract. Diabetes was induced experimentally in mice by intra peritoneally injecting alloxan (150 mg/kg i.p.). In acute study, methanolic H. tetrasperma extracts of various parts of plant were evaluated for anti-diabetic potential in alloxan induced diabetic mice. Extracts of leaves, bark and seeds (250 mg/kg, i.p) and metformin (250 mg/kg i.p) were given intra peritoneal in alloxan treated diabetic mice and blood glucose levels were measured at 0, 360 and 24 h. There was significant lowering of blood glucose level at 1 h after treatment, in diabetic mice treated with methanolic extracts of bark (182.3 ± 3.6 mg/dL), leaves (178.5 ± 1.2 mg/dL) and seeds (156.3 ± 11.3 mg/dL) when compared with control diabetic group (280 ± 7.92 mg/dL). Highly significant results were also obtained at 24 h after treatment with methanolic extracts of bark (187.67 ±1.2 mg/dL), leaves (170.66 ± 2.3 mg/dL) and seeds (142 ± 8.7 mg/dL) when compared with control diabetic group (257.7 ± 6.7 mg/dL). It is concluded that methanolic extract of all parts possess significant anti-diabetic activity which is due to the presence of phytochemicals, i.e. alkaloids, flavonoids, phenols, saponins, tannins and it can be further evaluated for the mechanism involved. (author)

  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. Types and rate of cataract development in mice irradiated at different ages

    International Nuclear Information System (INIS)

    Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.; Chomiczewski, K.; Kulig, A.

    1977-01-01

    The effect of age on the development of radiation cataract has been investigated in an inbred A strain of mice and, as a result, the patterns of age dependence and senile mice cataract development were obtained. In general, the lenses of mice 1 to 3 days old were the most sensitive to radiation; the maximum resistance was noted in 5-day-old mice, and from this age up to 3 to 7 weeks of life there was a period of increasing sensitivity. In older animals the lens sensitivity tends to level off. The early stages of cataract occurred in all irradiated groups at a younger age than in the control group, but the late stages occurred in irradiated groups at the same age as the senile cataract occurred in the control group. Two types of cataract were observed. One was typical for young irradiated mice 1 to 5 days of age and the other was typical for all remaining irradiated groups and for a control group. Also, an attempt was made to correlate the obtained results with the cell kinetics in normal lens epithelium

  20. 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.

  1. Differences in correlation of mRNA gene expression in mice sensitive and resistant to radiation-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Johnston, C.J.; Piedboeuf, B.; Finkelstein, J.N.; Baggs, R.; Rubin, P.

    1995-01-01

    Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The purpose of this study was to determine if extracellular matrix protein and transforming growth factor β mRNA expression are altered late in the course of pulmonary fibrosis after irradiation, and then to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor β 1 and β 3 . Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceralde-hyde-3-phosphate dehydrogenase. Alterations in mRNA abundance were observed in the sensitive mice at all times, while levels in the resistant mice were unaffected until 26 weeks after irradiation. The relationship between extracellular matrix protein per se and increased mRNA abundance suggests that late matrix protein accumulation may be a function of gene expression. Differences in levels of transforming growth factor βmRNA may lead to strain-dependent variation in fibrotic response and may also contribute to the radiation-induced component of pulmonary fibrosis. 32 refs., 5 figs

  2. Differences in micronucleus induction in peripheral blood reticulocytes of mice exposed to N-ethyl-N-nitrosourea at light and dark dosing times.

    Science.gov (United States)

    Itoh, Keiichi; Masumori, Shoji; Nakajima, Madoka; Hayashi, Makoto; Sakakibara, Hiroyuki; Shimoi, Kayoko

    2012-01-01

    Mammals, including human beings, have a circadian clock system to regulate behavioral and physiological processes. In this study, we investigated the effect of dosing time on micronucleus induction in the bone marrow by evaluating the frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity to chemicals between light and dark periods (inactive phase for rodents and active phase for rodents). Male C3H/He mice were treated intraperitoneally with ENU (12.5 or 25 mg/kg body weight) at zeitgeber time (ZT) 3 in the light period or ZT15 in the dark period, and then the time courses of the frequencies of the MNRETs were determined. The frequencies of the MNRETs induced by ENU increased time-dependently and peaked at 48 hr after treatment for ZT3 and ZT15, and were obviously higher in the ZT15 treatment group than the ZT3 treatment group. The MNRETs were measured at 48 hr after treatment with ENU (25 mg/kg body weight) at various dosing times (ZT0, 3, 6, 12, 15 and 18). The frequencies of the MNRETs in mice treated at ZT0, 15 and 18 were significantly higher than those in mice treated at ZT3, 6 and 12. These results suggest that genotoxic sensitivity to chemicals in mouse bone marrow is different between light and dark periods maybe due to different biological responses (detoxification, cell cycle, DNA repair, etc.) related to circadian rhythms.

  3. Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

    Directory of Open Access Journals (Sweden)

    Jin Gang

    2009-10-01

    Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

  4. 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

  5. Embryonic/fetal mortality after exposure to tritiated water in pregnant Swiss albino mice during different gestation periods

    International Nuclear Information System (INIS)

    Sharma, Kalpana; Saini, M.R.

    1993-01-01

    Pregnant Swiss albino mice were given a priming injection(im) of tritiated water (HTO) at the dose rate of 2.3 and 5 μCi/ml body water (74, III or 185 K Bq/ml body water) at 0,6 and 14 day post conception (d.p.c) and were subsequently maintained on tritiated drinking water ad libitum during preimplantation (0-5 d.p.c), organogenetic (6-12 d.c.p.) or fetal (14-18 d.p.c) period, respectively. On day 18 of gestation the females were sacrificed by cervical dislocation to record the implant sites per dam and embryonic/fetal mortality. Significant reduction was observed in average implant sites per dam when the females were exposed to any of the three doses during the preimplantation period due to embryonic resorption before implantation. However, the same was found to be within the normal range when mothers were exposed during the organogenetic or fetal period. Prenatal mortality (embryonic resorption/fetal death) was higher after in utero exposure to different doses during preimplantation period as compared to organogenetic period, but mortality did not occur after exposure to any of the doses during the fetal period. Occurrence of mortality was found to be dose dependent. (author). 25 refs., 1 tab

  6. Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice.

    Science.gov (United States)

    Nasr, Magda; Selima, Eman; Hamed, Omar; Kazem, Amany

    2014-01-15

    No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of the anti-angiogenic agents: leflunomide; a disease modifying antirheumatic drug, perindopril; an angiotensin converting enzyme inhibitor (ACEI) and curcumin; the active principle of turmeric, on diethylnitrosamine (DEN)-induced HCC in mice. Eight weeks following DEN administration, there was a significant rise in immunohistochemical staining of CD31-positive endothelial cells and consequently hepatic microvessel density (MVD) as compared to normal liver. DEN treatment was associated with elevation in hepatic vascular endothelial growth factor (VEGF) level as compared to normal controls (Pcurcumin alone abrogated the DEN-induced increased MVD as well as the elevated expression of VEGF, while only curcumin inhibited HIF-1α hepatic expression. Combination of these agents showed further inhibitory action on neovascularization and synergistic attenuation of hepatic VEGF (1954.27±115pg/ml) when compared to each single agent. Histopathological examination revealed a more beneficial chemopreventive activity in the combination group compared to each monotherapy. In conclusion, the combination treatment of leflunomide, perindopril and curcumin targeting different angiogenic pathways, resulted in synergistic inhibition of angiogenesis and consequently more effective chemoprevention of HCC. © 2013 Published by Elsevier B.V.

  7. Significant difference in p53 and p21 protein immunoreactivity in HPV 16 positive and HPV negative breast carcinomas

    International Nuclear Information System (INIS)

    Hennig, E.M.; Norwegian Radium Hospital, Oslo; Kvinnsland, S.; Holm, R.; Nesland, J.M.

    1999-01-01

    Human papillomavirus (HPV) 16 has previously been found in 19/41 breast carcinomas (46%) in women with a history of HPV 16 positive CIN III lesions. There was no significant difference in distribution of histological subtypes, mean or median tumour diameter or number of regional lymph node metastases in the HPV positive and HPV negative breast carcinoma groups. P53, p21 and c-erbB-2 proteins were analyzed by immunohistochemistry in the HPV 16 positive and HPV negative breast carcinomas. There was a significant difference in p53 and p21 protein immunoreactivity between HPV 16 positive and HPV negative breast carcinomas (p=0.0091 and p=0.0040), with a significant less detectable p53 and p21 protein immunoreactivity in the HPV 16 positive cases. There was also a significant difference in the coexpression of p53/p21 between the HPV 16 positive and HPV 16 negative breast carcinomas (p=0.002). No significant difference in immunostaining for c-erbB-2 protein in the two groups was found (p=0.15), or for the coexpression of p53/c-erbB-2 (p=0.19). The significantly lower expression of p53 and p21 proteins in HPV 16 positive than in HPV 16 negative breast carcinomas supports the hypothesis of inactivation and degradation of wild-type p53 proteins by HPV 16 E6 and that p53 mutation is not necessary for transformation in the HPV 16 positive cases. (orig.)

  8. Differences in neonatal neurotoxicity of brominated flame retardants, PBDE 99 and TBBPA, in mice

    International Nuclear Information System (INIS)

    Viberg, Henrik; Eriksson, Per

    2011-01-01

    Highlights: → Neonatal exposure to PBDE 99, but not TBBPA, causes changes in the neonatal brain. → CaMKII increases in neonatal hippocampus after PBDE 99 exposure. → CaMKII, GAP-43 and synaptophysin increase in neonatal cortex after PBDE 99 exposure. → CaMKII increase in hippocampus has earlier been seen to proceed behavioral changes. → Neonatal exposure to PBDE 99, but not TBBPA, is known to cause behavioral deficits. -- Abstract: Flame retardants such as polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A are used as flame retardants and detected in the environmental, wildlife species and human tissues. Exposure to PBDEs during the neonatal development of the brain has been shown to affect behavior and learning and memory in adult mice, while neonatal exposure to TBBPA (another brominated flame retardant) did not affect behavioral variables in the adult. In this study, we hypothesized that the effects of these compounds could be reflected by changes in biochemical substrates and cholinergic receptors and have examined the levels of four proteins involved in maturation of the brain, neuronal growth and synaptogenesis and the densities of both muscarinic and nicotinic cholinergic receptors. We measured the levels of radioactivity in the brain after administration of 14 C-labelled TBBPA at different time points and saw that levels of TBBA peaked earlier and decreased faster than the earlier reported levels of PBDE 99. The protein analysis in the neonatal brain showed changes in the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), growth associated protein-43 (GAP-43) and synaptophysin following neonatal exposure to PBDE 99 (21 μmol/kg body weight), but not following exposure TBBPA. Furthermore, neonatal exposure to PBDE 99 and TBBPA caused a decrease in binding sites of the nicotinic ligand cytisine in frontal cortex. These results confirm earlier reported data that PBDE 99 can act as a developmental neurotoxicant, possibly

  9. Different radiosensitivities of mast-cell precursors in the bone marrow and skin of mice

    International Nuclear Information System (INIS)

    Kitamura, Y.; Yokoyama, M.; Sonoda, T.; Mori, K.J.

    1983-01-01

    Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D 0 values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F 1 +/+ mice after various doses of irradiation and injected into the skin of the congenic W/W/sup v/ mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determining the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bg/sup J//bg/sup J/, Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the backs of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosenitive than those localized in the skin. D 0 value was about 100 rad for the former and about 800 rad for the latter

  10. Different radiosensitivities of mast-cell precursors in the bone marrow and skin of mice

    International Nuclear Information System (INIS)

    Kitamura, Y.; Yokoyama, M.; Sonoda, T.; Mori, K.J.

    1983-01-01

    Although tissue mast cells are derived from the bone marrow, some descendants of bone marrow-derived precursors retain the ability to proliferate and differentiate into mast cells even after localization in the skin. The purpose of the present study was to determine the D0 values for mast-cell precursors in the bone marrow and those localized in the skin. Bone marrow cells were removed from (WB X C57BL/6)F1-+/+ mice after various doses of irradiation and injected into the skin of the congenic W/Wv mice which were genetically without mast cells. Radiosensitivity of mast-cell precursors in the bone marrow was evaluated by determining the proportion of the injection sites at which mast cells did not appear. For the assay of the radiosensitivity of mast-cell precursors localized in the skin, pieces of skin were removed from beige C57BL/6 (bgJ/bgJ. Chediak-Higashi syndrome) mice after various doses of irradiation and grafted onto the back of the normal C57BL/6 mice. Radiosensitivity of mast-cell precursors in the skin was evaluated by determining the decrease of beige-type mast cells which possessed giant granules. Mast-cell precursors in the bone marrow were much more radiosensitive than those localized in the skin. D0 value was about 100 rad for the former and about 800 rad for the latter

  11. Effects of Different Coumarin- 3-Carboxamide Agents on Scopolamine Induced Learning and Memory Deficit in Mice

    Directory of Open Access Journals (Sweden)

    Samaneh Ghanei Nasab

    2017-06-01

    Full Text Available Introduction: It has been shown that three new synthetic coumarins-3-carboxamides including 3-fluorobenzilchloride, 4-fluorobenzilchloride and 2-hidroxy-3 metoxybenzaldehyde, have acetylcholinesterase inhibitory activity. This study was performed to estimate ameliorating effect of these new coumarin-3-carboxamides on memory impairments induced by scopolamine (1 mg/kg, induced prolongation in mice. Methods: 30 male mice were divided into five groups, 6 mice in each group. Three experiment groups received coumarins-3- carboxamides (10 mg/kg body weight 30 min before scopalamin injection and two other groups considered as normal (saline-treated groups and finally one negative control (scopalamin only group. The experiment groups were treated with coumarins of 3-fluorobenzilchloride, 4-fluorobenzilchloride and 2-hidroxy-3 metoxybenzaldehyde. The passive avoidance test was performed in an automatic conventional shuttle box set-up. The stepped down latency and number of errors was recorded. Results: With reference to saline-treated group, scopolamine-treated mice demonstrated impairment of learning and memory as a reduction of latency and an increased numbers of errors in step-down testp < 0.01. Treated mice receiving these coumarins at the dose of 10 mg/kg showed an increase in the number of avoidances on the memory tests compared to the scopolamine group (p < 0.01. Conclusion: The study has demonstrated some therapeutic effects of coumarin-3-carboxamides on learning and memory deficit induced by scopolamine. Further investigation is needed to explore whether coumarin-3-carboxamides could be beneficial for memory impairment in Alzheimer’s disease in which cholinergic deficit is one of the hallmarks. 

  12. Effect of Sex Differences on Brain Mitochondrial Function and Its Suppression by Ovariectomy and in Aged Mice.

    Science.gov (United States)

    Gaignard, Pauline; Savouroux, Stéphane; Liere, Philippe; Pianos, Antoine; Thérond, Patrice; Schumacher, Michael; Slama, Abdelhamid; Guennoun, Rachida

    2015-08-01

    Sex steroids regulate brain function in both normal and pathological states. Mitochondria are an essential target of steroids, as demonstrated by the experimental administration of 17β-estradiol or progesterone (PROG) to ovariectomized female rodents, but the influence of endogenous sex steroids remains understudied. To address this issue, mitochondrial oxidative stress, the oxidative phosphorylation system, and brain steroid levels were analyzed under 3 different experimental sets of endocrine conditions. The first set was designed to study steroid-mediated sex differences in young male and female mice, intact and after gonadectomy. The second set concerned young female mice at 3 time points of the estrous cycle in order to analyze the influence of transient variations in steroid levels. The third set involved the evaluation of the effects of a permanent decrease in gonadal steroids in aged male and female mice. Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.

  13. Illness perceptions in the context of differing work participation outcomes: exploring the influence of significant others in persistent back pain

    Directory of Open Access Journals (Sweden)

    Brooks Joanna

    2013-01-01

    Full Text Available Abstract Background Previous research has demonstrated that the significant others of individuals with persistent back pain may have important influences on work participation outcomes. The aim of this study was to extend previous research by including individuals who have remained in work despite persistent back pain in addition to those who had become incapacitated for work, along with their significant others. The purpose of this research was to explore whether the illness beliefs of significant others differed depending on their relative’s working status, and to make some preliminary identification of how significant others may facilitate or hinder work participation for those with persistent back pain. Methods Interviews structured around the Illness Perception Questionnaire (chronic pain version were conducted with back pain patients recruited from a hospital pain management clinic along with their significant others. Some patients had remained in work despite their back pain; others had ceased employment. Data were analysed using template analysis. Results There were clear differences between beliefs about, and reported responses to, back pain symptoms amongst the significant others of individuals who had remained in employment compared with the significant others of those who had ceased work. Three overarching themes emerged: perceived consequences of back pain, specific nature of employment and the impact of back pain on patient identity. Conclusions Significant others of employed individuals with back pain focused on the extent to which activity could still be undertaken despite back pain symptoms. Individuals out of work due to persistent back pain apparently self-limited their activity and were supported in their beliefs and behaviours by their significant others. To justify incapacity due to back pain, this group had seemingly become entrenched in a position whereby it was crucial that the individual with back pain was perceived

  14. Different kinetic in incorporation and depletion of n-3 fatty acids in erythrocytes and leukocytes of mice

    DEFF Research Database (Denmark)

    Mu, Huiling; Thogersen, Regitze Louise; Maaetoft-Udsen, Kristina

    2006-01-01

    during a 6-wk feeding period. Over the first 3-wk period (the incorporation period) the mice were fed a special diet with a high n-3/n-6 PUFA ratio. In the following 3-wk period (the depletion period) the mice were fed a standard chow diet. A linear increase of the concentration of EPA and DHA...... in erythrocyte membranes was observed during the incorporation period, whereas a stagnation was observed after the second week for leukocytes. The level of EPA did not fall to the background level after the depletion period, and the level of DHA was kept almost constant during the depletion period...... in the erythrocyte membranes. In leukocytes the concentration of both EPA and DHA decreased during the depletion period, but did not reach the background level after the 3-wk depletion. In conclusion, the kinetics of EPA and DHA in the different cells are different. The rate of incorporation is faster than...

  15. Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control

    Czech Academy of Sciences Publication Activity Database

    Medříková, Daša; Jílková, Zuzana; Bardová, Kristina; Janovská, Petra; Rossmeisl, Martin; Kopecký, Jan

    2012-01-01

    Roč. 36, č. 2 (2012), s. 262-272 ISSN 0307-0565 R&D Projects: GA MŠk(CZ) 7E10059; GA MŠk(CZ) OC08008; GA ČR(CZ) GA303/08/0664 Institutional research plan: CEZ:AV0Z50110509 Keywords : sex differences * inflammation * adipose tissue expandability * insulin sensitivity * mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.221, year: 2012

  16. Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

    Science.gov (United States)

    Fanfa, Vinicius R.; Otto, Mateus A.; Gressler, Lucas T.; Tavares, Kaio C.S.; Lazzarotto, Cícera R.; Tonin, Alexandre A.; Miletti, Luiz C.; Duarte, Marta M.M.F.; Monteiro, Silvia G.

    2011-01-01

    The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2 (D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of 40.9±0.3 (C), 20±9.0 (D) and 35.6±9.3 (E) days compared to the control group (B) which was 4.3±0.5 days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas. PMID:22355213

  17. Regional Differences in Striatal Neuronal Ensemble Excitability Following Cocaine and Extinction Memory Retrieval in Fos-GFP Mice.

    Science.gov (United States)

    Ziminski, Joseph J; Sieburg, Meike C; Margetts-Smith, Gabriella; Crombag, Hans S; Koya, Eisuke

    2018-03-01

    Learned associations between drugs of abuse and the drug administration environment have an important role in addiction. In rodents, exposure to a drug-associated environment elicits conditioned psychomotor activation, which may be weakened following extinction (EXT) learning. Although widespread drug-induced changes in neuronal excitability have been observed, little is known about specific changes within neuronal ensembles activated during the recall of drug-environment associations. Using a cocaine-conditioned locomotion (CL) procedure, the present study assessed the excitability of neuronal ensembles in the nucleus accumbens core and shell (NAc core and NAc shell ), and dorsal striatum (DS) following cocaine conditioning and EXT in Fos-GFP mice that express green fluorescent protein (GFP) in activated neurons (GFP+). During conditioning, mice received repeated cocaine injections (20 mg/kg) paired with a locomotor activity chamber (Paired) or home cage (Unpaired). Seven to 13 days later, both groups were re-exposed to the activity chamber under drug-free conditions and Paired, but not Unpaired, mice exhibited CL. In a separate group of mice, CL was extinguished by repeatedly exposing mice to the activity chamber under drug-free conditions. Following the expression and EXT of CL, GFP+ neurons in the NAc core (but not NAc shell and DS) displayed greater firing capacity compared to surrounding GFP- neurons. This difference in excitability was due to a generalized decrease in GFP- excitability following CL and a selective increase in GFP+ excitability following its EXT. These results suggest a role for both widespread and ensemble-specific changes in neuronal excitability following recall of drug-environment associations.

  18. Human papillomavirus detection with genotyping by the cobas and Aptima assays: Significant differences in HPV 16 detection?

    Science.gov (United States)

    Chorny, Joseph A; Frye, Teresa C; Fisher, Beth L; Remmers, Carol L

    2018-03-23

    The primary high-risk human papillomavirus (hrHPV) assays in the United States are the cobas (Roche) and the Aptima (Hologic). The cobas assay detects hrHPV by DNA analysis while the Aptima detects messenger RNA (mRNA) oncogenic transcripts. As the Aptima assay identifies oncogenic expression, it should have a lower rate of hrHPV and genotype detection. The Kaiser Permanente Regional Reference Laboratory in Denver, Colorado changed its hrHPV assay from the cobas to the Aptima assay. The rates of hrHPV detection and genotyping were compared over successive six-month periods. The overall hrHPV detection rates by the two platforms were similar (9.5% versus 9.1%) and not statistically different. For genotyping, the HPV 16 rate by the cobas was 1.6% and by the Aptima it was 1.1%. These differences were statistically different with the Aptima detecting nearly one-third less HPV 16 infections. With the HPV 18 and HPV 18/45, there was a slightly higher detection rate of HPV 18/45 by the Aptima platform (0.5% versus 0.9%) and this was statistically significant. While HPV 16 represents a low percentage of hrHPV infections, it was detected significantly less by the Aptima assay compared to the cobas assay. This has been previously reported, although not highlighted. Given the test methodologies, one would expect the Aptima to detect less HPV 16. This difference appears to be mainly due to a significantly increased number of non-oncogenic HPV 16 infections detected by the cobas test as there were no differences in HPV 16 detection rates in the high-grade squamous intraepithelial lesions indicating that the two tests have similar sensitivities for oncogenic HPV 16. © 2018 Wiley Periodicals, Inc.

  19. Significant factors for work attractiveness and how these differ from the current work situation among operating department nurses.

    Science.gov (United States)

    Björn, Catrine; Lindberg, Magnus; Rissén, Dag

    2016-01-01

    The aim was to examine significant factors for work attractiveness and how these differ from the current work situation among operating department nurses. A second objective was to examine the associations between age, gender, length of employment, work engagement, work ability, self-rated health indicators and attractiveness of the current work situation. The attractiveness of work is rarely taken into account in research on nurse retention. To expand this knowledge, it is relevant to examine factors that make work attractive and their associations with related concepts. Correlational, cross-sectional survey using a convenience sample. Questionnaires were answered by 147 nurses in four operating departments in Sweden. Correlation and regression analyses were conducted. The nurses rated the significance of all factors of work attractiveness higher than they rated those factors in their current work situation; salary, organisation and physical work environment had the largest differences. The most significant attractive factors were relationships, leadership and status. A statistically significant positive correlation between work engagement and attractive work was found. In the multiple regression model, the independent variables work engagement and older age significantly predicted work attractiveness. Several factors should be considered in the effort to increase work attractiveness in operating departments and thereby to encourage nurse retention. Positive aspects of work seem to unite work engagement and attractive work, while work ability and self-rated health indicators are other important dimensions in nurse retention. The great discrepancies between the significance of attractive factors and the current work situation in salary, organisation and physical work environment suggest ways in which work attractiveness may be increased. To discover exactly what needs to be improved may require a deeper look into the construct of the examined factors. © 2015 John

  20. Different effects of valproic acid on photoreceptor loss in Rd1 and Rd10 retinal degeneration mice.

    Science.gov (United States)

    Mitton, Kenneth P; Guzman, Alvaro E; Deshpande, Mrinalini; Byrd, David; DeLooff, Camryn; Mkoyan, Kristina; Zlojutro, Paul; Wallace, Adrianne; Metcalf, Brandon; Laux, Kirsten; Sotzen, Jason; Tran, Trung

    2014-01-01

    injections with VPA (P9-P21) dramatically slowed the loss of rod photoreceptors in Pde6b(rd1/rd1) mice. At age P21, VPA-treated mice had several extra rows of rod photoreceptor nuclei compared to PBS-injected littermates. Dosing started later (P14) or dosing every second day also rescued photoreceptors. In contrast, systemic VPA treatment of Pde6b(rd10/rd10) mice (P17-P28) reduced visual function that correlated with a slight increase in photoreceptor loss. Treating Pde6b(rd10/rd10) mice earlier (P9-P21) also failed to rescue photoreceptors. Treating wild-type mice earlier (P9-P21) reduced the number of photoreceptors in VPA-treated mice by 20% compared to PBS-treated animals. A single systemic dose of VPA can change retinal neurotrophic factor and rod-specific gene expression in the immature retina. Daily VPA treatment from P17 to P28 can also alter gene expression in the mature neural retina. While daily treatment with VPA could significantly reduce photoreceptor loss in the rd1 model, VPA treatment slightly accelerated photoreceptor loss in the rd10 model. The apparent rescue of photoreceptors in the rd1 model was not the result of producing more photoreceptors before degeneration. In fact, daily systemic VPA was toxic to wild-type photoreceptors when started at P9. However, the effective treatment period for Pde6b(rd1/rd1) mice (P9-P21) has significant overlap with the photoreceptor maturation period, which complicates the use of the rd1 model for testing of VPA's efficacy. In contrast, VPA treatment started after P17 did not cause photoreceptor loss in wild-type mice. Thus, the acceleration of photoreceptor loss in the rd10 model may be more relevant where both photoreceptor loss and VPA treatment (P17-P28) started when the central retina was mature.

  1. Sex differences in shotgun proteome analyses for chronic oral intake of cadmium in mice.

    Directory of Open Access Journals (Sweden)

    Yoshiharu Yamanobe

    Full Text Available Environmental diseases related to cadmium exposure primarily develop owing to industrial wastewater pollution and/or contaminated food. In regions with high cadmium exposure in Japan, cadmium accumulation occurs primarily in the kidneys of individuals who are exposed to the metal. In contrast, in the itai-itai disease outbreak that occurred in the Jinzu River basin in Toyama Prefecture in Japan, cadmium primarily accumulated in the liver. On the other hand, high concentration of cadmium caused renal tubular disorder and osteomalacia (multiple bone fracture, probably resulting from the renal tubular dysfunction and additional pathology. In this study, we aimed to establish a mouse model of chronic cadmium intake. We administered cadmium-containing drinking water (32 mg/l to female and male mice ad libitum for 11 weeks. Metal analysis using inductively coupled plasma mass spectrometry revealed that cadmium accumulated in the kidneys (927 x 10 + 185 ng/g in females and 661 x 10 + 101 ng/g in males, liver (397 x 10 + 199 ng/g in females and 238 x 10 + 652 ng/g in males, and thyroid gland (293 + 93.7 ng/g in females and 129 + 72.7 ng/g in males of mice. Female mice showed higher cadmium accumulation in the kidney, liver, and thyroid gland than males did (p = 0.00345, p = 0.00213, and p = 0.0331, respectively. Shotgun proteome analyses after chronic oral administration of cadmium revealed that protein levels of glutathione S-transferase Mu2, Mu4, and Mu7 decreased in the liver, and those of A1 and A2 decreased in the kidneys in both female and male mice.

  2. Analysis of specific 3H-diazepam binding in the brain of emotionally difference mice

    International Nuclear Information System (INIS)

    Blednov, Yu.A.; Gordei, M.L.; Seredenin, S.B.

    1987-01-01

    A study of the behavior of inbred animals under conditions of emotional stress, of the biochemical parameters of the stress reaction, and of the effects of benzodiazepine tranquilizers, conducted in the authors' laboratory, showed that the character of the response to stress and the manifestation of the action of benzodiazepine depend on hereditary factors. The aim of this investigation was to study reception of tritium-labelled diazepam by brain cell membranes of C57BL/6 and BALB/c mice

  3. Effects of four kinds of electromagnetic fields (EMF) with different frequency spectrum bands on ovariectomized osteoporosis in mice.

    Science.gov (United States)

    Lei, Tao; Li, Feijiang; Liang, Zhuowen; Tang, Chi; Xie, Kangning; Wang, Pan; Dong, Xu; Shan, Shuai; Liu, Juan; Xu, Qiaoling; Luo, Erping; Shen, Guanghao

    2017-04-03

    Electromagnetic fields (EMF) was considered as a non-invasive modality for treatment of osteoporosis while the effects were diverse with EMF parameters in time domain. In present study, we extended analysis of EMF characteristics from time domain to frequency domain, aiming to investigate effects of four kinds of EMF (LP (1-100 Hz), BP (100-3,000 Hz), HP (3,000-50,000 Hz) and AP (1-50,000 Hz)) on ovariectomized (OVX) osteoporosis (OP) in mice. Forty-eight 3-month-old female BALB/c mice were equally assigned to Sham, OVX, OVX + LP, OVX + BP, OVX + HP and OVX + AP groups (n = 8). After 8-week exposure (3 h/day), LP and BP significantly increased serum bone formation markers and osteogenesis-related gene expressions compared with OVX. Bedsides, LP and BP also slightly increased bone resorption activity compared with OVX, evidenced by increased RANKL/OPG ratio. HP sharply decreased serum bone formation and resporption markers and osteogenesis and osteoclastogenesis related gene expressions compared with OVX. AP had accumulative effects of LP, BP and HP, which significantly increased bone formation and decreased bone resporption activity compared with OVX. As a result, LP, BP and HP exposure did not later deterioration of bone mass, microarchitecture and mechanical strength in OVX mice with OP. However, AP stimulation attenuated OVX-induced bone loss.

  4. Effects of Agave tequilana fructans with different degree of polymerization profiles on the body weight, blood lipids and count of fecal Lactobacilli/Bifidobacteria in obese mice.

    Science.gov (United States)

    Márquez-Aguirre, Ana Laura; Camacho-Ruiz, Rosa Maria; Arriaga-Alba, Myriam; Padilla-Camberos, Eduardo; Kirchmayr, Manuel Reinhart; Blasco, José Luis; González-Avila, Marisela

    2013-08-01

    Fructans are dietary fibers with beneficial effects on the gastrointestinal physiology and offer a promising approach for the treatment of some metabolic disorders associated with obesity. In vitro and in vivo studies were developed to test the safety of fructans obtained from Agave tequilana Weber var. azul. Additionally, an in vivo experiment using a diet-induced obesity model was performed to compare the effect of agave fructans with different degree of polymerization (DP) profiles: agave fructans with DP > 10 (LcF), agave FOS with DP agave fructans with and without demineralization (dTF, TF) versus commercial chicory fructans (OraftiSynergy1™) on the body weight change, fat, total cholesterol, triglycerides and count of fecal Lactobacillus spp. and Bifidobacterium spp. Results showed that A. tequilana fructans were not mutagenic and were safe even at a dose of 5 g per kg b.w. Obese mice that received ScF showed a significant decrease in body weight gain, fat tissue and total cholesterol without increasing the count of fecal Bifidobacteria. Whereas, obese mice that received LcF and TF showed decreased triglycerides and an increased count of fecal Bifidobacteria. Interestingly, although obese mice that received dTF did not show changes in body weight gain, fat tissue, total cholesterol or triglycerides, they showed an increase in the count of Bifidobacteria. These results demonstrate that both the degree of polymerization and the demineralization process can influence the biological activity of agave fructans.

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

    Science.gov (United States)

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

    2018-03-01

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

  6. SU-C-204-02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

    International Nuclear Information System (INIS)

    Eley, J; Zhang, C; Wolfe, T; Vichaya, E; Quini, C; Chadha, A; Sahoo, N; Krishnan, S; Davis, J; Dilmanian, F

    2016-01-01

    Purpose: Minibeam therapy using protons or light-ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad-beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams. Methods: Twenty-four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad-beam 10 Gy (BB10), minibeam 10Gy (MB10), broad-beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7-mm diameter were delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300-micron beam width and 1-mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation. Results: Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single-fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8-month study duration. The Morris water maze alternate-starting-position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad-beam arms compared with their minibeam dose counterparts. Conclusion: Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals. AAPM Research Seed Funding Grant

  7. SU-C-204-02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

    Energy Technology Data Exchange (ETDEWEB)

    Eley, J; Zhang, C [University of Maryland School of Medicine, Baltimore, MD (United States); Wolfe, T; Vichaya, E; Quini, C; Chadha, A; Sahoo, N; Krishnan, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Davis, J; Dilmanian, F [Stony Brook University Medical Center, Stony Brook, NY (United States)

    2016-06-15

    Purpose: Minibeam therapy using protons or light-ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad-beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams. Methods: Twenty-four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad-beam 10 Gy (BB10), minibeam 10Gy (MB10), broad-beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7-mm diameter were delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300-micron beam width and 1-mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation. Results: Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single-fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8-month study duration. The Morris water maze alternate-starting-position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad-beam arms compared with their minibeam dose counterparts. Conclusion: Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals. AAPM Research Seed Funding Grant.

  8. [The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats].

    Science.gov (United States)

    Feng, Jing; Liu, Haibing

    2015-07-01

    To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats. We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry. We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P 0.05). These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss.

  9. Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study

    Directory of Open Access Journals (Sweden)

    Riley Stuart A

    2008-11-01

    Full Text Available Abstract Background Markers of crypt cell proliferation are frequently employed in studies of the impact of genetic and exogenous factors on human colonic physiology. Human studies often rely on the assessment of tissue acquired at endoscopy. Modulation of cell proliferation by bowel preparation with oral laxatives may confound the findings of such studies, but there is little data on the impact of commonly used bowel preparations on markers of cell proliferation. Methods Crypt length, crypt cellularity and crypt cell proliferation were assessed in biopsies acquired after preparation with either Klean-Prep or Picolax. Crypt cell proliferation was assessed by whole-mount mitotic figure count, and by two different immunohistochemical (IHC labelling methods (Ki-67 and pHH3. Subsequent biopsies were obtained from the same patients without bowel preparation and similarly assessed. Parameters were compared between groups using analysis of variance and paired t-tests. Results There were significant differences in labelling indices (LI between biopsies taken after Klean-prep and those taken after Picolax preparation, for both Ki67 (p = 0.019 and pHH3 (p = 0.017. A similar trend was seen for whole-mount mitotic figure counts. Suppression or elevation of proliferation parameters by bowel preparation may mask any effect due to an intervention or disease. Conclusion Commonly used bowel preparations may have significant and different effects on crypt cell proliferation. This should be taken into account when designing studies and when considering the findings of existing studies.

  10. In vitro cell culture pO2 is significantly different from incubator pO2.

    Science.gov (United States)

    Bambrick, L L; Kostov, Y; Rao, G

    2011-07-01

    Continuous noninvasive monitoring of peri-cellular liquid phase pO2 in adherent cultures is described. For neurons and astrocytes, this approach demonstrates that there is a significant difference between predicted and observed liquid phase pO2. Particularly at low gas phase pO2s, cell metabolism shifts liquid phase pO2 significantly lower than would be predicted from the O2 gas/air equilibrium coefficient, indicating that the cellular oxygen uptake rate exceeds the oxygen diffusion rate. The results demonstrate the need for direct pO2 measurements at the peri-cellular level, and question the widely adopted current practice of relying on setting the incubator gas phase level as means of controlling pericellular oxygen tension, particularly in static culture systems that are oxygen mass transfer limited. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

  11. Expression and significance of MMP3 in synovium of knee joint at different stage in osteoarthritis patients.

    Science.gov (United States)

    Chen, Jun-Jie; Huang, Jie-Feng; Du, Wen-Xi; Tong, Pei-Jian

    2014-04-01

    To investigate the expression and significance of MMP-3 in synovium of knee joint at different stage in osteoarthritis (OA) patients. Knee synovial tissue were collected in 90 OA patients (the OA group). Patients in the OA group was divided into 3 subgroups: grade I subgroup (n=30), grade II subgroup (n=30), grade III; subgroup (n=30). Thirty patients served as control group. Immunohistochemical assay was used to detect the expression of MMP-3 protein in the knee synovial tissue. MMP-3 protein was detected in all knee synovial tissue. The expression of MMP-3 protein in the OA group was significantly higher that in the normal synovium (Posteoarthritis. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  12. Superfund explanation of significant difference for the record of decision (EPA Region 8): Lowry Landfill, Aurora, CO, October 24, 1997

    International Nuclear Information System (INIS)

    1999-03-01

    Please be advised that there is an error within Attachment E (Technical Evaluation of Proposed Ground-Water Treatment and Disposal Alternatives) of the ''Responsiveness Summary for the Second Explanation of Significant Differences, Lowry Landfill Superfund Site'' document. The evaluation table, which summarizes the rankings of the two cleanup alternatives, failed to include numerical values for State Acceptance and Community Acceptance. Enclosed is a copy of the table as it should have appeared in Attachment E. Copies of this errata sheet are being mailed to all recipients of the Responsiveness Summary

  13. Comparative study of two different Bombesin derivates labeled with 111In and biodistribution in normal mice

    International Nuclear Information System (INIS)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly 5 -BBN (6-14) ) and (DTPA-Phe-Gly 2 -BBN (6-14 )) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of 111 InCl 3 at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of 111 InCl 3 activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly 5 -BBN (6-14 ). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of 111 In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled peptides was 1.85 MBq/ μg. The maximum specific

  14. Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.

    Science.gov (United States)

    Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y; Warshaw, Andrew L; Thayer, Sarah P; Iafrate, A John

    2009-03-01

    To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.

  15. Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets.

    Science.gov (United States)

    Götz, Alexander A; Rozman, Jan; Rödel, Heiko G; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Klingenspor, Martin; Stoeger, Tobias

    2011-09-27

    Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants. Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors

  16. Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets

    Directory of Open Access Journals (Sweden)

    Hrabě de Angelis Martin

    2011-09-01

    Full Text Available Abstract Background Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested. In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP, as a surrogate for ambient/urban particulate air pollutants. Methods Mice were fed a high caloric carbohydrate-rich (CA or a fat-rich (HF diet for six weeks and were compared to mice kept on a purified low fat (LF diet, respectively. Bronchoalveolar lavage (BAL and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. Results and discussion The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. Conclusion The increase in BAL pro-inflammatory factors in high caloric

  17. Species difference in reactivity to lignin-like enzymatically polymerized polyphenols on interferon-γ synthesis and involvement of interleukin-2 production in mice.

    Science.gov (United States)

    Yamanaka, Daisuke; Ishibashi, Ken-Ichi; Adachi, Yoshiyuki; Ohno, Naohito

    2016-09-01

    Recent studies have revealed that lignin-like polymerized polyphenols can activate innate immune systems. In this study, we aimed to evaluate whether these polymerized polyphenols could activate leukocytes from different murine strains. Splenocytes from 12 mouse strains were investigated. Our results revealed species differences in reactivity to phenolic polymers on interferon-γ (IFN-γ) release. Mice that possessed the H2(a) or H2(k) haplotype antigens were the highly responsive strains. To clarify these different points in soluble factors, multiplex cytokine profiling analysis was carried out and we identified interleukin (IL)-2 as a key molecule for IFN-γ induction by polymerized polyphenols. Furthermore, inhibition of IL-2 and IL-2Rα by neutralizing antibodies significantly decreased cytokine production in the highly responsive mice strains. Our results indicate that species difference in reactivity to phenolic polymers is mediated by adequate release of IL-2 and its receptor, IL-2Rα. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Tissue Fatty Acid Profile is Differently Modulated from Olive Oil and Omega-3 Polyunsaturated Fatty Acids in ApcMin/+ Mice.

    Science.gov (United States)

    Tutino, Valeria; Caruso, Maria G; De Leonardis, Giampiero; De Nunzio, Valentina; Notarnicola, Maria

    2017-11-16

    Fatty acid profile can be considered an appropriate biomarker for investigating the relations between the patterns of fatty acid metabolism and specific diseases, as cancer, cardiovascular and degenerative diseases. Aim of this study was to test the effects of diets enriched with olive oil and omega-3 Polyunsaturated Fatty Acids (PUFAs) on fatty acid profile in intestinal tissue of ApcMin/+ mice. Three groups of animals were considered: control group, receiving a standard diet; olive oilgroup, receiving a standard diet enriched with olive oil; omega-3 group, receiving a standard diet enriched with salmon fish. Tissue fatty acid profile was evaluated by gas chromatography method. Olive oil and omega-3 PUFAs in the diet differently affect the tissue fatty acid profile. Compared to control group, the levels of Saturated Fatty Acids (SFAs) were lower in olive oil group, while an increase of SFAs was found in omega-3 group. Monounsaturated Fatty Acids (MUFAs) levels were enhanced after olive oil treatment, and in particular, a significant increase of oleic acid levels was detected; MUFAs levels were instead reduced in omega-3 group in line with the decrease of oleic acid levels. The total PUFAs levels were lower in olive oil respect to control group. Moreover, a significant induction of Saturation Index (SI) levels was observed after omega-3 PUFAs treatment, while its levels were reduced in mice fed with olive oil. Our data demonstrated a different effect of olive oil and omega-3 PUFAs on tissue lipid profile in APCMin/+ mice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity.

    Science.gov (United States)

    Sivayoganathan, Dhakshana; Maruthini, Deivanayagam; Glanville, Julie M; Balen, Adam H

    2011-12-01

    This study aimed to compare the spectrum of polycystic ovary syndrome (PCOS) symptoms in patients from four different specialist clinics. A prospective cross-sectional observational study. The study was conducted at the infertility, gynaecology, endocrine and dermatology clinics at Leeds General Infirmary, U.K. Seventy women presenting with features of PCOS: 20 from infertility, 17 from gynaecology, 17 from dermatology and 16 from endocrine clinics. Participants were assessed for symptoms and signs of PCOS and underwent a full endocrine and metabolic profile and a pelvic ultrasound scan. All subjects had experienced menstrual problems, 81% were overweight, 86% had polycystic ovaries on ultrasound, 56% had hirsutism, 53% had acne, 23% had acanthosis nigricans, 16% had alopecia and 38% had previously undiagnosed impaired glucose tolerance (IGT) or diabetes. A significant difference between the four clinic groups existed with regard to menstrual patterns (p = 0.0234), frequency distribution of presenting symptoms and the percentages of patients with PCOS who had already been diagnosed as having PCOS (p = 0.0088). This study emphasizes the importance of understanding the full spectrum of PCOS as presented to different specialty clinics. Not only is the syndrome under diagnosed but also are the significant associated morbidities such as IGT and type 2 diabetes. Different specialists need to appreciate the spectrum of health problems for women with PCOS that may extend beyond the specific symptoms that precipitated the initial referral.

  20. Dietary Intake of Structured Lipids with Different Contents of Medium-Chain Fatty Acids on Obesity Prevention in C57BL/6J Mice.

    Science.gov (United States)

    Zhou, Shengmin; Wang, Yueqiang; Jiang, Yuanrong; Zhang, Zhongfei; Sun, Xiangjun; Yu, Liangli Lucy

    2017-08-01

    Three medium- and long-chain triacylglycerols (MLCT) with different contents of medium-chain fatty acids (MCFA) (10% to 30%, w/w) were prepared and evaluated for their anti-obesity potential in C57BL/6J mice. The group fed with a high fat diet of MLCT containing 30% (w/w) MCFA showed significantly decreased body weight and fat mass (P obesity-inducing high fat rapeseed oil diet. In addition, serum parameters including triacylglycerols, total cholesterol, glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B in the treatment group fed with 30% (w/w) MCFA were close to those of mice fed with a low fat rapeseed oil diet, but significantly different (P obesity control group. Moreover, the intake of MLCT with high content of MCFA reduced the size of adipocytes. In addition, the visceral fat and liver weights, as well as the liver triacylglycerol for 3 treatment groups were lower than those of the obesity control group. These results demonstrate the great potential of MLCT with high content of MCFA in weight loss. © 2017 Institute of Food Technologists®.

  1. Humoral response to blastospores and mycelium in mice injected with different doses of Candida albicans.

    Science.gov (United States)

    Mesón, O E; Valdez, J C; de Alderete, N G; Sirena, A; Perdigón, G

    1992-01-01

    An indirect immunofluorescence assay was carry out to determine the IgM and IgG antibody responses to yeast and mycelial forms of Candida albicans in mice injected with a 5 x 5(5) and 5 x 10(7) live cells suspensions. Prior adsorption of the serum samples with heat-killed blastospores enabled us to follow the specific antimycelial response which were detected considerably later than expected. Slow level of antibodies were obtained within an infection of 5 x 10(5) cell for both antibody classes and for yeast and mycelial forms. When a 5 x 10(7) cell dose was used for inoculation, maximum titers of antibodies to blastospores and mycelium in non-adsorbed sera appeared almost simultaneously (days 15 and 13, respectively). When serum samples from mice infected with the same dose were previously adsorbed with blastospores, the antimycelium antibodies for both types of Igs, were detected delayed during the infection course. In this case the higher titer for IgG appeared on day 33 and on day 23 for IgM. We suggest that the high titer obtained with the blastospore forms for the 5 x 10(7) cell dose may be due to a major immunogenicity of this forms, for to induce an immune response in the host, or that the delay in the antimycelium antibodies detection could be due to that a blastospore form is the predominant in the infection early stages. Implications of this fact for pathogenesis are discussed.

  2. Toxicological studies on palytoxin and ostreocin-D administered to mice by three different routes.

    Science.gov (United States)

    Ito, Emiko; Yasumoto, Takeshi

    2009-09-01

    Palytoxin (PLT) first isolated from zoanthids is extremely lethal to animals by intraperitoneal or intravenous administration but shows little toxicity by gavage dosing in contradiction to the occurrence of fatal poisoning due to PLT-containing seafood. In order to fully elucidate its potential risks to human we evaluated the toxicological effects via three ways of dosing: gavage, intra-tracheal administration (IT) and sublingual administration. A new analog, 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin isolated from the dinoflagellate Ostreopsis siamensis and named ostreocin-D (OSD), was also used for comparison, additionally conducted by i.p. By gavage dosing, both toxins did not produce death in mice at the maximum dosage of 200 microg/kg of PLT and 300 microg/kg of OSD. Addition of dietary lipid components to PLT solutions for gavage or use of ulcerated mice did not alter the results, indicating no enhancement of PLT absorption. The two toxins were most toxic by the IT route, causing bleeding and alveolar destruction in the lung and resultant death at 2 microg/kg of PLT, and 11 microg/kg of OSD. Both toxins also induced organ injuries after 24h when dosed by sublingual administration at about 200 microg/kg. The injuries became fatal when PLT was dosed 2 or 3 times. The results pointed to the necessity of taking multiple approaches to assess the potential health risks due to PLT and its analogs in food and environments.

  3. Liver Proteome of Mice with Distinct Genetic Susceptibilities to Fluorosis Treated with Different Concentrations of F in the Drinking Water.

    Science.gov (United States)

    Khan, Zohaib Nisar; Sabino, Isabela Tomazini; de Souza Melo, Carina Guimarães; Martini, Tatiana; da Silva Pereira, Heloísa Aparecida Barbosa; Buzalaf, Marília Afonso Rabelo

    2018-04-29

    Appropriate doses of fluoride (F) have therapeutic action against dental caries, but higher levels can cause disturbances in soft and mineralized tissues. Interestingly, the susceptibility to the toxic effects of F is genetically determined. This study evaluated the effects of F on the liver proteome of mice susceptible (A/J) or resistant (129P3/J) to the effects of F. Weanling male A/J (n = 12) and 129P3/J (n = 12) mice were housed in pairs and assigned to two groups given low-F food and drinking water containing 15 or 50 ppm F for 6 weeks. Liver proteome profiles were examined using nano-LC-ESI-MS/MS. Difference in expression among the groups was determined using the PLGS software. Treatment with the lower F concentration provoked more pronounced alterations in fold change in liver proteins in comparison to the treatment with the higher F concentration. Interestingly, most of the proteins with fold change upon treatment with 15 ppm F were increased in the A/J mice compared with their 129P3/J counterparts, suggesting an attempt of the former to fight the deleterious effects of F. However, upon treatment with 50 ppm F, most proteins with fold change were decreased in the A/J mice compared with their 129P3/J counterparts, especially proteins related to oxidative stress and protein folding, which might be related to the higher susceptibility of the A/J animals to the deleterious effects of F. Our findings add light into the mechanisms underlying genetic susceptibility to fluorosis.

  4. On the mechanistic differences of benzene-induced leukemogenesis between wild type and p53 knockout mice

    International Nuclear Information System (INIS)

    Hirabayashi, Yoko; Yoon, Byung-Il; Kawasaki, Yasushi; Li, Guang-Xun; Kanno, Jun; Inoue, Tohru

    2003-01-01

    Leukemia induction by benzene inhalation was first reported by Le Noire in 1887, described multiple cases of leukemia among Parisian cobblers. However, experimental induction of leukemia by benzene exposure was not succeeded for a hundred years, until Snyder et al. and our group reported it nearly 20 years ago. Nevertheless, the mechanistic background of benzene-induced leukemia was still an enigma until recently a benzene-induced peculiar cell kinetics of the stem/progenitor cells has been elucidated by our study, demonstrated a marked repeated oscillatory decrease in peripheral blood and bone marrow (BM) cellularity during and after benzene exposure, which epigenetically preceded and developed the leukemia more than a year later. We utilized the BUUV (bromodeoxyuridine + UV exposure) method to study stem/progenitor cell kinetics during and/or after benzene exposure. Using these methods, we were able to measure the labeling rate, cycling fraction of clonogenic progenitor cells, and other cell cycle parameters. The cycling fraction of stem/progenitor cells was found not to turn into an active hematopoiesis but to remain low during benzene inhalation and further we found evidence that the cycling fraction depression may be mediated in part by a slowing of stem/progenitor cell cycling perse by up-regulation of p21. The benzene induced leukemogenicity between mice carrying wild-type p53 and mice lacking p53 seem to differ from one another. In the case of p53 knockout mouse, DNA damage such as weak mutagenicity and or chromosomal damages are retained, and those damages participated in the induction of a consequent activation of proto-oncogenes and the like, which led cells to further neoplastic changes. In contrast, in the case of wild type mice, a dramatic oscillational change in the cell cycle of the stem cell compartment seems to be an important factor for mice carrying the p53 gene. (author)

  5. THE PROGNOSIS SIGNIFICANCE OF CATHEPSIN-D EXPRESSION IN THE DIFFERENT LOCATIONS IN AXILLARY NODES NEGATIVE CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: The aim of this study was to investigate Cathepsin-D (Cath-D) expression in different location and its relationship with prognosis in the axillary lymph nodes negative (ANN) breast cancer patients. Methods: Cath-D expression in 192 cases of breast carcinoma were examined by immunohistochemistry. Depending on different parts of expression, three evaluating methods were used, compared and analysed. Results: The positive rate of Cath-D expression in ANN breast cancer with poor prognosis group and axillary nodes positive (ANP) group were significantly higher than that in ANN breast cancer with good prognosis group (x2=23.20, P0.05). Cath-D expression in stromal cells had no statistical difference among the three groups (x2=1.56, P>0.05). When the Cath-D expression in cancer and stromal cells were counted into the positive rate, it was near the same (u1=0.47, u2=1.41, P>0.05). Conclusion: These results suggest that Cath-D expression is one of the powerful prognostic markers in ANN breast cancer. It's a reliable, practical, and convenient method to observe and evaluate Cath-D expression in cancer cells.

  6. Effects of chronic vs. intermittent calorie restriction on mammary tumor incidence and serum adiponectin and leptin levels in MMTV-TGF-α mice at different ages

    Science.gov (United States)

    DOGAN, SONER; ROGOZINA, OLGA P.; LOKSHIN, ANNA E.; GRANDE, JOSEPH P.; CLEARY, MARGOT P.

    2010-01-01

    Calorie restriction prevents mammary tumor (MT) development in rodents. Usually, chronic calorie restriction (CCR) has been implemented. In contrast, intermittent calorie restriction (ICR) has been less frequently used. Recent studies indicate that when a direct comparison of the same degree of CCR vs. ICR was made using MMTV-TGF-α mice which develop MTs in the second year of life, ICR provided greater protection than CCR in delaying MT detection and reducing tumor incidence. Adiponectin and leptin are two adipocytokines secreted from adipose tissue which have opposite effects on many physiological functions, including proliferation of human breast cancer cells. A recent study indicated that a low adiponectin/leptin ratio was associated with breast cancer. We evaluated the relationship of adiponectin and leptin to MT development in MMTV-TGF-α calorie-restricted mice at several ages. Mice were enrolled at 10 weeks of age and subjected to 25% caloric reduction implemented either chronically or intermittently. Mice were euthanized at designated time points up to 74 weeks of age. Serum samples were collected to measure adiponectin and leptin concentrations. Both CCR and ICR mice had significantly reduced MT incidence. For the groups studied, serum leptin increased over time, while there was a trend for an increase in serum adiponectin levels in ad libitum and ICR mice, with no change in CCR mice between 10 and 74 weeks of age. The adiponectin/leptin ratio was significantly reduced as mice aged, but this ratio in ICR mice was significantly higher than that for ad libitum and CCR mice. No correlation was noted between serum adiponectin and leptin. These findings demonstrate that intermittent calorie restriction delays the early development of MTs. This delay was associated with reduced serum leptin levels following the restriction phases of the protocol. Additionally, serum leptin levels correlated with body weight and body fat in the groups studied. PMID:22966277

  7. DIFFERENCES IN WATER VAPOR RADIATIVE TRANSFER AMONG 1D MODELS CAN SIGNIFICANTLY AFFECT THE INNER EDGE OF THE HABITABLE ZONE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jun; Wang, Yuwei [Department of Atmospheric and Oceanic Sciences, School of Physics, Peking University, Beijing (China); Leconte, Jérémy; Forget, François [Laboratoire de Météorologie Dynamique, Institut Pierre Simon Laplace, CNRS, Paris (France); Wolf, Eric T. [Laboratory for Atmospheric and Space Physics, University of Colorado in Boulder, CO (United States); Goldblatt, Colin [School of Earth and Ocean Sciences, University of Victoria, Victoria, BC (Canada); Feldl, Nicole [Division of Geological and Planetary Sciences, California Institute of Technology, CA (United States); Merlis, Timothy [Department of Atmospheric and Oceanic Sciences at McGill University, Montréal (Canada); Koll, Daniel D. B.; Ding, Feng; Abbot, Dorian S., E-mail: junyang@pku.edu.cn, E-mail: abbot@uchicago.edu [Department of the Geophysical Sciences, University of Chicago, Chicago, IL (United States)

    2016-08-01

    An accurate estimate of the inner edge of the habitable zone is critical for determining which exoplanets are potentially habitable and for designing future telescopes to observe them. Here, we explore differences in estimating the inner edge among seven one-dimensional radiative transfer models: two line-by-line codes (SMART and LBLRTM) as well as five band codes (CAM3, CAM4-Wolf, LMDG, SBDART, and AM2) that are currently being used in global climate models. We compare radiative fluxes and spectra in clear-sky conditions around G and M stars, with fixed moist adiabatic profiles for surface temperatures from 250 to 360 K. We find that divergences among the models arise mainly from large uncertainties in water vapor absorption in the window region (10 μ m) and in the region between 0.2 and 1.5 μ m. Differences in outgoing longwave radiation increase with surface temperature and reach 10–20 W m{sup 2}; differences in shortwave reach up to 60 W m{sup 2}, especially at the surface and in the troposphere, and are larger for an M-dwarf spectrum than a solar spectrum. Differences between the two line-by-line models are significant, although smaller than among the band models. Our results imply that the uncertainty in estimating the insolation threshold of the inner edge (the runaway greenhouse limit) due only to clear-sky radiative transfer is ≈10% of modern Earth’s solar constant (i.e., ≈34 W m{sup 2} in global mean) among band models and ≈3% between the two line-by-line models. These comparisons show that future work is needed that focuses on improving water vapor absorption coefficients in both shortwave and longwave, as well as on increasing the resolution of stellar spectra in broadband models.

  8. DIFFERENCES IN WATER VAPOR RADIATIVE TRANSFER AMONG 1D MODELS CAN SIGNIFICANTLY AFFECT THE INNER EDGE OF THE HABITABLE ZONE

    International Nuclear Information System (INIS)

    Yang, Jun; Wang, Yuwei; Leconte, Jérémy; Forget, François; Wolf, Eric T.; Goldblatt, Colin; Feldl, Nicole; Merlis, Timothy; Koll, Daniel D. B.; Ding, Feng; Abbot, Dorian S.

    2016-01-01

    An accurate estimate of the inner edge of the habitable zone is critical for determining which exoplanets are potentially habitable and for designing future telescopes to observe them. Here, we explore differences in estimating the inner edge among seven one-dimensional radiative transfer models: two line-by-line codes (SMART and LBLRTM) as well as five band codes (CAM3, CAM4-Wolf, LMDG, SBDART, and AM2) that are currently being used in global climate models. We compare radiative fluxes and spectra in clear-sky conditions around G and M stars, with fixed moist adiabatic profiles for surface temperatures from 250 to 360 K. We find that divergences among the models arise mainly from large uncertainties in water vapor absorption in the window region (10 μ m) and in the region between 0.2 and 1.5 μ m. Differences in outgoing longwave radiation increase with surface temperature and reach 10–20 W m 2 ; differences in shortwave reach up to 60 W m 2 , especially at the surface and in the troposphere, and are larger for an M-dwarf spectrum than a solar spectrum. Differences between the two line-by-line models are significant, although smaller than among the band models. Our results imply that the uncertainty in estimating the insolation threshold of the inner edge (the runaway greenhouse limit) due only to clear-sky radiative transfer is ≈10% of modern Earth’s solar constant (i.e., ≈34 W m 2 in global mean) among band models and ≈3% between the two line-by-line models. These comparisons show that future work is needed that focuses on improving water vapor absorption coefficients in both shortwave and longwave, as well as on increasing the resolution of stellar spectra in broadband models.

  9. Different Techniques of Respiratory Support Do Not Significantly Affect Gas Exchange during Cardiopulmonary Resuscitation in a Newborn Piglet Model.

    Science.gov (United States)

    Mendler, Marc R; Maurer, Miriam; Hassan, Mohammad A; Huang, Li; Waitz, Markus; Mayer, Benjamin; Hummler, Helmut D

    2015-01-01

    There are no evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). We studied the short-term effects of different ventilatory support strategies along with CC representing clinical practice on gas exchange [arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2)], hemodynamics and cerebral oxygenation. We hypothesized that in newborn piglets with cardiac arrest, use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) improves gas exchange as measured by SaO2 during CPR as compared to using a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a mechanical ventilator without synchrony to CC. Thirty newborn piglets with asystole were randomized into three groups and resuscitated for 20 min [fraction of inspired oxygen (FiO2) = 0.21 for 10 min and 1.0 thereafter]. Group 1 received ventilation using a TPR [peak inspiratory pressure (PIP)/PEEP of 20/5 cm H2O, rate 30/min] with inflations interposed between CC (3:1 ratio). Group 2 received ventilation using a SIB (PIP of 20 cm H2O without PEEP, rate 30/min) with inflations interposed between CC (3:1 ratio). Group 3 received ventilation using a mechanical ventilator (PIP/PEEP of 20/5 cm H2O, rate 30/min). CC were applied with a rate of 120/min without synchrony to inflations. We found no significant differences in SaO2 between the three groups. However, there was a trend toward a higher SaO2 [TPR: 28.0% (22.3-40.0); SIB: 23.7% (13.4-52.3); ventilator: 44.1% (39.2-54.3); median (interquartile range)] and a lower PaCO2 [TPR: 95.6 mm Hg (82.1-113.6); SIB: 100.8 mm Hg (83.0-108.0); ventilator: 74.1 mm Hg (68.5-83.1); median (interquartile range)] in the mechanical ventilator group. We found no significant effect on gas exchange using different respiratory support strategies

  10. Do the levels of selected metals differ significantly between the roots of carious and non-carious teeth?

    International Nuclear Information System (INIS)

    Malara, Piotr; Kwapulinski, Jerzy; Malara, Beata

    2006-01-01

    Since the metals deposited in teeth during formation and mineralization processes are to a large extent retained, human teeth receive a considerable attention as the indicators of the heavy metal exposure. The use of permanent teeth is limited because the extraction of healthy permanent teeth just for this purpose is hardly acceptable. As the issue of the loss of elements from a carious lesion in the coronal part of a tooth remains controversial, the valuable material could only be the root of carious and fractured permanent teeth. However, to ensure the validity of the results, it should be ascertained that the levels of certain toxic and essential elements do not differ significantly between the roots of non-carious and carious teeth, and therefore this is the aim of this project. The levels of cadmium, chromium, copper, iron, manganese, lead, zinc, potassium, sodium, calcium and magnesium were determined in the roots of 344 permanent teeth (189 carious and 155 caries-free teeth) from the residents of Ruda Slaska, Poland, aged 18 to 34. No statistically significant difference between the concentration of these metals in the roots of non-carious and carious teeth was found. This finding applies to both the general population and after the grouping by donor's gender and tooth type. The concentration of lead, iron, calcium and manganese in the roots of non-carious and carious teeth exhibited dependence upon tooth type, as well as the concentration of potassium in the roots of carious teeth. Since the mineral composition of the roots of permanent teeth is similar for the non-carious, as well as the carious teeth, they can be indiscriminately selected for the tests required by a research project, as they will produce the comparable results. However, in the case of lead, iron, calcium, potassium and manganese, the comparison should be made after grouping by tooth type

  11. Quantifying Forest Spatial Pattern Trends at Multiple Extents: An Approach to Detect Significant Changes at Different Scales

    Directory of Open Access Journals (Sweden)

    Ludovico Frate

    2014-09-01

    Full Text Available We propose a procedure to detect significant changes in forest spatial patterns and relevant scales. Our approach consists of four sequential steps. First, based on a series of multi-temporal forest maps, a set of geographic windows of increasing extents are extracted. Second, for each extent and date, specific stochastic simulations that replicate real-world spatial pattern characteristics are run. Third, by computing pattern metrics on both simulated and real maps, their empirical distributions and confidence intervals are derived. Finally, multi-temporal scalograms are built for each metric. Based on cover maps (1954, 2011 with a resolution of 10 m we analyze forest pattern changes in a central Apennines (Italy reserve at multiple spatial extents (128, 256 and 512 pixels. We identify three types of multi-temporal scalograms, depending on pattern metric behaviors, describing different dynamics of natural reforestation process. The statistical distribution and variability of pattern metrics at multiple extents offers a new and powerful tool to detect forest variations over time. Similar procedures can (i help to identify significant changes in spatial patterns and provide the bases to relate them to landscape processes; (ii minimize the bias when comparing pattern metrics at a single extent and (iii be extended to other landscapes and scales.

  12. The clinical significance of axillary sentinel lymph node biopsy in different clinical stages breast cancer patients after neoadjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Juan Xu; Xinhong Wu; Yaojun Feng; Feng Yuan; Wei Fan

    2013-01-01

    Objective:We aimed to study the success and false negative rate of sentinel lymph node biopsy (SLNB) in dif-ferent clinical stages breast cancer patients being carried out with neoadjuvant chemotherapy (NAC), and the clinical signifi-cance of SLNB, we conducting this trial. Methods:One hunderd and thirty-seven cases were enrol ed in this clinical research from March 2003 to March 2007. Al of the patients’ sentinel lymph nodes were detected with 99mTc-Dx and methylene blue. There were 61 patients with stage T1-2N0M0 carried SLNB without NAC (group A), 76 cases were carried out NAC 3-4 cycles before SLNB, including 39 T2-4N0-1M0 cases (group B) and 27 T2-4N2-3M0 cases (group C). The success and false negative rate of SLNB were analysed with chi-square test. Results:In group A, the successful and false negative rate of SLNB were 92.31%(36/39), 8.57%(3/35), and in group B and C were 92.31%(36/39), 8.57%(3/35) and 74.07%(20/27), 18.52%(5/27), respectively. The successful rate of group C decreased and false negative rate increased significantly compared with group A and B (P0.05). Conclusion:The SLNB can accurately predict lymph node status of axil ary lymph node in N0-1 stage patients with NAC, but in N2-3 stage patients the success rate decreased and false rate increased negative significantly.

  13. Difference of ore-bearing and non-ore-bearing pegmatite in the Guangshigou area and its research significance

    International Nuclear Information System (INIS)

    Zuo Wenqian; Zhang Zhanshi; Sha Yazhou; Rao Chaojun

    2011-01-01

    Guangshigou uranium deposit is one of the typical granite-pegmatite uranium deposits in China, the ore-body are located in the density zone of the outside contact zone of granite pluton. To distinguish the ore-bearing and Non-ore-bearing pegmatite is one of the most practices and have great significance for the effect of mineral exploration. Based on the field investigation and former research results, contrast research on the characteristics of the pegmatite on petrology, geophysical, geochemistry and stable isotopes have been carried out. It is pointed out that the ore-bearing pegmatite differ from the non-ore-bearing one from macro-and-micro-view in Guangshigou Uranium deposits, the main characteristics are summarized; the macro-and-micro signs are established, the genetic difference between the ore-bearing and non-ore-bearing pegmatite are discussed primarily. The achievements would be helpful for prospecting and researching of this type uranium deposits in China. (authors)

  14. The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes.

    Science.gov (United States)

    Shoskes, Daniel A; Altemus, Jessica; Polackwich, Alan S; Tucky, Barbara; Wang, Hannah; Eng, Charis

    2016-06-01

    To study the urinary microbiome of patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) compared with controls. We identified 25 patients with CP/CPPS and 25 men who were either asymptomatic or only had urinary symptoms. Midstream urine was collected. Symptom severity was measured with the National Institutes of Health Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the urine pellet and bacterial-specific 16Sr-DNA-capture identified by MiSeq sequencing. Taxonomic and functional bioinformatic analyses used principal coordinate analysis (PCoA)/MacQIIME, LEfSe, and PiCRUSt algorithms. Patients and controls were similar ages (52.3 vs 57.0 years, P = .27). For patients, median duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0, and mean UPOINT domains was 3.6. Weighted 3D UniFrac PCoA revealed tighter clustering of controls distinct from the wider clustering of cases (P = .001; α-diversity P = .005). Seventeen clades were overrepresented in patients, for example, Clostridia, and 5 were underrepresented, eg, Bacilli, resulting in predicted perturbations in functional pathways. PiCRUSt inferred differentially regulated pathways between cases and controls that may be of relevance including sporulation, chemotaxis, and pyruvate metabolism. PCoA-derived microbiomic differences were noted for neurologic/systemic domains (P = .06), whereas LEfSe identified differences associated with each of the 6 clinical features. Urinary microbiomes from patients with CP/CPPS have significantly higher alpha(phylogenetic) diversity which cluster differently from controls, and higher counts of Clostridia compared with controls, resulting in predicted perturbations of functional pathways which could suggest metabolite-specific targeted treatment. Several measures of severity and clinical phenotype have significant microbiome differences. Copyright © 2016 Elsevier Inc. All rights

  15. Raman spectroscopy analysis of differences in composition of spent culture media of in vitro cultured preimplantation embryos isolated from normal and fat mice dams.

    Science.gov (United States)

    Fabian, Dušan; Kačmarová, Martina; Kubandová, Janka; Čikoš, Štefan; Koppel, Juraj

    2016-06-01

    The aim of the present study was to compare overall patterns of metabolic activity of in vitro cultured preimplantation embryos isolated from normal and fat mice dams by means of non-invasive profiling of spent culture media using Raman spectroscopy. To produce females with two different types of body condition (normal and fat), a previously established two-generation model was used, based on overfeeding of experimental mice during prenatal and early postnatal development. Embryos were isolated from spontaneously ovulating and naturally fertilized dams at the 2-cell stage of development and cultured to the blastocyst stage in synthetic oviductal medium KSOMaa. Embryos from fat mice (displaying significantly elevated body weight and fat) showed similar developmental capabilities in vitro as embryos isolated from normal control dams (displaying physiological body weight and fat). The results show that alterations in the composition of culture medium caused by the presence of developing mouse preimplantation embryos can be detected using Raman spectroscopy. Metabolic activity of embryos was reflected in evident changes in numerous band intensities in the 1620-1690cm(-1) (amide I) region and in the 1020-1140cm(-1) region of the Raman spectrum for KSOMaa. Moreover, multivariate analysis of spectral data proved that the composition of proteins and other organic compounds in spent samples obtained after the culture of embryos isolated from fat dams was different from that in spent samples obtained after the culture of embryos from control dams. This study demonstrates that metabolic activity of cultured preimplantation embryos might depend on the body condition of their donors. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. The influence of chronic stress on anxiety-like behavior and cognitive function in different human GFAP-ApoE transgenic adult male mice.

    Science.gov (United States)

    Meng, Fan-Tao; Zhao, Jun; Fang, Hui; Liu, Ya-Jing

    2015-01-01

    The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.

  17. Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice

    Directory of Open Access Journals (Sweden)

    Abhinoy Kishore

    2013-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the human central nervous system (CNS. Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59 induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG induces experimental autoimmune encephalomyelitis (EAE, a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

  18. Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Eva Ludvigsen

    2011-01-01

    Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

  19. Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.

    Science.gov (United States)

    Maciak, S; Bonda-Ostaszewska, E; Czarnołęski, M; Konarzewski, M; Kozłowski, J

    2014-03-01

    Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  20. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  1. Downhill Running Excessive Training Inhibits Hypertrophy in Mice Skeletal Muscles with Different Fiber Type Composition.

    Science.gov (United States)

    da Rocha, Alisson L; Pereira, Bruno C; Pauli, José R; de Souza, Claudio T; Teixeira, Giovana R; Lira, Fábio S; Cintra, Dennys E; Ropelle, Eduardo R; Júnior, Carlos R B; da Silva, Adelino S R

    2016-05-01

    The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80°C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type. © 2015 Wiley Periodicals, Inc.

  2. Religious Freedom and Equality as Celebration of Difference: A Significant Development in Recent South African Constitutional Case-Law

    Directory of Open Access Journals (Sweden)

    L du Plessis

    2009-12-01

    Full Text Available This contribution focuses on the way in which the South African Constitutional Court has, since 1997, been dealing with the (seemingly eccentric claims of (assumedly idiosyncratic 'religious Others'. Developments in this regard have, for the time being at least, culminated in the Constitutional Court's landmark judgment in MEC for Education: KwaZulu Natal v Pillay 2008 (2 BCLR 99 (CC, 2008 (1 SA 474 (CC (hereafter Pillay. Constitutional Court judgments since 1997 manifesting the adjudication of such unconventional claims are assessed, eventually getting to Pillay as benchmark. This remarkable judgment, dealing with a deceptively mundane issue, has played a considerable role in fleshing out a jurisprudence of difference, putting an adherent of a vulnerable, minority religion in the right. This is not just a high point in the adjudication of constitutional entitlements of the religious (and cultural Other in South Africa, but also a significant contribution to the growth of a jurisprudence sensitive to the predicaments and constitutional entitlements of unconventional, 'non-mainstream' claimants of religious (and cultural rights. Finally Pillay illustrates that the constitutional guarantee of the right to freedom of religion, conscience, belief and opinion (entrenched in section 15(1 of the Constitution of Republic of South Africa 1996 can be crucially dependent upon due effect being given to the proscription of unfair discrimination on the grounds of religion, conscience, belief and opinion elsewhere (namely in section 9(3 of the Constitution.

  3. Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice

    DEFF Research Database (Denmark)

    Overgaard, Agnete; Tena-Sempere, Manuel; Franceschini, Isabelle

    2013-01-01

    cells, only after axonal transport inhibition. Interestingly, the density of kisspeptin innervation in the anterior periventricular area was higher in female compared to male in both species. Species differences in the ARC were evident, with the mouse ARC containing dense fibers, while the rat ARC......-immunoreactivity in the mouse compared to the rat, independently of brain region and gender. In the female mouse AVPV high numbers of kisspeptin-immunoreactive neurons were present, while in the rat, the female AVPV displays a similar number of kisspeptin-immunoreactive neurons compared to the level of Kiss1 mRNA expressing...... contains clearly discernable cells. In addition, we show a marked sex difference in the ARC, with higher kisspeptin levels in females. These findings show that the translation of Kiss1 mRNA and/or the degradation/transportation/release of kisspeptins are different in mice and rats....

  4. Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice.

    Science.gov (United States)

    Aguayo, Antonio; Martin, Camille S; Huddy, Timothy F; Ogawa-Okada, Maya; Adkins, Jamie L; Steele, Andrew D

    2018-01-01

    Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice.

  5. Effects of irradiation at different dose rates on the onset of type I diabetes in model mice

    International Nuclear Information System (INIS)

    Nomura, Takashi; Sakai, Kazuo

    2003-01-01

    We previously demonstrated that low-dose irradiation (0.5 Gy) increased the level of antioxidants and decreased the level of lipid peroxide in normal mice. We also found that 0.5 Gy-irradiation of NOD mice suppressed the onset of type I diabetes. These results were obtained by the irradiation at high dose rate. The aim of the present study is to examine the effects at the low dose rate. The mice were acutely irradiated with 0.5 Gy of X-rays (300 kVp) at 94.2 Gy/hr at 10, 11, 12, 13 or 14 weeks of age, or chronically irradiated with 0.5 Gy of 137 Cs γ-rays at 0.95 mGy/hr starting at 10,11,12,13 or 14 weeks of age. When irradiated at 12th week with the high dose rate X-rays, the onset of diabetes suppressed, and the increase in the specific activity of superoxide dismutase (SOD) in pancreas was observed. On the other hand, the low dose rate γ-rays delivered from 12th week of age to 14th was less effective in the suppression of the incidence of diabetes than the high dose rate X-rays at the 12-14 weeks of age. Furthermore, the significant increase in pancreatic SOD activity was not observed after the low dose irradiation. Splenic macrophage activities of superoxide generation were not affected by the high dose rate irradiation nor the low dose rate irradiation. (author)

  6. Induction of albuminuria in mice: synergistic effect of two monoclonal antibodies directed to different domains of aminopeptidase A.

    Science.gov (United States)

    Mentzel, S; van Son, J P; Dijkman, H B; Wetzels, J F; Assmann, K J

    1999-04-01

    Aminopeptidase A is an enzyme that is present on podocytes and is involved in the degradation of angiotensin II. In previous studies in mice, we administered single monoclonal antibodies directed against aminopeptidase A. We observed that only monoclonal antibodies that inhibited aminopeptidase A enzyme activity caused albuminuria. In this study, the effects of the combined injections of two monoclonal anti-aminopeptidase A antibodies (mAbs) were studied, using a combination of anti-aminopeptidase A mAbs that were directed against two different domains involved in the aminopeptidase A enzyme activity (ASD-3 or ASD-37) and an anti-aminopeptidase A mAb not related to the enzyme active site (ASD-41). An injection of the combinations ASD-3/37 (total 4 mg, 1:1 ratio) and ASD-37/41 (total 4 mg, 1:1 ratio) in doses that do not cause albuminuria when given alone (4 mg) induced massive albuminuria at day 1 after injection. The combination ASD-3/41 had no effect. This albuminuria was not dependent on systemic immune mediators of inflammation and could not merely be related to a blockade of aminopeptidase A enzyme activity. However, a correlation was observed between the induction of albuminuria and the aggregation of the mAbs injected and aminopeptidase A on the podocytes. An injection of the combinations ASD-3/37 or ASD-37/41 did not cause an increase in systemic blood pressure. The treatment with a combination of enalapril and losartan lowered blood pressure (53 +/- 10 vs. 90 +/- 3 mm Hg in untreated mice) and reduced the acute albuminuria by 55% (11,145 +/- 864 vs. 24,517 +/- 2448 micrograms albumin/18 hr in untreated mice). However, similar effects were observed using triple therapy. Therefore, the reduction of albuminuria by the combined treatment of enalapril/losartan seems to be the consequence of the reduction in the systemic blood pressure. These findings argue against a specific role for angiotensin II in this model. The combined injection of two mAbs directed

  7. Distribution of biotransformation of methyl mercuric chloride in different tissues of mice

    International Nuclear Information System (INIS)

    Mehra, M.; Choi, B.H.

    1981-01-01

    The distribution of 203 Hg radioactivity has been studied in various organs of adult male and female mice from one hour to 21 days after treating with 203 Hg-labeled methyl mercuric chloride (MMC). The amount of methyl mercury (MeHg) and inorganic mercury (Hg) has also beam determined by injecting single doses of non-radioactive MMC, and subsequently measuring total, organic and inorganic Hg content by atomic absorption technique. In addition, photoemulsion histochemical method (PEHM) was used to demonstrate localization of Hg grains in various cellular compartments of organs and tissues. The highest levels of radioactivity were attained at 7 hours post-treatment on all organs except for brain and testis. The testis showed the highest radioactivity at one day and the brain at two days post-treatment. MeHg persisted in brain over a longer period though the level was not as high. The content of MeHg and inorganic Hg was maximum in kidneys as compared to other organs. The brain and the reproductive organs contained the least amoun of inorganic Hg. By PEHM, Hg grains were most prominently observed in the sinusoids, Kupfer cells, hepatic cells and bile duct epithelium of liver; in the lumen of blood vessels, convoluted and collecting tubules of kidneys; and in the gastrointestinal epithelium. The pattern of uptake and distribution of MeHg correlated well with the morphological demonstration of Hg grains in tissue sections. (author)

  8. Sex Differences in Maturation of Human Embryonic Stem Cell-Derived β Cells in Mice.

    Science.gov (United States)

    Saber, Nelly; Bruin, Jennifer E; O'Dwyer, Shannon; Schuster, Hellen; Rezania, Alireza; Kieffer, Timothy J

    2018-04-01

    Pancreatic progenitors derived from human embryonic stem cells (hESCs) are now in clinical trials for insulin replacement in patients with type 1 diabetes. Animal studies indicate that pancreatic progenitor cells can mature into a mixed population of endocrine cells, including glucose-responsive β cells several months after implantion. However, it remains unclear how conditions in the recipient may influence the maturation and ultimately the function of these hESC-derived cells. Here, we investigated the effects of (1) pregnancy on the maturation of human stage 4 (S4) pancreatic progenitor cells and (2) the impact of host sex on both S4 cells and more mature stage 7 (S7) pancreatic endocrine cells implanted under the kidney capsule of immunodeficient SCID-beige mice. Pregnancy led to increased proliferation of endogenous pancreatic β cells, but did not appear to affect proliferation or maturation of S4 cells at midgestation. Interestingly, S4 and S7 cells both acquired glucose-stimulated C-peptide secretion in females before males. Moreover, S4 cells lowered fasting blood glucose levels in females sooner than in males, whereas the responses with S7 cells were similar. These data indicate that the host sex may impact the maturation of hESC-derived cells in vivo and that this effect can be minimized by more advanced differentiation of the cells before implantation.

  9. Myc contribution to γ-ray induced thymic lymphomas in mice of different genetic predispositions

    International Nuclear Information System (INIS)

    Sato, Toshihiro

    2008-01-01

    Myc gene has been suggested to be one of radiation targets in early genesis of γ ray-induced thymic lymphoma where Myc trisomy often occurs, and Myc activation results in p53 activation and apoptosis. The purpose of this study is to see the effects of radiation and mutation on Myc activation in the mouse. The lymphoma was induced by a single exposure of 3 Gy γ ray in BALB/c Bcl11b/Rit+/- and MSM p53-/- mice at 4 weeks after birth and by 4 weekly exposures of 2.5 Gy in p53+/- mouse. Genetic allele analysis for trisomy identification in the lymphoma was done by quantitative PCR using brain DNA as a control. Myc trisomy was found in the lymphoma of p53+/- mouse in 62% (23/37 animals) and of p53+/+, 66% (23/25), a similar frequency, suggesting that the target of radiation was not only the Myc activation. In addition, Myc trisomy frequency was 15% (4/27) in the lymphoma of Bcl11b+/+p53+/- and 36% (9/25), in heterozygote Bcl11b+/-. This finding suggested that the functional failure of Bcl11b reduced the contribution of Myc trisomy to the genesis. It was concluded that contribution of Myc trisomy to genesis of the lymphoma was dependent on genetic predisposition, and Myc-activated-, Bcl11b/Rit1-signal pathways played a parallel role in the genesis. (R.T.)

  10. Sex differences between CRF1 receptor deficient mice following naloxone-precipitated morphine withdrawal in a conditioned place aversion paradigm: implication of HPA axis.

    Directory of Open Access Journals (Sweden)

    Juan-Antonio García-Carmona

    Full Text Available Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R and the different response of male and female mice in the expression and extinction of the aversive memory.We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10-60 mg/kg. Negative state associated with naloxone (1 mg/kg s.c.-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA paradigm. No sex differences for CPA expression were found in wild-type (n = 29 or CRF1R knockout (KO mice (n = 29. However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH levels observed in wild-type (n = 11 mice after CPA expression, were attenuated in CRF1R KO mice (n = 10. In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

  11. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.

    Science.gov (United States)

    Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H

    2018-02-01

    More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  12. High frequency mechanical ventilation affects respiratory system mechanics differently in C57BL/6J and BALB/c adult mice.

    Science.gov (United States)

    Hadden, Hélène

    2013-01-15

    We tested the hypothesis that high frequency ventilation affects respiratory system mechanical functions in C57BL/6J and BALB/c mice. We measured respiratory mechanics by the forced oscillation technique over 1h in anesthetized, intubated, ventilated BALB/c and C57BL/6J male mice. We did not detect any change in airway resistance, Rn, tissue damping, G, tissue elastance, H and hysteresivity, eta in BALB/c mice during 1h of ventilation at 150 or at 450 breaths/min; nor did we find a difference between BALB/c mice ventilated at 150 breaths/min compared with 450 breaths/min. Among C57BL/6J mice, except for H, all parameters remained unchanged over 1h of ventilation in mice ventilated at 150 breaths/min. However, after 10 and 30 min of ventilation at 450 breaths/min, Rn, and respiratory system compliance were lower, and eta was higher, than their starting value. We conclude that high frequency mechanical ventilation affects respiratory system mechanics differently in C57BL/6J and BALB/c adult mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Bioavailability and Brain-Targeting of Geniposide in Gardenia-Borneol Co-Compound by Different Administration Routes in Mice

    Directory of Open Access Journals (Sweden)

    Xuejiao Zhao

    2012-11-01

    Full Text Available Both geniposide (Ge and borneol (Bo are bioactive substances derived from traditional Chinese medicine. Injections containing co-compound of Gardenia-Borneol are widely used for stroke treatment in China, such as “Xingnaojing” multi-component injection. As more and more adverse reactions (especially drug allergy were reported, it is urgent to find more effective and safer routes of administration for such kinds of medicines. In this paper, bioavailabilities and brain-target effects of geniposide in Gardenia-Borneol co-compound through different administration routes in mice were investigated. Geniposide concentrations in plasma and in brain of mice were determined by reversed-phase high-performance liquid chromatography. The pharmacokinetics parameters of intranasal (i.n. and intragastric (i.g. administration were compared with intravenous (i.v. administration. The bioavailabilities of Ge were 85.38% and 28.76% for i.n. and i.g. while Tmax were 1 min and 30 min. Cmax were 21.881 ± 5.398, 1.914 ± 0.327 and 42.410 ± 6.268 μg/mL for i.n., i.g. and i.v., respectively. The AUC of Ge in brain were 32413.6 ± 4573.9, 6440.1 ± 863.7 and 37270.5 ± 4160.6 ng/g·min for i.n., i.g. and i.v., respectively. The drug target indexes (DTI were 1.02 and 0.60 for i.n. and i.g. The results demonstrated that geniposide could be absorbed promptly and thoroughly by i.n. administration in mice and basically transported into the brain though blood vessel passways.

  14. Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.

    Directory of Open Access Journals (Sweden)

    Julien Textoris

    Full Text Available BACKGROUND: Q fever, a zoonosis due to Coxiella burnetii infection, exhibits sexual dimorphism; men are affected more frequently and severely than women for a given exposure. Here we explore whether the severity of C. burnetii infection in mice is related to differences in male and female gene expression profiles. METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with C. burnetii for 24 hours, and gene expression was measured in liver cells using microarrays. Multiclass analysis identified 2,777 probes for which expression was specifically modulated by C. burnetti infection. Only 14% of the modulated genes were sex-independent, and the remaining 86% were differentially expressed in males and females. Castration of males and females showed that sex hormones were responsible for more than 60% of the observed gene modulation, and this reduction was most pronounced in males. Using functional annotation of modulated genes, we identified four clusters enriched in males that were related to cell-cell adhesion, signal transduction, defensins and cytokine/Jak-Stat pathways. Up-regulation of the IL-10 and Stat-3 genes may account for the high susceptibility of men with Q fever to C. burnetii infection and autoantibody production. Two clusters were identified in females, including the circadian rhythm pathway, which consists of positive (Clock, Arntl and negative (Per limbs of a feedback loop. We found that Clock and Arntl were down-modulated whereas Per was up-regulated; these changes may be associated with efficient bacterial elimination in females but not in males, in which an exacerbated host response would be prominent. CONCLUSION: This large-scale study revealed for the first time that circadian rhythm plays a major role in the anti-infectious response of mice, and it provides a new basis for elucidating the role of sexual dimorphism in human infections.

  15. Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Motl Robert W

    2012-03-01

    Full Text Available Abstract Background Researchers have recently advocated for the 2-minute walk (2MW as an alternative for the 6-minute walk (6MW to assess long distance ambulation in persons with multiple sclerosis (MS. This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O2 over the 6MW range. Objective This study examined the pattern of change in V·O2 over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status. Method Ninety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer. Results There was a time main effect on V·O2 during the 6MW (p = .0001 such that V·O2 increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (p = .84. Conclusions The pattern of change in V·O2 indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.

  16. [Differences between cold and hot natures of processed Radix ginseng rubra and Panax quinquefolius L. based upon mice temperature tropism].

    Science.gov (United States)

    Zhang, Xue-Ru; Zhao, Yan-Ling; Wang, Jia-Bo; Zhou, Can-Ping; Liu, Ta-Si; Zhao, Hai-Ping; Ren, Yong-Shen; Yan, Dan; Xiao, Xiao-He

    2009-07-28

    To establish an objective method to estimate the disparity between the cold and hot natures on the basis of an intrinsic correlation between temperature tropism of mice and the cold and hot natures of Chinese medicines. Male KM mice were randomly divided into 7 groups of 6 each, namely the normal group (NM), the weak model group (WM), the strong model group (SM), the weak model plus Radix ginseng rubra group (WM + RG), the weak model plus Panax quinquefolius L. group (WM + PQ), the strong model plus Radix ginseng rubra group (SM + RG) and the strong model plus Panax quinquefolius L. group (SM +PQ). The specific herbal drugs were administered intragastricly. To induce the weak model, mice were fed with a limited supply of feed and forced to swim in cold water until almost drowning while the strong model induced by feeding a high-protein diet with an unlimited feed access. The doses of Radix ginseng rubra and Panax quinquefolius L. were 35 mg/g of body weight per day (counted by the quantity of crude material) and lasting for seven days. The NM and model groups without dosing were intragastricly administered with physiological saline of the same volume to the dosing groups. The percentage of the remaining time of mouse on a high temperature (40 degrees C) pad to the total monitoring time was recorded by a self-designed intelligent animal behavior monitoring system. Meanwhile, the drinking volume of mice in each group was measured. Immediately after experiment, the activities of Na(+)K(+)-ATPase and superoxide dismutase (SOD) in liver tissue were measured by assay kits of phosphorus and xanthine oxidase methods respectively. The features of deficient and cold symptom, such as fatigue, stagnant weight growth, decreased water intake, cold limbs and tail etc, were observed in WM group. And the features of heat symptom, such as increased weight and water intake, hyperactivity etc, were observed in SM group. The percentage of time that the mouse remained on 40 degrees C

  17. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  18. Brain histological changes in young mice submitted to diets with different ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy and lactation.

    Science.gov (United States)

    Tian, Chunyu; Fan, Chaonan; Liu, Xinli; Xu, Feng; Qi, Kemin

    2011-10-01

    N-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for brain development and function, but the appropriate quantity of dietary n-3 PUFAs and ratio of n-6/n-3 PUFAs have not been clearly determined. In this study, we investigated the effects of different dietary ratios of n-6/n-3 PUFAs on the brain structural development in mice and the expression of associated transcription factors. C57 BL/6J mice were fed with one of two categories of n-3 PUFA-containing diets (a flaxseed oil diet and a flaxseed/fish oil mixed diet) or an n-3 PUFA-deficient diet. For each of the n-3 PUFA diets, flaxseed oil or flaxseed/fish oil was combined with other oils to yield three different n-6/n-3 ratios, which ranged from 15.7:1 to 1.6:1. The feeding regimens began two months before mouse conception and continued throughout lactation for new pups. As compared with the n-3 PUFA-deficient diet, both the flaxseed oil n-3 PUFA diets and the flaxseed/fish oil n-3 PUFA diets significantly increased the expression levels of brain neuron-specific enolase, glial fibrillary acidic protein and myelin basic protein, somewhat dose-dependently, in new pup mice at 21 d and 42 d of age. The expression of PPAR-γ in the brains of pup mice was increased only at 7 d of age with the n-3 PUFA diet, and no changes in the expression of PPAR-α and PPAR-β were found among all the diet groups. These results suggest that the higher intake amount of n-3 PUFAs with a low ratio of n-6/n-3 PUFAs at about 1-2:1, supplied during both maternal pregnancy and lactation, may be more beneficial for early brain development, and PPAR-γ may act in one of the pathways by which n-3 PUFAs promote early brain development. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. 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.

  20. T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice.

    Science.gov (United States)

    Ono, Yuichi; Kanai, Takanori; Sujino, Tomohisa; Nemoto, Yasuhiro; Kanai, Yasumasa; Mikami, Yohei; Hayashi, Atsushi; Matsumoto, Atsuhiro; Takaishi, Hiromasa; Ogata, Haruhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Mamoru; Hibi, Toshifumi

    2012-11-01

    T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. LTα(-/-) and RORγt(-/-) mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3(-)CD4(+/-)interleukin-7Rα(+)c-kit(+)CCR6(+)NKp46(-) lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα(-/-) and LTα(-/-) × recombination activating gene (RAG)-2(-/-) mice, compared with wild-type mice, but were absent from RORγt(-/-) mice. Parabiosis of wild-type and LTα(-/-) mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα(-/-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTα(-/-)×RAG-2(-/-) mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high) T cells. Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation

  1. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Jean Pierre Schatzmann Peron

    Full Text Available Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC, which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

  2. 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

  3. 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.

  4. [Anatomy and histology characteristics of lymph node in nude mice].

    Science.gov (United States)

    Sun, R; Gao, B; Guo, C B

    2017-10-18

    To compare the differences of anatomical and histological characteristics of lymph nodes between BALB/c nude mice and BALB/c mice. Firstly, twenty BALB/c nude mice and twenty BALB/c mice were dissected by using a surgical microscope. Secondly, the differences of T cells and B cells at the lymph node were compared by the expressions of CD 3 and CD 20 immunohistochemistry dyes. There were, on average, 23 nodes per mouse contained within the large lymph node assembly in the BALB/c nude mouse. The anatomical features of the lymph node distribution in the nude mice were mainly found in the neck with relatively higher density. There were two lymph nodes both in the submandible lymph nodes group and in the superficial cervical lymph nodes group (the constituent ratios were 95% and 90%, respectively) in the BALB/c nude mice, but there were four lymph nodes (the constituent ratios were 95% and 90%, respectively) in the BALB/c mice. There were significant difference between the BALB/c nude mice and the BALB/c mice. Mostly there were two lymph nodes of deep cervical lymph nodes both in the BALB/c nude mice and the BALB/c mice (the constituent ratios were 95% and 100%, respectively). There were no significant difference between the BALB/c nude mice and the BALB/c mice. We confirmed that the number of CD 3 -positive T lymphocytes in lymph nodes of the nude mice decreased greatly as compared with the BALB/c mice. Expressions of CD3 in T cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There were significant differences between the BALB/c nude mice and the BALB/c mice. Expressions of CD20 in B cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There was no significant difference between the BALB/c nude mice and BALB/c mice. The anatomical pictures of lymph node distribution in the nude mouse will be benefit to those who are interested. The anatomical features of the lymph node local higher density in neck of

  5. Are age and sex differences in brain oxytocin receptors related to maternal and infanticidal behavior in naïve mice?

    Science.gov (United States)

    Olazábal, Daniel E; Alsina-Llanes, Marcela

    2016-01-01

    This article is part of a Special Issue "Parental Care". There is significant variability in the behavioral responses displayed by naïve young and adult mice when first exposed to pups. This variability has been associated with differences in the expression of oxytocin receptors (OXTRs) in the brain in several species. Experiment I investigated the behavioral responses of juvenile, adolescent, and adult CB57BL/6 males and females when first exposed to pups. We found an age increase in maternal females (11% of juveniles, 20% of adolescents, and 50% of young adults), and infanticidal males (0% of juveniles, 30% of adolescents, 44.5% of young adults, and 100% of older adults). Experiment II investigated OXTR density in the brain of juvenile and adult mice. Our results revealed an age decline in the density of OXTR in several brain regions, including the lateral septum, cingulated and posterior paraventricular thalamic nucleus in both males and females. Adult females had higher OXTR density in the ventromedial nucleus/postero-ventral hypothalamus (VMH) and the accessory olfactory bulb (AOB), but lower density in the ventral region of the lateral septum (LSv) than juveniles. Males had lower OXTR density in the anterior olfactory area (AOA) compared to juveniles. No age or sex differences were found in the medial preoptic area, and amygdaloid nuclei, among other brain regions. This study suggests that 1) maturation of parental and infanticidal behavioral responses is not reached until adulthood; 2) the pattern of development of OXTR in the mouse brain is unique, region specific, and differs from that observed in other rodents; 3) either up or down regulation of OXTR in a few brain regions (VMH/AOB/LSv/AOA) might contribute to age or sex differences in parental or infanticidal behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Sex differences in sleep : the response to sleep deprivation and restraint stress in mice

    NARCIS (Netherlands)

    Koehl, Muriel; Battle, Sally; Meerlo, Peter

    2006-01-01

    Study Objectives: Numerous clinical studies and sleep surveys have shown pronounced sex differences in the occurrence of insomnia and other sleep pathologies. It has been suggested that sex differences in sleep, while subtle under baseline conditions, may increase in magnitude under biological or

  7. Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

    Energy Technology Data Exchange (ETDEWEB)

    Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S. (Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii)

    A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intestinal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mouse groups. Repair of single-strand DNA breaks of elderly mice is slower than that of young animals.

  8. Radiosensitivity of mice of different lines and age as determinated with reference to ''intestinal'' death and DNA repair in intestinal epithelium cells

    International Nuclear Information System (INIS)

    Konoplyannikova, O.A.; Sklobovskaya, M.V.; Konoplyannikov, A.G.; Saenko, A.S.

    1982-01-01

    A study was made of the influence of strain- and age-related differences on mouse mortality after irradiation with doses lying within the ''intest+nal'' dose range, and also damages to stem cells of intestinal epithelium and induction and repair of single-strand DNA breaks in intestinal epitherium cells. Mice of different lines and age vary in LDsub(50/4) and stem cell radiosensitivity. There are no differences in the sedimentation constants of DNA fragments in alkaline lysates of intestinal crypts of intact mice of different age. Radiosensitivity determined with reference to single-strand breaks induction in DNA is similar with different mo use groups. Repair of single-strand DNA breaks of eldery mice is slower than that of young animals

  9. 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

  10. 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.

  11. Effect of different culture systems and 3, 5, 3'-triiodothyronine/follicle-stimulating hormone on preantral follicle development in mice.

    Directory of Open Access Journals (Sweden)

    Cheng Zhang

    Full Text Available The mechanical method to isolate preantral follicle has been reported for many years. However, the culture systems in vitro are still unstable. The aim of this study was to analyze the effect of the culture system of mice preantral follicles on the follicular development in vitro. The results showed that the 96-well plate system was the most effective method for mice follicle development in vitro (volume change: 51.71%; survival rate: 89%, at day 4. Follicle-stimulating hormone (FSH and Thyroid hormone (TH are important for normal follicular development and dysregulation of hormones are related with impaired follicular development. To determine the effect of hormone on preantral follicular development, we cultured follicle with hormones in the 96-well plate culture system and found that FSH significantly increased preantral follicular growth on day 4. The FSH-induced growth action was markedly enhanced by T₃ although T₃ was ineffective alone. We also demonstrated by QRT-PCR that T₃ significantly enhanced FSH-induced up-regulation of Xiap mRNA level. Meanwhile, Bad, cell death inducer, was markedly down-regulated by the combination of hormones. Moreover, QRT-PCR results were also consistent with protein regulation which detected by Western Blotting analysis. Taken together, the findings of the present study demonstrate that 96-well plate system is an effective method for preantral follicle development in vitro. Moreover, these results provide insights on the role of thyroid hormone in increasing FSH-induced preantral follicular development, which mediated by up-regulating Xiap and down-regulating Bad.

  12. The combined effect of two different bone-seeking radionuclides on the induction of osteosarcomas in mice

    International Nuclear Information System (INIS)

    Mueller, W.A.; Luz, A.; Linzner, U.; Murray, A.B.

    1991-01-01

    The effect of injection of 1.85kBq/kg of the long-lived radionuclide 227 Ac on the induction of osteosarcomas in female NMRI-mice by different dose levels of the short-lived radionuclide 227 Th (18.5, 74, and 185 kBq/kg), of the short-lived radionuclide 224 Ra (18.5 kBq/kg and 185 kBq/kg) and of the short-lived β-emitter 177 Lu (100 MBq/kg and 200 MBq/kg) was investigated. The results showed in all cases that combined incorporation of two radionuclides at the levels of radioactivity studied has a lower biological effect than the sum of the effects of the components administered singly. (author)

  13. Comparative study of different methods used to isolate Trypanosoma cruz i for defibrinated blood of irradiated mice

    International Nuclear Information System (INIS)

    Fontes, G.; Romanha, A.J.; Brener, Z.

    1991-01-01

    Different methods are being used for the isolation and purification of Trypanosoma cruzi blood forms from infected vertebrate hosts. In this study, we compare four of these methods (differential centrifugation, Ficoll-Hypaque, Histopaque 1077 and metrizamide) in terms of parasite recovery rates, contamination with cells, duration of the process and role of host irradiation. Male albino Swiss mice irradiated in a Gamma Cell 220(500 rads) were inoculated with C L and V-10 T.cruzi strains and bled at the peak of parasitemia. Infected defibrinated blood was then used for the isolation. Although all methods permitted the recovery of viable trypomastigotes, the best results were obtained with Ficoll-Hypaque and Histopaque 1077. Recovery rates ranged between 71% to 88% and parasite-enriched preparations were obtained in approximately 75 min. Irradiation and blood defibrination drastically reduced platelet and leukocyte contamination of the preparations. (author)

  14. Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.

    Science.gov (United States)

    Abe, Jun; Tomigahara, Yoshitaka; Tarui, Hirokazu; Omori, Rie; Kawamura, Satoshi

    2018-02-28

    A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.

  15. [Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents].

    Science.gov (United States)

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

    1985-08-01

    It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.

  16. Cytogenetical and morphological features reveal significant differences among Venezuelan and Brazilian samples of Mugil curema (Teleostei: Mugilidae

    Directory of Open Access Journals (Sweden)

    Mauro Nirchio

    Full Text Available Karyotype of M. curema from the Gulf of Mexico and Brazil have been reported as possessing chromosome complement with 2n=28 and FN=48, whereas specimens from Venezuela has been reported as possessing a diploid number 2n=24 and a conserved FN (48. Although at first sight this variation suggests the presence of a chromosomal intraspecific (interpopulational variability, the possibility that we are dealing with two different species was examined. This work revisit the karyotypes of M. curema from Venezuela and Brazil, including new data on C-banding, and NOR localization, and compares morphologic characteristics of samples from both localities. Thus, besides diploid number, the constitutive heterochromatin distribution and NORs location, mark other differences between M. curema Cytotype 1 (2n=28; FN=48 and Cytotype 2 (2n=24; NF=48. Moreover, morphologic comparison revealed differences in the scale counts and pectoral fin rays: 35 scales in the middle body line and 15 pectoral fin rays in specimens possessing the karyotype 2n=28, compared with 37-39 scales in the middle body line and 17 pectoral fin rays in specimens with the karyotype 2n=24. These differences lead us to suggest that both cytotypes are not related merely to geographic polytipic variations but could correspond to different species.

  17. [Different explanatory models for addictive behavior in Turkish and German youths in Germany: significance for prevention and treatment].

    Science.gov (United States)

    Penka, S; Krieg, S; Hunner, Ch; Heinz, A

    2003-07-01

    Due to cultural and social barriers, immigrants seldom frequent centers for information, counseling, and treatment of addictive disorders. We examine cultural differences in the explanatory models of addictive behavior among Turkish and German youths in Germany with statistical devices that map the concepts associated with problems of addiction. Relevant differences were found between the disorder concepts of Turkish and German youth. German but not Turkish youths classified eating disorders among severe addictive disorders and associated them with embarrassment and shame. Concerning substance abuse, German but not Turkish youths clearly differentiated between illegal drug abuse and the abuse of alcohol and nicotine. Nearly half of all Turkish youths rejected central medical concepts such as "physical dependence" or "reduced control of substance intake" as completely inadequate to characterize problems of addictive behavior. Preventive information programs must consider these differences and use concepts that are accepted and clearly associated with addictive behavior by immigrant populations.

  18. Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, a 250-Fold Selective Melanocortin-4 Receptor (MC4R) Antagonist over the Melanocortin-3 Receptor (MC3R), Affects Energy Homeostasis in Male and Female Mice Differently.

    Science.gov (United States)

    Lensing, Cody J; Adank, Danielle N; Doering, Skye R; Wilber, Stacey L; Andreasen, Amy; Schaub, Jay W; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-09-21

    The melanocortin-4 receptor (MC4R) has been indicated as a therapeutic target for metabolic disorders such as anorexia, cachexia, and obesity. The current study investigates the in vivo effects on energy homeostasis of a 15 nM MC4R antagonist SKY2-23-7, Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, that is a 3700 nM melanocortin-3 receptor (MC3R) antagonist with minimal MC3R and MC4R agonist activity. When monitoring both male and female mice in TSE metabolic cages, sex-specific responses were observed in food intake, respiratory exchange ratio (RER), and energy expenditure. A 7.5 nmol dose of SKY2-23-7 increased food intake, increased RER, and trended toward decreasing energy expenditure in male mice. However, this compound had minimal effect on female mice's food intake and RER at the 7.5 nmol dose. A 2.5 nmol dose of SKY2-23-7 significantly increased female food intake, RER, and energy expenditure while having a minimal effect on male mice at this dose. The observed sex differences of SKY2-23-7 administration result in the discovery of a novel chemical probe for elucidating the molecular mechanisms of the sexual dimorphism present within the melanocortin pathway. To further explore the melanocortin sexual dimorphism, hypothalamic gene expression was examined. The mRNA expression of the MC3R and proopiomelanocortin (POMC) were not significantly different between sexes. However, the expression of agouti-related peptide (AGRP) was significantly higher in female mice which may be a possible mechanism for the sex-specific effects observed with SKY2-23-7.

  19. Influence of different dose irradiation on genetic effect in mice somatic and germ cells

    International Nuclear Information System (INIS)

    Kostrova, L.N.; Molofej, V.P.; Mosseh, I.B.

    2007-01-01

    Comparison of clastogenic effects of different radiation doses in somatic and germ cells of one the same animals has been studied. Correlation analysis allows to extrapolate genetic effects from somatic cells to germ ones. This can be useful for human model elaboration. (authors)

  20. 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

  1. Organizational Citizenship Behavior, Job Satisfaction and Commitment to School: Is There Any Significant Difference between Male and Female Teachers?

    Science.gov (United States)

    Jenaabadi, Hossein; Okati, Ehsan; Sarhadi, Aliyavar

    2013-01-01

    This research investigated the gender differences in job satisfaction, organizational commitment and organizational citizenship behavior in sample included 200 male and 200 female teachers and 80 male managers in boy elementary schools in Zahedan. Data was collected by means of questionnaires and was analyzed through Factorial Analysis of…

  2. Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life.

    Science.gov (United States)

    El-Rabbat M, Sarah; Mahmoud, Nermeen K; Gheita, Tamer A

    2017-04-11

    To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. In the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). Fibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. Altered Brain Excitability and Increased Anxiety in Mice With Experimental Colitis: Consideration of Hyperalgesia and Sex Differences

    Directory of Open Access Journals (Sweden)

    Kewir D. Nyuyki

    2018-04-01

    Full Text Available Crohn’s disease (CD and ulcerative colitis (UC are incurable lifelong inflammatory bowel diseases (IBD with a rising worldwide incidence. IBD is characterized by diarrhea, rectal bleeding, severe cramping and weight loss. However, there is a growing evidence that IBD is also associated with anxiety- and depression-related disorders, which further increase the societal burden of these diseases. Given the limited knowledge of central nervous system (CNS changes in IBD, we investigated CNS-related comorbidities in a mouse model of experimental colitis induced by dextran sulfate sodium (DSS administration in drinking water for 5 days. In male and female C57BL6J mice, DSS treatment caused increased brain excitability, revealed by a decrease in seizure onset times after intraperitoneal administration of kainic acid. Moreover, both sexes showed increased anxiety-related behavior in the elevated plus-maze (EPM and open field (OF paradigms. We assessed somatic pain levels, because they may influence behavioral responses. Only male mice were hyperalgesic when tested with calibrated von Frey hairs and on the hotplate for mechanical and thermal pain sensitivity respectively. Administration of diazepam (DZP; ip, 1 mg/kg 30 min before EPM rescued the anxious phenotype and improved locomotion, even though it significantly increased thermal sensitivity in both sexes. This indicates that the altered behavioral response is unlikely attributable to an interference with movement due to somatic pain in females. We show that experimental colitis increases CNS excitability in response to administration of kainic acid, and increases anxiety-related behavior as revealed using the EPM and OF tests.

  4. Effect of the methanolic extracts of different parts of Ferula assa-foetida on naloxone-induced withdrawal behavior in morphine-dependent mice

    Directory of Open Access Journals (Sweden)

    Mahnaz Khanavi

    2017-08-01

    Full Text Available Objective: Ferula assa-foetida, a native species in Iran, is used for treatment of several diseases particularly for neurological disorders in Iranian Traditional Medicine. The aim of this study is to investigate the effect of methanolic roots, fruits, and aerial parts extracts of Ferula assa-foetida on withdrawal syndrome in morphine-dependent mice. Materials and Methods: Aerial parts, roots, and fruits of the plant were separately extracted with 80% MeOH. For induction of dependence, morphine (50, 50 and 75 mg/kg was injected subcutaneously three times daily (10 am, 1 pm and 4 pm for three days and a last dose of morphine (50 mg/kg was administrated on the fourth day. Withdrawal syndrome was induced by injection of naloxone (5 mg/kg, intraperitoneal 2 hr after the final dose of morphine. Different doses of the extracts were administered i.p. 60 minutes before naloxone injection and withdrawal sign was recorded 2 minutes after naloxone injection for a period of 60 minutes.   Results: Pre-treatment of animals with different doses (2.5, 5, 10, 20 mg/kg of methanolic extract of the aerial parts of F. assa-foetida caused a significant decrease in naloxone-induced behavior. Intraperitoneal administration of different doses (10, 15, 20, 25 mg/kg of methanolic extract of the fruit significantly reduced the naloxone-induced withdrawal behavior (p

  5. Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods

    DEFF Research Database (Denmark)

    Pressler, T.; Karpati, F.; Granstrom, M.

    2008-01-01

    to characterize patients with different infection status. Elevated levels of specific anti-Pseudomonas antibodies showed to be the risk factor for developing chronic Pa infection. Due to the specificity of the tests, antibiotic treatment based on serology might be considered in selected cases. There is a window...... of opportunity for suppression and eradication of initial P. aeruginosa infection making measurement of specific anti-Pseudomonas antibodies helpful Udgivelsesdato: 2009/1...

  6. Differences in radiosensitivity among cells in culture and in experimental tumours: Significance for the effectiveness of human cancer therapy

    International Nuclear Information System (INIS)

    Barendsen, G.W.; Amsterdam Univ.

    1987-01-01

    Problems in the application of radiobiological data on various types of models, cell in vitro, experimental tumours, and clinical models, to the prediction of tumour radiocurability are discussed. On the basis of observations on cells in culture and experimental tumours it is suggested that heterogeneity in responsiveness of tumours in patients is caused in a large part by differences in intrinsic cellular radiosensitivity. Methods and developments are reviewed, which may yield better assays for the prediction of tumour responsiveness to treatments. (Auth.)

  7. The Expression of miR-192 and Its Significance in Diabetic Nephropathy Patients with Different Urine Albumin Creatinine Ratio

    Directory of Open Access Journals (Sweden)

    Xiaoyu Ma

    2016-01-01

    Full Text Available Objective. To investigate the expression of miR-192 and its significance in diabetic nephropathy (DN patients. Methods. 464 patients with type 2 diabetes mellitus (T2DM were divided into normal albuminuria group (NA, n=157, microalbuminuria group (MA, n=159, and large amount of albuminuria group (LA, n=148. 127 healthy persons were selected as the control group (NC, n=127. The serum miR-192 levels were detected by Real-Time PCR and transforming growth factor-β1 (TGF-β1 and fibronectin (FN were detected by enzyme-linked immunosorbent assay. The relationships among these parameters were analyzed by Pearson correlation analysis and multiple linear regression analysis. Results. The miR-192 in the LA group was significantly lower than other groups, which was lower in the MA group than in the NA group (P<0.01. The TGF-β1 and FN in the LA group were significantly higher than other groups, which were higher in the MA group than in the NA group (P<0.01. The expression of miR-192 was negatively correlated with TGF-β1, FN, and Ln (UACR and miR-192, TGF-β1, and FN were independent relevant factors affecting Ln (UACR in T2DM (P<0.01. Conclusions. These findings indicate that the levels of miR-192 were lower accompanied by the decrease of urine albumin creatinine ratio (UACR and the association between miR-192 and nephritic fibrosis in DN.

  8. Significant contribution of stacking faults to the strain hardening behavior of Cu-15%Al alloy with different grain sizes.

    Science.gov (United States)

    Tian, Y Z; Zhao, L J; Chen, S; Shibata, A; Zhang, Z F; Tsuji, N

    2015-11-19

    It is commonly accepted that twinning can induce an increase of strain-hardening rate during the tensile process of face-centered cubic (FCC) metals and alloys with low stacking fault energy (SFE). In this study, we explored the grain size effect on the strain-hardening behavior of a Cu-15 at.%Al alloy with low SFE. Instead of twinning, we detected a significant contribution of stacking faults (SFs) irrespective of the grain size even in the initial stage of tensile process. In contrast, twinning was more sensitive to the grain size, and the onset of deformation twins might be postponed to a higher strain with increasing the grain size. In the Cu-15 at.%Al alloy with a mean grain size of 47 μm, there was a stage where the strain-hardening rate increases with strain, and this was mainly induced by the SFs instead of twinning. Thus in parallel with the TWIP effect, we proposed that SFs also contribute significantly to the plasticity of FCC alloys with low SFE.

  9. Acclimatization of mice to different cage types and social groupings with respect to fecal secretion of IgA and corticosterone metabolites

    DEFF Research Database (Denmark)

    Bundgaard, Cathrine Juel; Kalliokoski, Otto; Abelson, Klas Sp

    2012-01-01

    genders were housed either in groups of eight in different cage types in open conventional cages, in Individual Ventilated Cages (IVC), in open conventional cages inside a plastic isolator, or in different group sizes (8, 4, 8, 10 or 12 mice in each group) in open conventional cages. Feces were collected...

  10. Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2009-02-01

    Full Text Available Abstract Background Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines. Methods We investigated the association between intraperitoneal injection of pristine C60 fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE-/- with different degree of atherosclerosis. Results The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium nitroprusside-induced vasorelaxation response in young apoE-/- mice. Conclusion Treatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene treatment. These findings represent an important step in the hazard characterization of C60 fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.

  11. No significant difference in depression rate in employed and unemployed in a pair-matched study design.

    Science.gov (United States)

    Mihai, Adriana; Ricean, Alina; Voidazan, Septimiu

    2014-01-01

    The main objective of this study was to evaluate the differences of depression rate in employed and unemployed persons in the period of financial and economic crisis in Romania, in a pair-matched study design. The cross-sectional study uses a pair match design (395 pairs) of two groups of employed and unemployed persons. Other socio-demographic risk factors of depression (gender, age, marital status, residence, ethnicity, educational level, and profession) were controlled. The study was done in a historical period of economic crisis, 2009-2010. For the screening of depression we used the patient health questionnaire-9. There were no statistical differences (p = 0.054) between the depression rates in the employed (17.98%) and unemployed (23.80%) samples. The depression rate in both groups was higher in females, age (51-55), marital status (divorced), living in the rural area, with a low level of education and poverty. Suicidal ideas are more frequent in men, employed persons with low level of education and in unemployed persons with medium level of education. The exposure to short term unemployment status was not associated with change in depression rate in the period of financial and economic crisis in Romania, comparing with controls pair-matched. Unemployment status increases the depression rate only in vulnerable groups such as single or divorced women; and suicidal ideas were associated with the unemployment status (longer than 8 months) in men from rural area with medium level of education.

  12. No significant difference in depression rate in employed and unemployed in a pair-matched study design

    Directory of Open Access Journals (Sweden)

    Adriana eMihai

    2014-07-01

    Full Text Available The main objective of this study was to evaluate the differences of depression rate in employed and unemployed persons in the period of financial and economic crisis in Romania, in a pair-matched study design.Method: The cross sectional study uses a pair match design (395 pairs of two groups of employed and unemployed persons. Other socio-demographic risk factors of depression (gender, age, marital status, residence, ethnicity, educational level and profession were controlled. The study was done in a historical period of economic crisis, 2009-2010. For the screening of depression we used the Patient Health Questionnaire PHQ – 9.Results: There were no statistical differences (p=0.054 between the depression rates in the employed (17.98% and unemployed (23.80% samples. The depression rate in both groups was higher in females, age (51-55, marital status (divorced, living in the rural area, with a low level of education, poverty. Suicidal ideas are more frequent in men, employed persons with low level of education and in unemployed persons with medium level of education.Conclusion: The exposure to short term unemployment status was not associated with change in depression rate in the period of financial and economic crisis in Romania, comparing with controls pair-matched. Unemployment status increases the depression rate only in vulnerable groups such as single or divorced women; and suicidal ideas were associated with the unemployment status (longer than 8 months in men from rural area with medium level of education.

  13. Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    Full Text Available MicroRNAs (miRNAs are small noncoding RNAs which play essential roles in many important biological processes. Therefore, their dysfunction is associated with a variety of human diseases, including cancer. Increasing evidence shows that miRNAs can act as oncogenes or tumor suppressors, and although there is great interest in research into these cancer-associated miRNAs, little is known about them. In this study, we performed a comprehensive analysis of putative human miRNA oncogenes and tumor suppressors. We found that miRNA oncogenes and tumor suppressors clearly show different patterns in function, evolutionary rate, expression, chromosome distribution, molecule size, free energy, transcription factors, and targets. For example, miRNA oncogenes are located mainly in the amplified regions in human cancers, whereas miRNA tumor suppressors are located mainly in the deleted regions. miRNA oncogenes tend to cleave target mRNAs more frequently than miRNA tumor suppressors. These results indicate that these two types of cancer-associated miRNAs play different roles in cancer formation and development. Moreover, the patterns identified here can discriminate novel miRNA oncogenes and tumor suppressors with a high degree of accuracy. This study represents the first large-scale bioinformatic analysis of human miRNA oncogenes and tumor suppressors. Our findings provide help for not only understanding of miRNAs in cancer but also for the specific identification of novel miRNAs as miRNA oncogenes and tumor suppressors. In addition, the data presented in this study will be valuable for the study of both miRNAs and cancer.

  14. Significant differences in the use of healthcare resources of native-born and foreign born in Spain

    Science.gov (United States)

    Carrasco-Garrido, Pilar; Jiménez-García, Rodrigo; Barrera, Valentin Hernández; de Andrés, Ana López; de Miguel, Ángel Gil

    2009-01-01

    Background In the last decade, the number of foreign residents in Spain has doubled and it has become one of the countries in the European Union with the highest number of immigrants There is no doubt that the health of the immigrant population has become a relevant subject from the point of view of public healthcare. Our study aimed at describing the potential inequalities in the use of healthcare resources and in the lifestyles of the resident immigrant population of Spain. Methods Cross-sectional, epidemiological study from the Spanish National Health Survey (NHS) in 2006, from the Ministry of Health and Consumer Affairs. We have worked with individualized secondary data, collected in the Spanish National Health Survey carried out in 2006 and 2007 (SNHS-06), from the Ministry of Health and Consumer Affairs. The format of the SNHS-06 has been adapted to the requirements of the European project for the carrying out of health surveys. Results The economic immigrant population resident in Spain, present diseases that are similar to those of the indigenous population. The immigrant population shows significantly lower values in the consumption of alcohol, tobacco and physical activity (OR = 0.76; CI 95%: 0.65–0.89, they nonetheless perceive their health condition as worse than that reported by the autochthonous population (OR = 1.63, CI 95%: 1.34–1.97). The probability of the immigrant population using emergency services in the last 12 months was significantly greater than that of the autochthonous population (OR = 1.31, CI 95%: 1.12–1.54). This situation repeats itself when analyzing hospitalization data, with values of probability of being hospitalized greater among immigrants (OR = 1.39, CI 95%: 1.07–1.81). Conclusion The economic immigrants have better parameters in relation to lifestyles, but they have a poor perception of their health. Despite the fact that immigrant population shows higher percentages of emergency attendance and hospitalization than

  15. Peripheral arterial volume distensibility: significant differences with age and blood pressure measured using an applied external pressure

    International Nuclear Information System (INIS)

    Zheng, Dingchang; Murray, Alan

    2011-01-01

    A new arterial distensibility measurement technique was assessed in 100 healthy normotensive subjects. Arterial transmural pressures on the whole right arm were reduced with a 50 cm long cuff inflated to 10, 20, 30 and 40 mmHg. The electrocardiogram, and finger and ear photoplethysmograms were recorded simultaneously. Arm pulse propagation time, pulse wave velocity (PWV) and arterial volume distensibility were determined. With a 40 mmHg reduction in transmural pressure, arm pulse propagation time increased from 61 to 83 ms, PWV decreased from 12 to 8 m s −1 and arterial distensibility increased from 0.102% to 0.232% per mmHg (all P < 0.0001). At all cuff pressures, arterial distensibility was significantly related to resting mean arterial pressure (MAP), diastolic blood pressure (DBP) and age, and for systolic blood pressure at 30 and 40 mmHg (all P < 0.05). At 40 mmHg cuff pressure, arterial distensibility fell by 54% for a MAP increase from 75 to 105 mmHg, 57% for a DBP increase from 60 to 90 mmHg and 47% for an age increase from 20 to 70 years. These changes were more than double than those without cuff pressure. Our technique showed that systemic volume distensibility of the peripheral arm artery reduced with age, with a greater effect at higher external and lower transmural pressures

  16. Influence of affective significance on different levels of processing using pupil dilation in an analogical reasoning task.

    Science.gov (United States)

    Prehn, Kristin; Heekeren, Hauke R; van der Meer, Elke

    2011-02-01

    The present study investigates the interaction of cognition and emotion in decision making, using an analogical reasoning task. In this task, two word pairs were presented simultaneously. Each word pair could be characterized by an associative conceptual relation (object, actor, or location relation) as well as an emotional relation (negative, neutral, or positive valence). Both types of relations were equally task-relevant: Participants had to identify both types of relations, to compare them, and to decide whether or not the word pairs were analogous, i.e., corresponding in both conceptual and emotional relations. Behavioral data showed that emotional relations were identified preferentially and faster than conceptual relations. Pupil dilations reflected the descending difficulty of the conditions and were greatest in amplitude when both conceptual and emotional correspondence was shown, intermediate when only one type of relation (either the emotional or the conceptual) corresponded, and least when neither correspondence existed. Additionally, a negative valence of the word material slowed down response times and increased pupil dilation relative to positive and neutral items. In summary, pupil and response time data together support recent (neurobiological) models concerning the interaction of emotion and cognition by showing that affective significance leads to a processing advantage at a cognitively lower level of information processing (here, identification or retrieval of relations from long-term memory) but can also distract people from higher level cognitive processes (here, from the controlled comparison of retrieved relations). Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Differences in self-regulatory skills among talented athletes: the significance of competitive level and type of sport.

    Science.gov (United States)

    Jonker, Laura; Elferink-Gemser, Marije T; Visscher, Chris

    2010-06-01

    Research has shown that talented athletes outscore their mainstream peers on the basis of self-regulation. Although valuable, this does not tell us more about the distinction between good athletes and the best, which is a prerequisite in talent development. Therefore, we examined the self-regulatory skills of 222 male and female talented athletes aged 12-16 years as a function of competitive sport level (junior international or junior national athletes) and type of sport (individual or team sports). Multivariate analyses of covariance in combination with a discriminant function analysis revealed that "reflection" distinguishes between athletes at the highest levels of excellence. Furthermore, athletes playing individual sports had higher scores on "planning" and "effort" than team sport athletes, highlighting the importance of differences between types of sport. In conclusion, we emphasize the importance of reflection as a self-regulatory skill. Reflection facilitates the development of sport-specific characteristics, which may vary by type of sport. This means that an advanced sense of reflection may help talented athletes to acquire desirable characteristics during their "talent" years to ultimately reach adult elite levels of competition.

  18. Characteristic differences in essential oil composition of six Zanthoxylum bungeanum Maxim. (Rutaceae) cultivars and their biological significance.

    Science.gov (United States)

    Liu, Shu-Ming; Wang, Shi-Jun; Song, Si-Yao; Zou, Yong; Wang, Jun-Ru; Sun, Bing-Yin

    Great variations have been found in composition and content of the essential oil of Zanthoxylum bungeanum Maxim. (Rutaceae), resulting from various factors such as harvest time, drying and extraction methods (Huang et al., 2006; Shao et al., 2013), solvent and herbal parts used (Zhang, 1996; Cao and Zhang, 2010; Wang et al., 2011). However, in terms of artificial introduction and cultivation, there is little research on the chemical composition of essential oil extracted from Z. bungeanum Maxim. cultivars, which have been introduced from different origins. In this study, the composition and content of essential oil from six cultivars (I-VI) have been investigated. They were introduced and cultivated for 11 years in the same cultivation conditions. Cultivars were as followings: Qin'an (I) cultivar originally introduced from Qin'an City in Gansu Province; Dahongpao A (II) from She County in Hebei Province; Dahongpao B (III) from Fuping County; Dahongpao C (IV) from Tongchuan City; Meifengjiao (V) from Feng County; and, Shizitou (VI) from Hancheng City, in Shaanxi Province, China. This research is expected to provide a theoretical basis for further introduction, cultivation, and commercial development of Z. bungeanum Maxim.

  19. Making a difference? Societal entrepreneurship and its significance for a practical theological ecclesiology in a local Western Cape context

    Directory of Open Access Journals (Sweden)

    Ignatius Swart

    2011-10-01

    Full Text Available This article is concerned with the question of whether and how a local church or congregation can, as indissoluble dimension of its vocation as a Christian faith agent, make a difference by influencing the dynamics of social and economic change that are transforming the face and structures of ‘traditional’ social and religious life in its community. Based upon the authors’ own interest in the specific context of the Dutch Reformed congregation of Simondium in the Western Cape and the case study work that they have conducted in this context, an argument about the potential role of this congregation is developed through the conceptual lens of ‘societal entrepreneurship’. After exploring some recent thoughts on this concept in the literature, the authors use the results of their recently conducted case study work to show how the dynamics of a new entrepreneurial drive amongst long-established residents and newcomers in the Simondium region shape the social reality of both the region and the congregation in a forceful way. This insight leads the authors to develop a sociologically and theologically motivated argument about the way in which this changing reality offers newfound opportunities to the Simondium congregation to fulfil its Christian calling. As such, the notion of becoming an ‘entrepreneurial church’ is introduced and a more detailed perspective is offered on those factors that a contextually orientated practical theological ecclesiology should take into account in building the entrepreneurial model in the congregation.

  20. Garden and Landscape-Scale Correlates of Moths of Differing Conservation Status: Significant Effects of Urbanization and Habitat Diversity

    Science.gov (United States)

    Bates, Adam J.; Sadler, Jon P.; Grundy, Dave; Lowe, Norman; Davis, George; Baker, David; Bridge, Malcolm; Freestone, Roger; Gardner, David; Gibson, Chris; Hemming, Robin; Howarth, Stephen; Orridge, Steve; Shaw, Mark; Tams, Tom; Young, Heather

    2014-01-01

    Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria. However, vulnerable species were more strongly negatively affected by urbanization than increasing species. Two hypotheses are proposed to explain this observation: (1) that the underlying factors causing declines in vulnerable species (e.g., possibilities include fragmentation, habitat deterioration, agrochemical pollution) across Britain are the same in urban areas, but that these deleterious effects are more intense in urban areas; and/or (2) that urban areas can act as ecological traps for some vulnerable species of

  1. Different surgical strategies for chronic pancreatitis significantly improve long-term outcome: a comparative single center study

    Directory of Open Access Journals (Sweden)

    Hildebrand P

    2010-08-01

    Full Text Available Abstract Objective In general, chronic pancreatitis (CP primarily requires conservative treatment. The chronic pain syndrome and complications make patients seek surgical advice, frequently after years of progression. In the past, surgical procedures involving drainage as well as resection have been employed successfully. The present study compared the different surgical strategies. Patients and Methods From March 2000 until April 2005, a total of 51 patients underwent surgical treatment for CP at the Department of surgery, University of Schleswig-Holstein, Campus Lübeck. Out of those 51 patients, 39 (76.5% were operated according to the Frey procedure, and in 12 cases (23.5% the Whipple procedure was performed. Patient data were documented prospectively throughout the duration of the hospital stay. The evaluation of the postoperative pain score was carried out retrospectively with a validated questionnaire. Results Average operating time was 240 minutes for the Frey group and 411 minutes for the Whipple group. The medium number of blood transfusions was 1 in the Frey group and 4.5 in the Whipple group. Overall morbidity was 21% in the Frey group and 42% in the Whipple group. 30-day mortality was zero for all patients. During the median follow-up period of 50 months, an improvement in pain score was observed in 93% of the patients of the Frey group and 67% of the patients treated according to the Whipple procedure. Conclusion The results show that both the Frey procedure as well as partial pancreaticoduodenectomy are capable of improving chronic pain symptoms in CP. As far as later endocrine and exocrine pancreatic insufficiency is concerned, however, the extended drainage operation according to Frey proves to be advantageous compared to the traditional resection procedure by Whipple. Accordingly, the Frey procedure provides us with an organ-preserving surgical procedure which treats the complications of CP sufficiently, thus being an

  2. Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity.

    Directory of Open Access Journals (Sweden)

    Adam J Bates

    Full Text Available Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union criteria. However, vulnerable species were more strongly negatively affected by urbanization than increasing species. Two hypotheses are proposed to explain this observation: (1 that the underlying factors causing declines in vulnerable species (e.g., possibilities include fragmentation, habitat deterioration, agrochemical pollution across Britain are the same in urban areas, but that these deleterious effects are more intense in urban areas; and/or (2 that urban areas can act as ecological traps for some

  3. Significance and function of different spinal collateral compartments following thoracic aortic surgery: immediate versus long-term flow compensation.

    Science.gov (United States)

    Meffert, Philipp; Bischoff, Moritz S; Brenner, Robert; Siepe, Matthias; Beyersdorf, Friedhelm; Kari, Fabian A

    2014-05-01

    Iatrogenic paraplegia has been accompanying cardiovascular surgery since its beginning. As a result, surgeons have been developing many theories about the exact mechanisms of this devastating complication. Thus, the impact of single arteries that contribute to the spinal perfusion is one of the most discussed subjects in modern surgery. The subsequent decision of reattachment or the permanent disconnection of these intercostal arteries divides the surgical community. On the one hand, the anatomical or vascular approach pleads for the immediate reimplantation to reconstruct the anatomical situation. On the other hand, the decision of the permanent disconnection aims at avoiding stealing phenomenon away from the spinal vascular network. This spinal collateral network can be described as consisting of three components-the intraspinal and two paraspinal compartments-that feed the nutrient arteries of the spinal cord. The exact functional impact of the different compartments of the collateral network remains poorly understood. In this review, the function of the intraspinal compartment in the context of collateral network principle as an immediate emergency backup system is described. The exact structure and architectural principles of the intraspinal compartment are described. The critical parameters with regard to the risk of postoperative spinal cord ischaemia are the number of anterior radiculomedullary arteries (ARMAs) and the distance between them in relation to the longitudinal extent of aortic disease. The paraspinal network as a sleeping reserve is proposed as the long-term backup system. This sleeping reserve has to be activated by arteriogenic stimuli. These are presented briefly, and prior findings regarding arteriogenesis are discussed in the light of the collateral network concept. Finally, the role of preoperative visualization of the ARMAs in order to evaluate the risk of postoperative paraplegia is emphasized.

  4. Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice

    Directory of Open Access Journals (Sweden)

    Dahlén Sven-Erik

    2008-02-01

    Full Text Available Abstract Background Deep inspirations (DI have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation. Methods Balb/c mice were sensitized to ovalbumin (OVA and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics. Results DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH2O·s·mL-1 in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH2O·s·mL-1 in acute airway inflammation (both P P P P P Conclusion We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

  5. Superfund explanation of significant difference for the record of decision (EPA Region 3): Westinghouse Elevator Company Plant, Gettysburg, PA, August 3, 1998

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    The document explains significant differences to the remedy selected in the Record of Decision (ROD) for the Site signed by the Regional Administrator on June 30, 1992 (PB93-963911) for Operable Unit 1. The Significant Difference between the remedy presented in the June 30, 1992 ROD and the changes to the ROD that will be implemented are explained.

  6. Comparative efficiency of three different tests for estimation mutogenicity of some factors in mammals. 2. The frequency of abnormal spermhead in mice treated with different factors

    International Nuclear Information System (INIS)

    Pomerantseva, M.D.; Ramaya, L.K.; Vilkina, G.A.

    1980-01-01

    The effect of certain chemical and physical factors, such as cyclophosphamide (CP) N-nitroso-N-methylurea (NMU), N-nitrosomorpholine (NM); CdCl 2 ; ZnCl 2 microwaves of superhigh frequency (SHF) and 60 Co γ rays on the frequency of anomalous spermatozoon head (ASH) in hybrid F 1 male mice (CBAxC57 BL) is studied. The factors which have a mutagenous effect found using the test of accounting the frequency of dominant lethal mutations (DLM) and chromosomal aberrations in marrow cells (CP, NMU and 60 Co γ-rays) increased the frequency 35 days after effect in maximum doses. CdCl 2 which has not caused the increase of DLM freouency also increased ASH frequency. The increase of ASH frequency in all the cases is accompanied by the decrease in the spermatory-weight, the increase of pre-implantation losses and the decrease of the level of effective matings at the effect on premitotic cells. This points out to the fact that ASH reflects not only mutagenous but also cytolytic and/or cytotoxic effects, ASH test can be used to prescreen mutageneity of different factors when using them in rather high doses [ru

  7. 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

  8. Differences in the effects of 5-HT1A receptor agonists on forced swimming behavior and brain 5-HT metabolism between low and high aggressive mice

    NARCIS (Netherlands)

    Veenema, AH; Cremers, TIFH; Jongsma, ME; Steenbergen, PJ; de Boer, SF; Koolhaas, JM; Jongsma, Minke E.

    Rationale: Male wild house- mice genetically selected for long attack latency ( LAL) and short attack latency ( SAL) differ in structural and functional properties of postsynaptic serotonergic- 1A ( 5- HT1A) receptors. These mouse lines also show divergent behavioral responses in the forced swimming

  9. 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

  10. 不同频率音乐对小鼠空间学习记忆能力的影响%Impact of music of different frequencies on the spatial learning and memory ability of mice

    Institute of Scientific and Technical Information of China (English)

    袁徐蕾; 杨梅; 韩文莉; 谭冬梅; 范尧; 谭毅

    2017-01-01

    目的 初步探究音乐对成年小鼠学习记忆能力是否产生影响.方法 80只C57小鼠随机分成10组,每组雌雄各半.空白对照组:不给予音乐刺激,高频音乐3组、中频音乐3组、低频音乐3组,分别用高频、中频、低频各3首进行音乐刺激,每天5 h,连续6 d.第7天进行水迷宫测试,期间保持音乐刺激不变,测试指标为潜伏期,经过平台次数和平台象限停留时间.结果 音乐组与空白组相比,小鼠逃避潜伏期明显缩短(P0.05).各音乐组之间检测指标差异无显著性(P>0.05).结论 所选9首音乐能提高成年小鼠学习记忆能力,而不同频率音乐之间产生的影响未发现显著性差异.推测音乐刺激对小鼠的影响与音乐分类的标准、刺激周期长短、刺激时间点选择等因素密切相关.%Objective To explore the impact of music of different frequencies on the spatial learning and memory a?bility of mice. Methods A total of 80 healthy 6~8 weeks old C57 mice were randomly divided into 10 groups, half male and half female in each group. The mice in the control group were not stimulated by music. The mice of the 3 groups of high?frequency music, 3 groups of medium?frequency music and 3 groups of low?frequency music were stimulated by music in cor?responding range of frequency, respectively, for 5 h each day. After 6 d, the ability of spatial learning and memory of the mice was tested in the Morris water maze, with the same stimulation of music during the test. The indicators of the test in?cluded the avoiding latency, the frequency of passing the platform and the time spent to pass the quadrant of the mice in each group. Results Compared with the control group, the avoiding latency of the mice in the groups with stimulation by music was significantly shorter (P 0. 05). Moreover, there was no significant difference between the indica?tors of the 9 groups receiving music stimulation (P> 0. 05). Conclusions The 9 pieces of music we have

  11. Dietary analysis of Late Cenozoic Mexican equids from three different geographic/geologic settings using stable carbon isotopes: Coincidences, differences and paleobiologic significance

    Science.gov (United States)

    Pérez-Crespo, Víctor Adrian; Ferrusquía-Villafranca, Ismael; Bravo-Cuevas, Víctor Manuel; Morales-Puente, Pedro; Ruiz-González, José E.

    2016-03-01

    The development of Vertebrate Paleontology in Mexico is uneven, so that there is a strong bias in favor of Neogene/Quaternary mammals largely collected in the Trans-Mexican Volcanic Belt (TMVB hereafter) and Central Plateau (CeP hereafter) Morphotectonic Provinces [MP hereafter]; however, the time is ripe for pursuing research in other than taxonomic areas. Here we investigate C3/C4 plant consumption in the equid lineage in three such provinces, which provide different geographic/geologic and paleoecologic scenarios during the Barstovian, Hemphillian and Rancholabrean times. Our results show that the Barstovian equids from Oaxaca, Sierra Madre del Sur MP Cormohipparion aff. C. quinni, Merychippus cf. M. sejunctus and Pliohippus sp. largely fed on C3 plants, which were the chief food stuff of horses in Mexico, particularly in the Southeast. On the other hand, the Hemphillian equid from Guanajuato, CeP Astrohippus stocki, was an unbalanced C3/C4 mixed feeders in favor of C4 plants, a fact that indicates a profound plant diversification due to the inception and rapid diversification of C4 plants that occurred there at this time, as it occurred in temperate North America, resulting in the differential consumption of C4 plants over that of C3 plants. Such trend prevailed until the Rancholabrean, as born out by the inferred diet for Equus conversidens and Equus sp. from Hidalgo, TMVB. Clearly then, the coeval diet change observed in Mexico and temperate North America implies a correlative vegetation change resulting in the appearance and rapid diversification of C4 plants, which largely formed the preferred food stuff of equids since the Hemphillian, although some C3 plant consumption was maintained till the Rancholabrean. It should be noted that the development of hypsodonty in equids and many artiodactyls, has long been interpreted as the adaptive mammalian response to the new feeding conditions.

  12. 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.

  13. 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

  14. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice.

    Science.gov (United States)

    Mineur, Yann S; Bentham, Matthew P; Zhou, Wen-Liang; Plantenga, Margreet E; McKee, Sherry A; Picciotto, Marina R

    2015-10-01

    The a2A-noradrenergic agonist guanfacine can decreases stress-induced smoking in female, but not male, human smokers. It is not known whether these effects are due to effects on mood regulation and/or result from nicotinic-cholinergic interactions. The objective of the study was to determine whether there are sex differences in the effect of guanfacine in tests of anxiolytic and antidepressant efficacy in mice at baseline and in a hypercholinergic model of depression induced by the acetylcholinesterase inhibitor physostigmine. The effects of guanfacine were measured in the light/dark box, tail suspension, and the forced swim test in female and male C57BL/6J mice. In parallel, electrophysiological properties were evaluated in the prefrontal cortex, a critical brain region involved in stress responses. c-fos immunoreactivity was measured in other brain regions known to regulate mood. Despite a baseline sex difference in behavior in the forced swim test (female mice were more immobile), guanfacine had similar, dose-dependent, antidepressant-like effects in mice of both sexes (optimal dose, 0.15 mg/kg). An antidepressant-like effect of guanfacine was also observed following pre-treatment with physostigmine. A sex difference in the paired-pulse ratio in the prefrontal cortex (PFC) (male, 1.4; female, 2.1) was observed at baseline that was normalized by guanfacine. Other brain areas involved in cholinergic control of depression-like behaviors, including the basolateral amygdala and lateral septum, showed sex-specific changes in c-fos expression. Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased acetylcholine (ACh) signaling. These data suggest that different brain areas are recruited in female and male mice, despite similar behavioral responses to guanfacine.

  15. Zinc metabolism in genetically obese mice

    International Nuclear Information System (INIS)

    Kennedy, M.L.; Failla, M.L.

    1986-01-01

    Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When administered 0.1 and 1 umole 65 Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of 65 Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of 65 Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of 65 Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice

  16. Sex-Specific Diurnal Immobility Induced by Forced Swim Test in Wild Type and Clock Gene Deficient Mice

    Directory of Open Access Journals (Sweden)

    Ningyue Li

    2015-03-01

    Full Text Available Objective: The link between alterations in circadian rhythms and depression are well established, but the underlying mechanisms are far less elucidated. We investigated the circadian characteristics of immobility behavior in wild type (WT mice and mice with mutations in core Clock genes. Methods: All mice were tested with forced swim test (FST at 4 h intervals. Results: These experiments revealed significant diurnal rhythms associated with immobility behavior in both male and female WT mice with sex-different circadian properties. In addition, male mice showed significantly less immobility during the night phase in comparison to female mice. Female Per1Brdm1 mice also showed significant rhythmicity. However, the timing of rhythmicity was very different from that observed in female wild type mice. Male Per1Brdm1 mice showed a pattern of rhythmicity similar to that of wild type mice. Furthermore, female Per1Brdm1 mice showed higher duration of immobility in comparison to male Per1Brdm1 mice in both daytime and early night phases. Neither Per2Brdm1 nor ClockΔ19 mice showed significant rhythmicity, but both female Per2Brdm1 and ClockΔ19 mice had lower levels of immobility, compared to males. Conclusions: This study highlights the differences in the circadian characteristics of immobility induced by FST in WT, ClockΔ19, Per1, and Per2 deficient mice.

  17. Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

    Directory of Open Access Journals (Sweden)

    Nuernberg Karin

    2011-08-01

    Full Text Available Abstract Background Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue. Methods The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6 leading to rapid obesity development, or selected for high treadmill performance (DUhTP leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein, or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways. Results Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue. Conclusions A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.

  18. Reduced alcohol consumption in mice lacking preprodynorphin.

    Science.gov (United States)

    Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

    2006-10-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

  19. Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

    Directory of Open Access Journals (Sweden)

    Amanda Clause

    2017-06-01

    Full Text Available Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing.

  20. NEUROTROPHINS OPERATE AT DIFFERENT LEVELS OF THE RESPIRATORY TRACT IN RESPONSES OF ALLERGIC MICE TO DIESEL EXHAUST PARTICLES (DEP)

    Science.gov (United States)

    Neurotrophins including NGF, NT-3, and BDNF are linked to allergic responses. Treatment with anti-p75 (pan-neurotrophin receptor) prevents the increase in airflow obstruction caused by exposure to DEP in ovalbumin (OVA)-allergic mice (Toxicol Sci 84(S1):91, 2005). Our present goa...

  1. Behavioral phenotype and BDNF differences related to apoE isoforms and sex in young transgenic mice

    DEFF Research Database (Denmark)

    Reverte, Ingrid; Klein, Anders Bue; Ratner, Cecilia

    2012-01-01

    , very little information is available on apoE2 genotype. In the present study, we have characterized behavioral and learning phenotypes in young transgenic mice apoE2, apoE3 and apoE4 of both sexes. We have also determined the levels of brain-derived neurotrophic factor (BDNF) and its receptor Trk...

  2. Induction of TNF-alfa and CXCL-2 mRNAs in different organs of mice infected with pathogenic Leptospira.

    Science.gov (United States)

    da Silva, Josefa B; Carvalho, Enéas; Covarrubias, Ambart E; Ching, Ana Tung C; Mattaraia, Vania G M; Paiva, Delhi; de Franco, Marcelo; Fávaro, Regiane Degan; Pereira, Martha M; Vasconcellos, Silvio; Zorn, Telma T M; Ho, Paulo Lee; Martins, Elizabeth A L

    2012-04-01

    The role of innate immune response in protection against leptospirosis is poorly understood. We examined the expression of the chemokine CXCL2/MIP-2 and the cytokine TNF-α in experimental resistant and susceptible mice models, C3H/HeJ, C3H/HePas and BALB/c strains, using a virulent strain of Leptospira interrogans serovar Copenhageni. Animals were infected intraperitoneally with 10(7) cells and the development of the disease was followed. Mortality of C3H/HeJ mice was observed whereas C3H/HePas presented jaundice and BALB/c mice remained asymptomatic. The infection was confirmed by the presence of leptospiral DNA in the organs of the animals, demonstrated by PCR. Sections of the organs were analyzed, after H&E stain. The relative expression of mRNA of chemokine CXCL2/MIP-2 and cytokine TNF-α was measured in lung, kidney and liver of the mice by qPCR. The concentrations of these proteins were measured in extracts of tissues and in serum of the animals, by ELISA. Increasing levels of transcripts and protein CXCL2/MIP-2 were detected since the first day of infection. The highest expression was observed at third day of infection in kidney, liver and lung of BALB/c mice. In C3H/HeJ the expression of CXCL2/MIP-2 was delayed, showing highest protein concentration in lung and kidney at the 5th day. Increasing in TNF-α transcripts were detected after infection, in kidney and liver of animals from the three mice strains. The expression of TNF-α protein in C3H/HeJ was also delayed, being detected in kidney and lung. Our data demonstrated that Leptospira infection stimulates early expression of CXCL2/MIP-2 and TNF-α in the resistant strain of mice. Histological analysis suggests that the expression of those molecules may be related to the influx of distinct immune cells and plays a role in the naturally acquired protective immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Two types of T helper cells in mice: Differences in cellular immune functions and cytokine secretion - selective reduction of one type after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bass, H.Z.

    1989-01-01

    As observed from a large panel of mouse T helper clones, there are at least two subsets of CD4 + T cells that both differ in function and demonstrate distinct patterns of cytokine secretion after antigen or mitogen stimulation. Th1 cells synthesize IL-2, INF-γ and lymphotoxin. They produce a DTH reaction in the footpads of naive mice. In addition, Th1 cells are required for the generation of CTL, and they appear to augment IgG2a antibody production. In contrast, by secreting IL-4, IL-5, and IL-6, Th2 cells play an essential role in humoral immunity. TLI consists of high dose, fractionated irradiation delivered selectively to the major lymphoid tissues. Four to six weeks after TLI, the CD4 + cells of the treated mice (counted as a percentage of the total spleen lymphocytes) recover to the similar levels as those in normal BALB/c mice. These CD4 + cells can help normal syngeneic B cells to produce a vigorous antibody response to TNP-KLH in adoptive cell transfer experiments, but the same cells are inactive in the MLR, and they fail to transfer DTH in TNP-KLH primed syngeneic BALB/c mice

  4. Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Bechtold, W.E.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

    1988-01-01

    Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene, were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity

  5. Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice.

    Directory of Open Access Journals (Sweden)

    Marie-Eve Laramée

    Full Text Available In blind individuals, visually deprived occipital areas are activated by non-visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An, was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed.

  6. Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice.

    Science.gov (United States)

    Laramée, Marie-Eve; Smolders, Katrien; Hu, Tjing-Tjing; Bronchti, Gilles; Boire, Denis; Arckens, Lutgarde

    2016-01-01

    In blind individuals, visually deprived occipital areas are activated by non-visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An), was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed.

  7. Measurement of DNA breakage and breakage repair in mice spleen cells induced by ionizing radiation

    International Nuclear Information System (INIS)

    Wang Qin; Xue Jingying; Li Jin; Mu Chuanjie; Fan Feiyue

    2007-01-01

    Objective: To investigate the radioresistance mechanism of IBM-2 mice through measuring DNA single-strand break(SSB) and double-strands break (DSB) as well as their repair. Methods: Pulsed-field gel electrophoresis was used to measure DSB and SSB in IRM-2 mice and their parental mice ICR/JCL and 615 mice after exposure to different doses of γ-ray at different postirradiation time. Results: The initial DNA damages, ie the quantities of DSB and SSB in unirradiation IRM-2 mice were less serious than that of their parental mice ICR/JCL and 615 alice(P<0.01). The percent- age of DSB and SSB in IBM -2 mice was significantly lower than that of ICB/JCL and 615 mice after exposure to various doses of γ-ray(P<0.01 and P<0.05). There were not statistic differences in DSB and SSB repair between IRM-2 mice and their parental mice after exposure to 2Gy radiation. The DNA damage repair rate induced by 4Gy and 8Gy radiation in IRM - 2 mice was rapid, ie the repair rate of SSB and DSB after 0.5h and 1h postirradiation in IRM-2 mice was higher than that of their' parental mice (P<0.01 and P<0.05). And remaining damages after repair in IRM-2 mice were lower than that of ICR/JCL and 615 mice. Conclusion: The DNA damages in IBM-2 mice were lower than that of their parental mice after exposure to ionizing radiation. Moreover, the repair rate of SSB and DSB was higher than that of their parental mice, which perhaps were the radioresistance causes of IBM-2 mice. Therefore IRM-2 mice are naturally resistant to DNA damages induced by ionizing radiation. (authors)

  8. Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin.

    Science.gov (United States)

    Latour, Chloé; Besson-Fournier, Céline; Meynard, Delphine; Silvestri, Laura; Gourbeyre, Ophélie; Aguilar-Martinez, Patricia; Schmidt, Paul J; Fleming, Mark D; Roth, Marie-Paule; Coppin, Hélène

    2016-01-01

    Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor-2 (TfR2), and hemojuvelin (HJV) genes. However, it is still not clear whether these molecules intersect in vivo with bone morphogenetic protein 6 (BMP6)/mothers against decapentaplegic (SMAD) homolog signaling, the main pathway up-regulating hepcidin expression in response to elevated hepatic iron. To answer this question, we produced double knockout mice for Bmp6 and β2-microglobulin (a surrogate for the loss of Hfe) and for Bmp6 and Tfr2, and we compared their phenotype (hepcidin expression, Bmp/Smad signaling, hepatic and extrahepatic tissue iron accumulation) with that of single Bmp6-deficient mice and that of mice deficient for Hjv, alone or in combination with Hfe or Tfr2. Whereas the phenotype of Hjv-deficient females was not affected by loss of Hfe or Tfr2, that of Bmp6-deficient females was considerably worsened, with decreased Smad5 phosphorylation, compared with single Bmp6-deficient mice, further repression of hepcidin gene expression, undetectable serum hepcidin, and massive iron accumulation not only in the liver but also in the pancreas, the heart, and the kidneys. These results show that (1) BMP6 does not require HJV to transduce signal to hepcidin in response to intracellular iron, even if the loss of HJV partly reduces this signal, (2) another BMP ligand can replace BMP6 and significantly induce hepcidin expression in response to extracellular iron, and (3) BMP6 alone is as efficient at inducing hepcidin as the other BMPs in association with the HJV/HFE/TfR2 complex; they provide an explanation for the compensatory effect of BMP6 treatment on the molecular defect underlying Hfe hemochromatosis in mice. © 2015 by the American Association for the Study of Liver Diseases.

  9. Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.

    Directory of Open Access Journals (Sweden)

    Wing-Hon Lai

    Full Text Available Functional endothelial-like cells (EC have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC, human embryonic stem cells (hESC-EC and human induced pluripotent stem cells (hiPSC-EC, and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC and BM-EC (P>0.05. While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05, the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05. Compared with medium, transplanting BM-EC (n = 6, HUVEC (n = 6, hESC-EC (n = 8 or hiPSC-EC (n = 8 significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as "off-the-shelf" format for the treatment

  10. Attenuation of Hind-Limb Ischemia in Mice with Endothelial-Like Cells Derived from Different Sources of Human Stem Cells

    Science.gov (United States)

    Chan, Yau-Chi; Ng, Joyce H. L.; Au, Ka-Wing; Wong, Lai-Yung; Siu, Chung-Wah; Tse, Hung-Fat

    2013-01-01

    Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as “off-the-shelf” format for the treatment of

  11. Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity.

    Science.gov (United States)

    Kadiyala, Sridhar B; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M; Jayakumar, Sachidhanand; Herron, Bruce J; Ferland, Russell J

    2015-01-01

    Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2's seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ∼85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype

  12. Activity of Catalase (CAT, ALT and AST in Different Organs of Swiss Albino Mice Treated with Lead Acetate, Vitamin C and Magnesium-L-Threonate

    Directory of Open Access Journals (Sweden)

    Ilir Nazmi Mazreku

    2017-11-01

    Full Text Available Introduction: Lead is a natural element with toxic properties and is widespread in the environment. Lead toxicity is associated with generation of reactive oxygen and nitrogen species and consumption of antioxidants elements (vitamin E and C, glutathione, thioredoxin and lipoic acid, melatonin, carotenoids and natural flavonoids in the cell, and unbalancing oxidantsantioxidants levels. Aim: To evaluate the effects of different chemical combinations (lead acetate, Vitamin C and Magnesium-L-threonate on antioxidant enzyme activity (catalase-CAT of liver, kidney, spleen, pancreas and brain, and serum transaminases [Serum Alanine Transaminase (ALT and Serum Aspartate Transaminase (AST]. Materials and Methods: Experimental animals (49 male Mus musculus-swiss albino mice were separated into five different groups. The first group was used as a control, hence the other four groups were treated with sub-lethal doses (90 mg/kg of lead acetate (group 2, lead acetate (90 mg/kg and Vitamin C dose 40mg/kg (group 3, lead acetate (90 mg/kg and Magnesium-Lthreonate dose 100 mg/kg (group 4 and only with MagnesiumL-threonate dose 100 mg/kg (group 5, during the treatment period (40 days. Blood samples were taken from the facial vein and used for transaminase analysis. Organ tissue was collected after euthanizing anaesthetized animals with neck dislocation technique. Results: The results showed that lead acetate treatment has caused significant elevation in the activity of AST (group 2 and 3 and ALT (group 3. Also, CAT activity was significantly (p<0.05 increased in groups treated with lead acetate (liver, pancreas, kidney and brain but not in spleen. Treatment of lead intoxicated groups with Vitamin C and Magnesium L-threonate increased significantly CAT activity in brain. Conclusion: Lead effects by interacting with different molecular systems and increasing enzyme activity (CAT, ALT and AST. Effects on CAT activity of Magnesium-L-threonate and Vitamin C treatment

  13. The effect of 2 different housing systems on germ-free mice colonized with a complex gut microbiota

    DEFF Research Database (Denmark)

    Lundberg, Randi; Toft, Martin Fitzner; August, Benjamin

    2015-01-01

    Translational animal models are essential prerequisites in exploring functions and causality of the microbiome in human health and disease. Animal models targeted at microbiome research can be germ-free mice inoculated either with a monoculture or with defined (gnotobiotic) or undefined bacterial......, but there is a lack of knowledge on the stability of complex bacterial communities in IVCs. Germ-free SW mice were inoculated with a complex murine microbiota, housed in an isolator or in IVCs and bred for two generations, corresponding to a time course of 5 months. The gut microbiota was characterized by 16S...... Biosciences and Innovation Fund Denmark. The project is a collaboration between Taconic Biosciences, University of Copenhagen and the 3G Centre (Gut, Grain and Greens)....

  14. Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets

    Directory of Open Access Journals (Sweden)

    Sunhye Shin

    2018-02-01

    Full Text Available Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON or high-fat diets (HFD containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB, olive oil (oleic acid-rich oil; OO, safflower oil (linoleic acid-rich oil; SFO, or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo.

  15. Photoprotection against the UVB-induced oxidative stress and epidermal damage in mice using leaves of three different varieties of Lepidium meyenii (maca).

    Science.gov (United States)

    Gonzales-Castañeda, Cynthia; Rivera, Valery; Chirinos, Ana Lucía; Evelson, Pablo; Gonzales, Gustavo Francisco

    2011-08-01

    Skin exposure to ultraviolet (UV) B radiation leads to epidermal damage and generation of reactive oxygen species. The photoprotective effect of extracts of three varieties of leaves (red, yellow, and black) from maca (Lepidium meyenii), a plant from the Peruvian highlands, was assessed in mouse skin exposed to UVB radiation. The hydroalcoholic extracts of three varieties of maca leaves were applied topically to the dorsal skin of young-adult male mice prior to exposition to UVB radiation. The three varieties had UVA/UVB absorptive properties and presented antioxidant activity, being highest with red maca, followed by black and yellow maca. The three varieties of maca leaves prevented the development of sunburn cells, epidermal hyperplasia, leukocytic infiltration, and other alterations produced by UVB radiation. Mice treated with black maca showed the highest superoxide dismutase levels, and mice treated with black and yellow maca showed higher catalase levels in skin, whereas red maca protected the skin and liver against significant increases in the lipid peroxidation activity observed in the unprotected animals. The presence of significant antioxidant activity and the inhibition of lipid peroxidation suggest that the observed protection could be partly attributable to this mechanism. © 2011 The International Society of Dermatology.

  16. Quality of Life for Individuals with Hearing Impairment Who Have Not Consulted for Services and Their Significant Others: Same- and Different-Sex Couples

    Science.gov (United States)

    Kelly, Rebecca J.; Atcherson, Samuel R.

    2011-01-01

    The purpose of this exploratory study was to assess perceptions of quality of life for individuals with hearing impairment who have not consulted for services and their significant others who are in same-sex relationships vs. those who are in different-sex relationships. Data were collected on a total of 20 older couples: 10 in same-sex…

  17. Effect of antimicrobial ther