Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

Science.gov (United States)

Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-12-01

Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

Genetic effects of feeding irradiated wheat to mice

International Nuclear Information System (INIS)

Vijayalaxmi

1976-01-01

The effects of feeding irradiated wheat in mice on bone marrow and testis chromosomes, germ cell numbers and dominant lethal mutations were investigated. Feeding of freshly irradiated wheat resulted in significantly increased incidence of polyploid cells in bone marrow, aneuploid cells in testis, reduction in number of spermatogonia of types A, B and resting primary spermatocytes as well as a higher mutagenic index. Such a response was not observed when mice were fed stored irradiated wheat. Also there was no difference between the mice fed un-irradiated wheat and stored irradiated wheat. (author)

The effect of endotoxin on preirradiated mice

Energy Technology Data Exchange (ETDEWEB)

Oehlert, W.; Oehlert, M. (Freiburg Univ. (Germany). Inst. fuer Pathologie); Moenig, H.; Konermann, G. (Freiburg Univ. (Germany). Inst. fuer Biophysik und Strahlenbiologie)

1992-12-01

Adult male mice were given a whole body irradiation with non-lethal doses of 2.5 or 5 Gy. Unirradiated animals served as controls. The animals (including controls) received a single injection of endotoxin (LPS from Salmonella abortus equi) with doses of 100, 200 or 400 [mu]g one day up to one year after irradiation. Twelve, 24 or 48 hours after lipopolysaccharide (LPS) application the animals were killed and dissected. Animals which died spontaneously were also examined. Liver, lung, kidney, small intestine, and stomach were histologically investigated. The histological findings showed, that differences exist between irradiated and unirradiated mice and that the cause of death is also different for animals dying spontaneously. The investigations have shown that after irradiation phases of different degrees of sensitivity with regard to the endotoxin response exist. This behaviour can be observed by different lethality rates or in the light of the histological results. Moreover, the histological findings have shown, that distinct regenerative changes occur first of all in the liver, in the mucosa of small intestine, and the gastric mucosa, in which the number of differntiated cells compared with the mitotic active cells is reduced. It can be ascertained, that a whole body irradiation with 2.5 to 5 Gy enhances an additional injury by endotoxin weeks to months later. Contrary to this a preirradiation a few days before endotoxin application leads to a 'protection' against the efficacy of endotoxin. These findings can be explained by modes of action described in literature, according to which endotoxins induce the formation of highly active mediators especially the tumor necrosis factor. (orig.).

The effect of endotoxin on preirradiated mice

Energy Technology Data Exchange (ETDEWEB)

Oehlert, W; Oehlert, M [Freiburg Univ. (Germany). Inst. fuer Pathologie; Moenig, H; Konermann, G [Freiburg Univ. (Germany). Inst. fuer Biophysik und Strahlenbiologie

1992-12-01

Adult male mice were given a whole body irradiation with non-lethal doses of 2.5 or 5 Gy. Unirradiated animals served as controls. The animals (including controls) received a single injection of endotoxin (LPS from Salmonella abortus equi) with doses of 100, 200 or 400 [mu]g one day up to one year after irradiation. Twelve, 24 or 48 hours after lipopolysaccharide (LPS) application the animals were killed and dissected. Animals which died spontaneously were also examined. Liver, lung, kidney, small intestine, and stomach were histologically investigated. The histological findings showed, that differences exist between irradiated and unirradiated mice and that the cause of death is also different for animals dying spontaneously. The investigations have shown that after irradiation phases of different degrees of sensitivity with regard to the endotoxin response exist. This behaviour can be observed by different lethality rates or in the light of the histological results. Moreover, the histological findings have shown, that distinct regenerative changes occur first of all in the liver, in the mucosa of small intestine, and the gastric mucosa, in which the number of differntiated cells compared with the mitotic active cells is reduced. It can be ascertained, that a whole body irradiation with 2.5 to 5 Gy enhances an additional injury by endotoxin weeks to months later. Contrary to this a preirradiation a few days before endotoxin application leads to a 'protection' against the efficacy of endotoxin. These findings can be explained by modes of action described in literature, according to which endotoxins induce the formation of highly active mediators especially the tumor necrosis factor. (orig.).

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

International Nuclear Information System (INIS)

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

1978-01-01

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

Restoration of radiation therapy-induced salivary gland dysfunction in mice by post therapy IGF-1 administration

International Nuclear Information System (INIS)

Grundmann, Oliver; Fillinger, Jamia L; Victory, Kerton R; Burd, Randy; Limesand, Kirsten H

2010-01-01

Radiotherapy for head and neck cancer results in severe and chronic salivary gland dysfunction in most individuals. This results in significant side effects including xerostomia, dysphagia, and malnutrition which are linked to significant reductions in patients' quality of life. Currently there are few xerostomia treatment approaches that provide long-term results without significant side effects. To address this problem we investigated the potential for post-therapeutic IGF-1 to reverse radiation-induced salivary gland dysfunction. FVB mice were treated with targeted head and neck radiation and significant reductions in salivary function were confirmed 3 days after treatment. On days 4-8 after radiation, one group of mice was injected intravenously with IGF-1 while a second group served as a vehicle control. Stimulated salivary flow rates were evaluated on days 30, 60, and 90 and histological analysis was performed on days 9, 30, 60, and 90. Irradiated animals receiving vehicle injections have 40-50% reductions in stimulated salivary flow rates throughout the entire time course. Mice receiving injections of IGF-1 have improved stimulated salivary flow rates 30 days after treatment. By days 60-90, IGF-1 injected mice have restored salivary flow rates to unirradiated control mice levels. Parotid tissue sections were stained for amylase as an indicator of functioning acinar cells and significant reductions in total amylase area are detected in irradiated animals compared to unirradiated groups on all days. Post-therapeutic injections of IGF-1 results in increased amylase-positive acinar cell area and improved amylase secretion. Irradiated mice receiving IGF-1 show similar proliferation indices as untreated mice suggesting a return to tissue homeostasis. Post-therapeutic IGF-1 treatment restores salivary gland function potentially through normalization of cell proliferation and improved expression of amylase. These findings could aid in the rational design of

Detection of genomic instability in descendants of male mice exposed to chronic low-level gamma-radiation using the test 'adaptive response'

International Nuclear Information System (INIS)

Rozanova, O.M.; Zaichkina, S.I.; Akhmadieva, A.; Aptikaeva, G.F.; Klokov, D.J.

2003-01-01

Full text: The goal of the present study was to examine whether the genomic instability can be revealed in vivo using the test 'adaptive response' (AR). Two-month-old BALB/C male mice were subjected to chronic irradiation in the gamma-field with a dose of 0.1 Gy (0.01 Gy/day) and a dose of 0.5 Gy (0.01 and 0.05 Gy/day). Control animals were kept under similar conditions but without irradiation. Fifteen days after the irradiation, males from the irradiated and control groups were mated in separate cages with unirradiated females for 2 weeks. The males, descendants from irradiated and unirradiated parents, at an age of two months were subjected to additional irradiation with a dose of 1.5 Gy. To reveal the genetic instability using the AR test, another group of males, the descendants from irradiated and unirradiated parents, were exposed to acute irradiation by the scheme of AR: with an adapting dose (D1) of 0.1 Gy (0.125 Gy/min) followed after a day by a challenging dose (D2) of 1.5 Gy (0.47 Gy/min). After 28 h, the animals of all groups were killed. Bone marrow specimens for calculating micronuclei (MN) in polychromatophyl erythrocytes (PCE) were prepared. It was found that in descendants that resulted from unirradiated parents and the parents irradiated with a dose of 0.1 Gy, the percentages of PCE with injuries were nearly equal. Upon irradiation of parents with a dose of 0.5 Gy, the percentage of PCE with MN in descendants increased. The examination of radiosensitivity of descendants from irradiated parents showed that the percentage of PCE with MN decreased three-to-fourfold (depending on the dose of irradiation of the parents) compared to descendants from unirradiated parents. If the descendants from exposed parents were irradiated by the scheme of AR, no AR was observed. Thus, the experimental data indicated that, it is possible to detect the transition of gamma-radiation-induced genomic instability in sex cells of male parents into somatic cells of mice (F1

Effects of low dose radiation on antioxidant enzymes after radiotherapy of tumor-bearing mice

International Nuclear Information System (INIS)

Li Jin; Gao Gang; Wang Qin; Tang Weisheng; Liu Xiaoqiu; Wang Zhiquan

2005-01-01

Objective: To search for effects of low dose radiation on the activities of antioxidant enzymes after radiotherapy of tumor-bearing mice. Methods: Superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) were all determined by chemical colorimetry. Results: Low dose radiation increase the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) in serum of tumor-bearing mice more markedly than those in the unirradiated controls. The activities of antioxidant enzymes SOD, GST, CAT in serum of tumor-bearing mice (d 5 , d 3 ) irradiated with 5cGy 6h before 2.0 Gy radiation are obviously higher than those of the group (c 3 , c 5 ) given with radiotherapy only. Conclusion: The increase in the activities of antioxidant enzymes in serum of tumor-bearing mice triggered by low dose radiation could partly contribute to the protective mechanism. (authors)

Safety analysis report for packaging: the ORNL HFIR unirradiated fuel element shipping container

International Nuclear Information System (INIS)

Evans, J.H.; Boulet, J.A.M.; Eversole, R.E.

1977-11-01

The ORNL HFIR unirradiated fuel element shipping container was designed and fabricated at the Oak Ridge National Laboratory for the transport of HFIR unirradiated fuel elements. The container was evaluated analytically and experimentally to determine its compliance with the applicable regulations governing containers in which radioactive and fissile materials are transported, and the evaluation is the subject of this report. Computational and test procedures were used to determine the structural integrity and thermal behavior of the cask relative to the general standards for normal conditions of transport and the standards for the hypothetical accident conditions. The results of the evaluation demonstrate that the container is in compliance with the applicable regulations

The influence of late-stage pupal irradiation and increased irradiated: un-irradiated male ratio on mating competitiveness of the malaria mosquito Anopheles arabiensis Patton.

Science.gov (United States)

Helinski, M E H; Knols, B G J

2009-06-01

Competitiveness of released males in genetic control programmes is of critical importance. In this paper, we explored two scenarios to compensate for the loss of mating competitiveness after pupal stage irradiation in males of the malaria mosquito Anopheles arabiensis. First, competition experiments with a higher ratio of irradiated versus un-irradiated males were performed. Second, pupae were irradiated just prior to emergence and male mating competitiveness was determined. Males were irradiated in the pupal stage with a partially or fully-sterilizing dose of 70 or 120 Gy, respectively. Pupae were irradiated aged 20-26 h (young) as routinely performed, or the pupal stage was artificially prolonged by cooling and pupae were irradiated aged 42-48 h (old). Irradiated males competed at a ratio of 3:1:1 to un-irradiated males for mates in a large cage design. At the 3:1 ratio, the number of females inseminated by males irradiated with 70 Gy as young pupae was similar to the number inseminated by un-irradiated males for the majority of the replicates. At 120 Gy, significantly fewer females were inseminated by irradiated than by un-irradiated males. The irradiation of older pupae did not result in a significantly improved male mating competitiveness compared to the irradiation of young pupae. Our findings indicate that the loss of competitiveness after pupal stage irradiation can be compensated for by a threefold increase of irradiated males, but only for the partially-sterilizing dose. In addition, cooling might be a useful tool to facilitate handling processes of large numbers of mosquitoes in genetic control programmes.

Influence of paternal 252Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F1 offspring of mice

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Takahashi, Tadateru; Lee, Juing-Yi

1996-01-01

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with 252 Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P 1 generation may be caused by genetic transmission of hepatoma-associated trait (s) induced by 252 Cf neutron irradiation. (author)

Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

Science.gov (United States)

Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

2015-01-01

The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

A highway accident involving unirradiated nuclear fuel in Springfield, Massachusetts, on December 16, 1991

International Nuclear Information System (INIS)

Carlson, R.W.; Fischer, L.E.

1992-06-01

In the early morning of Dec. 16, 1991, a severe accident occurred when a passenger vehicle traveling in the wrong direction collided with a tractor trailer carrying 24 unirradiated nuclear fuel assemblies in 12 containers on Interstate I-91 in Springfield, Massachusetts. The purpose of this report is to document the mechanical circumstances of the severe accident, confirm the nature and quantity of the radioactive materials involved, and assess the physical environment to which the containers were exposed and the response of the containers and their contents. The report consists of five major sections. The first section describes the circumstances and conditions of the accident and the finding of facts. The second describes the containers, the unirradiated nuclear fuel assemblies, and the tie down arrangement used for the trailer. The third describes the damage sustained during the accident to the tractor, trailer, containers, and unirradiated nuclear fuel assemblies. The fourth evaluates the accident environment and its effects on the containers and their contents. The final section gives conclusions derived from the analysis and fact finding investigation. During this severe accident, only minor injuries occurred, and at no time was the public health and safety at risk

The enhancing effect of fractionated whole-body x-irradiation on replication of endogenous leukemia viruses in BALB/c mice

International Nuclear Information System (INIS)

Takamori, Yasuhiko; Okumoto, Masaaki; Iwai, Mineko; Iwai, Yoshiaki

1976-01-01

The incidence of leukemia, changes in the tissue weight of spleen and thymus, and the expression of endogenous viruses were examined with BALB/c mice following 4 weekly fractionated whole-body x-irradiation of 170 R each, starting at 4 weeks of age. The leukemia incidence was quite low for the unirradiated controls, while 60% of the irradiated male mice developed thymic lymphoma. The virus-positive cells appeared earlier in the spleen than in the thymus and bone marrow, and increased with aging. The time of appearance of virus-positive cells in these tissues was remarkably promoted by the fractionated x-irradiation, and its frequency was also enhanced. (auth.)

Stress corrosion crack growth in unirradiated zircaloy

International Nuclear Information System (INIS)

Pettersson, K.

1978-10-01

Experimental techniques suitable for the determination of stress corrosion crack growth rates in irradiated Zircaloy tube have been developed. The techniques have been tested on unirradiated. Zircaloy and it was found that the results were in good agreement with the results of other investigations. Some of the results were obtained at very low stress intensities and the crack growth rates observed, gave no indication of the existance of a K sub(ISCC) for iodine induced stress corrosion cracking in Zircaloy. This is of importance both for fuel rod behavior after a power ramp and for long term storage of spent Zircaloy-clad fuel. (author)

Unirradiated cladding rip-propagation tests

International Nuclear Information System (INIS)

Hu, W.L.; Hunter, C.W.

1981-04-01

The size of cladding rips which develop when a fuel pin fails can affect the subassembly cooling and determine how rapidly fuel escapes from the pin. The object of the Cladding Rip Propagation Test (CRPT) was to quantify the failure development of cladding so that a more realistic fuel pin failure modeling may be performed. The test results for unirradiated 20% CS 316 stainless steel cladding show significantly different rip propagation behavior at different temperatures. At room temperature, the rip growth is stable as the rip extension increases monotonically with the applied deformation. At 500 0 C, the rip propagation becomes unstable after a short period of stable rip propagation. The rapid propagation rate is approximately 200 m/s, and the critical rip length is 9 mm. At test temperatures above 850 0 C, the cladding exhibits very high failure resistances, and failure occurs by multiple cracking at high cladding deformation. 13 figures

Dominant lethal mutations research in mice fed with irradiated black beams

International Nuclear Information System (INIS)

Andrade, Z.P.

1982-01-01

To evaluate the potential mutagenic effects of irradiated black beans (Phaseolus vulgaris) with conservation purpose, in germ cells of mice, dominant lethal assay were employed. Three groups of albino swiss male mice (S W-55) were fed with a normal ration, or unirradiated or irradiated (0,2; 0,5; 1; 5; 10; 15 e 20 KGy) test diets for eight weeks. After the feeding period the males were mated with groups of untreated females mice for four consecutive weeks. Numbers of pregnancy rates females were observed. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. (author)

High Temperature Tensile Properties of Unirradiated and Neutron Irradiated 20 Cr-35 Ni Austenitic Steel

Energy Technology Data Exchange (ETDEWEB)

Roy, R B; Solly, B

1966-12-15

The tensile properties of an unirradiated and neutron irradiated (at 40 deg C) 20 % Cr, 35 % Ni austenitic steel have been studied at 650 deg C, 750 deg C and 820 deg C. The tensile elongation and mode of fracture (transgranular) of unirradiated specimens tested at room temperature and 650 deg C are almost identical. At 750 deg C and 820 deg C the elongation decreases considerably and a large part of the total elongation is non-uniform. Furthermore, the mode of fracture at these temperatures is intergranular and microscopic evidence suggests that fracture is caused by formation and linkup of grain boundary cavities. YS and UTS decrease monotonically with temperature. Irradiated specimens show a further decrease in ductility and an increase in the tendency to grain boundary cracking. Irradiation has no significant effect on the YS, but the UTS are reduced. The embrittlement of the irradiated specimens is attributed to the presence of He and Li atoms produced during irradiation and the possible mechanisms are discussed. Prolonged annealing of irradiated and unirradiated specimens at 650 deg C appears to have no significant effect on tensile properties.

Entire litters developed from transferred eggs in whole body x-irradiated female mice

International Nuclear Information System (INIS)

Lin, T.P.

1980-01-01

The sensitivity of mouse eggs to sublethal x-irradiation was determined in vitro and in vivo with regard to the development of donor litters in foster mothers. One thousand seven hundred fifty-eight unfertilized eggs of agouti dark-eyed donor mice were transferred into 293 unirradiated or x-irradiated, mated female pink-eyed mice. Two hundred thirty-nine recipients became pregnant; of these 35 produced litters containing solely dark-eyed fetuses. Sublethal doses of x-radiation administered to donor eggs in vitro before transferring into unirradiated recipients did not influence significantly the number of litters of exclusively dark-eyed fetuses produced. However, recipients irradiated by 250 roentgens (r) produced more solely dark-eyed litters than did those irradiated with 100 r. In 21 pregnant females irradiated by 100 r, only 3 (14%) developed solely dark-eyed fetuses as compared to 22 pregnant females irradiated by 250 r, of which 13 (59%) developed solely dark-eyed fetuses, all from unirradiated, transferred eggs. Of another group of 22 pregnant females which received 250 r body irradiation and subsequently received eggs also irradiated by 250 r, only 7 (32%) produced litters of dark-eyed fetuses. No one female of these three groups carried native fetuses. Such radiation-induced infertility resulting from damage of native eggs rather than loss of mother's ability to carry a pregnancy, is frequently remedied by egg transfer

Safety of dried sambiloto Andrographis paniculata (Burm. F.) nees gamma irradiated based on acute toxicity aspect in mice swiss webster

International Nuclear Information System (INIS)

Ermin Katrin; Susanto; Hendig Winarno

2014-01-01

Andrographis paniculata nees (Family: Acanthaceae) is a medicinal plant commonly cultivated in Asian countries. The purpose of this study was to evaluate the safety of gamma irradiated sambiloto against to animal test (mice) and to support the application of nuclear techniques for radiation pasteurization of sambiloto as health products without changing the properties. In the acute toxicity test was observed the effects of the tested material on behavioral changes, abnormalities in the function of several organs and body weight changes in animal test every day for 2 weeks. The results showed that the ethanol extract of unirradiated and irradiated with dose of 7.5 kGy) sambiloto were not toxic to mice. Lethal Dose 50 (DL 50 ) of ethanol extract from sambiloto unirradiated or irradiated at the dose of 7.5 kGy was > 5000 mg/kg BW. At the highest dose tested 5000 mg/kg BW mice there were no significant toxic effects and no mice that died during the experiment, therefore ethanol extracts of un irradiated and irradiated samples could be declared safe. (author)

Thermogravimetric studies of the thermo-oxidative stability of irradiated and unirradiated polyethylene

International Nuclear Information System (INIS)

Novakovic, L.; Gal, O.; Markovic, V.; Stannett, V.T.

1985-01-01

In part one of this series the effects of a phenolic, an amine and a thioester antioxidant on the thermo-oxidative stability of irradiated and unirradiated low-density polyethylene was reported. In this paper the effects of combined phenolic and thioester stabilizers are described. Isothermal thermogravimetric analysis was used to study the systems. Pronounced synergism was observed with the induction periods, the time when the initial weight loss begins and the 5% weight loss. At about 50% of each stabilizer increases greater than twofold were observed both with the unirradiated and irradiated polymers. The rate constants for oxygen uptake were decreased. However, the rates of degradation at 5% weight loss fell between the values of the two pure stabilizers with no pronounced synergism in either case. In the absence of oxygen little effect of either antioxidant or their mixtures was observed. The corresponding activation energies were somewhat higher, however, with the irradiated samples containing antioxidants. Dynamic thermogravimetry was used for this study. A kinetic analysis indicated that there were somewhat different modes of degradation at lower- and higher-temperature ranges. (author)

Dominant lethal mutations in male mice fed γ-irradiated diet

International Nuclear Information System (INIS)

Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

1975-01-01

Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

Characterization of un-irradiated and irradiated reactor graphite; Karakterizacija neozracenog i ozracenog reaktorskog grafita

Energy Technology Data Exchange (ETDEWEB)

Marinkovic, S [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

1965-11-15

This report contains three parts: characterization of Yugoslav nuclear graphite development of methods and obtained results, characterization of un-irradiated and irradiated domestic nuclear graphite; calculation of electrical conductivity changes due to vacancies in the graphite crystal lattice.

Plant-scale anodic dissolution of unirradiated N-Reactor fuel

International Nuclear Information System (INIS)

Gay, E.C.; Miller, W.E.; Laidler, J.J.

1995-01-01

Anodic dissolution tests were made with unirradiated N-Reactor fuel to determine the fuel segment length, diameter, and shape required for high throughput electrorefiner treatment for ultimate disposal in a geologic repository. Based on these tests, a conceptual design was produced of an electrorefiner for a full-scale plant to process N-Reactor spent fuel. In this design, the diameter of an electrode assembly is about 0.6 m (25 in.). Eight of these assemblies in an electrorefiner would accommodate a 1.333-metric-ton batch of N-Reactor fuel. Electrorefining would proceed at a rate of 40 kg uranium per hour

Dissolution experiments of unirradiated uranium dioxide pellets

International Nuclear Information System (INIS)

Ollila, K.

1985-01-01

The purpose of this study was to measure the dissolution rate of uranium from unirradiated uranium dioxide pellets in deionized water and natural groundwater. Moreover, the solubility limit of uranium in natural groundwater was measured. Two different temperatures, 25 and 60 deg C were used. The low oxygen content of deep groundwater was simulated. The dissolution rate of uranium varied from 10 -7 to 10 -8 g cm -2 d -1 . The rate in reionized water was one order of magnitude lower than in groundwater. No great difference was observed between the natural groundwaters with different composition. Temperature seems to have effect on the dissolution rate. The solubility limit of uranium in natural groundwater in reducing conditions, at 25 deg C, varied from 20 to 600 μg/l and in oxidizing conditions, at 60 deg C, from 4 to 17 mg/l

The dissolution of unirradiated UO2 fuel pellets under simulated disposal conditions

International Nuclear Information System (INIS)

Ollila, K.; Leino-Forsman, H.

1993-03-01

The dissolution behaviour of unirradiated UO 2 pellets was studied as a function of water composition under oxidizing and reducing conditions at 25 deg C. The waters included deionized water as the reference water, sodium bicarbonate solutions with varying bicarbonate content, and two different synthetic groundwaters. The release of uranium was measured during static batch dissolution experiments of long duration (3-4 years)

Micronucleus test in mice fed on irradiated whole diet

International Nuclear Information System (INIS)

Reddy, P.P.; Reddi, O.S.; Pentiah, P.R.; Rani, M.V.U.; Devi, K.R.; Goud, S.N.

1981-01-01

Eight week old Swiss albino male mice were fed on freshly irradiated or unirradiated whole diet for one week. (Exposure was to 75 or 200 kR γ rays from a 1000 Ci 60 Co γ source at a dose rate of 584 R/min.) On the seventh day, six hours after feeding, the mice were killed and bone marrow preparations were made by the Schmid technique. From each group three animals were taken and from each animal 2000 polychromatic and normochromatic erythrocytes were scored. It was evident from the data obtained that the irradiated whole diet failed to induce any significant increase in the incidence of micronuclei in polychromatic erythrocytes. Similarly, there was no significant increase in the frequency of micronuclei in normochromatic erythrocytes when compared with control data. The polychromatic to normochromatic ratio was also unaffected. The diet consisted of wheat flour (60%). groundnut cake (20%), fish meal (8%), Bengal gram flour (8%), dried yeast (3%), salt/mineral mixture (1%) and traces of vitamins. (U.K.)

In vivo mutagenicity studies in rats mice and Chinese hamsters fed irradiated foodstuffs - chicken, fish, dates, pulses, mangoes and cocoa beans

International Nuclear Information System (INIS)

Renner, H.W.

1982-01-01

Three in vivo genetic toxicity tests were performed in rats, mice and Chinese hamsters to detect possible mutagenic effects of irradiated chicken, dried dates, fish, cocoa beans, pulses and mangoes. The tests employed were the micronucleus test and sister-chromatid exchange (SCE) test for irradiated and unirradiated samples of all foodstuffs listed, and the spermatogonia test, (including SCE technique) in mice for irradiated and unirradiated chicken, fish and dates only. In the case of cocoa beans, the mutagenicity tests were performed on an additional test group fed beans fumigated with ethylene oxide. The different mammalian species used for the various experiments are given below. None of the tests provided any evidence of mutagenicity induced by irradiation in any of the foodstuffs studied. Moreover, these tests are currently considered to be the most sensitive in vivo mutagenicity tests in mammals. (orig.)

Plant-scale anodic dissolution of unirradiated N-Reactor fuel

International Nuclear Information System (INIS)

Gay, E.C.; Miller, W.E.; Laidler, J.J.

1995-01-01

Anodic dissolution tests were made with unirradiated N-Reactor fuel to determine the fuel segment length, diameter, and shape required for high throughput electro-refiner treatment for ultimate disposal in a geologic repository. Based on these tests, a conceptual design was produced of an electro-refiner for a full-scale plant to process N-Reactor spent fuel. In this design, the diameter of an electrode assembly is about 0.6 m (25 in.). Eight of these assemblies in an electro-refiner would accommodate a 1.333-metric-ton batch of N-Reactor fuel. Electrorefining would proceed at a rate of 40 kg uranium per hour. (author)

Studies on the mutagenic and cytogenetic effects of irradiated wheat in mice

International Nuclear Information System (INIS)

Reddy, P.P.; Reddi, O.S.; Ebenezer, D.N.; Naidu, N.V.; Goud, S.N.

1978-01-01

A series of experiments were conducted to test the mutagenic and cytogenetic potentials of freshly and stored irradiated wheat in mice. In the first series, the effects of feeding of CBA mice for 8 weeks with the diet containing 60% of wheat freshly irradiated ( 3 H/He mice were undertaken. Feeding of both freshly and stored irradiated wheat showed neither an increase in dominant lethals and chromosomal aberrations nor a reduction in germ cells. In another series, the reproductive performance of the CBA females fed stored irradiated (75 krad) wheat was investigated and it was observed that the average total number of litters and the litter size did not vary from those of the females fed unirradiated wheat. (author)

Investigation of genomic instability by assay of DNA fingerprint from the offspring of male mice exposed to chronic low-level γ-radiation

International Nuclear Information System (INIS)

Bezlepkin, V.G.; Vasil'eva, G.V.; Lomaeva, M.G.; Sirota, N.P.; Gaziev, A.I.

2000-01-01

By polymerase chain reaction with arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F 1 generation) from male parents of mice exposed to chronic low-dose γ-radiation was studied. Male mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old mice progeny for DNA separation. Primer in the AP-PCR was 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on chromosome 11 of the mouse. Comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of micro-satellite-associated sequences in the genome of the offspring of males exposed to 25 and 50 cGy. DNA-fingerprints of the offspring of male mice exposed to chronic irradiation doses 10 and 25 cGy. 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of non-parent bands. Result of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-dose radiation prior to fertilization [ru

Carcinogenic effects of ionizing radiation administered at perinatal stage of mice

International Nuclear Information System (INIS)

Sasaki, Shunsaku; Sato, Fumiaki; Kasuga, Takeshi; Kawashima, Naoyuki

1978-01-01

Mice of F 1 hybrids of (C57BL/6 x WHT) strains (B6WF 1 ) were exposed to 200 kVp x-rays at the late fetal stage (17 days postcoitum, 150 R, 300 R), the neonatal stage (0 - 24 hr postpartum, 400 R) or the juvenile stage (5-week-old, 400 R). Mice were allowed to live through their life span, and incidences of various tumors were compared with those of the unirradiated control mice. Characteristics of each of the ages concerning radiation-induced carcinogenesis have been revealed as follows. The late fetal stage: This stage of mice was shown to have a susceptibility to carcinogenic action of x-rays, which was not so high and was restricted to several organs and tissues. Pituitary tumors, pulmonary tumors and hepatocellular tumors developed in excess, but lympho-reticular tissue tumors and myeloid leukemias were not induced by x-irradiation at the late fetal stage. The neonatal stage: X-irradiation to the neonatal mice resulted in enhancement of incidences of various tumors such as thymic lymphomas, hepatocellular tumors, pituitary tumors, ovarian tumors and Harderian gland tumors. Expecially, hepatocellular tumors developed at a very high incidence. The juvenile stage: Incidences of ovarian tumors and Harderian gland tumors were higher in mice irradiated at the juvenile stage than those irradiated at the younger age. These results lead to a conclusion that the age-dependency of susceptibility to radiation-induced carcinogenesis differs with organs and tissues. (author)

Revised ANL-reported tensile data for unirradiated and irradiated (FFTF, HFIR) V-Ti and V-Cr-Ti alloys

International Nuclear Information System (INIS)

Billone, M.C.

1998-01-01

The tensile data for all unirradiated and irradiated vanadium alloys samples tested at Argonne National Laboratory (ANL) have been critically reviewed and, when necessary, revised. The review and revision are based on reanalyzing the original load-displacement strip chart recordings by a methodology consistent with current ASTM standards. For unirradiated alloys (162 samples), the revised values differ from the previous values as follows: -11±19 MPa (-4±6%) for yield strength (YS), -3±15 MPa (-1±3%) for ultimate tensile strength (UTS), -5±2% strain for uniform elongation (UE), and -4±2% strain for total elongation (TE). Of these changes, the decrease in -1±6 MPa (0±1%) for UTS, -5±2% for UE, and -4±2% for TE. Of these changes, the decrease in UE values for alloys irradiated and tested at 400--435 C is the most significant. This decrease results from the proper subtraction of nongauge-length deformation from measured crosshead deformation. In previous analysis of the tensile curves, the nongauge-length deformation was not correctly determined and subtracted from the crosshead displacement. The previously reported and revised tensile values for unirradiated alloys (20--700 C) are tabulated in Appendix A. The revised tensile values for the FFTF-irradiated (400--600 C) and HFIR-irradiated (400 C) alloys are tabulated in Appendix B, along with the neutron damage and helium levels. Appendix C compares the revised values to the previously reported values for irradiated alloys. Appendix D contains previous and revised values for the tensile properties of unirradiated V-5Cr-5Ti (BL-63) alloy exposed to oxygen

TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

Energy Technology Data Exchange (ETDEWEB)

Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I [Henry Ford Health System, Detroit, MI (United States); Sethi, S [Karmanos Cancer Center, Detroit, MI (United States); Klein, M [Children' s Hospital of Michigan, Detroit, MI (United States)

2014-06-15

Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

International Nuclear Information System (INIS)

Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I; Sethi, S; Klein, M

2014-01-01

Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

[Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation].

Science.gov (United States)

Bezlepkin, V G; Vasil'eva, G V; Lomaeva, M G; Sirota, N P; Gaziev, A I

2000-01-01

By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.

Selenium inhibits UV-light-induced skin carcinogenesis in hairless mice

International Nuclear Information System (INIS)

Overvad, Kim; Thorling, E.B.; Bjerring, Peter; Ebbesen, Peter

1985-01-01

Female hairless inbred hr/hr mice were exposed to UV-B irradiation from Philips TL 40W/13 fluorescent tubes. Fractionated irradiation, given as single daily doses 5 days a week, was gradually increased from 0.04 to 0.4 J/cm 2 over 2 weeks. Irradiation at 0.4 J/cm 2 was continued for 20 weeks. Selenium supplementation given as sodium selenite in the drinking water at 2, 4 and 8 mg/l began 3 weeks before UV-irradiation and continued thereafter. Development of skin tumors was followed by weekly examinations. Statistical analyses revealed significant dose-dependent selenium-mediated protection against UV-light-induced skin cancer. Leukemia developed in 5 of 150 UV-irradiated mice as opposed to none in a group of 60 unirradiated mice. (author)

Comparison of the growth of Listeria monocytogenes in unirradiated and irradiated cook-chill roast beef and gravy at refrigeration temperatures

International Nuclear Information System (INIS)

Grant, I.R.; Nixon, C.R.; Patterson, M.F.

1993-01-01

Specific growth rates of two strains of Listeria monocytogenes in unirradiated and irradiated (2 kGy) roast beef and gravy stored at 5° and 10°C were found to be similar. However, exponential growth of L. monocytogenes after irradiation was preceded by an extended lag period of 6–9 d at 5°C and 3–4 d at 10°C, compared with lag periods of 1–2 d and <0.1 d in unirradiated beef and gravy stored similarly

Distribution and tumour cytotoxicity of the radiosensitizer misonidazole (Ro-07-0582) in C57 mice

International Nuclear Information System (INIS)

Pedersen, J.E.; Smith, M.R.; Bugden, R.D.; Peckham, M.J.

1979-01-01

The distribution and clearance of misonidazole (MIS=Ro-07-0582) were studied in C57 mouse tissued and in transplants of Lewis lung tumour. The half life of the drug in blood after a dose of 1mg/g i.p. was 3 h. Some tissues, such as liver, were found to have consistently low MIS levels, and this was found to be due to degradation of the drug after removal of the tissues from the host. The in vivo cytotoxicity of MIS to Lewis lung tumour cells was studied using an in-vitro colony assay. After half of the tumours had been irradiated with 10 Gy to kill most of the oxic cells, the mice received i.p. injections of MIS. To simulate the longer drug exposure of human tumour cells (due to the longer half life in man) a repeated injection regime was used in some mice. There was no significant cell kill after a single dose, but with a prolonged exposure to the drug in the multiply injected animals, cell survival was reduced to 50% of control in both the irradiated and unirradiated tumours. Since the hypoxic fraction of the unirradiated tumour is probably not more than 30%, it would appear that MIS is not selectively cytotoxic to hypoxic cells. However, MIS had a much greater cytotoxic effect upon hypoxic Lewis lung tumour cells in vitro, with very little or no effect on cells grown in air. This would support the theory that the presence of hypoxic cells is essential for the expression of MIS cytotoxicity. (author)

Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

Energy Technology Data Exchange (ETDEWEB)

Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J. (Department of Veterinary Microbiology, Immunology and Parasitology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States))

1991-06-01

Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 {times} 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished.

Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

International Nuclear Information System (INIS)

Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J.

1991-01-01

Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 x 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished

Cell proliferation and ageing in mouse colon

International Nuclear Information System (INIS)

Hamilton, E.; Franks, L.M.

1980-01-01

Cell kinetic parameters in the descending colon of unirradiated mice, 3-30-months-old were compared with those in mice irradiated repeatedly from the age of 6 or 24 months. The latter animals were given 1250 rad local X-irradiation to the colon every 6 weeks. Dose-survival curves showed the colon crypts of 6 and 24-months-old mice were similarly radiosensitive. In unirradiated mice the number of crypts per colon section decreased significantly at 30 months, but no significant age-related changes were seen in crypt size or labelling index (LI). Cell proliferation returned to control levels within 6 weeks of each X-ray dose and remained at this level for 20 weeks after the final dose. Later, cell proliferation in the irradiated colon fell significantly below control. A total of 6 or 7 doses each of 1250 rad produced only 1 colon carcinoma amongst 50 mice kept until they died. (author)

A review of the rates of reaction of unirradiated uranium in gaseous atmospheres

International Nuclear Information System (INIS)

Pearce, R.J.

1989-10-01

The review collates available quantitative rate data for the reaction of unirradiated uranium in dry and moist air, steam and carbon dioxide based atmospheres at temperatures ranging from room temperature to above the melting point of uranium. Reactions in nitrogen and carbon monoxide are also considered. The aim of the review is to provide a compilation of base data for the hazard analysis of fault conditions relating to Magnox fuel. (author)

Induction of lethal mutations in the x-chromosome of unirradiated Drosophila oocytes after fertilization by irradiated spermatozoa

International Nuclear Information System (INIS)

Shaposhnikov, M.V.; Zainullin, V.G.

2003-01-01

Full text: In primary study on Drosophila it was found that irradiated male X-chromosomes induce recessive lethals in unirradiated female homologues (Abeleva et al., 1961, Radiobiologya. 1:123-126). The same effects were obtained in Drosophila in some recent investigations. The mechanisms of these effects is unknown. However it may be responsible for low-dose radiation effects as it induce mutations in unirradiated DNA. We assume that this effect may be a result of activation of error prone repair in response to preliminary DNA lesions in irradiated chromosome. In this research we analyse the frequencies of the recessive lethal mutations in the X-chromosome of Drosophila females mated with irradiated Basc males. We used acute irradiation with a dose rate of 10 Gy. For testing our hypothesis we use the mus209 and mei-41 mutant females. Mus209 is a PCNA gene homologue and mei-41 is a homologue of ATM gene. These genes are involved in post-replication DNA repair which may be error prone repair in Drosophila. It was obtained the tendency to decreasing the mutation rate at the mei-41[D5] background and decreasing mutation rate in mus209[B1] background in comparison with wild type strains CS (p<0.05). The obtained results demonstrate the possible role of mus209[B1] and mei-41[D5] genes in the inducing of mutations in the unirradiated X-chromosome in the presence of irradiated homologue

Scintillation activity in an unirradiated single crystal of 3-hydroxyxanthine

International Nuclear Information System (INIS)

Cooke, D.W.; Jahan, M.S.; Alexander, C. Jr.

1976-01-01

A method of growing single crystals (approximately 4mm long) of 3-hydroxyxanthine is described. Observed scintillations occurring in an unirradiated single crystal of this potent oncogen as the temperature is lowered from 300 to 90 K are shown. It was found that these scintillations occur upon heating or cooling and do not diminish in activity as the number of heating and cooling cycles increase. It was found that a short duration u.v. exposure would terminate the scintillation activity and various attempts (such as annealing and pressure changes) to rejuvenate them were unsuccessful. With these observations in mind speculation is made concerning the mechanisms associated with the production of purine N-oxide derivatives. (U.K.)

Thermogravimetric studies of the thermo-oxidative stability of irradiated and unirradiated polyethylene. 2. Combined antioxidants

Energy Technology Data Exchange (ETDEWEB)

Novakovic, L; Gal, O; Markovic, V; Stannett, V T

1985-01-01

In part one of this series the effects of a phenolic, an amine and a thioester antioxidant on the thermo-oxidative stability of irradiated and unirradiated low-density polyethylene was reported. In this paper the effects of combined phenolic and thioester stabilizers are described. Isothermal thermogravimetric analysis was used to study the systems. Pronounced synergism was observed with the induction periods, the time when the initial weight loss begins and the 5% weight loss. At about 50% of each stabilizer increases greater than twofold were observed both with the unirradiated and irradiated polymers. The rate constants for oxygen uptake were decreased. However, the rates of degradation at 5% weight loss fell between the values of the two pure stabilizers with no pronounced synergism in either case. In the absence of oxygen little effect of either antioxidant or their mixtures was observed. The corresponding activation energies were somewhat higher, however, with the irradiated samples containing antioxidants. Dynamic thermogravimetry was used for this study. A kinetic analysis indicated that there were somewhat different modes of degradation at lower- and higher-temperature ranges. (author).

Histochemical differentiation between unirradiated and gamma-irradiated tissue in commercial use of some irradiated vegetables

International Nuclear Information System (INIS)

Foa, E.

1978-01-01

The use of gamma irradiation as a commercial method for the preservation of fruits and vegetables calls for methods of differentiation between unirradiated and irradiated products. A new approach to studying the influence of gamma irradiation on vegetable tissue at the cellular level by histochemical techniques has been developed by the authors and already applied to a number of fruits and vegetables. The possibility of evidencing radiation effects in the polysaccharide components of the cell wall suggested that these detected differences could be applied to differentiate irradiated from unirradiated tomatoes and potatoes. Some work done to determine changes in the cell wall polysaccharides of gamma-irradiated potatoes and tomatoes and to relate these changes to some other factors, such as storage time and vegetable variety, is reported here. While significant differences have been found in the optical densities of the total polysaccharides of the cell wall as a function of irradiation and of the other variables mentioned, it is not yet possible to use these values as a means of reliable differentiation. (author)

Cellular radiation response as a function of tumor size, host hematocrit, and erythrokinetics in CA755 tumor-bearing mice

International Nuclear Information System (INIS)

Jirtle, R.L.

1977-01-01

Experiments were performed which both characterized the kinetics of host anemia when CA755 mammary adenocarcinomas were grown in either preirradiated or unirradiated host tissue of C57B1/2J (BDF 1 ) mice, and determined whether a correlation exists between the extent of host anemia and the cellular radiosensitivity of the grossly viable tumor tissue. The red cell destruction rate and the total red cell volume (TRCV) were simultaneously measured throughout tumor growth, and from this information the erythrocyte production per day could be estimated. Increased erythrocyte production was accompanied by a corresponding increase in circulating reticulocytes. The application of these methods to a tumor-bearing mouse system demonstrated that the erythrocyte production rates increased to a maximum of 6 to 10 times normal in mice bearing tumors growing in either preirradiated or unirradiated graft sites. It was concluded that tumor host anemia was due to accelerated random loss of erythrocytes and the nearly simultaneous decrease in erythrocyte potential life span rather than to a decrease in the erythrocyte production

T-cell-dependent control of acute Giardia lamblia infections in mice.

Science.gov (United States)

Singer, S M; Nash, T E

2000-01-01

We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alphabeta- or gammadelta-T-cell receptor (TCR)-expressing T cells, we show that the alphabeta-TCR-expressing T cells are required to control parasites but that the gammadelta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells.

Concentration of metallothionein in mice livers after a small dose of irradiation

Energy Technology Data Exchange (ETDEWEB)

Saitou, Mikio; Yanai, Takanori; Hasegawa, Hidenao; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan); Akata, Naofumi; Kanaiwa-Kudo, Shouko; Matsumoto, Tsuneya; Noda, Yuko

1998-12-01

This study was made to determine whether metallothionein (MT) is induced by a small dose (0.5 Gy) irradiation. One hundred B6C3F1/Nrs mice of each sex, 8-10 weeks old, were used in the sham study (unirradiated controls) and experimental (irradiated) groups. Eighty mice of each sex were given acute whole body irradiation with {sup 197}Cs{gamma}-rays under SPF conditions; two doses of 0.5 and 5.0 Gy at 30 cm distance from the source at the rate of 0.563 Gy/min. Twenty mice of each sex were used in the sham study. Every ten male and female mouse was killed by cervical dislocation on days 1, 7, 14 and 21 after irradiation. The same numbers of male and female control mice were killed on days 0 and 21. Livers were removed immediately after death, and concentration of MT was examined. In both the males and females, the MT concentration of the 5 Gy-group peaked on the first day after irradiation, and there was no difference in comparison with the control values between the 7th and 21st days. In contrast, on no day did the MT concentration for the 0.5 Gy-group showed a significant difference from the control group. The time dependency patterns of the female and male mice also showed no significant differences for 5 Gy- and 0.5 Gy-groups, but the mean values of the MT concentration was lower in the males than in the females on the 1st day. Results of the direct quantitation of MT by the enzyme-linked immunoabsorbent assay (ELISA) also showed peak MT accumulation on the 1st day for both male and female mice. These were also shown by the atomic absorption spectrometry (AAS) and the inductively coupled plasma mass spectrometry (ICP-MS) analyses. But peak heights for the males and females showed a tendency inverse to that of the AAS and ICP-MS analyses. This discrepancy is attributable to the technical problem encountered in the experiment. On the basis of our findings, MT does not seem to be related to acquired radioresistance in mice. (K.H.)

Truck accident involving unirradiated nuclear fuel

International Nuclear Information System (INIS)

Carlson, R.W.; Fischer, L.E.

1993-01-01

In the early morning of Dec. 16, 1991, a severe accident occurred when a passenger vehicle traveling in the wrong direction collided with a tractor trailer carrying 24 unirradiated nuclear fuel assemblies in 12 containers on Interstate I-91 in Springfield, Massachusetts. This paper documents the mechanical circumstances of the accident and assesses the physical environment to which the containers were exposed and the response of the containers and their contents. The accident involved four impacts where the truck was struck by the car, impacted on the center guardrail, impacted on the outer concrete barrier and came to rest against the center guardrail. The impacts were followed by a fire that began in the engine compartment, spread to the tractor and cab, and eventually spread to the trailer and payload. The fire lasted for about three hours and the packages were involved in the fire for about two hours. As a result of the fire, the tractor-trailer was completely destroyed and the packages were exposed to flames with temperatures between 1,300 F and 1,800 F. The fuel assemblies remained intact during the accident and there was no release of any radioactive material during the accident. This was a very severe accident; however, the injuries were minor and at no time was the public health and safety at risk

Oxide particle size distribution from shearing irradiated and unirradiated LWR fuels in Zircaloy and stainless steel cladding: significance for risk assessment

Energy Technology Data Exchange (ETDEWEB)

Davis, W. Jr.; West, G.A.; Stacy, R.G.

1979-03-22

Sieve fractionation was performed with oxide particles dislodged during shearing of unirradiated or irradiated fuel bundles or single rods of UO/sub 2/ or 96 to 97% ThO/sub 2/--3 to 4% UO/sub 2/. Analyses of these data by nonlinear least-squares techniques demonstrated that the particle size distribution is lognormal. Variables involved in the numerical analyses include lognormal median size, lognormal standard deviation, and shear cut length. Sieve-fractionation data are presented for unirradiated bundles of stainless-steel-clad or Zircaloy-2-clad UO/sub 2/ or ThO/sub 2/--UO/sub 2/ sheared into lengths from 0.5 to 2.0 in. Data are also presented for irradiated single rods (sheared into lengths of 0.25 to 2.0 in.) of Zircaloy-2-clad UO/sub 2/ from BWRs and of Zircaloy-4-clad UO/sub 2/ from PWRs. Median particle sizes of UO/sub 2/ from shearing irradiated stainless-steel-clad fuel ranged from 103 to 182 ..mu..m; particle sizes of ThO/sub 2/--UO/sub 2/, under these same conditions, ranged from 137 to 202 ..mu..m. Similarly, median particle sizes of UO/sub 2/ from shearing unirradiated Zircaloy-2-clad fuel ranged from 230 to 957 ..mu..m. Irradiation levels of fuels from reactors ranged from 9,000 to 28,000 MWd/MTU. In general, particle sizes from shearing these irradiated fuels are larger than those from the unirradiated fuels; however, unirradiated fuel from vendors was not available for performing comparative shearing experiments. In addition, variations in particle size parameters pertaining to samples of a single vendor varied as much as those between different vendors. The fraction of fuel dislodged from the cladding is nearly proportional to the reciprocal of the shear cut length, until the cut length attains some minimum value below which all fuel is dislodged. Particles of fuel are generally elongated with a long-to-short axis ratio usually less than 3. Using parameters of the lognormal distribution estimates can be made of fractions of dislodged fuel having

Safety of dried sambiloto Andrographis paniculata (Burm. F.) nees gamma irradiated based on acute toxicity aspect in mice swiss webster; Keamanan sambiloto (Andrographis paniculata nees) kering yang diiradiasi gamma berdasarkan aspek toksisitas akutnya terhadap mencit galur swiss webster

Energy Technology Data Exchange (ETDEWEB)

Katrin, Ermin; Susanto,; Hendig Winarno, E-mail: erminkk@batan.go.id [Laboratorium Bahan Kesehatan PAIR - BATAN, Jl. Lebak Bulus Raya No. 49, Pasar Jumat, Jakarta 12440 (Indonesia)

2014-08-15

Andrographis paniculata nees (Family: Acanthaceae) is a medicinal plant commonly cultivated in Asian countries. The purpose of this study was to evaluate the safety of gamma irradiated sambiloto against to animal test (mice) and to support the application of nuclear techniques for radiation pasteurization of sambiloto as health products without changing the properties. In the acute toxicity test was observed the effects of the tested material on behavioral changes, abnormalities in the function of several organs and body weight changes in animal test every day for 2 weeks. The results showed that the ethanol extract of unirradiated and irradiated with dose of 7.5 kGy) sambiloto were not toxic to mice. Lethal Dose 50 (DL{sub 50}) of ethanol extract from sambiloto unirradiated or irradiated at the dose of 7.5 kGy was > 5000 mg/kg BW. At the highest dose tested 5000 mg/kg BW mice there were no significant toxic effects and no mice that died during the experiment, therefore ethanol extracts of un irradiated and irradiated samples could be declared safe. (author)

Alpha-methyl-homocysteine thiolactone protects lung of BALB/c mice irradiated with 6 Gy

International Nuclear Information System (INIS)

Lubec, G.; Tichatschek, E.; Foltinova, J.; Leplawy, T.; Mallinger, R.; Getoff, N.

1996-01-01

The radiation protective activity of intaperitoneally administered alpha-methyl-homocysteine thiolactone (α-MHCTL); 100 mg/kg body weight) in female BALB/c mice and such treated with cysteine treated (100 mg/kg body weight), using unirradiated and placebo treated irradiated mice were tested as controls. 6Gy whole body irradiated was applied and after a period of three weeks the animals were sacrificed and lungs were taken for morphometry and the determination of o-tyrosine. Septal areas were highest in the irradiated, placebo treated mice (68.67 + 9.82% septal area to total area) and lowest in the α-MHCTL treated irradiated mice (55.67 + 11.29%), significant at the p < 0.05 level. Morphometric data were accompanied by highest levels of o-tyrosine, a reliable parameter for OH-attack, in the irradiated, placebo treated group with 1.87 + 0.40 μM/g lung tissue and 0.32 + 0.13 μM/g lung tissue in the αMHCTL treated group; the statistical difference was significant. Significant radiation protection in the mammalian system at the morphological and biochemical level were found. The potent effect could be explained by the influence of alpha-alkylation in homocysteine thiolactone (HCTL) which renders amino acids unmetabolizeable, nontoxic, increases lipophilicity and therefore improving permeability through membranes. The present report confirms morphological data on the radiation protective activity of this interesting thiol compound. (Author)

Tensile and fracture toughness properties of copper alloys and their HIP joints with austenitic stainless steel in unirradiated and neutron irradiated condition

International Nuclear Information System (INIS)

Taehtinen, S.; Pyykkoenen, M.; Singh, B.N.; Toft, P.

1998-03-01

The tensile strength and ductility of unirradiated CuAl25 IG0 and CuCrZr alloys decreased continuously with increasing temperature up to 350 deg C. Fracture toughness of unirradiated CuAl25 IG0 alloy decreased continuously with increasing temperature from 20 deg C to 350 deg C whereas the fracture toughness of unirradiated CuCrZr alloy remained almost constant at temperatures up to 100 deg C, was decreased significantly at 200 deg C and slightly increased at 350 deg C. Fracture toughness of HIP joints were lower than that of corresponding copper alloy and fracture path in HIP joint specimen was always within copper alloy side of the joint. Neutron irradiation to a dose level of 0.3 dpa resulted in hardening and reduction in uniform elongation to about 2-4% at 200 deg C in both copper alloys. At higher temperatures softening was observed and uniform elongation increased to about 5% and 16% for CuAl25 IG0 and CuCrZr alloys, respectively. Fracture toughness of CuAl25 IG0 alloy reduced markedly due to neutron irradiation in the temperature range from 20 deg C to 350 deg C. The fracture toughness of the irradiated CuCrZr alloy also decreased in the range from 20 deg C to 350 deg C, although it remained almost unaffected at temperatures below 200 deg C and decreased significantly at 350 deg C when compared with that of unirradiated CuCrZr alloy. (orig.)

The effect of compressive stress on the Young's modulus of unirradiated and irradiated nuclear graphites

International Nuclear Information System (INIS)

Oku, T.; Usui, T.; Ero, M.; Fukuda, Y.

1977-01-01

The Young's moduli of unirradiated and high temperature (800 to 1000 0 C) irradiated graphites for HTGR were measured by the ultrasonic method in the direction of applied compressive stress during and after stressing. The Young's moduli of all the tested graphites decreased with increasing compressive stress both during and after stressing. In order to investigate the reason for the decrease in Young's modulus by applying compressive stress, the mercury pore diameter distributions of a part of the unirradiated and irradiated specimens were measured. The change in pore distribution is believed to be associated with structural changes produced by irradiation and compressive stressing. The residual strain, after removing the compressive stress, showed a good correlation with the decrease in Young's modulus caused by the compressive stress. The decrease in Young's modulus by applying compressive stress was considered to be due to the increase in the mobile dislocation density and the growth or formation of cracks. The results suggest, however, that the mechanism giving the larger contribution depends on the brand of graphite, and in anisotropic graphite it depends on the direction of applied stress and the irradiation conditions. (author)

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

Energy Technology Data Exchange (ETDEWEB)

Popp, R A; Stratton, L P; Hawley, D K; Effron, K [Oak Ridge National Lab., TN (USA)

1979-01-15

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F/sub 1/ offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of ..cap alpha..-chains normally found in all SEC mice. The deficient ..cap alpha..-chain synthesis caused these mice to exhibit an ..cap alpha..-thalassemia similar to human ..cap alpha..-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with ..cap alpha..-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining ..beta..-chain structure) produced twice as much SEC as 101 ..beta..-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC ..beta..-chain gene.

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

International Nuclear Information System (INIS)

Popp, R.A.; Stratton, L.P.; Hawley, D.K.; Effron, K.

1979-01-01

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F 1 offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of α-chains normally found in all SEC mice. The deficient α-chain synthesis caused these mice to exhibit an α-thalassemia similar to human α-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with α-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining β-chain structure) produced twice as much SEC as 101 β-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC β-chain gene. (author)

Transient changes of enzyme activity of five acid hydrolases in the supernatants of homogenates of hearts of mice due to ultraviolet irradiation

International Nuclear Information System (INIS)

Droba, B.; Jagiellonian Univ., Krakow

1977-01-01

Enzymatic activity of five lysosomal hydrolases: acid p-nitrophenyl phosphatase (EC 3.1.3.2), acid β-glycerophosphatase (EC 3.1.3.2), arylsulphatase (EC 3.1.6.1), β-galactosidase (EC 3.2.1.23) and β-N-acetylhexoaminidase (EC 3.2.1.30) was studied in the supernatants of homogenates of hearts of unirradiated mice, serving as controls, and a group of UV-irradiated mice. In the control group, determinations made at 6-hr intervals showed rhythmic diurnal changes in activities of three acid hydrolases. These changes were statistically significant in the case of acid p-nitrophenyl phosphatase, acid β-glycerophosphatase, and β-N-acetylhexosaminidase. The effect of UV-irradiation was manifested mainly by depression of enzyme activities of the acid hydrolases during the first few hours after exposure. Depression of activities of arylsulphatase and β-N-acetylhexosaminidase by UV light was statistically significant. Presumably, the fall in enzyme activities of the acid hydrolases was due to chemical mediators formed in the skin under the influence of UV-radiation and adrenal corticoids secreted into the blood

Molecular dynamics study on interfacial thermal conductance of unirradiated and irradiated SiC/C

International Nuclear Information System (INIS)

Wang, Qingyu; Wang, Chenglong; Zhang, Yue; Li, Taosheng

2014-01-01

SiC f /SiC composite materials have been considered as candidate structural materials for several types of advanced nuclear reactors. Both experimental and computer simulations studies have revealed the degradation of thermal conductivity for this material after irradiation. The objective of this study is to investigate the effect of SiC/graphite interface structure and irradiation on the interfacial thermal conductance by using molecular dynamics simulation. Five SiC/graphite composite models were created with different interface structures, and irradiation was introduced near the interfaces. Thermal conductance was calculated by means of reverse-NEMD method. Results show that there is a positive correlation between the interfacial energy and interfacial C–Si bond quantity, and irradiated models showed higher interfacial energy compared with their unirradiated counterparts. Except the model with graphite atom plane parallel to the interface, the interfacial thermal conductance of unirradiated and irradiated (1000 eV) models, increases as the increase of interfacial energy, respectively. For all irradiated models, lattice defects are of importance in impacting the interfacial thermal conductance depending on the interface structure. For the model with graphite layer parallel to the interface, the interfacial thermal conductance increased after irradiation, for the other models the interfacial thermal conductance decreased. The vibrational density of states of atoms in the interfacial region was calculated to analyze the phonon mismatch at the interface

Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes

Science.gov (United States)

Yin, Xiaoming; Tian, Wenqian; Wang, Longxiao; Wang, Jingdong; Zhang, Shuyu; Cao, Jianping; Yang, Hongying

2015-01-01

Traditional radiation biology states that radiation causes damage only in cells traversed by ionizing radiation. But radiation-induced bystander effect (RIBE), which refers to the biological responses in unirradiated cells when the neighboring cells are exposed to radiation, challenged this old dogma and has become a new paradigm of this field. By nature, RIBEs are the consequences of intercellular communication between irradiated and unirradiated cells. However, there are still some important questions remain unanswered such as whether RIBE is dependent on radiation quality, what are the determining factors if so, etc. Using a transwell co-culture system, we found that HaCaT keratinocytes irradiated with α-particles but not X-rays could induce bystander micronucleus formation in unirradiated WS1 fibroblasts after co-culture. More importantly, the activation of TGF-β1-Smad2 pathway and the consistent decrease of miR-21 level in α-irradiated HaCaT cells were essential to the micronucleus induction in bystander WS1 cells. On the other hand, X-irradiation did not induce bystander effect in unirradiated WS1 cells, accompanied by lack of Smad2 activation and consistent decrease of miR-21 in X-irradiated HaCaT cells. Taken together, these results suggest that the radiation quality-dependence of bystander effect may be associated with the TGF-β1-Smad2 pathway and miR-21 in irradiated cells. PMID:26080011

Special Analysis for the Disposal of the INL Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) Waste Stream at the Area 5 Radioactive Waste Management Site

Energy Technology Data Exchange (ETDEWEB)

Shott, Gregory [National Security Technologies, LLC, Las Vegas, NV (United States)

2017-03-21

This special analysis (SA) evaluates whether the Idaho National Laboratory (INL) Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) waste stream (INEL167203QR1, Revision 0) is suitable for shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS) on the Nevada National Security Site (NNSS). Disposal of the INL Waste Associated with the Unirradiated LWBR waste meets all U.S. Department of Energy (DOE) Manual DOE M 435.1-1, “Radioactive Waste Management Manual,” Chapter IV, Section P performance objectives (DOE 1999). The INL Waste Associated with the Unirradiated LWBR waste stream is recommended for acceptance with the condition that the total uranium-233 (²³3U) inventory be limited to 2.7E13 Bq (7.2E2 Ci).

Special Analysis for the Disposal of the Idaho National Laboratory Unirradiated Light Water Breeder Reactor Rods and Pellets Waste Stream at the Area 5 Radioactive Waste Management Site, Nevada National Security Site, Nye County, Nevada

Energy Technology Data Exchange (ETDEWEB)

None

2014-08-31

The purpose of this special analysis (SA) is to determine if the Idaho National Laboratory (INL) Unirradiated Light Water Breeder Reactor (LWBR) Rods and Pellets waste stream (INEL103597TR2, Revision 2) is suitable for disposal by shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS). The INL Unirradiated LWBR Rods and Pellets waste stream consists of 24 containers with unirradiated fabricated rods and pellets composed of uranium oxide (UO2) and thorium oxide (ThO2) fuel in zirconium cladding. The INL Unirradiated LWBR Rods and Pellets waste stream requires an SA because the 229Th, 230Th, 232U, 233U, and 234U activity concentrations exceed the Nevada National Security Site (NNSS) Waste Acceptance Criteria (WAC) Action Levels.

Fusarium growth on culture media made of tissue juice from irradiated and unirradiated potato tubers

International Nuclear Information System (INIS)

Taczanowski, M.

1994-01-01

Fusarium Sulphureum Schlecht is one of the tuber pathogens causing potato storage disease knowing as dry rot. Because irradiation can disturb the tissue defence mechanism against the pathogen, it was decided to carry out experiments on influence of the treatment on subsequent tuber tissue reaction to a maceration process. The maceration as a physical stress was a substitute for the pathogen activity. Tubers of two potato varieties were tested: Mila -a resistant variety to Fusarium and Atol - susceptible one. Tubers of both varieties were irradiated with a dose of 105 kGy. Unirradiated tubers were taken as a control. A day after irradiation the cortex tissue was macerated using an ordinary rasper and the resulted tissue pulp was strained through medical gauze to obtain crude juice. The juice was clarified by centrifugation and then added to dissolved PDA. The volume ratio of juice to PDA was 1:1. The prepared media were dispensed into Petri dishes. Small pieces of the Fusarium culture were put on the surface of the medium at the centre of each Petri dish. Subsequent growth of the fungus was assessed by measurement of culture diameters every 24 hours. Linear functions of the Fusarium growth were obtained for Mila control and Atol control. In the case of Mila, the Fusarium found more favourable conditions for its growth in the presence of juice from irradiated tubers than from the control ones. Making the same comparison for Atol, no difference was detected. (author)

Oxide particle size distribution from shearing irradiated and unirradiated LWR fuels in Zircaloy and stainless steel cladding: significance for risk assessment

International Nuclear Information System (INIS)

Davis, W. Jr.; West, G.A.; Stacy, R.G.

1979-01-01

Sieve fractionation was performed with oxide particles dislodged during shearing of unirradiated or irradiated fuel bundles or single rods of UO 2 or 96 to 97% ThO 2 --3 to 4% UO 2 . Analyses of these data by nonlinear least-squares techniques demonstrated that the particle size distribution is lognormal. Variables involved in the numerical analyses include lognormal median size, lognormal standard deviation, and shear cut length. Sieve-fractionation data are presented for unirradiated bundles of stainless-steel-clad or Zircaloy-2-clad UO 2 or ThO 2 --UO 2 sheared into lengths from 0.5 to 2.0 in. Data are also presented for irradiated single rods (sheared into lengths of 0.25 to 2.0 in.) of Zircaloy-2-clad UO 2 from BWRs and of Zircaloy-4-clad UO 2 from PWRs. Median particle sizes of UO 2 from shearing irradiated stainless-steel-clad fuel ranged from 103 to 182 μm; particle sizes of ThO 2 --UO 2 , under these same conditions, ranged from 137 to 202 μm. Similarly, median particle sizes of UO 2 from shearing unirradiated Zircaloy-2-clad fuel ranged from 230 to 957 μm. Irradiation levels of fuels from reactors ranged from 9,000 to 28,000 MWd/MTU. In general, particle sizes from shearing these irradiated fuels are larger than those from the unirradiated fuels. In addition, variations in particle size parameters pertaining to samples of a single vendor varied as much as those between different vendors. The fraction of fuel dislodged from the cladding is nearly proportional to the reciprocal of the shear cut length, until the cut length attains some minimum value below which all fuel is dislodged. Particles of fuel are generally elongated with a long-to-short axis ratio usually less than 3. Using parameters of the lognormal distribution deduced from experimental data, realistic estimates can be made of fractions of dislodged fuel having dimensions less than specified values

Leukemic transformation of donor spleen cells following their transplantation into supralethally irradiated mice with pre-existing viral leukemia. [X Radiation

Energy Technology Data Exchange (ETDEWEB)

Kuhnert, P M; OKunewick, J P; Erhard, P

1974-01-01

Fialkow et al. previously reported leukemia induction in donor-type cells after treating patients for acute lymphoblastic leukemia with total-body irradiation and hematopoietic cell transplantation. Utilizing a murine model and paralleling their treatment protocol, we have documented that induction of leukemia can occur in normal donor cells transplanted into Rauscher viral leukemic mice at 0, 1 and 2 days after irradiation. The induction of leukemia in the grafted cells was verified by: the occurrence of splenomegaly; and secondary spleen cell transplants, whereby the secondary donors were transplanted mice still alive at 30 days and the secondary recipients were normal unirradiated mice. The spleen weights of the grafted leukemic mice were found to be significantly greater than those of the controls and all secondary recipients that received spleen cells from the primary grafted leukemic mice also died of leukemia. Verification that the regenerating hematopoietic tissue was from donor (males) and not host source (females) was accomplished by spleen chromosome preparations taken from randomly selected mice at 14 and at 30 days after cell transplantation. In these preparations, the Y chromosome was clearly distinguishable on the basis of size, shape, and differential staining. The data indicate that induction of leukemia after whole-body irradiation and hematopoietic cell transplantation can occur in immunologically matched donor cells when a viral agent is present and that the incidence of this induction is not affected by a time delay between irradiation and transplant.

The effect of local irradiation on the immune response in mice. I. Effect of sham-irradiation

International Nuclear Information System (INIS)

Gauci, C.L.; Gerber, M.; Dubois, J.-B.; Serrou, B.

1979-01-01

In C57BL/6 mice exposed to 1600 rads to the left foot pad, an important decrease of non-specific inflammatory responsiveness initiated by the injection of oyster glycogen into the peritoneal cavity was observed on the one hand and a diminution of the delayed hypersensitivity response following tuberculin injection, on the other hand. Nevertheless, the same immunosuppression was noted both in sham irradiated mice and in those receiving hydrocortisone. In irradiated mice this transient immunosuppression was related to a normal adrenal function. Bi-laterally adrenalectomised mice did not exhibit this reaction which reappeared after hydrocortisone administration. The reduction of delayed hypersensitivity is irrespective of the irradiated zone, but the duration of immune depression is longer in irradiated than in unirradiated tissue. During the depression of delayed hypersensitivity response an increase in the number of splenic B-lymphocytes and macrophages and a decrease of the number of splenic T-lymphocytes was observed these observations suggest that immunosuppression following irradiation is related to acute stress

Safety Analysis Report for Packaging: The unirradiated fuel shipping container USA/9853/AF

International Nuclear Information System (INIS)

1991-01-01

The HFBR Unirradiated Fuel Shipping Container was designed and fabricated at the Oak Ridge National Laboratory in 1978 for the transport of fuel for the High Flux Beam Reactor (HFBR) for Brookhaven National Laboratory. The package has been evaluated analytically, as well as the comparison to tests on similar packages, to demonstrate compliance with the applicable regulations governing packages in which radioactive and fissile materials are transported. The contents of this Safety Analysis Report for Packaging (SARP) are based on Regulatory Guide 7.9 (proposed Revision 2 - May 1986), 10 CFR Part 71, DOE Order 1540.2, DOE Order 5480.3, and 49 CFR Part 173

Age and sex dependence in tumorigenesis in mice by continuous low-dose-rate gamma-ray whole-body irradiation

International Nuclear Information System (INIS)

Otsu, Hiroshi; Kobayashi, Shigeru; Furuse, Takeshi; Noda, Yuko; Shiragai, Akihiro; Sato, Fumiaki.

1992-01-01

We investigated the dependency of sex and age in mice in the induction of neoplasms by gamma-rays from cesium-137 at a low dose rate of 0.375Gy/22h/day. Thymic lymphomas occurred significantly at the same incidence in both sexes, and more frequently when younger mice were exposed to radiation. Strain C57BL/6J mice were divided into 8 groups, which were whole-body irradiated with a total dose of 39Gy for 105 days each. The exposure was begun at 28 days of age (male:AM1, female:AF1), and then stepwise increasing the starting age by 105 days, i.e., from 133 days (AM2 and AF2), from 238 days (AM3 and AF3), and from 343 days (AM4 and AF4), respectively. Unirradiated mice served as control (UM and UF). The incidence of thymic lymphomas was about 60 % in AM1, AM2, AF1 and AF2, 40 % in AM3 and AF3 and 20 % in AF4 and AF4, demonstrating no sex dependency, but a distinct age dependency, for lymphomogenesis. It was proven that mice showed a tendency to become less susceptible to radiation induced thymic lymphoma with increasing age. Concomitantly, life-shortening also was caused, and the greater the degree of life-shortening was, the younger the mice were the start of exposure. Life-shortening was attributed to thymic lymphoma, and hemorrhage and infectious diseases due to the depletion of bone marrow cells. (author)

Thermal studies on unirradiated and γ-irradiated polymer of allyl diglycol carbonate

International Nuclear Information System (INIS)

Kalsi, P.C.; Pandey, A.K.; Iyer, R.H.; Singh Mudher, K.D.

1995-01-01

The thermal decomposition of unirradiated and γ-irradiated (5.93-15.5 MRad dose range) allyl diglycol carbonate polymer (trade name, CR-39) was studied by thermogravimetry (TG) and differential thermal analysis (DTA). These studies indicate four main decomposition steps in CR-39 polymer in air. Assessment of the influence of radiation dose on the above range shows that while the 5.93 MRad γ-irradiated polymer CR-39 degrades in three steps, the 15.5 MRad γ-irradiated polymer degrades in only two steps. The kinetics of the different stages of degradation were also evaluated from the TG curves. Irradiation enhances the decomposition rate and the effect increases further with increasing radiation dose. The activation energy values calculated for all the decomposition stages decrease on irradiation

Factors related to resistance to hematopoietic death in mice

International Nuclear Information System (INIS)

Mori, Nobuko; Okumoto, Masaaki; Yonezawa, Morio; Nishikawa, Ryosuke; Takamori, Yasuhiko; Esaki, Kozaburo.

1994-01-01

Mouse strain difference in the radiosensitivity to hematopoietic death is thought to be determined by several factors besides radiosensitivity and the initial number of hematopoietic stem cells. Factors related to the survival of mice exposed to X-irradiation were analyzed using BALB/cHeA and STS/A strains whose LD 50/30 values differ markedly (BALB/cHeA, 5.55 Gy; STS/A, 8.45 Gy). STS/A mice exposed to 4 Gy of X-irradiation showed a small reduction but rapid recovery of blood cells (leukocytes, erythrocytes, and thrombocytes) when compared with BALB/cHeA mice. The survival of endogenous and exogenous CFU-S was much higher, by a magnitude of one log or more, in STS/A mice than those in BALB/cHeA mice; whereas the initial numbers of femoral CFU-S were similar for the two strains. The recovery of exogenous CFU-S was much more rapid in STS/A mice than it was in BALB/cHeA mice after 4 Gy of X-irradiation. Furthermore, spleen colonies produced by the transfusion of STS/A marrow cells into syngeneic recipients were significantly larger than those produced by BALB/cHeA marrow cells, regardless of whether the mice used for sources of marrow cells had been irradiated. But, there was no such difference when unirradiated marrow cells from the two strains were transfused into (BALB/cHeA X STS/A) F 1 recipients. These results indicate the possible contribution of a host factor (s) that stimulates the growth of spleen colonies after radiation to the radioresistance of STS/A mice, in addition to the primary effect of higher number of survivals of endogenous and exogenous CFU-S in STS/A mice. (author)

Morphological and histochemical study of cleft palate induced in CD-1 mice by whole body x-radiation

International Nuclear Information System (INIS)

Lewis, C.E.

1977-01-01

Palatogenesis in CD-1 mice exposed to 300 or 400 rads of x-radiation in utero was compared with palate development of unirradiated fetuses to determine whether any correlation exists between time of irradiation (days nine through twelve) and the incidence of morphological or histochemical variations in fetal palate tissues. Data accumulated indicate that although x-radiation reduces fetal weight and crown-rump length and retards palate closure, growth, ossification and SDH activity, fetuses exhibit some recovery from radiation damage

CISH controls bacterial burden early after infection with Mycobacterium tuberculosis in mice.

Science.gov (United States)

Carow, Berit; Gao, Yu; Terán, Graciela; Yang, Xuexian O; Dong, Chen; Yoshimura, Akihiko; Rottenberg, Martin E

2017-12-01

CISH gene has been associated with increased susceptibility to human tuberculosis. We found that cish -/- mice had higher M. tuberculosis load in spleens and lungs up to 2.5 weeks after infection but not later compared to controls. Cish mRNA levels were increased in lungs at early and late time points after M. tuberculosis infection. In relation, the titers of inos and tnf mRNA in lungs were reduced early after infection of cish -/- mice. The transfer of cish -/- and control T cells conferred rag1 -/- mice similar protection to infection with M. tuberculosis. Macrophages showed increased cish mRNA levels after M. tuberculosis infection in vitro. However, mycobacterial uptake and growth in cish -/- and control macrophages was similar. Thus, we here show that CISH mediates control of M. tuberculosis in mice early after infection via regulation of innate immune mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Criticality Safety Study on Storing Unirradiated Cintichem-Type Targets at Sandia National Laboratories

International Nuclear Information System (INIS)

Romero, D.J.; Parma, E.J.; Busch, R.D.

1999-01-01

This criticality safety analysis is performed to determine the effective multiplication factor (k eff ) for a storage cabinet filled with unirradiated Cintichem-type targets. These targets will be used to produce 99 Mo at Sandia National Laboratories and will be stored on-site prior to irradiation in the Annular Core Research Reactor. The analysis consisted of using the Monte Carlo code MCNP (Version 4A) to model and predict the k eff for the proposed dry storage configuration under credible loss of geometry and moderator control. Effects of target pitch, non-uniform loading, and target internal/external flooding are evaluated. Further studies were done with deterministic methods to verify the results obtained from MCNP and to obtain a clearer understanding of the parameters affecting system criticality. The diffusion accelerated neutral particle transport code ONEDANT was used to model the target in a one-dimensional, infinite half-slab geometry and determine the critical slab thickness. Hand calculations were also completed to determine the critical slab thickness with modified one-group, and one-group, two region approximations. Results obtained from ONEDANT and the hand calculations were compared to applicable cases in a commonly used criticality safety analysis handbook. Overall, the critical slab thicknesses obtained in the deterministic analysis were much larger than the dimensions of the cabinet and further support the predictions by MCNP that a critical system cannot be attained for the base case or in conditions where loss of geometry and moderation control occur

Effects of Zinc Compound on Body Weight and Recovery of Bone Marrow in Mice Treated with Total Body Irradiation

Directory of Open Access Journals (Sweden)

Ming-Yii Huang

2007-09-01

Full Text Available This study aimed to investigate if zinc compound would have effects on body weight loss and bone marrow suppression induced by total body irradiation (TBI. ICR mice were divided randomly into two groups and treated with test or control compounds. The test compound contained zinc (amino acid chelated with bovine prostate extract, and the control was reverse osmosis pure water (RO water. One week after receiving the treatment, mice were unirradiated, or irradiated with 6 or 3 Gy by 6MV photon beams to the total body. Body weight changes were examined at regular intervals. Three and 5 weeks after the radiation, animals were sacrificed to examine the histologic changes in the bone marrow. Lower body weight in the period of 1-5 weeks after radiation and poor survival rate were found after the 6 Gy TBI, as compared with the 3 Gy groups. The median survival time after 6 Gy and 3 Gy TBI for mice given the test compound were 26 and 76 days, respectively, and the corresponding figures were 14 and 70 days, respectively, for mice given the control compound (p < 0.00001. With zinc supplement, the mean body weight in mice which received the same dose of radiation was 7-8 g heavier than in the water-supplement groups during the second and third weeks (p < 0.05. Hence, there was no statistically significant difference in survival rate between zinc and water supplement in mice given the same dose of irradiation. Histopathologically there was less recovery of bone marrow cells in the 6Gy groups compared with the 3Gy groups. In the 3 Gy water-supplement group, the nucleated cells and megakaryocytes were recovered in the fifth week when recovery was still not seen in the 6Gy group. With zinc supplement, these cells were recovered in the third week. In this study, we found that zinc is beneficial to body weight in mice treated with TBI. Histologic examination of bone marrow showed better recovery of bone marrow cells in groups of mice fed with zinc. This study

Differentiation of bone marrow cells to functional T lymphocytes following implantation of thymus grafts and thymic stroma in nude and ATxBM mice

International Nuclear Information System (INIS)

Splitter, G.A.; McGuire, T.C.; Davis, W.C.

1977-01-01

Cardiac allografts were used to compare the immunologic capacity of nude mice and adult, thymectomized, lethally irradiated, bone marrow-reconstituted (AT x BM) mice. Neither nude nor AT x BM mice were able to reject cardiac allografts of any party. However, both rejected grafts of any party following implantation of neonatal thymus or thymus from 3-week-old syngeneic mice. Irradiated syngeneic thymus grafts (800 R) were equally effective in restoring host responsiveness against allografts. In contrast, allogeneic thymus grafts restored the capacity to reject second-party heart grafts only in AT x BM mice. Second-party grafts persisted indefintely when placed on nude mice implanted with an allogeneic, unirradiated thymus graft. Third-party grafts transplanted 17 weeks after reconstitution, however, were rejected. Irradiated nude mice given normal littermate bone marrow and simultaneously grafted with second-party thymus and heart allografts also failed to reject their second-party heart grafts. The difference in ultimate capacity to respond between AT x BM and nude mice suggests that a maturational defect exists in the nude mouse environment which impedes development of precursor T lymphocytes

Mutagenicity studies on alcohol extracts from gamma-irradiated potatoes

International Nuclear Information System (INIS)

Shibuya, Tohru; Murora, Tetsuro; Iwahara, Shigeo; Hashimoto, Koroku; Minegishi, Atsuko.

1982-01-01

Alcohol extracts freshly prepared from gamma-irradiated and unirradiated potatoes were tested for the ability to induce dominant lethals in BDF 1 mice. Male mice were given 0.5 ml of extract twice a day, p.o., for 7 days and then mated with untreated female mice. Female mice were sacrificed on about the 13th day of pregnancy. No significant difference was observed in the number of living inplants between the group treated with extract prepared from unirradiated potatoes and that treated with the extract from 150 Gy (15 krad) irradiated potatoes. (author)

The Analysis of the General Performance and Mechanical Behavior of Unirradiated FeCrAl Alloys Before and After Welding

Energy Technology Data Exchange (ETDEWEB)

Gussev, Maxim N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-06-03

The present report summarizes and discusses the preliminary results for the in-depth characterization of the modern, nuclear-grade FeCrAl alloys currently under development. The alloys were designed for enhanced radiation tolerance and weldability, and the research is currently being pursued by the Department of Energy (DOE) Nuclear Energy Enabling Technologies (NEET) program. Last year, seven candidate FeCrAl alloys with well-controlled chemistry and microstructures were designed and produced; welding was performed under well-controlled conditions. The structure and general performance of unirradiated alloys were assessed using standardized and advanced microstructural characterization techniques and mechanical testing. The primary objective is to identify the best candidate alloy, or at a minimum to identify the contributing factors that increase the weldability and radiation tolerance of FeCrAl alloys, therefore enabling future generations of FeCrAl alloys to deliver better performance parameters. This report is structured so as to describe these critical assessments of the weldability; radiation tolerance will be reported on in later reports from this program.

Damage and failure of unirradiated and irradiated fuel rods tested under film boiling conditions

International Nuclear Information System (INIS)

Mehner, A.S.; Hobbins, R.R.; Seiffert, S.L.; MacDonald, P.E.; McCardell, R.K.

1979-01-01

Power-cooling-mismatch experiments are being conducted as part of the Thermal Fuels Behavior Program in the Power Burst Facility at the Idaho National Engineering Laboratory to evaluate the behavior of unirradiated and previously irradiated light water reactor fuel rods tested under stable film boiling conditions. The observed damage that occurs to the fuel rod cladding and the fuel as a result of film boiling operation is reported. Analyses performed as a part of the study on the effects of operating failed fuel rods in film boiling, and rod failure mechanisms due to cladding embrittlement and cladding melting upon being contacted by molten fuel are summarized

Coping with parvovirus infections in mice: health surveillance and control.

Science.gov (United States)

Janus, Lydia M; Bleich, Andre

2012-01-01

Parvoviruses of mice, minute virus of mice (MVM) and mouse parvovirus (MPV), are challenging pathogens to eradicate from laboratory animal facilities. Due to the impediment on rodent-based research, recent studies have focused on the assessment of re-derivation techniques and parvoviral potential to induce persistent infections. Summarizing recent data, this review gives an overview on studies associated with parvoviral impact on research, diagnostic methods, parvoviral persistence and re-derivation techniques, demonstrating the complex nature of parvovirus infection in mice and unfolding the challenge of controlling parvovirus infections in laboratory animal facilities.

A study of the behaviour of irradiated or unirradiated grafts in the camera aquosa of irradiated and unirradiated animals

International Nuclear Information System (INIS)

Djalali-Behzad, G.

1969-06-01

Following grafts of new born mice spinal ganglia in the 'camera aquosa' of adult mice, the authors tried hematopoietic tissue grafts in the same conditions. The growth of iso-logous and hetero-logous bone marrow in the 'camera aquosa' showed that this tissue, even after exposure to supralethal doses, was capable of survival and growth. A counter-experiment with non irradiated bone marrow grafts in the 'camera aquosa' of rats delivered 700 rads led to the conclusion that the environment, intoxicated by exposure, acted on the graft so that after vascularization it became unable to grow. (author) [fr

An analysis of facial nerve function in irradiated and unirradiated facial nerve grafts

International Nuclear Information System (INIS)

Brown, Paul D.; Eshleman, Jeffrey S.; Foote, Robert L.; Strome, Scott E.

2000-01-01

Purpose: The effect of high-dose radiation therapy on facial nerve grafts is controversial. Some authors believe radiotherapy is so detrimental to the outcome of facial nerve graft function that dynamic or static slings should be performed instead of facial nerve grafts in all patients who are to receive postoperative radiation therapy. Unfortunately, the facial function achieved with dynamic and static slings is almost always inferior to that after facial nerve grafts. In this retrospective study, we compared facial nerve function in irradiated and unirradiated nerve grafts. Methods and Materials: The medical records of 818 patients with neoplasms involving the parotid gland who received treatment between 1974 and 1997 were reviewed, of whom 66 underwent facial nerve grafting. Fourteen patients who died or had a recurrence less than a year after their facial nerve graft were excluded. The median follow-up for the remaining 52 patients was 10.6 years. Cable nerve grafts were performed in 50 patients and direct anastomoses of the facial nerve in two. Facial nerve function was scored by means of the House-Brackmann (H-B) facial grading system. Twenty-eight of the 52 patients received postoperative radiotherapy. The median time from nerve grafting to start of radiotherapy was 5.1 weeks. The median and mean doses of radiation were 6000 and 6033 cGy, respectively, for the irradiated grafts. One patient received preoperative radiotherapy to a total dose of 5000 cGy in 25 fractions and underwent surgery 1 month after the completion of radiotherapy. This patient was placed, by convention, in the irradiated facial nerve graft cohort. Results: Potential prognostic factors for facial nerve function such as age, gender, extent of surgery at the time of nerve grafting, preoperative facial nerve palsy, duration of preoperative palsy if present, or number of previous operations in the parotid bed were relatively well balanced between irradiated and unirradiated patients. However

Production of anti-SRBC antibodies after DDC administration in whole-body irradiated mice

International Nuclear Information System (INIS)

Kautska, J.; Hosek, B.; Misustova, J.

1990-01-01

Production of antibody-forming cells (PFC) was studied in mice subjected to a single whole-body radiation dose of 3.8 Gy following an injection of sodium diethyl dithiocarbamate (DDC, 800 mg/kg) 30 min before irradiation. The animals were immunized (1% SRBC) 4 hours and 5 and 10 days after irradiation, and the number of PFC was determined by a modified Jerne plaque technique on days 4, 7 and 10 after immunization. After irradiation alone, the PFC levels were markedly reduced at all time intervals in comparison with unirradiated controls. Upon immunization of animals on day 10 after irradiation the peak PFC levels were observed on day 7 after immunization in the irradiated only group and in the group irradiated after DDC administration (in controls on day 4 after immunization). The administration of DDC entirely eliminated the unfavourable effect of radiation if immunization was performed 4 h after irradiation, in terms of the number and the peak level of PFC. Upon immunization of animals on day 5 and day 10 after irradiation the PFC levels were not markedly influenced by DDC injection. (author). 3 figs., 25 refs

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)

Pimonidazole labelling and response to fractionated irradiation of five human squamous cell carcinoma (hSCC) lines in nude mice: The need for a multivariate approach in biomarker studies

International Nuclear Information System (INIS)

Yaromina, Ala; Zips, Daniel; Thames, Howard D.; Eicheler, Wolfgang; Krause, Mechthild; Rosner, Andrea; Haase, Michael; Petersen, Cordula; Raleigh, James A.; Quennet, Verena; Walenta, Stefan; Mueller-Klieser, Wolfgang; Baumann, Michael

2006-01-01

Objective: To investigate the influence on local control after fractionated radiotherapy of hypoxia measured in unirradiated tumours using the hypoxic marker Pimonidazole, using multivariate approaches. Material and methods: Five human squamous cell carcinoma lines (FaDu, UT-SCC-15, UT-SCC-14, XF354, and UT-SCC-5) were transplanted subcutaneously into the right hind-leg of NMRI nude mice. Histological material was collected from 60 unirradiated tumours after injection of Pimonidazole. The relative hypoxic area within the viable tumour area (Pimonidazole hypoxic fraction, pHF) was determined in seven serial 10 μm cross-sections per tumour by fluorescence microscopy and computerized image analysis. Local tumour control was evaluated in a total of 399 irradiated tumours at 120 days after 30 fractions given within 6 weeks with total doses between 30 and 115 Gy. Results: Tumour lines showed pronounced heterogeneity in both pHF and TCD 5 . Mean pHF values varied between 5% and 37%, TCD 5 values between 47 and 130 Gy. A Cox Proportional Hazards model of time to recurrence with two covariates, dose and pHF, yielded significant contributions of both parameters on local control (p < 0.005) but violated the proportional hazards assumption, suggesting that other factors also influence tumour control. Introduction of histological grade as an example of a confounding factor into the model improved the fit significantly. Local control rates decreased with increasing pHF and this effect was more pronounced at higher doses. Conclusions: This study confirms that tumour hypoxia measured using Pimonidazole in untreated tumours is a significant determinant of local control after fractionated irradiation. The data support the use of multivariate approaches for the evaluation of a single prognostic biomarker such as Pimonidazole, and more generally, suggest that they are required to establish accurate prognostic factors for tumour response

Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

Science.gov (United States)

Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

2017-10-01

1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice

International Nuclear Information System (INIS)

Leakey, Julian E.A.; Seng, John E.; Latendresse, John R.; Hussain, Nursreen; Allen, Laura J.; Allaben, William T.

2003-01-01

Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F 1 mice in a 2-year bioassay of chloral hydrate. Male B6C3F 1 mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined 'idealized' weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation

Reactor Materials Program electrochemical potential measurements by ORNL with unirradiated and irradiated stainless steel specimens

Energy Technology Data Exchange (ETDEWEB)

Baumann, E.W.; Caskey, G.R. Jr.

1993-07-01

Effect of irradiation of stainless steel on electrochemical potential (ECP) was investigated by measurements in dilute HNO{sub 3} and H{sub 2}O{sub 2} solutions, conditions simulating reactor moderator. The electrodes were made from unirradiated/irradiated, unsensitized/sensitized specimens from R-reactor piping. Results were inconclusive because of budgetary restrictions. The dose rate may have been too small to produce a significant radiolytic effect. Neither the earlier CERT corrosion susceptibility tests nor the present ECP measurements showed a pronounced effect of irradiation on susceptibility of the stainless steel to IGSCC; this is confirmed by the absence in the stainless steel of the SRS reactor tanks (except for the C Reactor tank knuckle area).

Reactor Materials Program electrochemical potential measurements by ORNL with unirradiated and irradiated stainless steel specimens

International Nuclear Information System (INIS)

Baumann, E.W.; Caskey, G.R. Jr.

1993-07-01

Effect of irradiation of stainless steel on electrochemical potential (ECP) was investigated by measurements in dilute HNO 3 and H 2 O 2 solutions, conditions simulating reactor moderator. The electrodes were made from unirradiated/irradiated, unsensitized/sensitized specimens from R-reactor piping. Results were inconclusive because of budgetary restrictions. The dose rate may have been too small to produce a significant radiolytic effect. Neither the earlier CERT corrosion susceptibility tests nor the present ECP measurements showed a pronounced effect of irradiation on susceptibility of the stainless steel to IGSCC; this is confirmed by the absence in the stainless steel of the SRS reactor tanks (except for the C Reactor tank knuckle area)

Distribution of copper-64 in control mice and in mice bearing ascitic Krebs tumor cells

International Nuclear Information System (INIS)

Apelgot, S.; Coppey, J.; Grisvard, J.; Guille, E.; Sissoeeff, I.

1981-01-01

Three to 20 hr after an i.p. injection of 64 Cu (half-life, 12.8 hr) into mice bearing Krebs ascites cells, a high amount of the radioisotope was recovered in the ascites cells themselves. In the control group, the radioisotope was mainly present in the liver. Similar amounts of 64 Cu were recovered in regenerating as well as in normal liver, whereas in the liver of mice bearing ascites cells, this amount was lower by 40 to 50% regardless of the ascitic volume. Thus, the copper metabolism seems to be disturbed at the hepatic level in mice bearing ascites cells. The distribution of 64 Cu was 'analyzed in DNA, RNA, and proteins from cellular lysates fractionated by CsCl gradient. There was a uniform pattern of distribution in the macromolecules from ascites cells, while 64 Cu' was preferentially associated with the protein fraction from liver. Further experiments indicated that, in vivo, 64 Cu was bound to the DNA of ascites cells

Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells

International Nuclear Information System (INIS)

Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

2015-01-01

Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E–mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell–related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E–mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells. (author)

Application of fire-retardant treatment to the wood in Type A unirradiated nuclear fuel outer containers

International Nuclear Information System (INIS)

Whitlow, J.D.; Luna, R.E.

1992-01-01

Packagings for transporting unirradiated nuclear fuel assemblies in the United States are commonly constructed as rectangular boxes consisting of a metal inner container, a wooden outer container, and cushioning material separating the two. The wood in the outer container is a potential source of fuel for fire. Use of a fire-retardant treatment on the wood may reduce or eliminate the damage to nuclear fuel assemblies in some types of accidents involving fire. The applicability of using fire-retardant treatments on the wood of outer containers is addressed. An approximate cost-benefit analysis to determine if fire-retardant treatments are economically justified is presented. (Author)

Some mechanisms of disturbances and recovery of T-lymphocyte migratory properties in irradiated mice

International Nuclear Information System (INIS)

Anokhin, G.N.; Yarilin, A.A.

1984-01-01

Migration of 51 Cr-labelled T cells from irradiated mice into lymph nodes of syngeneic unirradiated recipients decreased in a dose-dependent fashion. Influx of labelled T cells between 4 and 24 hr after injection (secondary migration) is more radiosensitive than lymph-node migration of T cells in the first 4 hr (primary migration). Treatment of T cells from irradiated mice in vitro with Con A or with trypsin does not enhance radiation-induced alteration of their migratory properties, but irradiation enhances the effects of Con A and trypsin on T-cell migration. Recovery of primary migration of irradiated T cells is completed 3 months after irradiation; it is probably caused by T-cell renewal. The defect of T-cell secondary migration is more stable: it remains 6 months after irradiation in a dose of 4 gy. Post-irradiation defects of the T-cell differentiation process as a cause of long-lasting alteration of T-cell secondary migration are discussed. (author)

Chromosome aberrations in F1 from irradiated male mice studied by their synaptonemal complexes

International Nuclear Information System (INIS)

Kalikinskaya, E.I.; Kolomiets, O.L.; Shevchenko, V.A.; Bogdanov, Yu.F.

1986-01-01

Possible implications of surface-spread synaptonemal complex (SC) karyotyping in analysing the causes of sterility of F 1 from irradiated male mice are demonstrated in this work. After irradiation by 137 Cs γ-rays at a dose of 5 Gy the males were mated to unirradiated females and genetic analysis of fertility in the F 1 progeny was carried out. Males with abnormal fertility were examined for the presence of chromosome aberrations in diakinesis-metaphase I and in pachytene by the method of surface-spread SC karyotyping. In most cases, SC karyotyping provides additional information and permits the detection and analysis of aberrations that are not revealed in diakinesis. Two reciprocal translocations, one X autosomal and one nonreciprocal translocation were discovered in five F 1 males studied. It is concluded that the method is efficient in detecting translocations in pachytene in partially fertile F 1 hybrids of irradiated and normal mice. (orig.)

Kinetics of thermal decomposition of γ-irradiated and unirradiated complexes of mandelhydroxamic acid

International Nuclear Information System (INIS)

Hassan, R.M.; Farid, T.; El-Bellihi, A.A.

1992-01-01

The thermal decomposition of γ-irradiated and unirradiated complexes of mandelhydroxamic acid (HMA), Co (HMA) 2 .1/2H 2 O, Mn (HMA) 2 .2H 2 O, Ba (HMA) 2 .2H 2 O and Cd (HMA) 2 .2H 2 O have been studied thermogravimetrically (under isothermal conditions). The thermal dehydration of each complex occured in one step, while the decomposition of dehydrated complexes occured in two steps. The kinetic parameters for dehydration were computed by different models. The thermal dehydration is regulated by random nucleation A 3 for Co-, Mn-, and Cd-complexes and by phase-boundary (R 3 ) for Ba-complex. The effect of γ-irradiation on the kinetic parameters of thermal decomposition is discussed. Radiation did not modify the mechanism of the reaction but accelarated the dehydration steps in the case of Mn- and Co-complexes. (author) 7 refs.; 1 fig.; 4 tabs

Flow sheet development for the dissolution of unirradiated Mark 42 fuel tubes in F-Canyon, Part II

International Nuclear Information System (INIS)

Murray, A.M.

1999-01-01

Two dissolution flow sheets were tested for the desorption of unirradiated Mark 42 fuel tubes. Both the aluminum (from the can, cladding, and fuel core) and the plutonium oxide (PuO 2 ) are dissolved simultaneously, i.e., a co-dissolution flow sheet. In the first series of tests, 0.15 and 0.20 molar (M) potassium fluoride (KF) solutions were used and the dissolution extended over several days. In the other series of tests, solutions with higher concentrations of fluoride (0.25 to 0.30 M) were used. Calcium fluoride (CaF 2 ) was used in those tests as the fluoride source

Augmentation of transfer of experimental autoimmune thyroiditis (EAT) in mice by irradiation of recipients

International Nuclear Information System (INIS)

Williams, W.V.; Kyriakos, M.; Sharp, G.C.; Braley-Mullen, H.

1987-01-01

Experimental autoimmune thyroiditis (EAT) can be adoptively transferred to normal syngeneic recipients using spleen cells from susceptible strains of mice primed in vivo with mouse thyroglobulin (MTg) and lipopolysaccharide (LPS) following in vitro activation of spleen cells by culture with MTg. Irradiation of recipient animals markedly augments the severity of thyroiditis induced in this system. Irradiation of recipients does not alter the time course of the development of thyroiditis, nor does it alter the requirement for both in vivo priming and in vitro activation of spleen cells for the development of EAT. Spleen cells from EAT-resistant strains of mice (e.g., Balb/c) do not induce EAT in irradiated recipients. Irradiated recipients develop significant levels of anti-MTg antibodies while unirradiated recipients have little detectable antibody response. The augmenting effect of irradiation can be substantially reversed by transferring naive spleen cells to recipients prior to the transfer of MTg/LPS-primed in vitro-activated spleen cells. In addition athymic CBA/Tufts nude mice develop more severe EAT than CBA/Tufts nude/+ littermates following transfer of activated CBA/J spleen cells. These data suggest that natural suppressor cells may regulate the development of EAT at the effector cell level

Effect of sublethal gamma radiation on host defenses in experimental scrub typhus

International Nuclear Information System (INIS)

Kelly, D.J.; Rees, J.C.

1986-01-01

The effect of sublethal gamma radiation on inbred mice chronically infected with scrub typhus rickettsiae was examined. Inbred mice which were inoculated with the Gilliam or Karp strain of Rickettsia tsutsugamushi by the subcutaneous route harbored the infection for at least 1 year. Irradiation of these animals at 12 or 52 weeks postinoculation with normally sublethal levels induced a significantly higher percentage of rickettsemic mice (recrudescence) than was seen in the unirradiated, similarly infected control animals. In addition, sublethal irradiation at 12 weeks induced a quantitative increase in total rickettsiae. Homologous antibody titers to the rickettsiae were examined for 5 weeks after irradiation to determine the role of the humoral response in radiation-induced recrudescence. Unirradiated, infected mice showed consistent titers of about 320 throughout the 5-week observation period, and the titer was not affected by exposure of up to 500 rads of gamma radiation. Drug dose-dependent radioprotection and modification of recrudescence was noted in infected, irradiated mice treated with the antiradiation compound S-2-(3-aminopropylamino)ethyl phosphorothioic acid. The results of this investigation supported the conclusion that the recrudescence of a chronic rickettsial infection in the appropriate host after immunological impairment due to gamma radiation can result in an acute, possibly lethal rickettsemia

Evaluation of staphylococcus aureus growth in unirradiated and irradiated cured meats using the Gompertz equation

International Nuclear Information System (INIS)

Szczawinski, J.; Szczawinska, M.

1993-01-01

1. Sodium nitrite, in concentration of 156 mg/kg, exerted little (from practical point of view) inhibitory effect on S. aureus in cured meat. Its addition caused lag time extension, increase of exponential growth rate, decrease of generation time and maximum population density of staphylococci in samples of cured meat stored at 20 C. 2. Growth curves of Staphylococcus aureus in unirradiated and irradiated (50 kGy) meats cured without sodium nitrite were similar. 3. Irradiation of meat cured with 156 mg/kg sodium nitrite with increasing doses of ionizing radiation (0, 10, 30, 50 kGy) progressively decreased growth rates and lag time and increased generation time and maximum population densities of Staphylococcus aureus in samples inoculated after radiation treatment and incubated at 20 C. (orig.)

Bakery products from irradiated and unirradiated eggs - detection of irradiation in a processed food

International Nuclear Information System (INIS)

Pfordt, J.; Grabowski, H.U. von

1995-01-01

The detection of radiation-specific degradation products in fat has become an established method which has successfully been applied to egg products. This study is making evident the detectability of irradiated eggs as an ingredient of specified processed foods. Tart layers were produced from both irradiated and non-irradiated liquid whole egg. When the fat components were isolated from the tart layers and investigated by GC/MS, the presence of irradiated eggs could clearly be shown. While the radiation-induced hydrocarbons and 2-alkylcyclobutanones could not be found in unirradiated samples, tart layers from irradiated eggs contained these substances. Especially for the hydrocarbons a satisfying correlation between radiation dose and concentration could be observed. The concentrations of radiation-induced compounds were generally lower in the tart layers than in the liquid egg samples they had been produced from. (orig.) [de

Characterization of un-irradiated MIMAS MOX fuel by Raman spectroscopy and EPMA

Science.gov (United States)

Talip, Zeynep; Peuget, Sylvain; Magnin, Magali; Tribet, Magaly; Valot, Christophe; Vauchy, Romain; Jégou, Christophe

2018-02-01

In this study, Raman spectroscopy technique was implemented to characterize un-irradiated MIMAS (MIcronized - MASter blend) MOX fuel samples with average 7 wt.% Pu content and different damage levels, 13 years after fabrication, one year after thermal recovery and soon after annealing, respectively. The impacts of local Pu content, deviation from stoichiometry and self-radiation damage on Raman spectrum of the studied MIMAS MOX samples were assessed. MIMAS MOX fuel has three different phases Pu-rich agglomerate, coating phase and uranium matrix. In order to distinguish these phases, Raman results were associated with Pu content measurements performed by Electron Microprobe Analysis. Raman results show that T2g frequency significantly shifts from 445 to 453 cm-1 for Pu contents increasing from 0.2 to 25 wt.%. These data are satisfactorily consistent with the calculations obtained with Gruneisen parameters. It was concluded that the position of the T2g band is mainly controlled by Pu content and self-radiation damage. Deviation from stoichiometry does not have a significant influence on T2g band position. Self-radiation damage leads to a shift of T2g band towards lower frequency (∼1-2 cm-1 for the UO2 matrix of damaged sample). However, this shift is difficult to quantify for the coating phase and Pu agglomerates given the dispersion of high Pu concentrations. In addition, 525 cm-1 band, which was attributed to sub-stoichiometric structural defects, is presented for the first time for the self-radiation damaged MOX sample. Thanks to the different oxidation resistance of each phase, it was shown that laser induced oxidation could be alternatively used to identify the phases. It is demonstrated that micro-Raman spectroscopy is an efficient technique for the characterization of heterogeneous MOX samples, due to its low spatial resolution.

Profiling of differentially expressed genes induced by ionizing radiation in thymus cells of C57 mice

International Nuclear Information System (INIS)

Li Zhiheng; Li Yu

2007-01-01

Objective: Microarrays was used to text changes, of gene expression of thymus cell in C57 mice one moth after exposed to 1 Gy γ-ray irradiation. Methods: The difference of gene express between irradiated and un-irradiated mice being analysis by Agilent mouse oligo microarrays. Results: In the observed 21319 known genes, 107 up-regulated at least 2-fo1d (13 excess 4-fold); whereas 9 genes were down-regulated 2-fold (2 more 4-fo1d). The function of theses genes are known as some basic metabolic process. Conclusions: The gene changed in the experiment involved embryo development, organ formation and maintain, immunity or stress, protein compose, apoptosis, signal transduction. The number of gene is much more than that of down-regulated. It ought to be noticed that the gens which coding horny protein in embryo development, and ought also to be noticed that the gens which involve the function of PI3-K. (authors)

Effect of helium pressure on the response of unirradiated UO2 subjected to thermal transients

International Nuclear Information System (INIS)

Fenske, G.R.; Chapello, P.M.; Emerson, J.E.; Poeppel, R.B.

1983-01-01

The effect of helium pressure on the transient response of unirradiated depleted UO 2 subjected to simulated hypothetical loss-of-flow accidents in a gas-cooled fast reactor was examined by use of the direct electrical heating technique. Transient tests were performed at pressures ranging from 7 to 10 X 10 5 Pa(7 to 10 atm) to 7 to 8 MPa (70 to 80 atm) on radially restrained and unrestrained fuel segments. The average heating rates ranged from about17 to 240 J/g x s. The results indicate that while the mechanical integrity of the fuel segment was independent of the test pressure, the rapid ejection of molten fuel from pellet interfaces of unrestrained fuel, observed at the lower pressures, was delayed or suppressed at the higher pressures

Quinine controls body weight gain without affecting food intake in male C57BL6 mice

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Cettour-Rose Philippe

2013-02-01

Full Text Available Abstract Background Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5. Results Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice. Conclusion Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.

Properties of unirradiated fuel element graphites H-451 and SO818. [Bulk density, tensile properties, thermal expansion, thermal conductivity

Energy Technology Data Exchange (ETDEWEB)

Engle, G.B.; Johnson, W.R.

1976-10-08

Nuclear graphites H-451, lot 440 (Great Lakes Carbon Corporation (GLCC)), and SO818 (Airco Speer Division, Air Reduction Corporation (AS)) are described, and physical, mechanical, and chemical property data are presented for the graphites in the unirradiated state. A summary of the mean values of the property data and of data on TS-1240 and H-451, lot 426, is tabulated. A direct comparison of H-451, lot 426, chosen for Fort St. Vrain (FSV) fuel reload production, TS-1240, and SO818 may be made from the table. (auth)

Impact of taurine depletion on glucose control and insulin secretion in mice.

Science.gov (United States)

Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

2015-09-01

Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chromosome dosimetry: the influence of culture media on the proliferation of irradiated and unirradiated human lymphocytes

International Nuclear Information System (INIS)

Purrott, R.J.; Lloyd, D.C.; Vulpis, N.

1981-01-01

The proliferation of phytohaemagglutinin stimulated human lymphocytes in four types of synthetic culture medium has been studied using the fluorescence plus Giemsa staining technique to determine cell cycle status. 48 hour cultures of unirradiated cells containing Ham's F10 or RPMI 1640 media yielded significant numbers of second cycle metaphases. Cultures containing Eagle's MEM or TC 199 media, however, required longer incubation times to produce appreciable numbers of second division cells. Intrinsic differences between donors in the rate of proliferation had little effect on the relative ranking of the media. Radiation induced mitotic delay of about 1 hour per Gray was observed for each medium. The relevance of these results to the accuracy of radiation dose estimation by chromosome aberration analysis is discussed. (author)

Rasgrf2 controls dopaminergic adaptations to alcohol in mice.

Science.gov (United States)

Easton, Alanna C; Rotter, Andrea; Lourdusamy, Anbarasu; Desrivières, Sylvane; Fernández-Medarde, Alberto; Biermann, Teresa; Fernandes, Cathy; Santos, Eugenio; Kornhuber, Johannes; Schumann, Gunter; Müller, Christian P

2014-10-01

Alcohol abuse leads to serious health problems with no effective treatment available. Recent evidence suggests a role for ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) in alcoholism. Rasgrf2 is a calcium sensor and MAPK/ERK activating protein, which has been linked to neurotransmitter release and monoaminergic receptor adaptations. Rasgrf2 knock out (KO) mice do not develop a dopamine response in the nucleus accumbens after an alcohol challenge and show a reduced consumption of alcohol. The present study aims to further characterise the role of Rasgrf2 in dopaminergic activation beyond the nucleus accumbens following alcohol treatment. Using in vivo microdialysis we found that alcohol induces alterations in dopamine levels in the dorsal striatum between wildtype (WT) and Rasgrf2 KO mice. There was no difference in the expression of dopamine transporter (DAT), dopamine receptor regulating factor (DRRF), or dopamine D2 receptor (DRD2) mRNA in the brain between Rasgrf2 KO and WT mice. After sub-chronic alcohol treatment, DAT and DRRF, but not DRD2 mRNA expression differed between WT and Rasgrf2 KO mice. Brain adaptations were positively correlated with splenic expression levels. These data suggest that Rasgrf2 controls dopaminergic signalling and adaptations to alcohol also in other brain regions, beyond the nucleus accumbens. Copyright © 2014 Elsevier Inc. All rights reserved.

Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21.

Science.gov (United States)

Li, Yu; Wong, Kimberly; Giles, Amber; Jiang, Jianwei; Lee, Jong Woo; Adams, Andrew C; Kharitonenkov, Alexei; Yang, Qin; Gao, Bin; Guarente, Leonard; Zang, Mengwei

2014-02-01

The hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice. Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry. Prolonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting up-regulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased

The influence of sex on life shortening and tumor induction in CBA/Cne mice exposed to x rays or fission neutrons

International Nuclear Information System (INIS)

Di Majo, V.; Coppola, M.; Rebessi, S.; Saran, A.

1996-01-01

An experimental study of male and female CBA/Cne mice was set up at Casaccia primarily to investigate the influence of sex on long-term survival and tumor induction after exposure to high- and low-LET radiation. Mice were whole-body-irradiated at 3 months of age with fission-neutron doses of 0.1, 0.2, 0.4, 0.8, 1.2 and 1.8 Gy at the RSV-TAPIRO reactor (mean neutron energy 0.4 MeV, in terms of kerma, y D = 51.5 KeV/μm), or with 250 KVp X-ray doses of 1, 3, 5 and 7 Gy. Control and irradiated animals were then followed for their entire life span. As a general finding, male CBA/Cne mice appear more susceptible to tumori-genesis than females. In particular, the incidences of induced acute myeloid leukemia and malignant lymphomas are significant only in male mice. Benign and malignant solid tumors of many types are observed in mice of both sexes, the most frequent being in the lung, liver and ovary. However, evidence for a radiation response is limited to the case of Harderian gland neoplasms. In addition, a comparison of the observed frequency of all irradiated compared to unirradiated animals bearing solid tumors shows that the total tumor occurrence is not altered markedly by radiation exposure. A decrease in survival time is observed for both sexes and radiation types and correlates well with increasing dose. Moreover, both sex and radiation quality appear to influence the life shortening. A similar dose dependence of survival time is found when tumor-free animals alone are considered, suggesting a non-specific component of life-shortening. 18 refs., 3 figs., 5 tabs

The influence of Boron on creep-rupture behaviour of austenitic unstabilized and Nb-stabilized stainless steel X8CrNi 1613 in unirradiated and irradiated condition

International Nuclear Information System (INIS)

Sen, Susant Kumar.

1976-10-01

The present study deals with influence of boron on creep-rupture behaviour in unirradiated condition at 650 0 C along with precipitation behaviour, heat-treatment and recrystallization of unstabilized and stabilized steel. The results of creep-rupture tests on unirradiated specimens show that boron exerts a beneficial effect on the rupture life and ductility. Boron losses its beneficial effect on creep properties in unstabilized steel by prolong creeping. The magnitude of beneficial effect of Boron on creep properties depends upon the initial boron distribution which influences the number, size and distribution of the precipitates. Boron promotes the precipitation of type M 23 C 6 Carbides in the grain as well as at the grain boundary. Boron segregates in atomic form during slow cooling from austenitizing temperature. The recrystallization will be delayed by the presence of boron. The results of creep tests at 650 0 C shows that boron exerts a beneficial effect on creep life of irradiated steels. (orig./GSC) [de

Chronic UVA (365-nm) irradiation induced scratching in hairless mice: dose-time dependency and the effect of ketanserin

International Nuclear Information System (INIS)

Laat, J.M.T. de; Groenendijk, M.; Vloten, W.A. van; Gruijl, F.R. de; Seite, S.

1997-01-01

In a study on the dose-response relationship for longwave UVA (UVA1; 340-400 nm) carcinogenesis in hairless mice scratch marks appeared after months of daily exposure as an unwanted side effect. Tumor induction in the highest of the 4 tested dose groups (receiving a daily dose of 430 kJ/m 2 of 365-nm radiation) could not be determined because extensive scarification occurred prior to the development of any tumors. The induction of scratch marks could be scored and quantified in all 4 dose groups tested. The UVA1 dose-dependencies for the induction of tumors and scratch marks were compared. We found that the induction of scratch marks depended mainly on the cumulative UVA1 exposure, whereas tumor induction showed a lesser dose-dependency. An attempt was made to prevent the apparent pruritogenic effect of UVA1 irradiation and to understand its mechanism. The influence of ketanserin, a serotonin/histamine antagonist, on the UVA1 induction of scratch marks was tested in groups of 8 mice daily irradiated with 430 kJ/m 2 . No difference was found between treated and untreated animals. Histological examination of skin biopsies from irradiated mice from the 430-kJ/m 2 dose group from the UVA1 carcinogenic experiment, showed no changes in numbers of mast cells or other inflammatory features when compared to skin biopsies from unirradiated control mice. This indicated that UVA1-induced scratching is not mediated through mast cell release of serotonin and/or histamine. An adequate therapeutic treatment which can prevent UVA1-induced scratching would enable us to test tumor induction with UVA1 over a larger dose range, and may provide additional insight in how this radiation damages the skin. It remains conjectural whether there exists and analogous UVA-induced pruritus in human skin. (au)

Transformation of bone marrow stem-cells and radiation-induced myeloid leukemia in mice

International Nuclear Information System (INIS)

Hirashima, K.; Bessho, M.; Hayata, I.; Nara, N.; Kawase, Y.; Ohtani, M.

1982-01-01

After a single whole-body X-irradiation of 300R to male RFM/MsNrs strain mice, the occurrence of myeloid leukemia initiated since four months and ceased at eleven months after irradiation. The cumulative incidence reached 24.5%. A time course study on the kinetics of pluripotential stem-cells (CFU-S) and granuloid committed stem-cells (CFU-C) in the marrow after 300R was also performed. The repopulation of CFU-S was accomplished within one month whereas that of CFU-C needed 210 days after irradiation. The incidence of leukemia was very rare after the complete repopulation of CFU-C. Simultaneously, collected spleen cells from the irradiated mice without overt leukemia were transplanted into 300-600R irradiated recipients of another sex. Three months thereafter, recipients were sacrificed to detect leukemic changes and the origin of leukemic cells by chromosome analysis. The results revealed that leukemic cell transformation of donor cells began 18 days after irradiation and on an average, 37.1% of the irradiated mice carried potentially leukemic cells for seven months after exposure, whereas none of the unirradiated mice carried leukemic cells at 7 months after irradiation. To investigate host factor(s) contributing to the proliferation of leukemic cells, the suppression of cellular immunity after 300R was measured by GVH mortality assay. However, the recovery of cellular immunity was observed until three months after irradiation and the role of cellular immunity to proliferation of leukemic cells after three months was negligible. (author)

Response of unirradiated and irradiated PWR fuel rods tested under power-cooling-mismatch conditions

International Nuclear Information System (INIS)

MacDonald, P.E.; Quapp, W.J.; Martinson, Z.R.; McCardell, R.K.; Mehner, A.S.

1978-01-01

This report summarizes the results from the single-rod power-cooling-mismatch (PCM) and irradiation effects (IE) tests conducted to date in the Power Burst Facility (PBF) at the U.S. DOE Idaho National Engineering Laboratory. This work was performed for the U.S. NRC under contact to the Department of Energy. These tests are part of the NRC Fuel Behavior Program, which is designed to provide data for the development and verification of analytical fuel behavior models that are used to predict fuel response to abnormal or postulated accident conditions in commercial LWRs. The mechanical, chemical and thermal response of both previously unirradiated and previously irradiated LWR-type fuel rods tested under power-cooling-mismatch condition is discussed. A brief description of the test designs is presented. The results of the PCM thermal-hydraulic studies are summarized. Primary emphasis is placed on the behavior of the fuel and cladding during and after stable film boiling. (orig.) [de

Overview and Critical Assessment of the Tensile Properties of unirradiated and irradiated EUROFER97

Energy Technology Data Exchange (ETDEWEB)

Lucon, E.; Vandermeulen, W.

2007-10-15

Material research represents a crucial issue for the assessment of fusion as a future viable source of energy. Structural materials, in particular, need to show a superior mechanical and chemical behaviour to guarantee the safe operation of the reactor during its whole lifetime, while retaining low activation characteristics to minimise the environmental impact of the produced waste. In this context, specific efforts have been focused for the last twenty years in Europe, Japan and the US, on developing suitable Reduced Activation Ferritic Martensitic (RAFM) steels as candidate structural materials. EUROFER97 has recently emerged in Europe as the reference material for the DEMO design. In the framework of the Long-Term Programme of EFDA (European Fusion Development Agreement), a coordinated effort has been launched aimed at providing a critical assessment of the mechanical and microstructural properties of EUROFER97 in the unirradiated and irradiated conditions, based on the results accumulated since the late 90ies within numerous EFDA tasks.

Storage for the Fast Flux Test Facility unirradiated fuel in the Plutonium Finishing Plant Complex, Hanford Site, Richland, Washington

International Nuclear Information System (INIS)

1992-01-01

This Environmental Assessment evaluates the proposed action to relocate and store unirradiated Fast Flux Test Facility fuel in the Plutonium Finishing Plant Complex on the Hanford Site, Richland, Washington. The US Department of Energy has decided to cease fuel fabrication activities in the 308 Building in the 300 Area. This decision was based on a safety concern over the ability of the fuel fabrication portion of the 308 Building to withstand a seismic event. The proposed action to relocate and store the fuel is based on the savings that could be realized by consolidating security costs associated with storage of the fuel. While the 308 Building belowgrade fuel storage areas are not at jeopardy by a seismic event, the US Department of Energy is proposing to cease storage operations along with the related fabrication operations. The US Department of Energy proposes to remove the unirradiated fuel pins and fuel assemblies from the 308 Building and store them in Room 192A, within the 234-5Z Building, a part of the Plutonium Finishing Plant Complex, located in the 200 West Area. Minor modifications to Room 192A would be required to accommodate placement of the fuel. The US Department of Energy estimates that removing all of the fuel from the 308 Building would save $6.5 million annually in security expenditures for the Fast Flux Test Facility. Environmental impacts of construction, relocation, and operation of the proposed action and alternatives were evaluated. This evaluation concluded that the proposed action would have no significant impacts on the human environment

9 CFR 355.16 - Control of flies, rats, mice, etc.

Science.gov (United States)

2010-01-01

... INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF...

Interaction of spermine with DNA, vitamin C and bovine serum albumin in the unirradiated and gamma irradiated states

International Nuclear Information System (INIS)

Upadhyay, S.N.; Lal, C.; Bhardwaj, R.; Chaturvedi, S.; Chaudhury, N.K.

2006-01-01

Structural deformability of spermine with radiation dose (maximum 10 Gy) has been proved. Complex formation of spermine with DNA, vitamin C and BSA took place. Calibration and radiation-induced absorption changes in spermine by ninhydrin reagent has been followed quantitatively. Interaction of vitamin C with DNA and their radiation-induced changes have been reported. Interaction of spermine with DNA in the unirradiated and gamma irradiated states in 10 -3 M phosphate buffer and water have been compared. Addition of spermine and vitamin C to DNA makes DNA structure more condensed. Bovine serum albumin also binds with spermine and protects it from radiation-induced degradation. (author)

Solubility of unirradiated UO2 fuel in aqueous solutions. Comparison between experimental and calculated (EQ3/6) data

International Nuclear Information System (INIS)

Ollila, K.

1995-11-01

The solubility behaviour of unirradiated UO 2 pellets was studied under oxic (air-saturated) and anoxic (N 2 ) conditions in deionized water, in sodium bicarbonate solutions with varying bicarbonate content (60 - 600 ppm), in Allard groundwater simulating granitic fresh groundwater conditions, and in bentonite water simulating the effects of bentonite on granitic fresh groundwater (25 deg C). The release of uranium was measured during static batch dissolution experiments of long duration (2-6 years). A comparison was made with the theoretical solubility data calculated with the geochemical code EQ3/6 in order to evaluate solubility (steady state) limiting factors. (orig.) (26 refs., 32 figs., 13 tabs.)

Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

Directory of Open Access Journals (Sweden)

Marco Redaelli

Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

Effect of gamma irradiation on acute oral toxicity of ethanolic extract of red ginger (zingiber officinale)

International Nuclear Information System (INIS)

Ermin Katrin; Winarti Andayani; Susanto; Hendig Winarno

2014-01-01

Red ginger is widely used in traditional medicine to treat various types of diseases. Evaluation of the toxic properties of red ginger is very important to know the negative harmful impact to human health. Therefore, before it is consumed by humans, it is needed to conduct acute oral toxicity of red ginger extract in mice. Thin rhizome of red ginger in poly ethylene plastic packaging was irradiated by gamma rays at a dose of 10 kGy with a dose rate of 10 kGy/h. The ethanol extract of unirradiated as well as irradiated red ginger was then tested for the acute oral toxicity using OECD Guideline test method. The results showed that throughout the 14 days of treatment there was a change in behavior pattern, clinical symptoms and body weight of control mice and treatment groups. Histopathological examination of kidneys, heart, liver, lungs and spleen of the dose less than 1250 mg/kg body weight showed normal condition and no significant side effects observation. While central venous damage and a reduced number of hepatocyte cells in male mice occurred in the test dose higher than 2000 mg/kg body weight, whereas in female mice it occurred in the test group dose higher than 1250 mg/kg bw. Based on renal histology of male and female mice at doses higher than 1250 mg/kg body weight, there were damage to Bowman's capsule, glomerulus, proximal vessel and distal vessels. LD50 of unirradiated and irradiated with 10 kGy of ethanol extract of red ginger were 1887 mg/kg body weight and 2639 mg/kg body weight, respectively, and it can be categorized as moderately toxic. Oral administration of ethanol extract of red ginger with dose of 1250 mg/kg body weight gave an effect in mice organs. From these results it can be concluded that oral administration of both unirradiated and irradiated with a dose 10 kGy of ethanol extract consider safe at a dose less than 1250 mg/kg body weigh. (author)

Immunological investigations of antigens released by normal and irradiated schistosomasa mansoni cercariae in vitro. Part of a coordinated programme on preparation of irradiated vaccines against some human diseases

International Nuclear Information System (INIS)

Catty, D.

1982-07-01

S.mansoni cercariae were γ-irradiated at 1-15 K rads, syringe transformed, and injected into groups of 20 mice (200 dose), with unirradiated controls. Aliquots of 1,500 cercariae irradiated at 1-40 K rads (plus unirradiated controls) were cultured in serum-free medium. It was found that irradiation does not inhibit release of a broad spectrum of antigens in culture over 6 hours until 20 K rads is delivered. Mice used as hosts for the graded cercarial irradiation vaccine were subdivided into groups of 10 and either left unchallenged or challenged at 6 weeks with a normal infection of 200 cercariae. Serum samples were taken from every mouse at regular intervals and antibodies titrated by solid phase radioimmunoassay. Injected parasites, whether irradiated or normal, always gave higher antibody titres to cercarial and egg antigens than the equivalent dose of normal (challenge) parasites infecting by the natural route. Challenge infection depressed anti-cercarial responses in mice exposed to irradiated larvae but boosted the response to normal injected parasites. Antibodies to SEA were in lower titre in all groups but rose from week 7 (1 week post-challenge) in the groups injected with normal and 1 K rad-treated parasites, where adults were previously established in the hosts. At 12 weeks all mice were sacrificed and perfused for adults. Egg yields in liver and intestine were determined. There was no evidence of protective immunity to challenge infection induced by injected unirradiated or 1 K rad-irradiated, transformed, cercariae, even though both sources of parasite gave rise to egg-laying adults. By contrast, the 5, 10 and 15 K rad vaccines gave protection of 36-49%, even though they gave rise to no persistent adults or any deposited eggs. The protective (immunising) properties of irradiation-attenuated vaccines of S.mansoni cercariae can thus be clearly correlated with their capacity to release antigens in the immediate post irradiation period

A novel instrumented multipeg running wheel system, Step-Wheel, for monitoring and controlling complex sequential stepping in mice.

Science.gov (United States)

Kitsukawa, Takashi; Nagata, Masatoshi; Yanagihara, Dai; Tomioka, Ryohei; Utsumi, Hideko; Kubota, Yasuo; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo

2011-07-01

Motor control is critical in daily life as well as in artistic and athletic performance and thus is the subject of intense interest in neuroscience. Mouse models of movement disorders have proven valuable for many aspects of investigation, but adequate methods for analyzing complex motor control in mouse models have not been fully established. Here, we report the development of a novel running-wheel system that can be used to evoke simple and complex stepping patterns in mice. The stepping patterns are controlled by spatially organized pegs, which serve as footholds that can be arranged in adjustable, ladder-like configurations. The mice run as they drink water from a spout, providing reward, while the wheel turns at a constant speed. The stepping patterns of the mice can thus be controlled not only spatially, but also temporally. A voltage sensor to detect paw touches is attached to each peg, allowing precise registration of footfalls. We show that this device can be used to analyze patterns of complex motor coordination in mice. We further demonstrate that it is possible to measure patterns of neural activity with chronically implanted tetrodes as the mice engage in vigorous running bouts. We suggest that this instrumented multipeg running wheel (which we name the Step-Wheel System) can serve as an important tool in analyzing motor control and motor learning in mice.

Effects of x-irradiation on cell kinetics of oral epithelium in mice

International Nuclear Information System (INIS)

Jinnouchi, Kenichi

1982-01-01

The acute radiation effects on the tongue and lip mucosa epithelium were cytokinetically investigated after the local irradiation at the head part of C 3 Hf/He mice with single dose of 516 mC/kg(2000R) of X rays. The microautoradiographic study was performed for these two kinds of oral epithelium at various times after the pulse-labeling with 3 H-thymidine, which followed immediately after the irradiation. The cell kinetics of irradiated as well as unirradiated basal cells were investigated by observing the changes in frequencies of the labeled cells and the labeled mitoses in the epithelium along the time course after irradiation. The results of the analysis of the percent frequencies of mitotic cells as a function of time after the labeling and the irradiation showed that the movement of the labeled cells were blocked at G 2 phase for about 6 hr and that the cell cycle time after the 1st post irradiation mitoses became shorter than that of the unirradiated cells. However, no change was found in the migration rate of the tongue epithelium, i.e., the time required for labeled cells to migrate from basal cell layer to prickle-granular cell layer. On the other hand, only 25% of labeled cells in the lip mucosa epithelium migrated into prickle-granular cell layer until 40 hr after irradiation, and it was hardly observed that the labeled cells moved into mitotic phase. These results suggest that basal cell of the lip mucosa is more radiosensitive than that of the tongue epithelium. (author)

Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

Science.gov (United States)

do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

2011-05-01

Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

The Effect of E-Selen Antioxidant on the Fatty Acids Content of the Homogenate of Unirradiated and Irradiated Pupae of Ceratitis Capitata

International Nuclear Information System (INIS)

Zaghloul, Y.S.; Abbassy, S.A.; Elakhdar, E.A.H.; Elakhdar, E.A.H.

2011-01-01

As antioxidant E-selen was added to the larval artificial diets of the Mediterranean fruit fly, Ceratitis capitata. The produced full grown pupae were exposed to gamma rays at dose rate of 90 Gy. The fatty acid contents of the normal and irradiated insects were analyzed to test to what extent, the uptake of the antioxidant will ameliorate the physiological damage induced to the medfly pupae, as a result of their exposure to irradiation. The results obtained by using Gas-liquid chromatography of fatty acid methyl esters, showed the palmitic and oleic acids to be the most predominant fatty acids in all pupal homogenates in both normal and irradiated pupae, either by the uptake of doses of the E-selen or without. The uptake of E-Selen with a dose of 0.3 mg led to a complete absence of the lauric and myristic acids in the homogenates of the unirradiated pupae of the medfly. This absence of lauric and myristic acids was accompanied by a decrease in the concentrations of the palmitic and linoleic acids reaching 25.17% and 32.98%, respectively as compared to pupae without the uptake of antioxidant. The concentrations of both the stearic and oleic acids showed an obvious increment reaching 199.22% and 58.94%, respectively, relative to those reared on the defined media and no added E.Selen. Exposure of the pupae to a dose of 90 Gy, resulted in an increment in the concentrations of the saturated lauric and myristic acid reaching 96.77% and 34.07%, respectively, relative to the untreated ones. While, at the same dose level, there were decrements in the concentrations of the palmitic, stearic, oleic and linoleic acids with percentages reaching 6.4, 9.22, 3.65 and 1.15%, respectively as compared to unirradiated controls. Irradiation of the pupae with sterilizing dose (90 Gy) after up taking the E-Selen in their larval diets, led to the increase of the concentrations of lauric, oleic and linoleic acids by ratios of 16.82, 8.84 and 29.26%, respectively as compared to their

Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

Directory of Open Access Journals (Sweden)

Mathieu Paul Rodero

2013-06-01

Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

Effects of low dose rate irradiation on induction of myeloid leukemia in mice

International Nuclear Information System (INIS)

Furuse, Takeshi

1999-01-01

We investigated the induction of myeloid leukemia and other kinds of neoplasias in C3H male mice irradiated at several dose rate levels. We compared the incidence of neoplasias among these groups, obtained dose and dose rate effectiveness factors (DDREF) for myeloid leukemia. C3H/He male mice were exposed to whole body gamma-ray irradiation at 8 weeks of age. All mice were maintained for their entire life span and teh pathologically examined after their death. Radiation at a high dose-rate of 882 mGy/min (group H), a medium dose-rate of 95.6 mGy/min (group M), and low dose-rates of 0.298 mGy/min (group L-A), 0.067 mGy/min (group L-B) or 0.016 mGy/min (group L-C) were delivered from 137 Cs sources. The mice in group L were irradiated continuously for 22 hours daily up to total doses of 1, 2, 3, 4, 10 Gy over a period of 3 days to 200 days. As for the induction of neoplasias, myeloid leukemia developed significantly more frequently in irradiated groups than in unirradiated groups. The time distribution of mice dying from myeloid leukemia did not show a difference between groups H and L. The incidence of myeloid leukemia showed a greater increase in the high dose-rate groups than in the low and medium dose-rate groups in the dose range over 2 Gy, it also showed significant increases in the groups irradiated with 1 Gy of various dose rate, but the difference between these groups was not clear. These dose effect curves had their highest values on each curve at about 3 Gy. We obtained DDREF values of 2-3 by linear fittings for their dose response curves of dose ranges in which leukemia incidences were increasing. (author)

Electrochemical corrosion studies on copper-base waste package container materials in unirradiated 0.1 N NaNO3 at 95 degrees C

International Nuclear Information System (INIS)

Akkaya, M.; Verink, E.D. Jr.; Van Konynenburg, R.A.

1988-05-01

Three candidate materials were investigated in this study in terms of their electrochemical corrosion behavior in unirradiated 0.1 N NaNO 3 solutions at 95 degrees C. Anodic polarization experiments were conducted to determine the passive current densities, pitting potentials, and other parameters, together with Cyclic Current Reversal Voltammetry tests to evaluate the stability and protectiveness of the passive oxides formed. X-ray diffraction and Auger Electron Spectroscopy were used for identification of the corrosion products as well as Scanning Electron Microscopy for the surface morphology studies. 2 refs., 22 figs., 2 tabs

Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness

International Nuclear Information System (INIS)

Vadas, M.A.

1982-01-01

A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR x EO-LR)F 1 mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR→F 1 were high responders and EO-LR→F 1 were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy

IFNγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice

DEFF Research Database (Denmark)

Bartholdy, Christina; Høgh-Petersen, Mette; Storm, Pernille

2014-01-01

herpes virus infection, we infected IFNγ/perforin double deficient C57BL/6 mice and followed the outcome of infection. While absence of perforin prevented the splenic atrophy in IFNγ deficient mice, fibrosis did not disappear. Moreover, double deficient mice developed extreme splenomegaly, were unable...... in double deficient mice, other aspects are exaggerated, and the normal architecture of the spleen is completely destroyed. Thus, IFNγ and perforin work in concert to minimize pathology and control the viral load. In the absence of both effector molecules, the balancing race between the virus and the host...

Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.

Science.gov (United States)

Yamazaki-Nishioka, Miho; Shimizu, Makiko; Suemizu, Hiroshi; Nishiwaki, Megumi; Mitsui, Marina; Yamazaki, Hiroshi

2018-02-01

1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide. 3. Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.

Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice

DEFF Research Database (Denmark)

Meijer, Rick I; Bakker, Wineke; Alta, Caro-Lynn A F

2013-01-01

in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin......-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKa2(+/+) and AMPKa2......-induced vasodilation in an adiponectin-dependent manner. In conclusion, PVAT controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKa2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK....

The MICE Online Systems

CERN Multimedia

CERN. Geneva

2012-01-01

The Muon Ionization Cooling Experiment (MICE) is designed to test transverse cooling of a muon beam, demonstrating an important step along the path toward creating future high intensity muon beam facilities. Protons in the ISIS synchrotron impact a titanium target, producing pions which decay into muons that propagate through the beam line to the MICE cooling channel. Along the beam line, particle identification (PID) detectors, scintillating fiber tracking detectors, and beam diagnostic tools identify and measure individual muons moving through the cooling channel. The MICE Online Systems encompass all tools; including hardware, software, and documentation, within the MLCR (MICE Local Control Room) that allow the experiment to efficiently record high quality data. Controls and Monitoring (C&M), Data Acquisition (DAQ), Online Monitoring and Reconstruction, Data Transfer, and Networking all fall under the Online Systems umbrella. C&M controls all MICE systems including the target, conventional an...

Cosmetics-triggered percutaneous remote control of transgene expression in mice.

Science.gov (United States)

Wang, Hui; Ye, Haifeng; Xie, Mingqi; Daoud El-Baba, Marie; Fussenegger, Martin

2015-08-18

Synthetic biology has significantly advanced the rational design of trigger-inducible gene switches that program cellular behavior in a reliable and predictable manner. Capitalizing on genetic componentry, including the repressor PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae pathovar tomato DC3000 to sense and resist plant-defence metabolites of the paraben class, we have designed a set of inducible and repressible mammalian transcription-control devices that could dose-dependently fine-tune transgene expression in mammalian cells and mice in response to paraben derivatives. With an over 60-years track record as licensed preservatives in the cosmetics industry, paraben derivatives have become a commonplace ingredient of most skin-care products including shower gels, cleansing toners and hand creams. As parabens can rapidly reach the bloodstream of mice following topical application, we used this feature to percutaneously program transgene expression of subcutaneous designer cell implants using off-the-shelf commercial paraben-containing skin-care cosmetics. The combination of non-invasive, transdermal and orthogonal trigger-inducible remote control of transgene expression may provide novel opportunities for dynamic interventions in future gene and cell-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Lift-based up-ender and methods using same to manipulate a shipping container containing unirradiated nuclear fuel

Science.gov (United States)

Nilles, Michael J.

2017-08-01

A shipping container containing an unirradiated nuclear fuel assembly is lifted off the ground by operating a crane to raise a lifting tool comprising a winch. The lifting tool is connected with the shipping container by a rigging line connecting with the shipping container at a lifting point located on the shipping container between the top and bottom of the shipping container, and by winch cabling connecting with the shipping container at the top of the shipping container. The shipping container is reoriented by operating the winch to adjust the length of the winch cabling so as to rotate the shipping container about the lifting point. Shortening the winch cabling rotates the shipping container about the lifting point from a horizontal orientation to a vertical orientation, while lengthening the winch cabling rotates the shipping container about the lifting point from the vertical orientation to the horizontal orientation.

Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice.

Science.gov (United States)

Shao, Jiawei; Xue, Shuai; Yu, Guiling; Yu, Yuanhuan; Yang, Xueping; Bai, Yu; Zhu, Sucheng; Yang, Linfeng; Yin, Jianli; Wang, Yidan; Liao, Shuyong; Guo, Sanwei; Xie, Mingqi; Fussenegger, Martin; Ye, Haifeng

2017-04-26

With the increasingly dominant role of smartphones in our lives, mobile health care systems integrating advanced point-of-care technologies to manage chronic diseases are gaining attention. Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, we have engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice. A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light (FRL)-responsive optogenetic interface. To develop this wireless controller network, we designed and implanted hydrogel capsules carrying both engineered cells and wirelessly powered FRL LEDs (light-emitting diodes). In vivo production of a short variant of human glucagon-like peptide 1 (shGLP-1) or mouse insulin by the engineered cells in the hydrogel could be remotely controlled by smartphone programs or a custom-engineered Bluetooth-active glucometer in a semiautomatic, glucose-dependent manner. By combining electronic device-generated digital signals with optogenetically engineered cells, this study provides a step toward translating cell-based therapies into the clinic. Copyright © 2017, American Association for the Advancement of Science.

Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus

DEFF Research Database (Denmark)

Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard

1999-01-01

To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread...... in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome...... mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus...

The reaction of unirradiated and irradiated nuclear graphites with water vapor in helium

International Nuclear Information System (INIS)

Imai, Hisashi; Nomura, Shinzo; Kurosawa, Takeshi; Fujii, Kimio; Sasaki, Yasuichi

1980-10-01

Nuclear graphites more than 10 brands were oxidized with water vapor in helium and then some selected graphites were irradiated with fast neutron in the Japan Materials Testing Reactor to clarify the effect of radiation damage of graphite on their reaction behaviors. The reaction was carried out under a well defined condition in the temperature range 800 -- 1000 0 C at concentrations of water vapor 0.38 -- 1.30 volume percent in helium flow of total pressure of 1 atm. The chemical reactivity of graphite irradiated at 1000 +- 50 0 C increased linearly with neutron fluence until irradiation of 3.2 x 10 21 n/cm 2 . The activation energy for the reaction was found to decrease with neutron fluence for almost all the graphites, except for a few ones. The order of reaction increased from 0.5 for the unirradiated graphite to 1.0 for the graphite irradiated up to 6.0 x 10 20 n/cm 2 . Experiment was also performed to study a superposed effect between the influence of radiation damage of graphite and the catalytic action of barium on the reaction rate, as well as the effect of catalyser of barium. It was shown that these effects were not superposed upon each other, although barium had a strong catalytic action on the reaction. (author)

Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

Science.gov (United States)

Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

2009-06-01

Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with [1-14C]2-deoxyglucose

International Nuclear Information System (INIS)

Cooney, G.J.; Astbury, L.D.; Williams, P.F.; Caterson, I.D.

1987-01-01

The dose-response characteristics of several glucose-utilizing tissues (brain, heart, white adipose tissue, brown adipose tissue, and quadriceps muscle) to a single injection of insulin have been compared in control mice and mice made obese with a single injection of gold thioglucose (GTG). Tissue content of [1- 14 C]2-deoxyglucose 6-phosphate and blood disappearance rate of [1- 14 C]2-deoxyglucose (2-DG) were measured at nine different insulin doses and used to calculate rates of 2-DG uptake and phosphorylation in tissues from control and obese mice. The insulin sensitivity of tissues reflected in the ED50 of insulin response varied widely, and brown adipose tissue was the most insulin-sensitive tissue studied. In GTG-obese mice, heart, quadriceps, and brown adipose tissue were insulin resistant (demonstrated by increased ED50), whereas in white adipose tissue, 2-DG phosphorylation was more sensitive to insulin. Brain 2-DG phosphorylation was insulin independent in control and obese animals. The largest decrease in insulin sensitivity in GTG-obese mice was observed in brown adipose tissue. The loss of diet-induced thermogenesis in brown adipose tissue as a result of the hypothalamic lesion in GTG-obese mice could be a major cause of insulin resistance in brown adipose tissue. Because brown adipose tissue can make a major contribution to whole-body glucose utilization, insulin resistance in this tissue may have a significant effect on whole-animal glucose homeostasis in GTG-obese mice

Nucleotide-Binding Oligomerization Domain-1 and -2 Play No Role in Controlling Brucella abortus Infection in Mice

Directory of Open Access Journals (Sweden)

Fernanda S. Oliveira

2012-01-01

Full Text Available Nucleotide-binding oligomerization domain proteins (NODs are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. Further, several in vivo studies have demonstrated a role for Nod1 and Nod2 in host defense against bacterial pathogens. Here, we demonstrated that macrophages from NOD1-, NOD2-, and Rip2-deficient mice produced lower levels of TNF-α following infection with live Brucella abortus compared to wild-type mice. Similar reduction on cytokine synthesis was not observed for IL-12 and IL-6. However, NOD1, NOD2, and Rip2 knockout mice were no more susceptible to infection with virulent B. abortus than wild-type mice. Additionally, spleen cells from NOD1-, NOD2-, and Rip2-deficient mice showed unaltered production of IFN-γ compared to C57BL/6 mice. Taken together, this study demonstrates that NOD1, NOD2 and Rip2 are dispensable for the control of B. abortus during in vivo infection.

Low-dose-rate high-let radiation cytogenetic effects on mice in vivo as model of space radiation action on mammalian

Science.gov (United States)

Sorokina, Svetlana; Zaichkina, Svetlana; Rozanova, Olga; Aptikaeva, Gella; Romanchenko, Sergei; Smirnova, Helene; Dyukina, Alsu; Peleshko, Vladimir

At present time little is known concerning the biological effects of low-dose-rate high-LET radiation exposure in space. The currently available experimental data on the biological effect of low doses of chronic radiation with high-LET values, which occur under the conditions of aircraft and space flights, have been primarily obtained in the examinations of pilots and astronauts after flights. Another way of obtaining this kind of evidence is the simulation of irradiation conditions during aircraft and space flights on high-energy accelerators and the conduction of large-scale experiments on animals under these conditions on Earth. In the present work, we investigated the cytogenetic effects of low-dose-rate high-LET radiation in the dose ranges of 0.2-30 cGy (1 cGy/day) and 0.5-16 cGy (0.43 cGy/day) in the radiation field behind the concrete shield of the Serpukhov accelerator of 70 GeV protons that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights on SHK mice in vivo. The dose dependence, adaptive response (AR) and the growth of solid tumor were examined. For induction of AR, two groups of mice were exposed to adapting doses of 0.2-30 cGy and the doses of 0.5-16 cGy of high-LET radiation. For comparison, third group of mice from unirradiated males was chronically irradiated with X-rays at adapting doses of 10 cGy (1 cGy/day). After a day, the mice of all groups were exposed to a challenging dose of 1.5 Gy of X-rays (1 Gy/min). After 28 h, the animals of all groups were killed by the method of cervical dislocation. Bone marrow specimens for calculating micronuclei (MN) in polychromatic erythrocytes (PCE) were prepared by a conventional method with minor modifications. The influence of adapting dose of 16 cGy on the growth of solid tumor of Ehrlich ascite carcinoma was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells s.c. into the femur. It was

Local control of murine melanoma xenografts in nude mice by neutron capture therapy

International Nuclear Information System (INIS)

Allen, B.J.; Corderoy-Buck, S.; Moore, D.E.; Mishima, Y.; Ichihashi, M.

1992-01-01

In recent years considerable progress has been made in the development and implementation of neutron capture therapy (NCT) for the treatment of cancer. In particular, the boron analogue of the melanin precursor phenylalanine, i.e., DL-p-boronophenylalanine (BPA), has been used to demonstrate the regression and cure of Harding-Passey (HP) melanoma in syngeneic mice. However, 18 to 25% cures were obtained for neutron irradiations without boron, suggesting that the neutron dose alone plays an important role. Neutron capture therapy of B-16 melanoma xenografts in nude mice showed substantial tumor regression over 35 days, but the survival rate of NCT treated mice after 7 weeks was only 40-60%. In this paper the authors demonstrate the equivalence of the nude mouse model with a syngeneic model, using the same Harding-Passey murine melanoma line, and delineate the conditions required for maximum differential response between neutron irradiation with and without BPA administration, with complete local control as the end point

Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice.

Science.gov (United States)

Mannix, Rebekah C; Zhang, Jimmy; Park, Juyeon; Zhang, Xuan; Bilal, Kiran; Walker, Kendall; Tanzi, Rudolph E; Tesco, Giuseppina; Whalen, Michael J

2011-01-01

The apolipoprotein E4 (APOE4) gene leads to increased brain amyloid beta (Aβ) and poor outcome in adults with traumatic brain injury (TBI); however, its role in childhood TBI is controversial. We hypothesized that the transgenic expression of human APOE4 worsens the outcome after controlled cortical impact (CCI) in adult but not immature mice. Adult and immature APOE4 mice had worse motor outcome after CCI (P<0.001 versus wild type (WT)), but the Morris water maze performance was worse only in adult APOE4 mice (P=0.028 at 2 weeks, P=0.019 at 6 months versus WT), because immature APOE4 mice had performance similar to WT for up to 1 year after injury. Brain lesion size was similar in adult APOE4 mice but was decreased (P=0.029 versus WT) in injured immature APOE4 mice. Microgliosis was similar in all groups. Soluble brain Aβ(40) was increased at 48 hours after CCI in adult and immature APOE4 mice and in adult WT (P<0.05), and was dynamically regulated during the chronic period by APOE4 in adults but not immature mice. The data suggest age-dependent effects of APOE4 on cognitive outcome after TBI, and that therapies targeting APOE4 may be more effective in adults versus children with TBI.

Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice.

Science.gov (United States)

Jauch, Dominik; Martin, Maria; Schiechl, Gabriela; Kesselring, Rebecca; Schlitt, Hans Jürgen; Geissler, Edward K; Fichtner-Feigl, Stefan

2011-12-01

Colitis-associated tumorigenesis is a balance between proliferation of tumour cells and tumour immunosurveillance. The role of T-helper-cell-derived cytokines in tumour growth is not fully understood. In this study the authors investigated the influence of interleukin (IL) 21 on intestinal tumorigenesis. Chronic colitis was induced in IL-21(-/-) and littermate control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS) over 7 days followed by 7 days of drinking water. Mice received an azoxymethane injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry was performed on inflamed and tumour-bearing areas of colons. Cytokine expression of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of isolated colonic CD8 T cells targeting tumour cells was evaluated by flow cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was determined by TUNEL assay of colonic sections. Increasing expression of IL-21 was observed in chronic colitis, which showed functional importance, since IL-21 deficiency prevented chronic DSS-colitis development. Further, in the absence of IL-21, significantly fewer tumour nodules were detected, despite a similar extent of intestinal inflammation. In wild-type mice, 8.6±1.9 tumour nodules were found compared with 1.0±1.2 in IL-21-deficient mice. In tumour-bearing IL-21-deficient mice, intestinal inflammation was restored and partly dependent on interferon (IFN)-γ, whereas the inflammation in wild-type mice showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice, tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was increased, compared with wild-type mice. Increased IFNγ expression in tumour-bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated by cytotoxic CD8CD103 T cells targeting E-cadherin(+) colonic tumour cells and therefore limited tumour growth. These results indicate that IL-21

Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

Science.gov (United States)

Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

2017-03-01

Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An anticholinergic reverses motor control and corticostriatal LTD deficits in Dyt1 ΔGAG knock-in mice.

Science.gov (United States)

Dang, Mai T; Yokoi, Fumiaki; Cheetham, Chad C; Lu, Jun; Vo, Viet; Lovinger, David M; Li, Yuqing

2012-01-15

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder associated with mutations in DYT1 that codes for torsinA protein. The most common mutation seen in this gene is a trinucleotide deletion of GAG. We previously reported a motor control deficit on a beam-walking task in our Dyt1 ΔGAG knock-in heterozygous mice. In this report we show the reversal of this motor deficit with the anticholinergic trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. THP also restored the reduced corticostriatal long-term depression (LTD) observed in these mice. Corticostriatal LTD has long been known to be dependent on D2 receptor activation. In this mouse model, striatal D2 receptors were expressed at lower quantities in comparison to wild-type mice. Furthermore, the mice were also partially resistant to FPL64176, an agonist of L-type calcium channels that have been previously reported to cause severe dystonic-like symptoms in wild-type mice. Our findings collectively suggest that altered communication between cholinergic interneurons and medium spiny neurons is responsible for the LTD deficit and that this synaptic plasticity modification may be involved in the striatal motor control abnormalities in our mouse model of DYT1 dystonia. Copyright © 2011 Elsevier B.V. All rights reserved.

Ludwigia octovalvis extract improves glycemic control and memory performance in diabetic mice.

Science.gov (United States)

Lin, Wei-Sheng; Lo, Jung-Hsin; Yang, Jo-Hsuan; Wang, Hao-Wei; Fan, Shou-Zen; Yen, Jui-Hung; Wang, Pei-Yu

2017-07-31

Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK). Since AMPK has become a critical target for treating diabetes, we herein investigate the anti-hyperglycemic potential of LOE. Differentiated C2C12 muscle cells, HepG2 hepatocellular cells, streptozotocin (STZ)-induced diabetic mice and high fat diet (HFD)-induced diabetic mice were used to investigate the anti-hyperglycemic potential of LOE. The open field test and novel object recognition test were used to evaluate spontaneous motor activity and memory performance of HFD-induced diabetic mice. In differentiated C2C12 muscle cells and HepG2 hepatocellular cells, treatments with LOE and its active component (β-sitosterol) induced significant AMPK phosphorylation. LOE also enhanced uptake of a fluorescent glucose derivative (2-NBDG) and inhibited glucose production in these cells. The beneficial effects of LOE were completely abolished when an AMPK inhibitor, dorsomorphin, was added to the culture system, suggesting that LOE requires AMPK activation for its action in vitro. In streptozotocin (STZ)-induced diabetic mice, we found that both LOE and β-sitosterol induced an anti-hyperglycemic effect comparable to that of metformin, a drug that is commonly prescribed to treat diabetes. Moreover, LOE also improved glycemic control and memory performance of mice fed a HFD. These results indicate that LOE is a potent anti-diabetic intervention that may have potential for future clinical applications. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Studies on the effects of ionizing radiation on the normal and diseased liver in experimental animals

International Nuclear Information System (INIS)

Mahmoud, S.A.

1981-01-01

The experiments carried out in the present study primarily concerned with the effects of ionizing radiations on the normal and diseased liver in experimental animals (mice). Different radiation intensities and different exposure schemes were used to irradiate both healthy and schistosoma mansoni infected animals. A group of uninfected and unirradiated animals were used as controls. Follow up studies were performed every 6 weeks for 30 weeks. These included histopathological studies of the liver damage at every observation periods for all animal groups

Control of IgE and IgGl antibody production in mice

International Nuclear Information System (INIS)

De Macedo, M.S.; Braga, F.; Mota, I.

1976-01-01

The production of IgE and IgCl was studied in untreated, thymectomized, splenectomized, anti-thymocyte serum-treated, or sublethally X-irradiated mice. Dinitrophenyl, Ascaris, and ovalbumin were used as antigens, and aluminum hydroxide was used as adjuvant. A suppression of IgE production was observed in adult thymectomized mice, although the kinetic pattern of the antibody response was the same as in control animals. IgGl antibody production was not affected by thymectomy. Splenectomy did not change either IgE or IgGl production. A single dose of rabbit antithymocyte serum (ATS) given 8 days after immunization inhibited IgE antibody production. The effect of ATS was dose dependent and also varied with the amount of antigen used, the immune response to high doses being more susceptible to the effect of ATS. No alteration in IgGl production was caused by ATS even when IgE antibody formation was completely inhibited. When preceding immunization, sublethal irradiation enhanced IgE antibody formation and partially suppressed IgGl production; applied after immunization, irradiation caused an enhancement of IgE production which was inversely proportional to the interval elapsed between the two procedures. On the other hand, the IgGl antibody production was fairly resistant to the same treatment. The results suggest a clearcut separation between the mechanisms regulating IgE and IgGl production in mice

Evaluation of the role of both irradiation and albenazole in the control of hydatidosis in mice

International Nuclear Information System (INIS)

Moawad, M.A.F.

2005-01-01

The present study mainly aims to evaluate the role of irradiated hydatid cysts and treatment by albendazole on the control of hydatidosis. Eighty male mice were divided equally into four groups. The first group was infected with normal non-irradiated viable particular's. The second group was infected with non-irradiated particular's then treated with al bendazole at a dose of 0.52 mg/kg body weight. The third and fourth groups were infected with 45 Krad and 65 Krad irradiated protoscolices, respectively. Each animal was received 2000 protoscolices by intraperitoneal injection. After 12 and 16 weeks post-infection, parasitological and enzymatic aspects of the mice were examined. The group infected with irradiated protoscolices and the group infected with non-irradiated protoscolices then treated with albendazole showed significant decrease in the number of the developing cysts in both of the liver and omentum. Such decrease was more pronounced with higher dose level of gamma irradiation as compared to the control group (non-irradiated protoscolices). Furthermore, there were significant decreases in the enzyme levels of the liver of mice (y-GT, ALP, ALT and AST) in groups given irradiated viable protoscolices and group given albendazole drug after infection compared to groups given non-irradiated viable protoscolices (control group)

Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity

DEFF Research Database (Denmark)

Topham, D J; Cardin, R C; Christensen, Jan Pravsgaard

2001-01-01

resulted in a failure of most animals to drive the virus into latency, although lytic virus in the lung was reduced by approximately 1000-fold from its peak. Second, the absence of either perforin or Fas alone had no impact on the ability to reduce titres of lytic virus in the lung. Further neutralization...... of IFN-gamma in CD4-depleted P(+/+), P(-/-) or Fas(-/-) mice had no effect. To define the requirements for Fas or perforin more clearly, two sets of chimeric mice were constructed differing in perforin expression by the T cells, and Fas on infected epithelial cells or lymphocytes. Animals with P(-/-) T...... cells and a Fas(-/-) lung failed to limit the shedding of infectious virus, regardless of whether CD4 T cells were present. In addition, we noted that having P(-/-) T cells in irradiated Fas(+/+) hosts caused a lethal disease that was not apparent in the non-chimeric (unirradiated) P(-/-) (Fas...

Dissolution of unirradiated UO2 fuel in synthetic groundwater. Final report (1996-1998)

International Nuclear Information System (INIS)

Ollila, K.

1999-05-01

This study was a part of the EU R and D programme 1994-1998: Nuclear Fission Safety, entitled 'Source term for performance assessment of spent fuel as a waste form'. The research carried out at VTT Chemical Technology was focused on the effects of granitic groundwater composition and redox conditions on UO 2 solubility and dissolution mechanisms. The synthetic groundwater compositions simulated deep granitic fresh and saline groundwaters, and the effects of the near-field material, bentonite, on very saline groundwater. Additionally, the Spanish granite/bentonite water was used. The redox conditions (Eh), which are obviously the most important factors that influence on UO 2 solubility under the disposal conditions of spent fuel, varied from strongly oxidising (air-saturated), anaerobic (N 2 , O 2 2 , low Eh). The objective of the air-saturated dissolution experiments was to yield the maximum solution concentrations of U, and information on the formation of secondary phases that control the concentrations, with different groundwater compositions. The static batch solubility experiments of long duration (up to 1-2 years) were performed using unirradiated UO 2 pellets and powder. Under anaerobic and reducing conditions, the solubilities were also approached from oversaturation. The results of the oxic, air-saturated dissolution experiments with UO 2 powder showed that the increase in the salinity ( -5 M, were at the level of the theoretical solubility of schoepite or another uranyl oxide hydrate, e.g. becquerelite (possibly Na-polyuranate). The higher alkalinity of the fresh (Allard) composition increased the aqueous U concentration. Only some kind of oxidised U-phase (U 3 O 8 -UO 3 ) was identified with XRD when studying possible secondary phases after the contact time of one year with all groundwater compositions. Longer contact times are needed to identify secondary phases predicted by modelling (EQ3/6). In the anoxic dissolution experiments with UO 2 pellets, the

Host natural suppressor activity regulates hemopoietic engraftment kinetics in antibody-conditioned recipient mice

International Nuclear Information System (INIS)

Sadelain, M.W.; Green, D.R.; Wegmann, T.G.

1990-01-01

Resistance to semi-allogeneic or syngeneic hemopoietic stem cell engraftment can be reduced by treating the unirradiated host with anti-class I MHC antibody. In our previous studies we showed a direct correlation between such resistance and the level of natural suppressor (NS) activity in the host. Thus newborn mice that have high NS activity are very resistant to marrow engraftment, as are adults pretreated with CFA that increases NS activity in the bone marrow. We have now devised a method that allows us to follow hemopoietic engraftment kinetics within the marrow cavity itself by assaying individual CFU-granulocyte/macrophage progenitor cells for their host or donor origin over the immediate post-transplant period. By using this method, we find a close correlation between the rate of marrow engraftment and reduction in host NS activity. Marrow engraftment does not correlate with the reduction of either total host bone marrow cellular content or CFU-granulocyte/macrophage progenitor cell levels. NS activity is mediated by Thy-1-, partially radiosensitive, nylon wool nonadherent cells without NK activity. Adoptively transferred Thy-1-, irradiated spleen cells containing NS activity induced by pretreatment with CFA delayed engraftment kinetics in the marrow cavity. Thus hemopoietic engraftment in the marrow cavity appears to be controlled by an inhibitory regulatory activity that is reflected in the in vitro NS assay. These studies suggest new regulatory targets for selective host conditioning to eliminate resistance to marrow transplantation

Comparison of ring compression testing to three point bend testing for unirradiated ZIRLO cladding

Energy Technology Data Exchange (ETDEWEB)

None, None

2015-04-01

Safe shipment and storage of nuclear reactor discharged fuel requires an understanding of how the fuel may perform under the various conditions that can be encountered. One specific focus of concern is performance during a shipment drop accident. Tests at Savannah River National Laboratory (SRNL) are being performed to characterize the properties of fuel clad relative to a mechanical accident condition such as a container drop. Unirradiated ZIRLO tubing samples have been charged with a range of hydride levels to simulate actual fuel rod levels. Samples of the hydrogen charged tubes were exposed to a radial hydride growth treatment (RHGT) consisting of heating to 400°C, applying initial hoop stresses of 90 to 170 MPa with controlled cooling and producing hydride precipitates. Initial samples have been tested using both a) ring compression test (RCT) which is shown to be sensitive to radial hydride and b) three-point bend tests which are less sensitive to radial hydride effects. Hydrides are generated in Zirconium based fuel cladding as a result of coolant (water) oxidation of the clad, hydrogen release, and a portion of the released (nascent) hydrogen absorbed into the clad and eventually exceeding the hydrogen solubility limit. The orientation of the hydrides relative to the subsequent normal and accident strains has a significant impact on the failure susceptability. In this study the impacts of stress, temperature and hydrogen levels are evaluated in reference to the propensity for hydride reorientation from the circumferential to the radial orientation. In addition the effects of radial hydrides on the Quasi Ductile Brittle Transition Temperature (DBTT) were measured. The results suggest that a) the severity of the radial hydride impact is related to the hydrogen level-peak temperature combination (for example at a peak drying temperature of 400°C; 800 PPM hydrogen has less of an impact/ less radial hydride fraction than 200 PPM hydrogen for the same thermal

Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice.

Science.gov (United States)

Yulyaningsih, Ernie; Loh, Kim; Lin, Shu; Lau, Jackie; Zhang, Lei; Shi, Yanchuan; Berning, Britt A; Enriquez, Ronaldo; Driessler, Frank; Macia, Laurence; Khor, Ee Cheng; Qi, Yue; Baldock, Paul; Sainsbury, Amanda; Herzog, Herbert

2014-01-07

Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic and hormonal control of hepatic steatosis in female and male mice.

Science.gov (United States)

Norheim, Frode; Hui, Simon T; Kulahcioglu, Emre; Mehrabian, Margarete; Cantor, Rita M; Pan, Calvin; Parks, Brian W; Lusis, Aldons J

2017-01-01

The etiology of nonalcoholic fatty liver disease is complex and influenced by factors such as obesity, insulin resistance, hyperlipidemia, and sex. We now report a study on sex difference in hepatic steatosis in the context of genetic variation using a population of inbred strains of mice. While male mice generally exhibited higher concentration of hepatic TG levels on a high-fat high-sucrose diet, sex differences showed extensive interaction with genetic variation. Differences in percentage body fat were the best predictor of hepatic steatosis among the strains and explained about 30% of the variation in both sexes. The difference in percent gonadal fat and HDL explained 9.6% and 6.7% of the difference in hepatic TGs between the sexes, respectively. Genome-wide association mapping of hepatic TG revealed some striking differences in genetic control of hepatic steatosis between females and males. Gonadectomy increased the hepatic TG to body fat percentage ratio among male, but not female, mice. Our data suggest that the difference between the sexes in hepatic TG can be partly explained by differences in body fat distribution, plasma HDL, and genetic regulation. Future studies are required to understand the molecular interactions between sex, genetics, and the environment. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

A study of the healthy standard for radiation controlling insect of almond

International Nuclear Information System (INIS)

Wang Ying; Wang Weiguo; Li Fengmei

1992-01-01

The result of healthy standard research for disinfestation insects of almond by γ-ray irradiation is described. The mortality of insects is more effective by using 1.0 kGy dose. The comparison of good product rate between irradiated and un-irradiated has been studied. Result indicates that good product rate of irradiated sample is 20% higher than unirradiated. In addition, there are no significant difference between irradiated and unirradiated samples on nutrition and chemical parameters

Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)

1997-03-01

Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J.

1997-01-01

Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 μg/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice.

Science.gov (United States)

Belkacem, Nouria; Bourdet-Sicard, Raphaëlle; Taha, Muhamed-Kkeir

2018-04-10

The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection. We intranasally infected BALB/c mice with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice. Seven days later, a secondary bacterial infection was induced by intranasal administration of bioluminescent N. meningitidis. During the experiment, mice orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect of L. paracasei administration on secondary bacterial infection by N. meningitidis was evaluated. Oral consumption of L. paracasei CNCM I-1518 reduced the weight loss of infected mice and lowered the bioluminescent signal of infecting meningococci. This improvement was associated with higher recruitment of inflammatory myeloid cells, such as interstitial monocytes and dendritic cells, to the lungs. Our data highlight the role of the gut-lung axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and secondary bacterial infection, which should be further studied and validated in clinical trials.

Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

Directory of Open Access Journals (Sweden)

Mikael Bjursell

Full Text Available Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1, the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

Science.gov (United States)

Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

2013-01-01

Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

International Nuclear Information System (INIS)

Zhang, Y.; Woloschak, G.E.

1997-01-01

This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF 1 male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose γ irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

Science.gov (United States)

Xu, Minjun; Kitaura, Yasuyuki; Ishikawa, Takuya; Kadota, Yoshihiro; Terai, Chihaya; Shindo, Daichi; Morioka, Takashi; Ota, Miki; Morishita, Yukako; Ishihara, Kengo; Shimomura, Yoshiharu

2017-01-01

It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

Directory of Open Access Journals (Sweden)

Minjun Xu

Full Text Available It is known that the catabolism of branched-chain amino acids (BCAAs in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK. In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

Tensile and electrical properties of unirradiated and irradiated Hycon 3HP{trademark} CuNiBe

Energy Technology Data Exchange (ETDEWEB)

Zinkle, S.J.; Eatherly, W.S. [Oak Ridge National Lab., TN (United States)

1996-10-01

The unirradiated tensile properties of two different heats of Hycon 3HP{trademark} CuNiBe (HT Temper) have been measured over the temperature range of 20-500{degrees}C for longitudinal and long transverse orientations. The room temperature electrical conductivity has also been measured for both heats. Both heats exhibited a very good combination of strength and conductivity at room temperature. The strength remained relatively high at all test temperatures, with a yield strength of 420-520 MPa at 500{degrees}C. However, low levels of ductility (<5% uniform elongation) were observed at test temperatures above 200-250{degrees}C, due to flow localization adjacent to grain boundaries. Fission neutron irradiation to a dose of {approximately}0.7 dpa at temperatures between 100 and 240{degrees}C produced a slight increase in strength and a significant decrease in ductility. The measured tensile elongation increased with increasing irradiation temperature, with a uniform elongation of {approximately}3.3% observed at 240{degrees}C. The electrical conductivity decreased slightly following irradiation, due to the presence of defect clusters and Ni, Zn, Co transmutation products. The data indicate that CuNiBe alloys have irradiated tensile and electrical properties comparable or superior to CuCrZr and oxide dispersion strengthened copper at temperatures <250{degrees}C, and may be suitable for certain fusion energy structural applications.

56Fe accelerates development of atherosclerosis in apoE -/-mice

Science.gov (United States)

Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has

Comparison of toxin production by clostridium botulinum type E in irradiated and unirradiated vacuum-packed trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Hussain, M.; Ehlermann, D.; Diehl, J.F.

1977-01-01

Trouts obtained from a nearby Fish farm were slaughtered, gutted, cut into 100g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occured before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

Comparison of toxin production by clostridium botulinum type E in irradiated and unirradiated vacuum-packed trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Hussain, A.M.; Ehlermann, D.; Diehl, J.F.

1977-01-01

Trouts obtained from a nearby fish farm were slaughtered, gutted, cut into 100 g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occurred before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

[Effect of hedgehog hydnum on the delay of fatigue in mice].

Science.gov (United States)

Lu, Y H; Xin, C L; Zhou, Y F; Liu, X W; Chi, J W; Chang, X

1996-02-01

Two groups of mice were fed with either hedgehog hydnum powder or extract for sixty days. For the assay of fatigue, the activity of serum lactate dehydrogenase, the serum urea nitrogen content, blood lactic acid, hepatic and muscular glycogen, and the physical stamina of the mice were determined. The activity of serum lactate dehydrogenase and the hepatic and muscular glycogen content in the experimental mice were evidently higher than that in the control mice (P increase in blood lactic acid and serum urea nitrogen in the experimental mice was significantly lower than that in the control mice (P stamina swimming, the experimental mice drowned after a longer period of time than the control mice (P stamina and delaying fatigue in mice.

Early and late effects of fission-neutron or gamma irradiation on the clearance of bacteria from the lungs of B6CF1 mice

International Nuclear Information System (INIS)

Brennan, P.C.; Ainsworth, E.J.

1977-01-01

Enhanced susceptibility to experimental respiratory infection following chronic exposure to low-level gamma radiation has been reported, but no comparable information exists for neutron-irradiated animals. Such information is needed in view of the apparently greater additivity of repeated low fission-neutron doses. Consequently altered susceptibility to respiratory infection is being examined in the JANUS Neutron and Gamma-Ray Toxicity Program. Some B6CF 1 mice of various ages were challenged with Pasteurella pneumotropica either by intranasal instillation or by aerosol inhalation following single or fractionated doses of neutrons or 60 Co gamma radiation. Clearance of the bacteria from the lungs was assessed 4 days after challenge by a culture technique and by histological and immunofluorescence staining. From 5 to 21 days after a single dose of 288 neutron rads or 740 gamma rads, a ratio equal to the relative biological effectiveness (RBE) for cell killing, there was little repair of the radiation-damaged clearance mechanism evident in neutron-irradiated mice; 85% were unable to clear the organism as long as 21 days after irradiation. Over the same period only 25% of gamma-irradiated mice failed to eliminate P. pneumotropica. Immunofluorescent-stained lung sections at all time intervals between 5 and 21 days were strikingly similar among neutron- and gamma-irradiated mice and unirradiated mice. Alveolar macrophages were swollen with fluorescent P. pneumotropica cells, and macrophages surrounding the bronchi and in the bronchial exudate were also intensely fluorescent. These data, coupled with the culture data, indicate that pulmonary macrophages in the irradiated host are capable of engulfing P. pneumotropica cells but that the ability to kill them is impaired

Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

Directory of Open Access Journals (Sweden)

Catherine B. Lawrence

2012-09-01

Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS. However, the effect of diet-induced obesity (DIO on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p. injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg. LPS (100 μg/kg induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.

Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.

Science.gov (United States)

Suardíaz, M; Galan-Arriero, I; Avila-Martin, G; Estivill-Torrús, G; de Fonseca, F R; Chun, J; Gómez-Soriano, J; Bravo-Esteban, E; Taylor, J

2016-02-01

Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown. In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice. The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed. Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity. These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level. © 2015 European Pain Federation - EFIC®

1H-NMR METABONOMICS ANALYSIS OF SERA DIFFERENTIATES BETWEEN MAMMARY TUMOR-BEARING MICE AND HEALTHY CONTROLS

Science.gov (United States)

Global analysis of 1H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted 1H-NMR metabonomic analyses on serum samples ob...

A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice.

Science.gov (United States)

Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I

2017-07-01

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.

Development of ghrelin transgenic mice for elucidation of clinical implication of ghrelin.

Science.gov (United States)

Aotani, Daisuke; Ariyasu, Hiroyuki; Shimazu-Kuwahara, Satoko; Shimizu, Yoshiyuki; Nomura, Hidenari; Murofushi, Yoshiteru; Kaneko, Kentaro; Izumi, Ryota; Matsubara, Masaki; Kanda, Hajime; Noguchi, Michio; Tanaka, Tomohiro; Kusakabe, Toru; Miyazawa, Takashi; Nakao, Kazuwa

2017-01-01

To elucidate the clinical implication of ghrelin, we have been trying to generate variable models of transgenic (Tg) mice overexpressing ghrelin. We generated Tg mice overexpressing des-acyl ghrelin in a wide variety of tissues under the control of β-actin promoter. While plasma des-acyl ghrelin level in the Tg mice was 44-fold greater than that of control mice, there was no differences in the plasma ghrelin level between des-acyl ghrelin Tg and the control mice. The des-acyl ghrelin Tg mice exhibited the lower body weight and the shorter body length due to modulation of GH-IGF-1 axis. We tried to generate Tg mice expressing a ghrelin analog, which possessed ghrelin-like activity (Trp 3 -ghrelin Tg mice). The plasma Trp 3 -ghrelin concentration in Trp 3 -ghrelin Tg mice was approximately 85-fold higher than plasma ghrelin (acylated ghrelin) concentration seen in the control mice. Because Trp 3 -ghrelin is approximately 24-fold less potent than ghrelin, the plasma Trp 3 -ghrelin concentration in Trp 3 -ghrelin Tg mice was calculated to have approximately 3.5-fold biological activity greater than that of ghrelin (acylated ghrelin) in the control mice. Trp 3 -ghrelin Tg mice did not show any phenotypes except for reduced insulin sensitivity in 1-year old. After the identification of ghrelin O-acyltransferase (GOAT), we generated doubly Tg mice overexpressing both mouse des-acyl ghrelin and mouse GOAT in the liver by cross-mating the two kinds of Tg mice. The plasma ghrelin concentration of doubly Tg mice was approximately 2-fold higher than that of the control mice. No apparent phenotypic changes in body weight and food intake were observed in doubly Tg mice. Further studies are ongoing in our laboratory to generate Tg mice with the increased plasma ghrelin level to a greater extent. The better understanding of physiological and pathophysiological significance of ghrelin from experiments using an excellent animal model may provide a new therapeutic approach for human

State machine operation of the MICE cooling channel

International Nuclear Information System (INIS)

Hanlet, Pierrick

2014-01-01

The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The cooling channel for MICE has between 12 and 18 superconductnig solenoid coils in 3 to 7 magnets, depending on the staged development of the experiment. The magnets are coaxial and in close proximity which requires coordinated operation of the magnets when ramping, responding to quench conditions, and quench recovery. To reliably manage the operation of the magnets, MICE is implementing state machines for each magnet and an over-arching state machine for the magnets integrated in the cooling channel. The state machine transitions and operating parameters are stored/restored to/from the configuration database and coupled with MICE Run Control. Proper implementation of the state machines will not only ensure safe operation of the magnets, but will help ensure reliable data quality. A description of MICE, details of the state machines, and lessons learned from use of the state machines in recent magnet training tests will be discussed.

Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts

International Nuclear Information System (INIS)

Rude, J.M.; Friedberg, E.C.

1977-01-01

Rates of semiconservative DNA synthesis have been investigated in asynchronous xeroderma pigmentosum (XP), XP variant, and normal human skin fibroblasts using the technique of cellular autoradiography. In unirradiated cells, no differences in DNA synthesis rates were detected among the three cell strains. Exposure to UV radiation caused the rate of DNA synthesis to decrease for at least three hours in all three cell strains. In the normal cell strain, recovery of the DNA synthetic rate occurred at later times following a UV fluence of 5 J/m 2 . At this same UV fluence, recovery was absent in classical XP cells during a 24 h post-irradiation period while it was slower than normal in XP variant cells. When the UV fluence to classical XP and XP variant cells was reduced so that survival in all three cell strains was approximately the same (25%), recovery of the DNA synthetic rate was similar in all three cell strains. These results are discussed in terms of current models of DNA replication in UV-irradiated cells and indicate: (1) that pyrimidine dimers are very effective blocks to DNA synthesis and (2) that there is no inherent defect in semiconservative DNA synthesis in either classical XP or XP variant cells which is independent of a defect in DNA repair capacity

Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

International Nuclear Information System (INIS)

Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

1990-01-01

Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies

Dissolution of unirradiated UO{sub 2} fuel in synthetic groundwater. Final report (1996-1998)

Energy Technology Data Exchange (ETDEWEB)

Ollila, K. [VTT Chemical Technology, Espoo (Finland)

1999-05-01

This study was a part of the EU R and D programme 1994-1998: Nuclear Fission Safety, entitled `Source term for performance assessment of spent fuel as a waste form`. The research carried out at VTT Chemical Technology was focused on the effects of granitic groundwater composition and redox conditions on UO{sub 2} solubility and dissolution mechanisms. The synthetic groundwater compositions simulated deep granitic fresh and saline groundwaters, and the effects of the near-field material, bentonite, on very saline groundwater. Additionally, the Spanish granite/bentonite water was used. The redox conditions (Eh), which are obviously the most important factors that influence on UO{sub 2} solubility under the disposal conditions of spent fuel, varied from strongly oxidising (air-saturated), anaerobic (N{sub 2}, O{sub 2} < l ppm) to reducing (N{sub 2}, low Eh). The objective of the air-saturated dissolution experiments was to yield the maximum solution concentrations of U, and information on the formation of secondary phases that control the concentrations, with different groundwater compositions. The static batch solubility experiments of long duration (up to 1-2 years) were performed using unirradiated UO{sub 2} pellets and powder. Under anaerobic and reducing conditions, the solubilities were also approached from oversaturation. The results of the oxic, air-saturated dissolution experiments with UO{sub 2} powder showed that the increase in the salinity (< 1.7 M) had a minor effect on the measured steady-state concentrations of U. The concentrations, (1.2 ...2.5) x 10{sup -5} M, were at the level of the theoretical solubility of schoepite or another uranyl oxide hydrate, e.g. becquerelite (possibly Na-polyuranate). The higher alkalinity of the fresh (Allard) composition increased the aqueous U concentration. Only some kind of oxidised U-phase (U{sub 3}O{sub 8}-UO{sub 3}) was identified with XRD when studying possible secondary phases after the contact time of one year

Radiation induced synthesis of In{sub 2}O{sub 3} nanoparticles - Part II: Synthesis of In{sub 2}O{sub 3} nanoparticles by thermal decomposition of un-irradiated and γ-irradiated indium acetylacetonate

Energy Technology Data Exchange (ETDEWEB)

Al-Resheedi, Ajayb Saud; Alhokbany, Norah Saad [Department of Chemistry, College of Science, King Saud University, KSU, (Saudi Arabia); Mahfouz, Refaat Mohammed, E-mail: rmhfouz@science.au.edu.eg [Chemistry Department, Faculty of Science, Assiut University, AUN, (Egypt)

2015-09-15

Pure cubic phase, In{sub 2}O{sub 3} nanoparticles with porous structure were synthesized by solid state thermal oxidation of un-irradiated and γ-irradiated indium acetyl acetonate in presence and absence of sodium dodecyl sulphate as surfactant. The as- synthesized In{sub 2}O{sub 3} nanoparticles were characterized by X-ray diffraction (XRD), fourier transformation infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transition electron microscopy (TEM) and thermogravimetry (TG). The shapes and morphologies of as- synthesized In{sub 2}O{sub 3} nanoparticles were highly affected by γ-irradiation of indium acetyl acetonate precursor and by addition of sodium dodecyl sulphate as surfactant. Calcination of un-irradiated indium acetyl acetonate precursor to 4 hours of 600 °C leads to the formation of spherical- shaped accumulative and merged In{sub 2}O{sub 3} nanoparticles with porous structure, whereas irregular porous architectures composed of pure In{sub 2}O{sub 3} nanoparticles were obtained by using γ-irradiated indium acetylacetonate precursor. The as- prepared In{sub 2}O{sub 3} nano products exhibit photoluminescence emission (PL) property and display thermal stability in a wide range of temperature (25-800 °C) which suggest possible applications in nanoscale optoelectronic devices. (author)

Evidence against a systemic humoral factor controlling the intestinal compensatory response following X-irradiation

International Nuclear Information System (INIS)

Sharp, J.G.; Osborne, J.W.; Iowa Univ., Iowa City

1981-01-01

The investigation was devised to determine whether changes noted in the unirradiated duodenum and colon of single rats after X-irradiation of only the exteriorized rat jejunum and ileum are mediated by a systemic humoral factor. Littermate Holtzman male rats were joined in parabiosis and one month later, the temporarily exteriorized jejunum and ileum of one member was exposed to 1.000 R of 250 kVp X-irradiation. Two days after X-irradiation, and 1, 12 and 24 h after 1 μCi/g bodyweight 3 H-thymidine was injected i.p. rats were sacrificed and appropriate tissues removed. Single rats which had the exteriorized jejunum and ileum irradiated were studied from 1-3 days after irradiation. Crypt cell migration rates were determined employing autoradiography. Tritium content and columnar cell migration rate in duodenum and colon of unirradiated rats compared to irradiated rats indicated that irradiation of one member of the pair had no effect on tritium incorporation or epithelial cell migration in the duodenum or colon of the unirradiated partner. Epithelial cell proliferation and crypt cell migration were increased in unirradiated duodenum and colon of single intestine-irradiated rats. Essentially the same changes were seen in the irradiated member of a parabiotic pair, but none of these changes were noted in the unirradiated member. The absence of stimulation in the unirradiated parabiont suggests that either a systemic humoral factor is not present after X-irradiation or is not present in sufficient concentration to be detected by these methods. (orig./MG)

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

International Nuclear Information System (INIS)

Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

1985-01-01

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

1985-01-01

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.

Cell proliferation and ageing in mouse colon

International Nuclear Information System (INIS)

Hamilton, E.

1978-01-01

The descending colon of 4 month and 2 year old mice was exposed to 1250 rad X-rays. This killed most of the epithelial cells. The surviving cells formed new crypts and surface epithelium in animals of both ages. Not all of the crypts were replaced. The irradiated area contained not more than 80% of the control number of crypts per section for at least 6 weeks after irradiation. In the young mice new crypts were much larger and the labelling index (LI) was much higher than in unirradiated animals during the first week after irradiation. In the old mice the overshoot in LI and crypt size began later and continued longer than in young animals. This may be because the control of cell proliferation was much less precise in old than in young mice. The irradiation was repeated, in attempt to age prematurely the epithelial cells by increasing the number of divisions they underwent. The overshoot in LI and cells per crypt was smaller after a second dose than after the first in both young and old mice. There was almost no overshoot after a third dose was given to young mice. Increasing the number of divisions undergone by the surviving epithelial cells did not change the timing of repopulation in young mice compared to that found in old mice. Little evidence was found for the presence of a limited proliferative lifespan in colon epithelial cells. (author)

Metabolite analysis distinguishes between mice with epidermolysis bullosa acquisita and healthy mice.

Science.gov (United States)

Schönig, Sarah; Recke, Andreas; Hirose, Misa; Ludwig, Ralf J; Seeger, Karsten

2013-06-26

Epidermolysis bullosa acquisita (EBA) is a rare skin blistering disease with a prevalence of 0.2/ million people. EBA is characterized by autoantibodies against type VII collagen. Type VII collagen builds anchoring fibrils that are essential for the dermal-epidermal junction. The pathogenic relevance of antibodies against type VII collagen subdomains has been demonstrated both in vitro and in vivo. Despite the multitude of clinical and immunological data, no information on metabolic changes exists. We used an animal model of EBA to obtain insights into metabolomic changes during EBA. Sera from mice with immunization-induced EBA and control mice were obtained and metabolites were isolated by filtration. Proton nuclear magnetic resonance (NMR) spectra were recorded and analyzed by principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA) and random forest. The metabolic pattern of immunized mice and control mice could be clearly distinguished with PCA and PLS-DA. Metabolites that contribute to the discrimination could be identified via random forest. The observed changes in the metabolic pattern of EBA sera, i.e. increased levels of amino acid, point toward an increased energy demand in EBA. Knowledge about metabolic changes due to EBA could help in future to assess the disease status during treatment. Confirming the metabolic changes in patients needs probably large cohorts.

Distinct temporal and anatomical distributions of amyloid-β and tau abnormalities following controlled cortical impact in transgenic mice.

Directory of Open Access Journals (Sweden)

Hien T Tran

Full Text Available Traumatic brain injury (TBI is a major environmental risk factor for Alzheimer's disease. Intracellular accumulations of amyloid-β and tau proteins have been observed within hours following severe TBI in humans. Similar abnormalities have been recapitulated in young 3xTg-AD mice subjected to the controlled cortical impact model (CCI of TBI and sacrificed at 24 h and 7 days post injury. This study investigated the temporal and anatomical distributions of amyloid-β and tau abnormalities from 1 h to 24 h post injury in the same model. Intra-axonal amyloid-β accumulation in the fimbria was detected as early as 1 hour and increased monotonically over 24 hours following injury. Tau immunoreactivity in the fimbria and amygdala had a biphasic time course with peaks at 1 hour and 24 hours, while tau immunoreactivity in the contralateral CA1 rose in a delayed fashion starting at 12 hours after injury. Furthermore, rapid intra-axonal amyloid-β accumulation was similarly observed post controlled cortical injury in APP/PS1 mice, another transgenic Alzheimer's disease mouse model. Acute increases in total and phospho-tau immunoreactivity were also evident in single transgenic Tau(P301L mice subjected to controlled cortical injury. These data provide further evidence for the causal effects of moderately severe contusional TBI on acceleration of acute Alzheimer-related abnormalities and the independent relationship between amyloid-β and tau in this setting.

Hepatic response to oxidative injury in long-lived Ames dwarf mice.

Science.gov (United States)

Sun, Liou Y; Bokov, Alex F; Richardson, Arlan; Miller, Richard A

2011-01-01

Multiple stress resistance pathways were evaluated in the liver of Ames dwarf mice before and after exposure to the oxidative toxin diquat, seeking clues to the exceptional longevity conferred by this mutation. Before diquat treatment, Ames dwarf mice, compared with nonmutant littermate controls, had 2- to 6-fold higher levels of expression of mRNAs for immediate early genes and 2- to 5-fold higher levels of mRNAs for genes dependent on the transcription factor Nrf2. Diquat led to a 2-fold increase in phosphorylation of the stress kinase ERK in control (but not Ames dwarf) mice and to a 50% increase in phosphorylation of the kinase JNK2 in Ames dwarf (but not control) mice. Diquat induction of Nrf2 protein was higher in dwarf mice than in controls. Of 6 Nrf2-responsive genes evaluated, 4 (HMOX, NQO-1, MT-1, and MT-2) remained 2- to 10-fold lower in control than in dwarf liver after diquat, and the other 2 (GCLM and TXNRD) reached levels already seen in dwarf liver at baseline. Thus, livers of Ames dwarf mice differ systematically from controls in multiple stress resistance pathways before and after exposure to diquat, suggesting mechanisms for stress resistance and extended longevity in Ames dwarf mice.

Otolith dysfunction alters exploratory movement in mice.

Science.gov (United States)

Blankenship, Philip A; Cherep, Lucia A; Donaldson, Tia N; Brockman, Sarah N; Trainer, Alexandria D; Yoder, Ryan M; Wallace, Douglas G

2017-05-15

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system's contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency.

Science.gov (United States)

Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma

2017-05-04

Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl 4 )-induced liver damage compared to healthy controls (Wt Igf +/+ ). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/- ). Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+ ) were included in the protocol: untreated controls (Wt). Controls that received CCl 4 (Wt + CCl 4 ) and Wt + CCl 4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl 4  + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/- ) groups were studied: untreated Hz, Hz + CCl 4 , and Hz + CCl 4  + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl 4  + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl 4 . Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series

Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.

Science.gov (United States)

Zhang, Xiaoyu; Qin, Juliang; Zhao, Yihan; Shi, Jueping; Lan, Rong; Gan, Yunqiu; Ren, Hua; Zhu, Bing; Qian, Min; Du, Bing

2016-04-01

The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element-binding protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD. Copyright © 2016 Elsevier Inc. All rights reserved.

The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

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Ranieri Cancedda

Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice.

Science.gov (United States)

Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

2012-01-01

The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

Host defenses in experimental scrub typhus: effect of sublethal gamma radiation

International Nuclear Information System (INIS)

Kelly, D.J.

1983-01-01

The effect of sublethal gamma radiation on inbred mice chronically infected with scrub typhus rickettsiae was examined. Inbred mice which have been inoculated with Gilliam or Karp strain of Rickettsia tsutsugamushi by the subcutaneous route harbored the infection for at least one year. Irradiation of these animals at 12 or 52 weeks post inoculation at normally sublethal levels induced a significantly higher percentage of rickettsemic mice (recrudescence) than in the unirradiated similarly infected control animals. In addition, sublethal irradiation at 12 weeks also induced a quantitative increase in total rickettsiae. Homologous antibody titers to the rickettsiae were examined for five weeks following irradiation to determine the role of the humoral response in radiation induced recrudescence. Modification of recrudescence was investigated using radioprotective drugs. The expected results of this investigation supported the conclusion that the recrudescence of a chronic rickettsial infection in the appropriate host following immunological impairment due to battlefield or clinical exposure to gamma radiation can result in an acute, possibly lethal rickettsemia

Transcription factor YY1 can control AID-mediated mutagenesis in mice.

Science.gov (United States)

Zaprazna, Kristina; Basu, Arindam; Tom, Nikola; Jha, Vibha; Hodawadekar, Suchita; Radova, Lenka; Malcikova, Jitka; Tichy, Boris; Pospisilova, Sarka; Atchison, Michael L

2018-02-01

Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock-out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID-mediated mutations. Using mice that overexpress AID (IgκAID yy1 f/f ) or that express normal AID levels (yy1 f/f ), we found that conditional knock-out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the Sμ switch region, and reduced AID-mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1-AID physical interaction which blocks AID ubiquitination. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-lived ames dwarf mice are resistant to chemical stressors.

Science.gov (United States)

Bokov, Alex F; Lindsey, Merry L; Khodr, Christina; Sabia, Marian R; Richardson, Arlan

2009-08-01

To probe the connection between longevity and stress resistance, we compared the sensitivity of Ames long-lived dwarf mice and control littermates with paraquat, diquat, and dobutamine. In young adult animals, 95% of male and 39% of female controls died after paraquat administration, but no dwarf animals died. When the experiment was repeated at an older age or a higher dosage of paraquat, dwarf mice still showed greater resistance. Dwarf mice also were more resistant to diquat; 80% of male and 60% of female controls died compared with 40% and 20% of dwarf mice, despite greater sensitivity of dwarf liver to diquat. Dwarf mice were also less sensitive to dobutamine-induced cardiac stress and had lower levels of liver and lung F(2)-isoprostanes. This is the first direct in vivo evidence that long-lived Ames dwarf mice have enhanced resistance to chemical insult, particularly oxidative stressors.

Polymerase chain reaction detection of retinoblastoma gene deletions in paraffin-embedded mouse lung adenocarcinomas

International Nuclear Information System (INIS)

Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

1991-01-01

A Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene using microtomed sections from paraffin-embedded radiation-induced and spontaneous tumors as the DNA source. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (569 cGy of 60 Co γ rays or 60 cGy of JANUS neutrons) were analyzed. Tumors in six neutron-irradiated mice also had no mRb deletions. However, one of six tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

Science.gov (United States)

Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

2016-10-27

Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Rude' e, J.M.; Friedberg, E.C.

1977-03-01

Rates of semiconservative DNA synthesis have been investigated in asynchronous xeroderma pigmentosum (XP), XP variant, and normal human skin fibroblasts using the technique of cellular autoradiography. In unirradiated cells, no differences in DNA synthesis rates were detected among the three cell strains. Exposure to uv radiation caused the rate of DNA synthesis to decrease for at least three hours in all three cell strains. In the normal cell strain, recovery of the DNA synthetic rate occurred at later times following a uv fluence of 5 J/m2. At this same uv fluence, recovery was absent in classical XP cells during a 24 h post-irradiation period while it was slower than normal in XP variant cells. When the uv fluence to classical XP and XP variant cells was reduced so that survival in all three cell strains was approximately the same (25%), recovery of the DNA synthetic rate was similar in all three cell strains. These results are discussed in terms of current models of DNA replication in uv-irradiated cells and indicate: (1) that pyrimidine dimers are very effective blocks to DNA synthesis and (2) that there is no inherent defect in semi-conservative DNA synthesis in either classical XP or XP variant cells which is independent of a defect in DNA repair capacity.

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

Directory of Open Access Journals (Sweden)

Ramesh Chennupati

Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

Immunity to sporozoite-induced malaria infection in mice. I. The effect of immunization of T and B cell-deficient mice

International Nuclear Information System (INIS)

Chen, D.H.; Tigelaar, R.E.; Weinbaum, F.I.

1977-01-01

The cellular basis of immunity to sporozoites was investigated by examining the effect of immunization of T and B cell-deficient C57BL/6N x BALB/c AnN F 1 (BLCF 1 ) mice compared to immunocompetent controls. Immunization of T cell-deficient (ATX-BM-ATS) BLCF 1 mice with x-irradiated sporozoites did not result in the generation of protective immunity. The same immunization protocols protected all immunocompetent controls. In contrast, B cell-deficient (μ-suppressed) BLCF 1 mice were protected by immunization in the majority of cases. The absence of detectable serum circumsporozoite precipitins or sporozoite neutralizing activity in the μ-suppressed mice that resisted a sporozoite challenge suggests a minor role for these humoral factors in protection. These data demonstrate a preeminent role for T cells in the induction of protective immunity in BLCF 1 mice against a P. berghei sporozoite infection

Effect of Diets Containing Sucrose vs. D-tagatose in Hypercholesterolemic Mice

Energy Technology Data Exchange (ETDEWEB)

Police, S.; Harris, J; Lodder, R; Cassis, L

2008-01-01

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr-/-) mice. LDLr-/- male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

Effect of diets containing sucrose vs. D-tagatose in hypercholesterolemic mice.

Science.gov (United States)

Police, Sara B; Harris, J Clay; Lodder, Robert A; Cassis, Lisa A

2009-02-01

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr(-/-)) mice. LDLr(-/-) male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG-fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR-fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR-fed mice compared to TAG and CONTROL. Male and female SUCR-fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR-fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR-fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

DEFF Research Database (Denmark)

Thomsen, Allan Randrup; Johansen, J; Marker, O

1996-01-01

To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually...... this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient...... and that in their absence, the virus-specific CTL potential becomes exhausted. Together our results indicate that while CD8+ cells play a dominant role in acute virus control, all three major components of the immune system are required for long term virus control....

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

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Yun Seong-Jo

2012-01-01

Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice.

Science.gov (United States)

Pan, Qiong; Sun, Yiming; Jin, Qili; Li, Qixiang; Wang, Qing; Liu, Hao; Zhao, Surong

2016-11-01

To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

Does open-field exposure during infancy influence open-field behavior of the same adult mice?

OpenAIRE

Vidal Gómez, José

2013-01-01

The goal of this report is to find out whether early exposure of mice to the open-field results in altered behavior of the same adult mice in the same open-field. Early exposure to the open-field was carried out between birth and weaning; two control groups were included: control 2 (mice exposed to a reduced dark space) and control 1 (mice left undisturbed). The (male and female) mice were of the Balb/c and C57Bl/6 strains. Adult C57Bl/6 female mice of the openfield and control 2 groups ambul...

The food additive vanillic acid controls transgene expression in mammalian cells and mice.

Science.gov (United States)

Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

2012-03-01

Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

International Nuclear Information System (INIS)

Woloschak, G.E.; Libertin, C.R.; Weaver, P.; Churchill, M.; Chang-Liu, C.M.

1993-01-01

Mice recessive for the autosomal gene ''wasted'' (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/· mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/· mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/· and not from wst/wst or parental control BCF 1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

Rearrangement of RAG-1 recombinase gene in radiation-sensitive ``wasted`` mice

Energy Technology Data Exchange (ETDEWEB)

Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ., Maywood, IL (United States); Libertin, C.R.; Weaver, P. [Loyola Univ., Maywood, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

1993-09-01

Mice recessive for the autosomal gene ``wasted`` (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot} mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot} mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

Zinc metabolism in genetically obese (ob/ob) mice

International Nuclear Information System (INIS)

Kennedy, M.L.; Failla, M.L.

1987-01-01

Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from those in lean controls. In the present studies the absorption, retention and tissue distribution of zinc and constitutive levels of zinc-metallothionein (Zn-MT) in selected tissues were compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When 5-, 10- and 22-wk-old mice were administered 1.2 mumol 65 Zn by stomach tube the apparent absorption of 65 Zn by obese mice was 1.5, 2.2 and 3.9 times higher, respectively, than that in age-matched lean mice. Retention of orally administered 65 Zn after 96 h was also substantially higher in obese mice than in lean mice. To assess the possible influences of hyperphagia and intestinal hypertrophy on the enhanced apparent absorption of 65 Zn by obese mice food intake by an additional group of obese mice was restricted to that of age-matched lean controls. When actual absorption of zinc was determined according to the method of Heth and Hoekstra, groups of ad libitum--fed obese, pair-fed obese and lean mice absorbed 38, 32 and 18% of administered 65 Zn, respectively. In contrast, the rate of 65 Zn excretion 2-6 d after oral or subcutaneous administration of the metal was similar for obese and lean mice. Unrestricted and pair-fed obese mice had significantly lower percentages of carcass 65 Zn present in skin, muscle plus bone, spleen and testes and higher percentages present in liver, small intestine and adipose tissue than lean mice

Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

Science.gov (United States)

Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

2016-01-01

The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

Behavioural changes in mice exposed to low level microwave fields

International Nuclear Information System (INIS)

Goiceanu, C.; Gradinaru, F.; Danulescu, R.; Balaceanu, G.; Sandu, D. D.; Avadanei, O. G.

2001-01-01

The aim of our study is to point out some changes in mice behaviour due possibly to exposure to low-level microwave fields. Animals spontaneous behaviour were monitored and the exploring behaviour and motor activity were assessed. Ten selected Swiss male mice were exposed to low-level microwave fields of about 1 mW/cm 2 power density for a relatively long period of time (13 weeks), comparing to their lifetime. The exposure system consists in a transverse electromagnetic (TEM) Cell. A control lot of ten Swiss male mice was used. All twenty mice were selected to be of same age and of 202 g initial body weight. Each animal was placed in his own holder. The behaviour of the animals, from both exposed and control lots, was assessed by using a battery of three behavioural tests. The test sessions were performed every two weeks. During exposure period it was recorded a progressive but moderate loss of motor activity for both exposed and controls, probably due to weight gain and aging. Concerning exploratory activity there is a significant difference between control and exposed animals. Control mice had approximately constant performances in time. On the other hand exposed mice showed a progressive decrease in time of their exploratory ability. Motor activity of exposed animals does not seem to be affected by microwave exposure, in spite of moderate loss in time of motor activity in both lots, as long as it was recorded a quite similar evolution. The difference in performances of exposed and controls concerning exploratory activity seem to emphasise an effect of long-term low-level microwave exposure. The progressive loss in time of exploratory activity of exposed mice, in contrast with controls, could be due to the interference of microwaves with central nervous activity. (authors)

Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies

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Georges N. Kanaan

2018-04-01

Full Text Available Glutaredoxin 2 (GRX2, a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Keywords: Human heart, Mitochondria, Oxidative stress, Redox, Cardiac metabolism, Cardiac hypertrophy

Bacterial magnetic particles improve testes-mediated transgene efficiency in mice.

Science.gov (United States)

Wang, Chao; Sun, Guanghong; Wang, Ye; Kong, Nana; Chi, Yafei; Yang, Leilei; Xin, Qiliang; Teng, Zhen; Wang, Xu; Wen, Yujun; Li, Ying; Xia, Guoliang

2017-11-01

Nano-scaled materials have been proved to be ideal DNA carriers for transgene. Bacterial magnetic particles (BMPs) help to reduce the toxicity of polyethylenimine (PEI), an efficient gene-transferring agent, and assist tissue transgene ex vivo. Here, the effectiveness of the BMP-PEI complex-conjugated foreign DNAs (BPDs) in promoting testes-mediated gene transfer (TMGT) in mouse was compared with that of liposome-conjugated foreign DNAs. The results proved that through testes injection, the clusters of BPDs successfully reached the cytoplasm and the nuclear of spermatogenesis cell, and expressed in testes of transgene founder mice. Additionally, the ratio of founder mice obtained from BPDs (88%) is about 3 times higher than the control (25%) (p mice from BPD group were significantly improved, as compared with the control (p mice within the first filial was significantly higher in BPDs compared with the control (73.8% versus 11.6%, p mice in vivo.

Facilitation of syngeneic stem cell engraftment by anti-class I monoclonal antibody pretreatment of unirradiated recipients

International Nuclear Information System (INIS)

Voralia, M.; Semeluk, A.; Wegmann, T.G.

1987-01-01

We have established a murine model of syngeneic bone marrow transplantation based on the use of monoclonal antibody as the sole conditioning regimen in unirradiated recipients. Administration of a single injection of monoclonal antibody directed against major histocompatibility complex-encoded class I determinants facilitated permanent hemopoietic stem cell engraftment without any apparent side-effects. Whereas untreated hosts exhibited a maximal chimerism of 15% at donor cell doses of up to 12 X 10(7) bone marrow cells, pretreatment by 2 mg of anti-class I antibody one week prior to transplantation of 3 X 10(7) syngeneic bone marrow cells resulted in a mean donor representation of about 80%. The antibody can be given up to four weeks prior to transplantation, and the degree of donor engraftment observed is a function of the dose of antibody administered. The fact that specific antibody enhanced engraftment in two strain combinations indicates that antibody is the active agent in facilitating engraftment and that facilitation is not strain-restricted. Anti-class I antibodies of the IgG2a, but not IgG1, isotype are effective in promoting engraftment. Although the isotype requirement suggests a role for antibody-mediated cytotoxicity in promoting stem cell engraftment, the extensive time-frame of facilitation suggests that other effects of the antibody may also be involved. The model of syngeneic bone marrow transplantation we describe here will be useful in studying the mechanisms regulating stem cell engraftment and may have potential clinical application as an approach to autologous marrow transplantation

CD4(+) T cell-mediated control of a gamma-herpesvirus in B cell-deficient mice is mediated by IFN-gamma

DEFF Research Database (Denmark)

Christensen, Jan Pravsgaard; Cardin, R D; Branum, K C

1999-01-01

The lack of B cells and antibody does not prevent mice from dealing effectively with a pathogenic gamma-herpesvirus. Both CD4(+) and CD8(+) T cells contribute to the control of virus replication in the respiratory tract, with the depletion of either lymphocyte subset leading to increased titers...... for direct interaction with virus-infected targets expressing MHC class II glycoproteins, suggesting that the IFN-gamma produced by these lymphocytes is functioning at short range. The numbers of latently infected cells in the spleens of carrier mice are also significantly increased by the concurrent...

Magnetic biomineralisation in Huntington's disease transgenic mice

International Nuclear Information System (INIS)

Beyhum, W; Hautot, D; Dobson, J; Pankhurst, Q A

2005-01-01

The concentration levels of biogenic magnetite nanoparticles in transgenic R6/2 Huntington's disease (HD) mice have been investigated, using seven control and seven HD mice each from an 8 week-old litter and from a 12 week-old litter. Hysteresis and isothermal remnant magnetisation data were collected on a SQUID magnetometer, and analysed using a model comprising dia/paramagnetic, ferrimagnetic and superparamagnetic contributions, to extract the magnetite and ferritin concentrations present. It was found that magnetite was present in both superparamagnetic and blocked states. A larger spread and higher concentration of magnetite levels was found in the diseased mice for both the 8 week-old and 12 week-old batches, compared to the controls

Teratogenic effect of yogurt in mice fetus (Mus musculus

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Dwisari Dillasamola

2018-04-01

Full Text Available Yogurt is one of the dairy products made from lactic acid fermentation by using Lactobacillus bulgaricus and Streptococcus thermophilus. A study on teratogenic effects of yogurt on the white female mice fetus (Mus musculus has been carried out. Pregnant mice used were 20 which divided into 4 groups : the control group, D1, D2, and D3. The treatments giveThe mice were Distidelled water (control, 0.52 yogurt (D1, 1.04  yogurt (D2, and 2.08 g yogurt (D3. Data were analyzed using one-way ANOVA followed by Duncan multiple range test. Results showed that administration of yogurt during pregnancy could affect mother body weight of mice (P 0,05. Observations with Alizarin solution did not show skeletal defects in comparison to the control group. Observations with Bouin’s solution showed defective visceral cleft palate in fetal mice yogurt group D3. This study conclude that yogurt is safe to consume in groups D1 and D2. Yogurt has the potential to cause fetal teratogenic in group D3

Effect of spaceflight hardware on the skeletal properties of ground control mice

Science.gov (United States)

Bateman, Ted; Lloyd, Shane; Dunlap, Alex; Ferguson, Virginia; Simske, Steven; Stodieck, Louis; Livingston, Eric

Introduction: Spaceflight experiments using mouse or rat models require habitats that are specifically designed for the microgravity environment. During spaceflight, rodents are housed in a specially designed stainless steel meshed cage with gravity-independent food and water delivery systems and constant airflow to push floating urine and feces towards a waste filter. Differences in the housing environment alone, not even considering the spaceflight environment itself, may lead to physiological changes in the animals contained within. It is important to characterize these cage differences so that results from spaceflight experiments can be more reliably compared to studies from other laboratories. Methods: For this study, we examined the effect of NASA's Animal Enclosure Module (AEM) spaceflight hardware on the skeletal properties of 8-week-old female C57BL/6J mice. This 13-day experiment, conducted on the ground, modeled the flight experiment profile of the CBTM-01 payload on STS-108, with standard vivarium-housed mice being compared to AEM-housed mice (n = 12/group). Functional differences were compared via mechanical testing, micro-hardness indentation, microcomputed tomography, and mineral/matrix composition. Cellular changes were examined by serum chemistry, histology, quantitative histomorphometry, and RT-PCR. A Student's t-test was utilized, with the level of Type I error set at 95 Results: There was no change in elastic, maximum, or fracture force mechanical properties at the femur mid-diaphysis, however, structural stiffness was -17.5 Conclusions: Housing mice in the AEM spaceflight hardware had minimal effects on femur cortical bone properties. However, trabecular bone at the proximal tibia in AEM mice experi-enced large increases in microarchitecture and mineral composition. Increases in bone density were accompanied by reductions in bone-forming osteoblasts and bone-resorbing osteoclasts, representing a general decline in bone turnover at this site

Study on the behavior of unirradiated light water reactor fuel with iodine-127 under the reactivity initiated accident (RIA) conditions

International Nuclear Information System (INIS)

Sasajima, Hideo; Yanagisawa, Kazuaki; Kanazawa, Hiroyuki

1988-07-01

In a light water reactor fuel, a stress arised from pellet-cladding interaction (PCI) will have possibility to cause stress corrosion claddling (PCI failure) under an environment of corrosive fission product ; line iodine. A pulse irradiation experiment by NSRR was carried out to examine whether or not an unirradiated NSRR standard fuel rod in which 1.3 mg (33 x 10 -6 g/cm 2 ) of iodine was artificially filled could cause the PCI failure. Obtained results are: (1) The fuel rods with iodine did not fail both at deposited energy levels of 268 and 280 cal/g · UO 2 . On the other hand, the fuel rods without iodine failed at the same energy levels due to thinning of the cladding wall thickness. Within this experimental scope, PCI-failure did not occur on iodine filled fuel rods. (2) At a periphery of the fuel pellet of iodine filled rod, an uniform torus ring was formed. The torus ring consisted of an equi-axed large grains at 268 cal/g · UO 2 and a columnar ones at 280 cal/g · UO 2 . The torus ring was not formed in the fuel without iodine. (author)

Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice

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Holers V Michael

2007-05-01

Full Text Available Abstract Background The posttraumatic response to traumatic brain injury (TBI is characterized, in part, by activation of the innate immune response, including the complement system. We have recently shown that mice devoid of a functional alternative pathway of complement activation (factor B-/- mice are protected from complement-mediated neuroinflammation and neuropathology after TBI. In the present study, we extrapolated this knowledge from studies in genetically engineered mice to a pharmacological approach using a monoclonal anti-factor B antibody. This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice. Methods A focal trauma was applied to the left hemisphere of C57BL/6 mice (n = 89 using a standardized electric weight-drop model. Animals were randomly assigned to two treatment groups: (1 Systemic injection of 1 mg monoclonal anti-factor B antibody (mAb 1379 in 400 μl phosphate-buffered saline (PBS at 1 hour and 24 hours after trauma; (2 Systemic injection of vehicle only (400 μl PBS, as placebo control, at identical time-points after trauma. Sham-operated and untreated mice served as additional negative controls. Evaluation of neurological scores and analysis of brain tissue specimens and serum samples was performed at defined time-points for up to 1 week. Complement activation in serum was assessed by zymosan assay and by murine C5a ELISA. Brain samples were analyzed by immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL histochemistry, and real-time RT-PCR. Results The mAb 1379 leads to a significant inhibition of alternative pathway complement activity and to significantly attenuated C5a levels in serum, as compared to head-injured placebo-treated control mice. TBI induced histomorphological signs of neuroinflammation and neuronal apoptosis in the injured brain hemisphere of placebo-treated control mice for up to 7 days. In contrast, the

Influence of Intestinal Microbiota on the Catabolism of Flavonoids in Mice.

Science.gov (United States)

Lin, Weiqun; Wang, Wenting; Yang, Hai; Wang, Dongliang; Ling, Wenhua

2016-12-01

Although in vitro studies have shown that flavonoids are metabolized into phenolic acids by the gut microbiota, the biotransformation of flavonoids by intestinal microbiota is seldom studied in vivo. In this study, we investigated the impact of the gut microbiota on the biotransformation of 3 subclasses of flavonoids (flavonols, flavones, and flavanones). The ability of intestinal microbiota to convert flavonoids was confirmed with an in vitro fermentation model using mouse gut microflora. Simultaneously, purified flavonoids were administered to control and antibiotic-treated mice by gavage, and the metabolism of these flavonoids was evaluated. p-Hydroxyphenylacetic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, hydrocaffeic acid, coumaric acid, and 3-(4-hydroxyphenyl)propionic acid were detected in the serum samples from the control mice after flavonoid consumption. The serum flavonoid concentrations were similar in both groups, whereas the phenolic metabolite concentrations were lower in the antibiotic-treated mice than in the control mice. We detected markedly higher flavonoids excretion in the feces and urine of the antibiotic-treated mice compared to the controls. Moreover, phenolic metabolites were upregulated in the control mice. These results suggest that the intestinal microbiota are not necessary for the absorption of flavonoids, but are required for their transformation. © 2016 Institute of Food Technologists®.

The effect of embryonal thymic calf extracts on neonatally thymectomized mice and on mice lethally irradiated with gamma rays

International Nuclear Information System (INIS)

Czaplicki, J.; Blonska, B.; Stec, L.

1981-01-01

The effect of embryonal thymic calf extracts (ETCE) on mice thymectomized at birth was investigated. ETCE was found to induce an increase in leukopenia and decrease in the level of serum gamma globulins; it also reduced survival time in mice. The effect of ETCE on lethally irradiated mice was also examined. Only long-term administration of ETCE prior to gamma irradiation at 750 rad prolonged the survival time of mice (40% permanent survival) as compared with irradiated controls; the leukocytes from mice retained mitotic capability. Neither long-term treatment with ETCE prior to irradiation at 1000 rad, nor short-term administration prior to 750 rad affected survival time. ETCE administered after irradiation of mice with 750 rad caused a rapid decrease in blood leukocytes and a significantly lowered survival time. (Auth.)

Abrogation of genetically controlled resistance of mice to Treponema pallidum by irradiation

International Nuclear Information System (INIS)

Klein, J.R.; Monjan, A.A.; Hardy, P.H. Jr.; Cole, G.A.

1980-01-01

On intradermal infection, transient primary lesions, characteristic of those seen in naturally acquired human syphilis, can be produced regularly in some strains of mice but not others, indicating a genetic basis for host susceptibility. However strains of mice which normally fail to develop lesions, do so after exposure to ionising radiation. Here the importance of an intact immune system in the outcome of local infection is illustrated by the use of radiation-induced immunosuppression. The mice were exposed to lethal doses of total body irradiation from a 137 Ce source (137 rad per min), 850-1,050 rad depending on mouse strain. (UK)

Induction of myeloid leukaemia by whole-body single exposure of CBA male mice to X-rays

Energy Technology Data Exchange (ETDEWEB)

Major, I R [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1979-12-01

A curvilinear dose response of myeloid leukaemia induction in CBA male mouse was obtained after single whole-body X-irradiation at about 3 months of age. This strain has a very low spontaneous incidence of the disease and no cases were found in the unirradiated controls. The incidence was independent of dose rate over the range used (4.2-552 rad/min). Diagnosis required histopathological examination of various body tissues, the gross anatomical changes being easily confused with other haemopoietic disorders, but a few cases were recognized in life from blood samples. Curve-fitting to various models based on theories of radiocarcinogenic mechanism is described.

Female preproenkephalin-knockout mice display altered emotional responses

Science.gov (United States)

Ragnauth, A.; Schuller, A.; Morgan, M.; Chan, J.; Ogawa, S.; Pintar, J.; Bodnar, R. J.; Pfaff, D. W.

2001-01-01

The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear + shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark–light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001–20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety. PMID:11172058

EFFECT OF HYDROGEN SULFIDE ON ATRIUM CONTRACTILITY IN CONTROL AND DIABETHIC MICE

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A. S. Lifanova

2014-01-01

Full Text Available Hydrogen sulfide (H2S is endogenously synthesized gasotransmitter that has a regulatory effect in cardiovascular system. Diabetes mellitus leads to an increased risk of hypertension and cardiovascular diseases, so the purpose of the study was to analyze the contractility of the atria mice after application of L-cysteine and H2S. Contractile activity of the myocardium was investigated in the experiment on isolated mouse atria. Alloxan was used for modeling diabetes. Intraperitoneal injection of alloxan resulted in a significant increase of glucose concentration in blood, whereas the concentration of glucose didn’t change at the injection of physiological solution. In control, the addition of NaHS resulted in a significant dose-dependent decrease of the amplitude of contraction of the myocardium, whereas the negative inotropic effect of NaHS was significantly lower in terms of modeling diabetes compare to control conditions. In the control, L-cysteine reduced the amplitude contractions significantly, whereas L-cysteine did not lead to significant changes in the amplitude of contractions in terms of modeling diabetes. These data indicate that the sensitivity of mice’s atria reduced for H2S and L-cysteine in diabetes mellitus.

Lipidomic profiling of di- and tri-acylglycerol species in weight-controlled mice.

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Brenee S King

Full Text Available Weight control by dietary calorie restriction (DCR or exercise has been shown to prevent cancer in various models. However, the mechanisms as to how weight control is beneficial are not well understood. While previous reports have investigated the effects of weight control on total lipid levels or lipid composition within cellular membranes, there has been little work surrounding changes to individual lipids following weight control interventions. In this study, using a model of skin carcinogenesis centered on the tumor promotion stage, CD-1 mice were randomly assigned into 4 groups: ad libitum and sedentary (control, ad libitum with exercise (AL+Exe, exercise with pair feeding of a diet isocaloric with control (PF+Exe, and sedentary with 20% DCR compared to control. After ten weeks, body weight and body fat percentages significantly decreased in the PF+Exe and DCR groups but not AL+Exe when compared with sedentary controls. Murine skin and plasma samples were obtained for analysis. Lipidomics using electrospray ionization MS/MS was employed to profile triacylglycerol (TG and diacylglycerol (DG species. Both plasma and tissue TG species containing fatty acid chains with length 18:1 were significantly decreased following DCR when compared to sedentary control animals. In regards to DG, the most significant changes occurred in the plasma. DG species containing fatty acids with lengths 16:1 or 18:1 were significantly decreased in PF+Exe and DCR groups when compared to sedentary controls. Due to the significant role of TG in energy storage and DG in cellular signaling, our findings of the effects of weight control on individual TG and DG species in plasma and skin tissue following exposure to a tumor promoter, may provide insight into the mechanism of weight control on cancer prevention.

The chondrogenic response to exercise in the proximal femur of normal and mdx mice

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Nye David J

2010-09-01

Full Text Available Abstract Background Submaximal exercise is used in the management of muscular dystrophy. The effects of mechanical stimulation on skeletal development are well understood, although its effects on cartilage growth have yet to be investigated in the dystrophic condition. The objective of this study was to investigate the chondrogenic response to voluntary exercise in dystrophin-deficient mice. Methods Control and dystrophin-deficient (mdx mice were divided into sedentary and exercise-treated groups and tested for chondral histomorphometric differences at the proximal femur. Results Control mice ran 7 km/week further than mdx mice on average, but this difference was not statistically significant (P > 0.05. However, exercised control mice exhibited significantly enlarged femur head diameter, articular cartilage thickness, articular cartilage tissue area, and area of calcified cartilage relative to sedentary controls and exercised mdx mice (P Conclusions Mdx mice exhibit a reduced chondrogenic response to increased mechanical stimulation relative to controls. However, no significant reduction in articular dimensions was found, indicating loss of chondral tissue may not be a clinical concern with dystrophinopathy.

Teratogenic effect of yogurt in mice fetus (Mus musculus)

OpenAIRE

Dwisari Dillasamola; Almahdy A; Amirah Desri; Skunda Diliarosta

2018-01-01

Yogurt is one of the dairy products made from lactic acid fermentation by using Lactobacillus bulgaricus and Streptococcus thermophilus. A study on teratogenic effects of yogurt on the white female mice fetus (Mus musculus) has been carried out. Pregnant mice used were 20 which divided into 4 groups : the control group, D1, D2, and D3. The treatments giveThe mice were Distidelled water (control), 0.52 yogurt (D1), 1.04  yogurt (D2), and 2.08 g yogurt (D3). Data were analyzed using one-way ANO...

Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

International Nuclear Information System (INIS)

Woloschak, G.E.; Weaver, P.

1994-01-01

The recent cloning and characterization of recombinase genes (RAG- 1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice (wst). Our results revealed expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/sm-bullet mice). In thymus tissue, a small RAG-1 transcript was detected in wst/wst mice that was not evident in thymus from control mice. In wst/lg-bullet mice, a two-fold increase in RAG-1 mRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/sm-bullet and not from wst;/wst or parental control BCF 1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

Institute of Scientific and Technical Information of China (English)

TIAN Bei; LI Xiao-xin; SHEN Li; ZHAO Min; YU Wen-zhen

2010-01-01

Background Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.Methods Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.Results Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000).Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.Conclusion Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

Rearrangement of RAG-1 recombinase gene in DNA-repair deficient ``wasted`` mice

Energy Technology Data Exchange (ETDEWEB)

Woloschak, G.E.; Libertin, C.R.; Weaver, P. [Loyola Univ., Chicago, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

1993-11-01

Mice recessive for the autosomal gene ``wasted`` wst display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-l/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot}mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot}mice, a two-fold increase in RAG-1 mRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

Lymphoma of SJL/J mice strain, 3

International Nuclear Information System (INIS)

Takahashi, Masanori; Takeichi, Sanae; Otsuka, Hisashi

1976-01-01

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

Lymphocytes from wasted mice express enhanced spontaneous and {gamma}-ray-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ. Medical Center, Maywood, IL (United States); Chang-Liu, Chin-Mei [Argonne National Lab., IL (United States); Chung, Jen; Libertin, C.R. [Loyola Univ. Medical Center, Maywood, IL (United States)

1993-09-01

Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including faulty repair of DNA damage in lymphocytes after radiation exposure, neurologic abnormalities, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes; past work has shown an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in wst/wst mice relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from wasted and control mice for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (associated with apoptosis) in thymic lymphocytes and reduced expression in splenic lymphocytes of wst/wst mice relative to controls; expression of Rp-2 and Td-30 mRNA (induced during apoptosis) were not detectable in spleen or thymus. Higher spontaneous DNA fragmentation was observed in wasted mice than in controls; however, {gamma}-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in wasted mice relative to controls. These results provide evidence for high spontaneous and {gamma}-ray-induced apoptosis in T cells of wasted mice as a mechanism underlying the observed lymphocyte and DNA repair abnormalities.

X-Chromosome Control of Genome-Scale Recombination Rates in House Mice.

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Dumont, Beth L

2017-04-01

Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus , were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females. Copyright © 2017 by the Genetics Society of America.

Treadmill Exercise Attenuates Retinal Oxidative Stress in Naturally-Aged Mice: An Immunohistochemical Study

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Chan-Sik Kim

2015-09-01

Full Text Available In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological exercise has been shown to reduce oxidative stress in rats and mice, it is not known whether it has a similar effect in retinal tissues. The aim of this study was to evaluate retinal oxidative stress in naturally-aged mice. In addition, we evaluated the effects of aerobic training on retinal oxidative stress by immunohistochemically evaluating oxidative stress markers. A group of twelve-week-old male mice were not exercised (young control. Two groups of twenty-two-month-old male mice were created: an old control group and a treadmill exercise group. The old control group mice were not exercised. The treadmill exercise group mice ran on a treadmill (5 to 12 m/min, 30 to 60 min/day, 3 days/week for 12 weeks. The retinal thickness and number of cells in the ganglion cell layer of the naturally-aged mice were reduced compared to those in the young control mice. However, treadmill exercise reversed these morphological changes in the retinas. We evaluated retinal expression of carboxymethyllysine (CML, 8-hydroxy-2′-deoxyguanosine (8-OHdG and nitrotyrosine. The retinas from the aged mice showed increased CML, 8-OHdG, and nitrotyrosine immunostaining intensities compared to young control mice. The exercise group exhibited significantly lower CML levels and nitro-oxidative stress than the old control group. These results suggest that regular exercise can reduce retinal oxidative stress and that physiological exercise may be distinctly advantageous in reducing retinal oxidative stress.

Decreased thyroidal response to thyrotropin in diabetic mice

International Nuclear Information System (INIS)

Bagchi, N.; Brown, T.R.; Shivers, B.; Lucas, S.; Mack, R.E.

1981-01-01

The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased the proportion of 131I-. These effects of TSH were not observed in diabetic animals but were demonstrable in diabetic animals treated with insulin. For studies of hormone secretion, labeled thyroid glands were cultured in vitro in medium containing 1 mM mononitrotyrosine. The rate of the hydrolysis of labeled thyroglobulin was measured as the proportion of 131I-labeled iodotyrosines and 131I-labeled iodothyronines recovered at the end of culture and was used as an index of thyroid secretion. TSH in vivo stimulated the rate of thyroglobulin hydrolysis for 6 h, with a peak occurring after 2 h. The diabetic mice had a diminished response to TSH, which improved on treatment with insulin. The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone. The generation of thyroidal cAMP in response to TSH was higher in diabetic mice than in controls. The rise in plasma T4 and T3 2 h after the administration of TSH was less in diabetic mice than in control mice or diabetic mice treated with insulin. Our studies, therefore, indicate that the thyroidal response to TSH is decreased in diabetes mellitus. The defect appears to be at a step beyond the generation of cAMP

Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma

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Wang, Yiwei; Huang, Dan; Chen, Kai-Yuan; Cui, Min; Wang, Weihuan; Huang, Xiaoran; Awadellah, Amad; Li, Qing; Friedman, Ann; Xin, William W.; Di Martino, Luca; Cominelli, Fabio; Miron, Alex; Chan, Ricky; Fox, James; Xu, Yan; Shen, Xiling; Kalady, Mathew F.; Markowitz, Sanford; Maillard, Ivan; Lowe, John B.; Xin, Wei; Zhou, Lan

2016-01-01

Background & Aims De novo synthesis of GDP-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or TSTA3). GMDS deletions and mutations are found in 6%–13% of colorectal cancers; these mostly affect ascending and transverse colon. We investigated whether lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. Methods FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx–/– mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by ELISAs to measure cytokine levels; T cells were also collected and analyzed. Fecal samples were analyzed by 16s rRNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx–/– or control mice (Ly5.2) into irradiated 8-week old Fx–/– or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). Results Fx–/– mice developed colitis and serrated-like lesions. The intestinal pathology of Fx–/– mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx–/– mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency altered the composition of the fecal microbiota, reduced

Immunity to Babesia in mice I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice

NARCIS (Netherlands)

Kuil, H.; Zivkovic, D.; Seinen, W.; Albers-van Bemmel, C.M.G.; Speksnijder, J.E.

1984-01-01

Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide- controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with

[Experimental study of metabonomics in the diagnosis of allergic rhinitis in mice].

Science.gov (United States)

Wang, A; Li, Q F; Zhang, G Q; Zhao, C Q

2016-02-01

To investigate the application of metabonomics in the diagnosis of allergic rhinitis. Eighty male Kunming mice were randomly divided into two groups, control group (30 mice) and allergic rhinitis (AR) group (50 mice). After modeling, removal behavior score more than 6 and retain 30 mice behavior score equal to 6.Collect the mice peripheral blood and preparate blood serum, using UPLC-MS chromatographic separation and detection. The data were pretreated by SPSS and Excel, after chromatographic peak matching by MZmine. Firstly , delete interference data in accordance with the 80% rule .Then, the investigate data were analyzed by PLS-DA and PCA-X. Three-dimensional view of the control group (30 mice) and AR group (30 mice) blood serum data was drawn using PCA-X and PLS-DA method. The two groups of samples could be completely separated through views, which showed that there was a significant difference between the two groups of data. There were some differences in the blood metabolites between the control group and AR group . The study showed that it was scientific and feasible to diagnose AR using the metabonomics.

Effects of social isolation, re-socialization and age on cognitive and aggressive behaviors of Kunming mice and BALB/c mice.

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An, Dong; Chen, Wei; Yu, De-Qin; Wang, Shi-Wei; Yu, Wei-Zhi; Xu, Hong; Wang, Dong-Mei; Zhao, Dan; Sun, Yi-Ping; Wu, Jun-Cheng; Tang, Yi-Yuan; Yin, Sheng-Ming

2017-05-01

Both Kunming (KM) mice and BALB/c mice have been widely used as rodent models to investigate stress-associated mental diseases. However, little is known about the different behaviors of KM mice and BALB/c mice after social isolation, particularly cognitive and aggressive behaviors. In this study, the behaviors of KM and BALB/c mice isolated for 2, 4 and 8 weeks and age-matched controls were evaluated using object recognition, object location and resident-intruder tests. The recovery of behavioral deficits by re-socialization was also examined for the isolated mice in adolescence. Our study showed that isolation for 2, 4 and 8 weeks led to cognitive deficits and increased aggressiveness for both KM and BALB/c mice. An important finding is that re-socialization could completely recover spatial/non-spatial cognitive deficits resulted from social isolation for both KM and BALB/c mice. In addition, age only impacted aggressiveness of KM mice. Moreover, isolation duration showed different impacts on cognitive and aggressive behaviors for both KM and BALB/c mice. Furthermore, BALB/c mice showed weak spatial/non-spatial memory and low aggressiveness when they were at the same age and isolation duration, compared to KM mice. In conclusion, KM mice and BALB/c mice behaved characteristically under physiology and isolation conditions. © 2016 Japanese Society of Animal Science.

Impact of chocolate liquor on vascular lesions in apoE-knockout mice.

Science.gov (United States)

Yazdekhasti, Narges; Brandsch, Corinna; Hirche, Frank; Kühn, Julia; Schloesser, Anke; Esatbeyoglu, Tuba; Huebbe, Patricia; Wolffram, Siegfried; Rimbach, Gerald; Stangl, Gabriele I

2017-10-15

Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein, and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared with the control group, mice fed the chocolate liquor had larger plaque areas in the descending aorta and aortic root, which were attributed to a higher mass of vascular smooth muscle cells (VSMCs) and collagen. Vascular lipid deposits and calcification areas did not differ between the two groups. The aortic tissue level of interleukin-6 (IL-6) mRNA was 5-fold higher in the mice fed chocolate liquor than in the control mice. Chocolate-fed mice exhibited an increased hepatic saturated to polyunsaturated fatty acid ratio than the controls. Although the chocolate liquor contained 14 µg/kg of vitamin D 2 , the chocolate liquor-fed mice did not have measurable 25-hydroxyvitamin D 2 in the serum. These mice even showed a 25% reduction in the level of 25-hydroxyvitamin D 3 compared with the control mice. Overall, present data may contribute to our understanding how chocolate constituents can impact vascular lesion development. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Generation of transgenic mice producing fungal xylanase in the ...

African Journals Online (AJOL)

DR TONUKARI NYEROVWO

express exogenous digestive enzymes, since a single- stomached animal, such as a pig, can secret .... transgenic founder mice; 1 to15 are fifteen wild-type founder mice; M, marke; β-actin, endogenous control. (C) Identification of transgenic mice by ... 61.48±0.34%), gross energy digestibility (WT vs. TG = 68.79±0.51% vs.

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

Science.gov (United States)

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

2014-12-01

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

Detection of retinoblastoma gene deletions in spontaneous and radiation-induced mouse lung adenocarcinomas by polymerase chain reaction

International Nuclear Information System (INIS)

Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

1994-01-01

A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma gene using histological sections from radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60 Co γ rays or 0.6 Gy JANUS neutrons, which have been found to have approximately equal radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6 neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from γ-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected were in the 5' region of the mouse Rb gene. 36 refs., 2 figs., 2 tabs

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

International Nuclear Information System (INIS)

Huang, Peigen; Allam, Ayman; Perez, Luis A.; Taghian, Alphonse; Freeman, Jill; Suit, Herman D.

1995-01-01

Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm 3 , mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD 50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD 50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

Application of gamma irradiation for storage potato

International Nuclear Information System (INIS)

Rezaee, M.; Almasi, M.

2009-01-01

Since deficiency of controlled store in Iran and environmental problems of chemical material the use of gamma irradiation to control sprouting and increase the length of storage time of potatoes has been proposed as an alternative to cold storage or the use of chemical sprout suppressants. In this study potatoes of Agria Variety were irradiated at a dose of 0.10 KGY and stored along with the unirradiated controls at 12±3°C for a period of more than 6 month from October to April .After 4 month of storage the sprouting ranged from 5 to 12% in irradiated potatoes and 45 to 74% in unirradiated samples and after 6 month the unirradiated potatoes were discarded because of heavy sprouting and rotting. The rot attack was approximately double in unirradiated samples. It was found that losses through dehydration were 10.3 to 15.1 % in the irradiated potatoes. Also a comparative study of reducing and non-reducing sugars, vitamin-C content, total sugar, starch and protein was carried out between unirradiated and irradiated samples. The results suggested the efficacy of Gamma irradiation for ensuring availability of the storing quality of potato during lean periods from October to April. (author)

Germinated Brown Rice Attenuates Atherosclerosis and Vascular Inflammation in Low-Density Lipoprotein Receptor-Knockout Mice.

Science.gov (United States)

Zhao, Ruozhi; Ghazzawi, Nora; Wu, Jiansu; Le, Khuong; Li, Chunyang; Moghadasian, Mohammed H; Siow, Yaw L; Apea-Bah, Franklin B; Beta, Trust; Yin, Zhengfeng; Shen, Garry X

2018-05-02

The present study investigates the impact of germinated brown rice (GBR) on atherosclerosis and the underlying mechanism in low-density lipoprotein receptor-knockout (LDLr-KO) mice. The intensity of atherosclerosis in aortas of LDLr-KO mice receiving diet supplemented with 60% GBR (weight/weight) was significantly less than that in mice fed with 60% white rice (WR) or control diet ( p mice fed with WR diet was significantly more than that from mice receiving the control diet ( p mice in comparison to the WR diet ( p mice compared to WR. The anti-atherosclerotic effect of GBR in LDLr-KO mice at least in part results from its anti-inflammatory activity.

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

Energy Technology Data Exchange (ETDEWEB)

Huang, Peigen; Allam, Ayman; Perez, Luis A; Taghian, Alphonse; Freeman, Jill; Suit, Herman D

1995-04-30

Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-{alpha}) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-{alpha} with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm{sup 3}, mice were randomly assigned to treatment: rHuTNF-{alpha} alone compared with normal saline control; or local radiation plus rHuTNF-{alpha} vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-{alpha} on this tumor. The TCD{sub 50} (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-{alpha} with local radiation. Results: Tumor growth in mice treated with a dose of 150 {mu}g/kg body weight rHuTNF-{alpha}, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-{alpha} also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-{alpha} starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD{sub 50} from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-{alpha} exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD{sub 50} value in the treatment vs. the

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

Immunity to Trichinella spiralis in irradiated mice

International Nuclear Information System (INIS)

Wakelin, D.; Wilson, M.M.

1980-01-01

Irradiation prevented the accelerated expulsion of Trichinella spiralis from mice immunized by transfer of immune mesenteric lymph node cells (IMLNC) or by prior infection. Nevertheless, worms in irradiated immune mice were smaller and less fecund than those in controls. In adoptively immunized and irradiated mice expulsion could not be achieved by increasing the numbers of IMLNC transferred, although the effect upon worm length was more severe. Thus IMLNC express a direct, anti-worm immunity which is independent of their role in worm expulsion. IMLNC cause expulsion in irradiated mice only when adequate levels of bone marrow-derived cells are available. The results are discussed in terms of a possible antibody-mediated basis for direct anti-worm immunity. (author)

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

Directory of Open Access Journals (Sweden)

Hong Wang

2016-10-01

Full Text Available Objective: Compared to men, postmenopausal women suffer from a disproportionate burden of many co-morbidities associated with obesity, e.g. cardiovascular disease, cancer, and dementia. The underlying mechanism for this sex difference is not well understood but is believed to relate to absence of the protective effect of estrogen through the action of estrogen receptor alpha (ERα in the central nervous system. With the recently developed neuron-specific lipoprotein lipase deficient mice (NEXLPL−/− (Wang et al., Cell Metabolism, 2011 [15], we set to explore the possible role of lipid sensing in sex differences in obesity development. Methods: Both male and female NEXLPL−/− mice and littermate WT controls were subjected to pair feeding (pf where daily food amount given was adjusted according to body weight to match the food intake of ad libitum (ad fed control WT mice. Food intake and body weight were measured daily, and pair feeding was maintained to 42 wk in male mice and to 38 wk in female mice. Various brain regions of the mice were harvested, and ERα gene expression was examined in both male and female NEXLPL−/− and WT control mice under both ad- and pf-fed conditions. Results: Although both male and female NEXLPL−/− mice developed obesity similarly on standard chow, male NEXLPL−/− mice still developed obesity under with pair feeding, but on a much delayed time course, while female NEXLPL−/− mice were protected from extra body weight and fat mass gain compared to pair-fed WT control mice. Pair feeding alone induced extra fat mass gain in both male and female WT mice, and this was mostly driven by the reduction in physical activity. LPL deficiency resulted in an increase in ERα mRNA in the hypothalamus of ad-fed female mice, while pair feeding alone also resulted in an increase of ERα in both female WT control and NEXLPL−/− mice. The effect on increasing ERα by pair feeding and LPL deficiency was additive in

The carcinogenic effects of fetal and postnatal radiation in female mice

International Nuclear Information System (INIS)

Kusama, Tomoko; Yoshizawa, Yasuo

1982-01-01

The present study was designed to investigate the carcinogenic effects of fetal and postnatal irradiation in female mice. The C57BL/6J mice were subjected to whole-body exposure to 1-Gy or 4-Gy 137 Cs γ-ray irradiation on the 15th fetal day or the 30th postnatal day. Following this, all mice were observed throughout their respective life spans under conventional rearing conditions. The tumor incidence rate, average latent period and distributions of various tumors were used as the quantitative parameters of radiation-induced carcinogenesis. The following conclusions can be draw: (1) The mean life span of mice that underwent 4-Gy irradiation at the age of 30 days was shorter than that of non-irradiated control mice. (2) In control mice, the tumor incidence was 75.7%. (3) In order to estimate the mean age and tumor incidence, an adjustment for competing death is necessary. (4) The adjusted tumor incidences of thymic lymphoma and breast tumor of the irradiated groups were not different from those of control group. On the other hand, there was a significant difference between the two in the adjusted incidence of reticular tissue neoplasm. (author)

Slack channels expressed in sensory neurons control neuropathic pain in mice.

Science.gov (United States)

Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

2015-01-21

Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

Quality control in the process and in the irradiated food

International Nuclear Information System (INIS)

Farrar IV, H.

1997-01-01

In the irradiation process, absorbed dose is the key parameter that must be controlled. In general, the minimum absorbed dose needed to accomplish a desired effect, such as insect disinfestation or pathogen reduction, is already known from previous research, and is often prescribed by government regulations. The irradiation process is effective, however, only if the food can tolerate this dose without experiencing unwanted changes in flavor or appearance. The dose that food can tolerate often depends on such things as the variety of the fruit or vegetable, where it was grown, the season in which it was harvested and the length of time between harvesting and irradiation. Once the minimum and maximum doses are established, the irradiator operator must make sure that these dose limits are not exceeded. First, a dose mapping using many dosimeters must be undertaken to determine the locations of the minimum and maximum dose in the overall process load. From then on, the process load must always be the same, and, as a key step in the overall process control, dosimeters need to be placed from time to time only at the minimum or maximum locations. The dosimeters must be calibrated and directly trackable to national or international standards, and a fool-proof method of labelling and segregating irradiated from unirradiated product must be used. Radiation sensitive indicators that may help identify irradiated from unirradiated food should not be relied upon, and are not a substitute fro proper dosimetry. (Author)

Quality control in the process and in the irradiated food

Energy Technology Data Exchange (ETDEWEB)

Farrar, IV, H [Chairman, ASTM Subcommittee E10.01 ` Dosimetry for Radiation Processing` , 18 Flintlock Lane, Bell Canyon, California 91307-1127 (United States)

1998-12-31

In the irradiation process, absorbed dose is the key parameter that must be controlled. In general, the minimum absorbed dose needed to accomplish a desired effect, such as insect disinfestation or pathogen reduction, is already known from previous research, and is often prescribed by government regulations. The irradiation process is effective, however, only if the food can tolerate this dose without experiencing unwanted changes in flavor or appearance. The dose that food can tolerate often depends on such things as the variety of the fruit or vegetable, where it was grown, the season in which it was harvested and the length of time between harvesting and irradiation. Once the minimum and maximum doses are established, the irradiator operator must make sure that these dose limits are not exceeded. First, a dose mapping using many dosimeters must be undertaken to determine the locations of the minimum and maximum dose in the overall process load. From then on, the process load must always be the same, and, as a key step in the overall process control, dosimeters need to be placed from time to time only at the minimum or maximum locations. The dosimeters must be calibrated and directly trackable to national or international standards, and a fool-proof method of labelling and segregating irradiated from unirradiated product must be used. Radiation sensitive indicators that may help identify irradiated from unirradiated food should not be relied upon, and are not a substitute fro proper dosimetry. (Author)

Quality control in the process and in the irradiated food

Energy Technology Data Exchange (ETDEWEB)

Farrar IV, H. [Chairman, ASTM Subcommittee E10.01 `Dosimetry for Radiation Processing`, 18 Flintlock Lane, Bell Canyon, California 91307-1127 (United States)

1997-12-31

In the irradiation process, absorbed dose is the key parameter that must be controlled. In general, the minimum absorbed dose needed to accomplish a desired effect, such as insect disinfestation or pathogen reduction, is already known from previous research, and is often prescribed by government regulations. The irradiation process is effective, however, only if the food can tolerate this dose without experiencing unwanted changes in flavor or appearance. The dose that food can tolerate often depends on such things as the variety of the fruit or vegetable, where it was grown, the season in which it was harvested and the length of time between harvesting and irradiation. Once the minimum and maximum doses are established, the irradiator operator must make sure that these dose limits are not exceeded. First, a dose mapping using many dosimeters must be undertaken to determine the locations of the minimum and maximum dose in the overall process load. From then on, the process load must always be the same, and, as a key step in the overall process control, dosimeters need to be placed from time to time only at the minimum or maximum locations. The dosimeters must be calibrated and directly trackable to national or international standards, and a fool-proof method of labelling and segregating irradiated from unirradiated product must be used. Radiation sensitive indicators that may help identify irradiated from unirradiated food should not be relied upon, and are not a substitute fro proper dosimetry. (Author)

Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

International Nuclear Information System (INIS)

Sanchez, A.; Lundgren, D.L.; McClellan, R.O.

1976-01-01

The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90 Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD 50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90 Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

Lovastatin protects against experimental plague in mice.

Directory of Open Access Journals (Sweden)

Saravanan Ayyadurai

Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma.

Science.gov (United States)

Wang, Yiwei; Huang, Dan; Chen, Kai-Yuan; Cui, Min; Wang, Weihuan; Huang, Xiaoran; Awadellah, Amad; Li, Qing; Friedman, Ann; Xin, William W; Di Martino, Luca; Cominelli, Fabio; Miron, Alex; Chan, Ricky; Fox, James G; Xu, Yan; Shen, Xiling; Kalady, Mathew F; Markowitz, Sanford; Maillard, Ivan; Lowe, John B; Xin, Wei; Zhou, Lan

2017-01-01

De novo synthesis of guanosine diphosphate (GDP)-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or tissue specific transplantation antigen P35B [TSTA3]). GMDS deletions and mutations are found in 6%-13% of colorectal cancers; these mostly affect the ascending and transverse colon. We investigated whether a lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx-/- mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by enzyme-linked immunosorbent assays to measure cytokine levels; T cells also were collected and analyzed. Fecal samples were analyzed by 16s ribosomal RNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx-/- or control mice (Ly5.2) into irradiated 8-week-old Fx-/- or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). Fx-/- mice developed colitis and serrated-like lesions. The intestinal pathology of Fx-/- mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx-/- mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency

Effect of X-rays and u.v.-light on the levels of NAD(P), NAD(P)H and hydroxyproline in Pinus silvestris pollen

International Nuclear Information System (INIS)

Zelles, L.

1978-01-01

Pollen grains of Pinus Silvestris were irradiated with stimulating and inhibiting doses of X-rays and u.v.-light and the levels of NAD(P), NAD(P)H and hydroxyproline determined during tube growth. Pollen grains irradiated with stimulating doses of X-rays and u.v.-light developed longer tubes, while grains irradiated with inhibiting doses of X-rays and u.v.-light developed shorter tubes than the unirradiated controls. After 32 hr of incubation, the levels of NAD(P), NAD(P)H and hydroxyproline were at their lowest compared with unirradiated pollen. In samples with stimulating doses of irradiation NAD(P) reached its maximum earlier than in samples with inhibiting irradiation. The ratio between the concentrations of NAD(P) and NAD(P)H in the irradiated samples was higher than in the unirradiated control. The hydroxyproline content was higher in irradiated than in unirradiated pollen. (author)

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

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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.

A study on density, porosity and grain size of unirradiated ROX fuels and simulated ROX fuels

International Nuclear Information System (INIS)

Yanagisawa, Kazuaki; Shirasu, Noriko; Ohmichi, Toshihiko

1999-05-01

The unirradiated ROX fuels made of (1) 23wt%PuO 2 -17wt%SZR-56wt%Al 2 O 3 -4wt%MgO (ROX-SZR) and (2) 20wt%PuO 2 -29wt%ThO 2 -48wt%Al 2 O 3 -3wt%MgO (ROX-ThO 2 ) were fabricated by JAERI. Additionally, 9 simulated ROX fuels (used UO 2 instead of PuO 2 ) were fabricated by NFI. Densities, porosity and grain sizes of those were studied. Obtained results are: (1) ROX fuels: The estimated theoretical density (TD) was 5.6g/cc for the ROX-SZR and 6.2g/cc for the ROX-ThO 2 . Those were about half of that in UO 2 (10.96g/cc). As-fabricated density determined was 4.6g/cc (82%TD) for the former and 5.2g/cc (83%TD) for the latter. The %TD of those was low than that of UO 2 (95%TD). One of main reason is that the ROX fuels were sintered at temperature of 1,400degC while UO 2 was sintered at temperature of 1,700degC. The average pore diameter was about 3 μm and the porosity was 17-18%, implying that the ROX fuels were resulted in containing a lot of small pores 2 . As-fabricated density determined in the present study was about 4.5-5.5g/cc. The %TD of the simulated ROX fuels ranged about 94-98%TD. They were in the same as that of UO 2 because as high sintering temperature of 1,750degC as UO 2 . The average pore diameter was about 4-8 μm and the porosity was <6%. Grain size was revealed to be about 1-4 μm. (author)

DETECTION OF ANTIBODIES TO CANDIDA ALBICANS GERM TUBE BY IMMUNOFLUORESCENCE IN IMMUNOSUPPRESSED MICE WITH EXPERIMENTAL SYSTEMIC CANDIDIASIS

Directory of Open Access Journals (Sweden)

F. Zaini

2007-07-01

Full Text Available "nThe increasing incidence of systemic candidiasis, which parallels the use of invasive and immunosuppressive medical procedures, necessitates development of rapid and cost effective tests for diagnosis of systemic candidiasis. Therefore in this study 85 mice were first immunosuppressed by cyclophosphamide and then infected by Candida albicans NCPF 3153. Other 85 mice were employed as control. The case and control mice were bled and then autopsied. Hearts and kidneys were checked by direct, histopathological and cultural examination for systemic candidiasis. The 85 sera from histological proven cases and 85 control mice were adsorbed with heat killed blastospores of same strain of C. albicans. Anti-Candida albicans germ tube antibodies were detected by indirect immunofluorescence assay for diagnosis of invasive candidiasis in case and control mice. In addition, sera from 35 mice with proven cryptococcosis were also tested. While 84 mice with proven systemic candidiasis (100% had anti-germ tube antibodies, these antibodies were absent in all controls and mice with cryptococcosis. The specificity was 100%, indicating a high degree of discrimination was possible between systemic candidiasis and cryptococcosis in the mice studied. It must be concluded that anti-germ tube responses did not appear to be significantly reduced in immunocompromised mice.

The effects of pain sensitivity behaviour on Swiss White Mice ...

African Journals Online (AJOL)

This study evaluates the effects of Chloroquine phosphate on pain sensation in mice considering the fact that Chloroquine as s chemotherapic agent is known for its neurotoxicity effect. The mice were divided into three groups of 10 mice each. While group 1 as the control, 2 and 3 as the test groups and group 1 received ...

Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease

DEFF Research Database (Denmark)

Bregenholt, S; Claesson, Mogens Helweg

1998-01-01

Severe combined immunodeficient (scid) mice engrafted with small pieces of full thickness gut wall from immunocompetent syngenic donors develop a chronic and lethal colitis. Lymphocytes from the lamina propria of engrafted mice were analyzed for phorbol ester/ionomycin-induced cytokine production...... by intracellular staining. A 4-5-fold increase in the fraction of IFN-gamma-producing CD4+ lamina propria T cells was found in moderately and severely diseased mice when compared to healthy congenic C.B-17 control mice. The number of IL-2-producing T cells was increased by approximately 2-fold when comparing mice...... suffering from severe disease to healthy control mice. The fraction of TNF-alpha positive CD4+ T cells was increased by a factor of two in both moderately and severely diseased mice. When analyzing Th2 cytokines, it was found that the levels of IL-4-producing CD4+ T cells was not altered in diseased animals...

Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation.

Science.gov (United States)

Khan, Shaukat; Toyoda, Hidemi; Linehan, Melissa; Iwasaki, Akiko; Nomoto, Akio; Bernhardt, Günter; Cello, Jeronimo; Wimmer, Eckard

2014-08-01

An important step in poliovirus (PV) infection by the oral route in humans is replication of the virus in lymphatic tissues of the gastrointestinal (GI) tract, thought to be mainly in the Peyer's patches of the small intestine. No immunocompetent transgenic (tg) mice that express human PV receptor (CD155) under the control of different promoters can be infected orally. The mouse orthologue of human CD155 is Tage4, a protein expressed at the surface of enterocytes and in the Peyer's patches. We describe here the generation of a tg mouse model in which the Tage4 promoter was used to drive expression of the human PV receptor-coding region (Tage4-CD155tg mice). In this model, CD155 expression was observed by immunostaining in different regions in the Peyer's patches but not in their germinal centres. Although a similar pattern of staining was observed between 3- and 6-week-old Tage4-CD155tg mice, poliomyelitis was only seen in the younger mice after PV infection by the oral route. When compared with TgPVR21 mice that expressed CD155 driven by its human promoter, 3-week-old Tage4-CD155tg mice were more susceptible to gut infection and paralysis following feeding with PV. Also, Tage4-CD155tg mice exhibited higher susceptibility to poliomyelitis after parenteral inoculation of PV. Remarkably, the LD50 after intracerebral inoculation of PV was similar in both CD155 tg mouse strains. The CD155 tg mouse model reported here, although moderately susceptible to oral infection, may be suitable to study mechanisms of PV replication in the gastrointestinal tract and to dissect important aspects of PV neuroinvasiveness. © 2014 The Authors.

Seed quality preservation advantage of gamma irradiation seed pre-treatment during long term storage in soybean

International Nuclear Information System (INIS)

Guha, Sameer Kumar; Sumedha; Singh, Bhupinder

2014-01-01

The experiment was conducted to analyse the effect of gamma irradiation seed pre-treatment on insect damage and quality preservation of soybean seeds during long term storage at ambient temperature (27-42 ℃) and relative humidity (50-95%). Freshly harvested seeds of soybean (cv. Pusa-9814) were treated with control (0), 0.01, 0.05, 0.5, 1.0, 3.0, 5.0 kGy gamma radiation on a Gamma irradiator (Gamma Chamber 5000, 60 Co source, activity 12000 Ci, BRIT, Mumbai, India) at the Nuclear Research Laboratory, IARI, New Delhi and were stored over one year in cotton cloth bags under ambient conditions. Protein and oil per cent and fatty acid profile was measured in freshly harvested zero time unirradiated control, aged unirradiated control and other treatments of ionizing radiation. Seed oil was extracted through the soxhlet extraction method and oil profiling was done by gas chromatography. Change in saturated and unsaturated fatty acids like palmitic, stearic, oleic, linolic, linolenic acid and oleic to linoleic ratio was measured. Oil content of unirradiated stored seeds compared to that of the freshly harvested control was lower. However, radiation in general, helped in maintaining a higher seed oil during storage when compared with that of the aged unirradiated control and was insignificantly reduced over the fresh unirrradiated control. Further, gamma irradiation treatment did not yield any adverse affect on the seed protein even after prolonged storage. The results reveal a reduced rate of lipid degradation and improved seed hardness over untreated control with no significant change in fatty acid profile of the irradiated and the unirradiated seeds over a long term storage period. (author)

Precession electron diffraction for SiC grain boundary characterization in unirradiated TRISO fuel

International Nuclear Information System (INIS)

Lillo, T.M.; Rooyen, I.J. van; Wu, Y.Q.

2016-01-01

Highlights: • SiC grain orientation determined by TEM-based precession electron diffraction. • Orientation data improved with increasing TEM sample thickness. • Fraction of low angle grain boundaries lower from PED data than EBSD data. • Fractions of high angle and CSL-related boundaries similar to EBSD data. - Abstract: Precession electron diffraction (PED), a transmission electron microscopy-based technique, has been evaluated for the suitability for evaluating grain boundary character in the SiC layer of tristructural isotropic (TRISO) fuel. This work reports the effect of transmission electron microscope (TEM) lamella thickness on the quality of data and establishes a baseline comparison to SiC grain boundary characteristics, in an unirradiated TRISO particle, determined previously using a conventional electron backscatter diffraction (EBSD) scanning electron microscope (SEM)-based technique. In general, it was determined that the lamella thickness produced using the standard focused ion beam (FIB) fabrication process (∼80 nm), is sufficient to provide reliable PED measurements, although thicker lamellae (∼120 nm) were found to produce higher quality orientation data. Also, analysis of SiC grain boundary character from the TEM-based PED data showed a much lower fraction of low-angle grain boundaries compared to SEM-based EBSD data from the SiC layer of a TRISO-coated particle made using the same fabrication parameters and a SiC layer deposited at a slightly lower temperature from a surrogate TRISO particle. However, the fractions of high-angle and coincident site lattice (CSL)-related grain boundaries determined by PED are similar to those found using SEM-based EBSD. Since the grain size of the SiC layer of TRSIO fuel can be as small as 250 nm (Kirchhofer et al., 2013), depending on the fabrication parameters, and since grain boundary fission product precipitates in irradiated TRISO fuel can be nano-sized, the TEM-based PED orientation data

Metaproteomics of Colonic Microbiota Unveils Discrete Protein Functions among Colitic Mice and Control Groups.

Science.gov (United States)

Moon, Clara; Stupp, Gregory S; Su, Andrew I; Wolan, Dennis W

2018-02-01

Metaproteomics can greatly assist established high-throughput sequencing methodologies to provide systems biological insights into the alterations of microbial protein functionalities correlated with disease-associated dysbiosis of the intestinal microbiota. Here, the authors utilize the well-characterized murine T cell transfer model of colitis to find specific changes within the intestinal luminal proteome associated with inflammation. MS proteomic analysis of colonic samples permitted the identification of ≈10 000-12 000 unique peptides that corresponded to 5610 protein clusters identified across three groups, including the colitic Rag1 -/- T cell recipients, isogenic Rag1 -/- controls, and wild-type mice. The authors demonstrate that the colitic mice exhibited a significant increase in Proteobacteria and Verrucomicrobia and show that such alterations in the microbial communities contributed to the enrichment of specific proteins with transcription and translation gene ontology terms. In combination with 16S sequencing, the authors' metaproteomics-based microbiome studies provide a foundation for assessing alterations in intestinal luminal protein functionalities in a robust and well-characterized mouse model of colitis, and set the stage for future studies to further explore the functional mechanisms of altered protein functionalities associated with dysbiosis and inflammation. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Memory of MICE: The Configuration Database

International Nuclear Information System (INIS)

Wilson, A J; Colling, D J; Hanlet, P

2012-01-01

The configuration database (CDB) is the memory of the Muon Ionisation Cooling Experiment (MICE). Its principle aim is to store temporal data associated with the running of the experiment; these data are used throughout the life cycle of experiment, from running the experiment through data analysis. The CDB also serves as a moderator in the MICE state machine by defining allowable operating states of subsystems depending on the overall state of MICE and other subsystems. Master and slave CDBs, with multiple mirrored pair raid arrays, have been set up in different parts of the site to increase resilience, as well as off site backups. Access to the CDB is via a Python API, which communicates with a WSDL interface provided by a web-service on the CDB. The priority is to ensure availability of the CDB in the experiment control room. The master CDB is located in the MICE control where it is only used by the running experiment. In the event of the failure of the master, the slave can easily be promoted to master. Read only access to the CDB for data analysis and reconstruction is provided by the slave which has an up to the minute copy of the data. As MICE is a precision experiment which will measure a 10% muon cooling effect with 1% precision, it is imperative that we minimize our systematic errors; the CDB will ensure reproducible and documented running conditions in a highly resilient manner. A description of the hardware and software used in the the MICE CDB will be described in what follows.

Moderate beer consumption does not change early or mature atherosclerosis in mice

Directory of Open Access Journals (Sweden)

Blanco-Vaca Francisco

2004-01-01

Full Text Available Abstract Background Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis but not mature atherosclerosis in apolipoprotein (apo E-deficient (apoE-/- mice. Aim of the study To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. Methods Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. Results The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively and apoE-/- mice (p = 0.19 and p = 0.59, respectively. No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. Conclusions Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied.

Antitumour activity of cordycepin in mice.

Science.gov (United States)

Yoshikawa, Noriko; Nakamura, Kazuki; Yamaguchi, Yu; Kagota, Satomi; Shinozuka, Kazumasa; Kunitomo, Masaru

2004-12-01

1. The antitumour effect of orally administered cordycepin, a component isolated from water extracts of Cordyceps sinensis, was examined in mice inoculated with B16 melanoma (B16-BL6) cells. 2. B16-BL6 (1 x 10(6)) cells were inoculated subcutaneously into the right footpad of mice. At 2 weeks after the cell inoculation, the enlarged primary tumour lump was weighed. Cordycepin (0, 5 and 15 mg/kg per day) was administered orally to the mice for 2 weeks from the date of tumour inoculation. Cordycepin (15 mg/kg per day) significantly reduced by 36% the wet weight of the primary tumour lump compared to that of the untreated control mice, without any loss of bodyweight or systemic toxicity. 3. Cordycepin (15 mg/kg per day) administered orally for 2 weeks inhibited the tumour enlargement in the right thigh inoculated with B16-BL6 cells premixed with extracellular matrix (Matrigel). 4. These results indicate that orally administered cordycepin inhibits melanoma cell growth in mice with no adverse effects.

Enhancing the healing processes of chemical burns with He-Ne radiation

International Nuclear Information System (INIS)

Kakai, S.F.K.; Albarwari, S.E.; Alsenawi, T.A.

1988-02-01

The process by which He-Ne laser radiation (λ = 632.8 nm) enhances the healing of cutaneous wounds, made by concentrated nitric acid on mice has been studied. The dose used was of the order of 2.7 Joule per day, till the day of complete wound closure. The wounds were irradiated at three points on its periphery so that to form a semitriangular pattern this method was adopted, because chemical burns involve the killing of both the epidermis and dermis. The influence of the laser on the healing was estimated quantitatively and statistically, with a significance of p<0.001 over the control (the unirradiated). (author). 8 refs, 2 figs, 2 tabs

Aged Tg2576 mice are impaired on social memory and open field habituation tests.

Science.gov (United States)

Deacon, R M J; Koros, E; Bornemann, K D; Rawlins, J N P

2009-02-11

In a previous publication [Deacon RMJ, Cholerton LL, Talbot K, Nair-Roberts RG, Sanderson DJ, Romberg C, et al. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav Brain Res 2008;189:126-38] we found that very few cognitive tests were suitable for demonstrating deficits in Tg2576 mice, an amyloid over-expression model of Alzheimer's disease, even at 23 months of age. However, in a retrospective analysis of a separate project on these mice, tests of social memory and open field habituation revealed large cognitive impairments. Controls showed good open field habituation, but Tg2576 mice were hyperactive and failed to habituate. In the test of social memory for a juvenile mouse, controls showed considerably less social investigation on the second meeting, indicating memory of the juvenile, whereas Tg2576 mice did not show this decrement.As a control for olfactory sensitivity, on which social memory relies, the ability to find a food pellet hidden under wood chip bedding was assessed. Tg2576 mice found the pellet as quickly as controls. As this test requires digging ability, this was independently assessed in tests of burrowing and directly observed digging. In line with previous results and the hippocampal dysfunction characteristic of aged Tg2576 mice, they both burrowed and dug less than controls.

Effect of bcl-2 overexpression in mice on ovotoxicity caused by 4-vinylcyclohexene

International Nuclear Information System (INIS)

Flaws, Jodi A.; Marion, Samuel L.; Miller, Kimberly P.; Christian, Patricia J.; Babus, Janice K.; Hoyer, Patricia B.

2006-01-01

The occupational chemical 4-vinylcyclohexene (VCH) destroys small preantral ovarian follicles in mice following repeated daily dosing. The cell survival gene bcl-2 is thought to protect against follicular death during embryogenesis because primordial follicle numbers in newborn bcl-2 overexpressing (OE) mice are greater than in wild-type (WT) controls. Thus, this study was designed to determine if overexpression of bcl-2 protects against VCH-induced follicle loss during embryonic development. Pregnant bcl-2 OE or WT mice were dosed (p.o.) daily with VCH (500 mg/kg) or sesame oil (vehicle control) on days 8-18 of pregnancy. Ovaries were collected from moms and female pups on pup postnatal day (PND) 8. Nonpregnant OE and WT females were also treated with VCH (500 mg/kg p.o.) or vehicle and evaluated in the same manner. As previously reported, ovaries from PND8 OE female pups contained 50% more primordial follicles than WT pups (P < 0.05). Unlike WT pups, relative to vehicle controls, in utero exposure to VCH resulted in a reduction in primordial (25% of control), primary (38% of control), and secondary (33% of control) follicles in ovaries of OE pups (P < 0.05). VCH had no significant effect on follicle numbers in OE or WT moms. Conversely, in nonpregnant adults, VCH did not affect WT mice but caused loss of primordial (55% of control), primary (51% of control), and secondary (69% of control) follicles in OE mice (P < 0.05). These results demonstrate that bcl-2 overexpression does not protect against, but instead increases susceptibility to VCH-induced follicle loss in transplacentally exposed or in nonpregnant mice

Evaluation of antidepressant activity of vanillin in mice.

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Shoeb, Ahsan; Chowta, Mukta; Pallempati, Gokul; Rai, Amritha; Singh, Ashish

2013-01-01

The main objective of this study was to evaluate antidepressant activity of vanillin in mice models of depression. Animals were divided into five groups, consisting six mice in each group. Out of these, three groups served as control (distilled water, imipramine,and fluoxetine) and the remaining two groups received test drug in two different doses (10 mg/kg and 100 mg/kg). All the drugs were administered orally one hour before the test procedure for acute study and daily for ten days for chronic study. Mice were subjected to forced swim (FST) and tail suspension tests (TST). Both the doses of vanillin reduced the immobility duration in TST as well as in FST. In TST, there was a statistically significant decrease in the immobility in all the groups when compared to the control (distilled water) group. But the reduction of immobility in FST did not show statistically significant reduction in immobility in the groups treated with vanillin when compared with control. In the chronic study group that received vanillin at a dose of 100 mg/kg, the immobility reduction was significantly lower when compared to the group receiving fluoxetine. Vanillin at the dosage of 100 mg/kg has demonstrated antidepressant activity in mice, which is comparable with fluoxetine.

Effects of marrow grafting on preleukemia cells and thymic nurse cells in C57BL/Ka mice after a leukemogenic split-dose irradiation

International Nuclear Information System (INIS)

Defresne, M.P.; Greimers, R.; Lenaerts, P.; Boniver, J.

1986-01-01

A split-dose regimen of whole-body irradiation (4 X 175 rad at weekly intervals) induced thymic lymphomas in C57BL/Ka mice after a latent period of 3-9 months. Meanwhile, preleukemia cells arose in the thymus and bone marrow and persisted until the onset of lymphomas. Simultaneously, thymic lymphopoiesis was impaired; thymocyte numbers were subnormal and thymic nurse cells disappeared in a progressive but irreversible fashion. The depletion of these lymphoepithelial complexes, which are normally involved in the early steps of thymic lymphopoiesis, was related to altered prothymocyte activity in bone marrow and to damaged thymic microenvironment, perhaps as a consequence of the presence of preleukemia cells. The grafting of normal bone marrow cells after irradiation prevented the development of lymphomas. However, marrow reconstitution did not inhibit the induction of preleukemia cells. They disappeared from the thymus during the second part of the latent period. At the same time, thymic lymphopoiesis was restored; thymocytes and nurse cell numbers returned to normal as a consequence of the proliferation of grafted marrow-derived cells within the thymus. The results thus demonstrated an intimate relationship between preleukemia cells and an alteration of thymic lymphopoiesis, which particularly involved the nurse cell microenvironment. Some preleukemia cells in marrow-reconstituted, irradiated mice derived from the unirradiated marrow inoculate. Thus these cells acquired neoplastic potential through a factor present in the irradiated tissues. The nature of this indirect mechanism was briefly discussed

Hyperoxia Inhibits T Cell Activation in Mice

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Hughes-Fulford, M.; Meissler, J.; Aguayo, E. T.; Globus, R.; Aguado, J.; Candelario, T.

2013-02-01

Background: The immune response is blunted in mice and humans in spaceflight. The effects of hyperoxia in mice alter expression of some of the same immune response genes. If these two conditions are additive, there could be an increased risk of infection in long duration missions. Immunosuppression is seen in healthy astronauts who have flown in space; however little is known about the mechanisms that cause the reduced immunity in spaceflight. Here we examine the role of oxidative stress on mice exposed to periods of high O2 levels mimicking pre-breathing protocols and extravehicular activity (EVA). To prevent decompression sickness, astronauts are exposed to elevated oxygen (hyperoxia) before and during EVA activities. Spaceflight missions may entail up to 24 hours of EVA per crewmember per week to perform construction and maintenance tasks. The effectiveness and success of these missions depends on designing EVA systems and protocols that maximize human performance and efficiency while minimizing health and safety risks for crewmembers. To our knowledge, no studies have been conducted on the immune system under 100% oxygen exposures to determine the potential for immune compromise due to prolonged and repeated EVAs. Methods: Animals were exposed to hyperoxic or control conditions for 8 hours per day over a period of 3 days, initiated 4 hours into the dark cycle (12h dark/12h light), using animal environmental control cabinets and oxygen controller (Biospherix, Lacona, NY). Experimental mice were exposed to 98-100% oxygen as a model for pre-breathing and EVA conditions, while control mice were maintained in chambers supplied with compressed air. These are ground control studies where we use real-time RTPCR (qRTPCR) to measure gene expression of the early immune gene expression during bead activation of splenocytes of normoxic and hyperoxic mice. All procedures were reviewed and approved by the IACUC at Ames Research Center. After the last 8h of hyperoxic exposure

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

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Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

2015-10-01

Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

Open-field behavior of house mice selectively bred for high voluntary wheel-running.

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Bronikowski, A M; Carter, P A; Swallow, J G; Girard, I A; Rhodes, J S; Garland, T

2001-05-01

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Differential androgenesis in gamma irradiated mice

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Kim, Jihyang; Yoon, Yongdal [Hanyang Univ., Seoul (Korea, Republic of); Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

2002-07-01

The Leydig cells of the testis account for at least 75% of the total testosterone produced in the normal adult male. Whereas the production of estrogen from androgen is catalyzed by aromatase cytochrome P450, which is found in many tissues, including gonad, brain, adipose tissue, bone, and heart. The gamma-irradiation causes the impairment of spermatogenesis and steroidogenesis in male mice. The present study was performed to analyze changes in testosterone concentrations and expression of steroidogenic enzyme of mice after whole body gamma-irradiation. Eight-week-old male ICR mice were irradiated with 6.5 or 10 Gy. At days 1, 2, 3, 4, and 5 after irradiation, testes were removed and processed for paraffin sections and isolation of mRNA. We calculated the gonad index from body and testis weight, and checked the testis volume. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum and intratesticular fluid. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic gene and the cytochrome P450 aromatase gene after irradiation. In gamma-irradiated mice, the body weight reduced in comparison to that of the control group. Therefore, gonad indices increased. The testosterone concentrations in serum and intratesticular fluid were significantly reduced. RT- PCR data represented that the expression of Fas, Fas ligand, and aromatase cytochrome P450 showed the specific patterns against control groups. These results indicated that gamma- irradiation of adult mice induced the alteration of androgenesis and suggested that might counteract the spermatogenesis.

Differential effect of ionizing radiation on transcription in repair-deficient and repair-proficient mice

International Nuclear Information System (INIS)

Munson, G.P.; Woloschak, G.E.

1990-01-01

Experiments were designed to examine in vivo changes in total transcription and in the expression of the c-fos gene following whole-body exposure of mice to JANUS fission-spectrum neutrons. Radiation repair-deficient (wst/wst) and -proficient (wst/., C57BL/6 x C3H F1) mice were exposed to JANUS fission-spectrum neutrons calibrated to deliver a gut dose of 50 cGy. Animals were sacrificed less than 10 or at 60 min postirradiation, and gut tissues were removed for study. Our results revealed that, in repair-proficient mice, an immediate depression (relative to untreated control) in total transcription was evident that continued through 1 h postirradiation. Conversely, radiation-sensitive wst/wst mice displayed doubled transcription levels postirradiation. Expression of c-fos was consistently depressed following radiation exposure in control and wst/wst mice. However, the depression of c-fos mRNA was delayed in wst/wst mice relative to controls. These results demonstrate abnormal regulation of transcription and of c-fos mRNA accumulation in repair-deficient wasted mice following exposure to ionizing radiation. In addition, this work documents rapid total transcriptional depression in normal mice following radiation exposure

A high-fat diet delays age-related hearing loss progression in C57BL/6J mice.

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Takeshi Fujita

Full Text Available Age-related hearing loss (AHL, or presbycusis, is the most common sensory disorder among the elderly. We used C57BL/6J mice as an AHL model to determine a possible association between AHL and a high-fat diet (HFD.Forty C57BL/6J mice were randomly assigned to a control or HFD group. Each group was divided into the following subgroups: 1-, 3-, 5- and 12-month groups (HFD, n = 5/subgroup; control, n = 5/subgroup. Nine CBA/N-slc mice were also used as a 12-month control (n = 5 or 12-month HFD (n = 4 group. The mice were fed a HFD or normal (control diet throughout this study. Hearing function was evaluated at 1, 3, 5 and 12 months using auditory evoked brainstem responses (ABRs. Spiral ganglion cells (SGCs were also counted.The elevation of ABR thresholds (at 4 and 32 kHz at 3 and 5 months was significantly suppressed in the HFD group compared with the control groups for C57BL/6J mice. After 12 months, the elevation of ABR thresholds was significantly suppressed in the HFD group at all frequencies for C57BL/6J mice. In contrast, CBA/N-slc mice displayed opposite outcomes, as ABR thresholds at all frequencies at 12 months were significantly elevated in the HFD group compared with the control group. For the C57BL/6J mice at 12 months, SGC numbers significantly decreased in all parts of the cochleae in the control group compared with the HFD groups. In contrast, for the CBA/N-slc mice, SGC numbers significantly decreased, particularly in the upper parts of the cochleae in the HFD group compared with the control groups.The elevation in ABR thresholds and SGC loss associated with aging in the HFD-fed C57BL/6J mice were significantly suppressed compared with those in the normal diet-fed mice. These results suggest that HFD delays AHL progression in the C57B/6J mice.

A High-Fat Diet Delays Age-Related Hearing Loss Progression in C57BL/6J Mice

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Fujita, Takeshi; Yamashita, Daisuke; Uehara, Natsumi; Inokuchi, Go; Hasegawa, Shingo; Otsuki, Naoki; Nibu, Ken-ichi

2015-01-01

Objective Age-related hearing loss (AHL), or presbycusis, is the most common sensory disorder among the elderly. We used C57BL/6J mice as an AHL model to determine a possible association between AHL and a high-fat diet (HFD). Methods Forty C57BL/6J mice were randomly assigned to a control or HFD group. Each group was divided into the following subgroups: 1-, 3-, 5- and 12-month groups (HFD, n = 5/subgroup; control, n = 5/subgroup). Nine CBA/N-slc mice were also used as a 12-month control (n = 5) or 12-month HFD (n = 4) group. The mice were fed a HFD or normal (control) diet throughout this study. Hearing function was evaluated at 1, 3, 5 and 12 months using auditory evoked brainstem responses (ABRs). Spiral ganglion cells (SGCs) were also counted. Results The elevation of ABR thresholds (at 4 and 32 kHz) at 3 and 5 months was significantly suppressed in the HFD group compared with the control groups for C57BL/6J mice. After 12 months, the elevation of ABR thresholds was significantly suppressed in the HFD group at all frequencies for C57BL/6J mice. In contrast, CBA/N-slc mice displayed opposite outcomes, as ABR thresholds at all frequencies at 12 months were significantly elevated in the HFD group compared with the control group. For the C57BL/6J mice at 12 months, SGC numbers significantly decreased in all parts of the cochleae in the control group compared with the HFD groups. In contrast, for the CBA/N-slc mice, SGC numbers significantly decreased, particularly in the upper parts of the cochleae in the HFD group compared with the control groups. Conclusions The elevation in ABR thresholds and SGC loss associated with aging in the HFD-fed C57BL/6J mice were significantly suppressed compared with those in the normal diet-fed mice. These results suggest that HFD delays AHL progression in the C57B/6J mice. PMID:25625852

Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

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Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-01-01

Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

Influence of a sublethal irradiation on the immune response of the mouse against sheep erythrocytes

International Nuclear Information System (INIS)

Beaumariage, M.L.; Hiesche, K.; Moeller, E.; Revesz, L.; Haot, J.

1975-01-01

In the CBA mice, the immunological response of the spleen cells (RFC and PFC direct and indirect) against the sheep erythrocytes is highly depressed by a 400R dose of X rays. The recovery is not complete at the 30th day after irradiation. The response of the bone marrow cells either irradiated or unirradiated to the antigenic stimulation is very low [fr

Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

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Radhika V Seimon

Full Text Available Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled.Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change ÷ [(total energy intake of mice on CD or ID-(total average energy intake of controls]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding.Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05. There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01. Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups.Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative

Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice.

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Sena, Maria Clecia P; Nunes, Fabíola C; Salvadori, Mirian G S Stiebbe; Carvalho, Cleyton Charles D; Morais, Liana Clebia S L; Braga, Valdir A

2011-01-01

Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 ± 8 vs. 7 ± 2 s, n = 9) or sugarcane spirit (36 ± 9 vs. 7 ± 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 ± 1 for the control group, 27 ± 2 for the ethanol group, and 31 ± 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 ± 0.17 for the control group and 2.67 ± 0.17 for the sugarcane spirit group; n = 8 for each group). The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

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Maria Clecia P. Sena

2011-01-01

Full Text Available OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16 had access to sugarcane spirit + distilled water, the mice in Group B (n = 15 had access to ethanol + distilled water, and the mice in Group C (control, n = 14 had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9 or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9 compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group. In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group. CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

Evaluating fatigue in lupus-prone mice: preliminary assessments.

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Meeks, Allison; Larson, Susan J

2012-01-01

Fatigue is a debilitating condition suffered by many as the result of chronic disease, yet relatively little is known about its biological basis or how to effectively manage its effects. This study sought to evaluate chronic fatigue by using lupus-prone mice and testing them at three different time periods. Lupus-prone mice were chosen because fatigue affects over half of patients with Systemic Lupus Erythematosus. Eleven MLR⁺/(+) (genetic controls) and twelve MLR/MpJ-Fas/J (MRL/lpr; lupus-prone) mice were tested three times: once at 12, 16 and 20 weeks of age. All mice were subjected to a variety of behavioral tests including: forced swim, post-swim grooming, running wheel, and sucrose consumption; five of the MLR⁺/(+) and five of the MLR/lpr mice were also tested on a fixed ratio-25 operant conditioning task. MRL/lpr mice showed more peripheral symptoms of lupus than controls, particularly lymphadenopathy and proteinuria. Lupus mice spent more time floating during the forced swim test and traveled less distance in the running wheel at each testing period. There were no differences between groups in post-swim grooming or in number of reinforcers earned in the operant conditioning task indicating the behavioral changes were not likely due simply to muscle weakness or motivation. Correlations between performance in the running wheel, forced swim test and sucrose consumption were conducted and distance traveled in the running wheel was consistently negatively correlated with time spent floating. Based on these data, we conclude that the lupus-prone mice were experiencing chronic fatigue and that running wheel activity and floating during a forced swim test can be used to evaluate fatigue, although these data cannot rule out the possibility that both fatigue and a depressive-like state were mediating these effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Chronic intermittent fasting improves cognitive functions and brain structures in mice.

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Liaoliao Li

Full Text Available Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day fasting or high fat diet (45% caloric supplied by fat for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice. Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

Chronic intermittent fasting improves cognitive functions and brain structures in mice.

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Li, Liaoliao; Wang, Zhi; Zuo, Zhiyi

2013-01-01

Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

Autobacteriographic studies of clarithromycin and erythromycin in mice

International Nuclear Information System (INIS)

Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T.

1990-01-01

The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with [N-methyl-14C]clarithromycin and [N-methyl-14C]erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for [14C]clarithromycin than it was for [14C]erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed

Radioprotective effect of colony-stimulating factor on mice irradiated with 60Co γ-rays

International Nuclear Information System (INIS)

Zhang Junning; Wang Tao; Xu Changshao; Wang Hongyun

1995-01-01

Adult male mice were irradiated with γ-rays 6 Gy once or 3 Gy three times in 7 days and intraperitoneally injected with colony-stimulating factor (CSF) in high doses or low doses. Mice of the control group were injected with normal saline only. Within 30 days after irradiation, the survival rate of mice irradiated with 6 Gy γ-rays once and treated with high dose CSF was 9/25, while that in the control group was 2/25. The survival rate of mice irradiated with 3 Gy three times and treated with high dose CSF was 10/13, while that in the control group was 4/13. Moreover, the survival times of both irradiated groups treated with high dose CSF were much longer than the control groups (p<0.01). This experiment also showed that CSF could reduce the lowering of peripheral blood white blood cell counts and promote their recovery. The number of CFU-S in mice treated with CSF was much higher (23.8 +- 4.82) than in the control group (9.4 +- 4.39) (p<0.01). Therefore, CSF could recover and reconstruct the hematopoietic function of bone marrow, and prolong the survival of irradiated mice

Anti-Fatigue Properties of Tartary Buckwheat Extracts in Mice

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Ping Wei

2011-07-01

Full Text Available Anti-fatigue properties of tartary buckwheat extracts (TBE was investigated in male Kunming mice. The animals were divided into four groups. The first group, designated as the control group (control, was administered with distilled water by gavage every day for 28 days. The other three groups, designated as TBE treatment groups, were administered with TBE of 60, 120 and 240 mg/kg body weight, respectively, by gavage every day for 28 days. Exhaustive swimming time, blood lactic acid (BLA, blood urea nitrogen (BUN, tissue glycogen, glutathione peroxidase (GPx and superoxide dismutase (SOD of mice after swimming were determined. The results showed that tartary buckwheat extracts had anti-fatigue properties, which extended the exhaustive swimming time of mice, effectively inhibiting the increase of BLA, decreasing the level of BUN, increasing the tissue glycogen content and the activities of SOD and GPx of mice. However, further study is needed to elucidate the exact mechanism of the effect of TBE on fatigue.

Age-related changes in body composition of bovine growth hormone transgenic mice.

Science.gov (United States)

Palmer, Amanda J; Chung, Min-Yu; List, Edward O; Walker, Jennifer; Okada, Shigeru; Kopchick, John J; Berryman, Darlene E

2009-03-01

GH has a significant impact on body composition due to distinct anabolic and catabolic effects on lean and fat mass, respectively. Several studies have assessed body composition in mice expressing a GH transgene. Whereas all studies report enhanced growth of transgenic mice as compared with littermate controls, there are inconsistencies in terms of the relative proportion of lean mass to fat mass in these animals. The purpose of this study was to characterize the accumulation of adipose and lean mass with age and according to gender in a bovine (b) GH transgenic mouse line. Weight and body composition measurements were assessed in male and female bGH mice with corresponding littermate controls in the C57BL/6J genetic background. Body composition measurements began at 6 wk and continued through 1 yr of age. At the conclusion of the study, tissue weights were determined and triglyceride content was quantified in liver and kidney. Although body weights for bGH mice were significantly greater than their corresponding littermate controls at all time points, body composition measurements revealed an unexpected transition midway through analyses. That is, younger bGH mice had relatively more fat mass than nontransgenic littermates, whereas bGH mice became significantly leaner than controls by 4 months in males and 6 months in females. These results reveal the importance in timing and gender when conducting studies related to body composition or lean and fat tissue in GH transgenic mice or in other genetically manipulated mouse strains in which body composition may be impacted.

Altered neurological function in mice immunized with early endosome antigen 1

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Fritzler Marvin J

2004-01-01

Full Text Available Abstract Background Autoantibodies directed against the 160 kDa endosome protein early endosome antigen 1 (EEA1 are seen in patients with neurological diseases. To determine if antibodies to EEA1 have a neuropathological effect, mice from three major histocompatability haplotype backgrounds (H2q, H2b and H2d were immunized with EEA1 (amino acids 82–1411 that was previously shown to contain the target EEA1 epitopes. The mice were then subjected to five neuro-behavioural tests: grid walking, forelimb strength, open field, reaching and rotarod. Results The immunized SWR/J mice with sustained anti-EEA1 antibodies had significantly reduced forelimb strength than the control non-immune mice of the same strain, and BALB/CJ immune mice demonstrated significantly more forelimb errors on the grid walk test than the control group. Conclusions Antibodies to recombinant EEA1 in mice may mediate neurological deficits that are consistent with clinical features of some humans that spontaneously develop anti-EEA1 autoantibodies.

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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Zhu Zhu

2016-01-01

Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

Control of tapeworms by irradiation

International Nuclear Information System (INIS)

Verster, A.; Van den Heever, L.W.

1976-01-01

Cysticerci of Taenia solium were exposed to gamma radiation in doses varying from 20-140 krad. Radiation had an adverse effect on the ability of the cysticerci to evaginate in vitro after a time lag of 9 days. This effect was most marked at doses of 100 krad and higher, thus no cysticerci exposed to 140, 120 and 100 krad evaginated after 12, 18 and 21 days, respectively. On Day + 24, when 60% of the control cysticerci evaginated, 55%, 50%, 30% and 40% of the cysticerci exposed to 20, 40, 60, and 80 krad, respectively, evaginated in vitro. Cysticerci exposed to radiation doses of 20-120 krad are as infective to golden hamsters as are unirradiated cysticerci. Cestodes resulting from irradiated cysticerci, however, cannot maintain themselves indefinitely, and are excreted or digested at varying times from Day + 12 onwards. Moreover, cestodes resulting from such irradiated cysticerci do not grow, but are resorbed, and finally consist of only a scolex. By Day + 30 the mean length of the worms resulting from the unirradiated cysticerci is 173,8 mm, while those resulting from cysticerci exposed to 20 and 40 krad consist of scolices only and the hamsters fed material exposed to 60 krad were negative. It appears, therefore, that radiation inhibits the ability of the cells in the neck region to divide and thus form new proglottids. Carcasses infested with cysticercosis can possibly be rendered fit for human consumption by exposure to gamma radiation at doses between 20 and 60 krad

Effect of cadmium chloride on hepatic lipid peroxidation in mice

DEFF Research Database (Denmark)

Andersen, H R; Andersen, O

1988-01-01

Intraperitoneal administration of cadmium chloride to 8-12 weeks old CBA-mice enhanced hepatic lipid peroxidation. A positive correlation between cadmium chloride dose and level of peroxidation was observed in both male and female mice. A sex-related difference in mortality was not observed...... but at a dose of 25 mumol CdCl2/kg the level of hepatic lipid peroxidation was higher in male mice than in female mice. The hepatic lipid peroxidation was not increased above the control level in 3 weeks old mice, while 6 weeks old mice responded with increased peroxidation as did 8-12 weeks old mice....... The mortality after an acute toxic dose of cadmium chloride was the same in the three age groups. Pretreatment of mice with several low intraperitoneal doses of cadmium chloride alleviated cadmium induced mortality and lipid peroxidation. The results demonstrate both age dependency and a protective effect...

Antihyperglycemic and antihyperlipidemic effects of pirdot (saurauia vulcani korth.) leaves extract in mice

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Hutahaean, Salomo; Tanjung, Masitta; Puspita Sari, Diah; Elfia Ningsih, Vevy

2018-03-01

Approximately eighty percent of deaths in diabetic patients result from atherosclerosis, which is related to hyperlipidemia tendencies in diabetes. In North Sumatra, the use of plant-based ingredients as diabetes therapy has long been recognized. One of the local species which traditionally used was the pirdot plant (Saurauia vulcani Korth.). In this paper, we report the antihyperglycemic and antihyperlipidemic effects of the extract of pirdot leaves in model mice. In experiment I, twenty - five alloxan-induced diabetic mice was divided randomly into five groups of 5 mice, namely: control diabetic mice; diabetic mice + metformin; and three groups diabetic mice + pirdot leaves extract of 100, 200, or 300 mg/kg BW respectively. All the treatments were given daily for 21 days by oral gavage. In experiment II, another twenty-five mice were divided randomly into five groups of 5 mice. The treatments were as follows: a control group that did not receive any treatment; hyperlipidemic control (received quail yolk diet) for 30 days; and three groups of hyperlipidemic mice + orally treated pirdot leaves extract at a dose of 100, 200, or 300 mg/kg BW respectively. The result showed the pirdot leaves extract has the potential as antihyperglycemic. The effects obtained are equivalent to the effects of antidiabetic drug metformin. On the other hand, the antihyperlipidemic effect was not conclusive, because the extract lowered total cholesterol significantly, but no significant effect on triglyceride, marked reduced LDL, but significantly decreased the HDL level.

[Oxidative damage effects induced by CdTe quantum dots in mice].

Science.gov (United States)

Xie, G Y; Chen, W; Wang, Q K; Cheng, X R; Xu, J N; Huang, P L

2017-07-20

Objective: To investigate Oxidative damage effects induced by CdTe Quantum Dots (QDs) in mice. Methods: 40 ICR mice were randomly divided into 5 groups: one control group (normal saline) ; four CdTe QDs (exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 0、0.5、5.0、50.0 and 500.0 nmol/ml respectively) . After 24 h, the mice were decapitated and the blood was collected for serum biochemically indexes、hematology indexes, the activities of SOD、GSH-Px and the concentration of MDA were all detected. Results: The results showed in the four CdTe QDs exposure groups, the level of CRE、PLT and the concentration of MDA were all significantly lower than those of the control group ( P control group ( P <0.01) . Conclusion: It was suggested that CdTe QDs at 0.5 nmol/ml could induce Oxidative damage effects in mice.

Systemic buffers inhibit carcinogenesis in TRAMP mice.

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Ibrahim-Hashim, Arig; Cornnell, Heather H; Abrahams, Dominique; Lloyd, Mark; Bui, Marilyn; Gillies, Robert J; Gatenby, Robert A

2012-08-01

Hypoxia and acidosis develop in in situ tumors as cellular expansion increases the diffusion distance of substrates and metabolites from blood vessels deep to the basement membrane. Prior studies of breast and cervical cancer revealed that cellular adaptation to microenvironmental hypoxia and acidosis is associated with the transition from in situ to invasive cancer. We hypothesized that decreased acidosis in intraductal tumors would alter environmental selection pressures for acid adapted phenotypes and delay or prevent evolution to invasive cancer. A total of 37 C57BL/6 TRAMP mice were randomized to a control group or to 1 of 4 treatment groups. In the latter groups 200 mM sodium bicarbonate were added to drinking water starting between ages 4 and 10 weeks. In all 18 controls prostate cancer developed that was visible on 3-dimensional ultrasound at a mean age of 13 weeks. They died within 52 weeks (median 37). When sodium bicarbonate therapy commenced before age 6 weeks in 10 mice, all reached senescence (age 76 weeks) without radiographic evidence of prostate cancer. Histological sections of the prostates in this cohort showed hyperplasia but no cancer in 70% of mice and minimal well differentiated cancer in the remainder. When therapy commenced after age 6 weeks in 9 mice, prostate cancer development was no different from that in controls. Immunohistochemical staining for carbonic anhydrase 9 in regions of ductal hyperplasia showed increased expression in controls vs the early treatment group. Regional pH perturbation in in situ tumors may be a simple, inexpensive and effective cancer prevention strategy. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Organ specific mapping of in vivo redox state in control and cigarette smoke-exposed mice using EPR/NMR co-imaging

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Caia, George L.; Efimova, Olga V.; Velayutham, Murugesan; El-Mahdy, Mohamed A.; Abdelghany, Tamer M.; Kesselring, Eric; Petryakov, Sergey; Sun, Ziqi; Samouilov, Alexandre; Zweier, Jay L.

2014-01-01

In vivo mapping of alterations in redox status is important for understanding organ specific pathology and disease. While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals, it does not provide anatomic visualization of the body. Proton MRI is well suited to provide anatomical visualization. We applied EPR/NMR co-imaging instrumentation to map and monitor the redox state of living mice under normal or oxidative stress conditions induced by secondhand cigarette smoke (SHS) exposure. A hybrid co-imaging instrument, EPRI (1.2 GHz) / proton MRI (16.18 MHz), suitable for whole-body co-imaging of mice was utilized with common magnet and gradients along with dual EPR/NMR resonators that enable co-imaging without sample movement. The metabolism of the nitroxide probe, 3–carbamoyl–proxyl (3-CP), was used to map the redox state of control and SHS-exposed mice. Co-imaging allowed precise 3D mapping of radical distribution and reduction in major organs such as the heart, lungs, liver, bladder and kidneys. Reductive metabolism was markedly decreased in SHS-exposed mice and EPR/NMR co-imaging allowed quantitative assessment of this throughout the body. Thus, in vivo EPR/NMR co-imaging enables in vivo organ specific mapping of free radical metabolism and redox stress and the alterations that occur in the pathogenesis of disease. PMID:22296801

Radiation-induced diploid spermatids in mice

International Nuclear Information System (INIS)

Hacker-Klom, U.; Heiden, Th.; Otto, F.J.; Goehde, W.; Mauro, F.

1989-01-01

Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute 60 Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author)

Impact of short‐term, repeated water fasting on the weight of mice

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Zahra Mishmast

2014-09-01

Full Text Available Introduction: Caloric restriction is a strategy applied for weight loss. Water fasting is a popular way for obesity treatment. However, little is known about the impact of water fasting on weight. Therefore, this study was conducted to investigate the effect of short-term, repeated water fasting on the weight of mice. Methods: In this study, the physiological effect of short-term, repeated water fasting on the weight of female mice was evaluated. At 6 weeks of age, mice were randomly assigned to either repeated-fasting or control group (fed ad libitum. Each group consisted of twenty mice. As the fasting period started, the repeated-fasting group had access to only water; animals had free access to food and water on non-fasting days. Body weight of each group before, during, and after the fasting period was recorded. Results: Body weight of the fasting group significantly decreased, unlike the control group. However, the fasting group gained weight rapidly after being re-fed and became significantly heavier than mice in the control group (P

MAUS: MICE Analysis User Software

CERN Multimedia

CERN. Geneva

2012-01-01

The Muon Ionization Cooling Experiment (MICE) has developed the MICE Analysis User Software (MAUS) to simulate and analyse experimental data. It serves as the primary codebase for the experiment, providing for online data quality checks and offline batch simulation and reconstruction. The code is structured in a Map-Reduce framework to allow parallelization whether on a personal machine or in the control room. Various software engineering practices from industry are also used to ensure correct and maintainable physics code, which include unit, functional and integration tests, continuous integration and load testing, code reviews, and distributed version control systems. Lastly, there are various small design decisions like using JSON as the data structure, using SWIG to allow developers to write components in either Python or C++, or using the SCons python-based build system that may be of interest to other experiments.

Skewed X-inactivation in cloned mice

International Nuclear Information System (INIS)

Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

2004-01-01

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

Diacylglycerol lipase a knockout mice demonstrate metabolic and behavioral phenotypes similar to those of cannabinoid receptor 1 knockout mice

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David R Powell

2015-06-01

Full Text Available After creating >4650 knockouts (KOs of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1 KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase a or b (Dagla or Daglb, which catalyze biosynthesis of the endocannabinoid (EC 2-Arachidonoylglycerol (2-AG, or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild type (WT littermates; when data from multiple cohorts of adult mice were combined, body fat was 47% and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. In contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride and total cholesterol levels, and after a glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: 1 the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; 2 in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and 3 small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower body weight and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric

Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction.

Science.gov (United States)

Hua, Xu; Cao, Xin-Yuan; Wang, Xiao-Li; Sun, Peng; Chen, Ling

2017-11-01

Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is associated with hypothyroxinemia and decreases in placental glucose transporter expression and activity. The objective of this study was to investigate the influence of TCS on glucose homeostasis and insulin sensitivity in gestational mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to GD17 significantly increased their levels of fasting plasma glucose and serum insulin, and insulin content in pancreatic β-cells with reduced homeostasis model assessment (HOMA)-β index and increased HOMA-IR index. Area under curve (AUC) of glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice showed a significant decrease in the levels of thyroxine and triiodothyroninelevels, PPARγ and glucose transporter 4 (GLUT4) expression, and Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the levels of insulin, PPARγ and GLUT4 expression, and Akt phosphorylation. Activation of PPARγ by administration of rosiglitazone recovered the decrease in Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) in Ng-mice reduced thyroid hormones levels, it did not cause the insulin resistance or affect PPARγ and GLUT4 expression, and Akt phosphorylation. The findings indicate that the exposure of gestational mice to TCS (≥8 mg/kg) results in insulin resistance via thyroid hormones reduction. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice

DEFF Research Database (Denmark)

Thomsen, Annika Højrup Runegaard; Jensen, Kathrine L; Fitzpatrick, Ciarán M

2017-01-01

assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice...

Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice.

Science.gov (United States)

Liu, Jing-yu; Feng, Cui-ping; Li, Xing; Chang, Ming-chang; Meng, Jun-long; Xu, Li-jing

2016-05-01

To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 24 male and 24 female Kunming mice were randomly divided into four groups. The mice in the four experimental groups were administered 0 (normal control), 50, 100, or 200mg/kg/d body weight CMP via gavage. After 30 days, the viscera index, leukocyte count, differential leukocyte count, immunoglobulin (IgG) levels, and biochemical parameters were measured. The effect of CMP on the expression of tumor necrosis (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β in the spleens of experimental mice was investigated by real-time polymerase chain reaction. The results showed that the administration of CMP improved the immune function in mice, significantly increased the spleen and thymus indices, the spleen lymphocyte activity, the total quantity of white blood cells, and IgG function in mice serum. CMP exhibited significant antioxidative activity in mice, and decreased malondialdehyde levels in vivo. CMP upregulated the expression of TNF-α, IFN-γ, and IL-1β mRNA in high-dose groups compared to that observed for the control mice. We can thus conclude that CMP effectively improved the immune function through protection against oxidative stress. CMP thus shows potential for development as drugs and health supplements. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of BMPs on hematopoietic injury of acute radiation sickness in mice

International Nuclear Information System (INIS)

Tian Qiong; Zhang Shaozhang; Pu Qin; Zhang Fake; Hannah, X.H.

2000-01-01

The purpose of this paper is to investigate the effect of Bone morphogenetic proteins (BMPs) on hematopoietic acute radiation sickness in mice. BMP, rhBMP-2m and PBK/hBMP-2-NIH3T3 cells were obtained separately by chemistry, molecule biological method and genetherapy method. In this study, the effect of BMPs on hematopoiesis was detected at postirradiation: some hematological parameters, 30 days the survival ratio and formation of bone marrow CFU-GM colony. The experiments indicate that when phBMP (purified bovine bone morphogenetic protein) can increase the formation of bone narrow CFU-GM colony (p<0.05) at 10th d after irradiation. Irradiation control group's mice died in 30 days, but effect of rhBMP-2m on the survival of mice after 7.5Gy irradiation, was detected whereas there were 10%, 15% and 35% all mice of survived after injection i.p. with 0.5 mg, 1.0 mg and 2.0 mg of rhBMP-2m respectively. All hematological parameters of treated mice were significantly higher than control group (p<0.01). PBK/hBMP-2-NIH3T3 cells were established and transplanted into mice irradiated by 7.0Gy r ray by i.p., the survival ratio of treated mice higher than negative control group (p<0.01), and all hematopoietic parameters were increased statistically significant (p<0.01). These data support the our hypothesis: BMPs can treat the acute radiation sickness. The results indicate that in adult mice, BMPs can recover or treat the hematopoietic injury of acute radiation sickness in mice. (author)

Effects of polysaccharides from Cordyceps sinensis mycelium on physical fatigue in mice

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Feng yan

2012-08-01

Full Text Available This study was designed to determine the effects of polysaccharides from Cordyceps sinensis mycelium (CSP on physical fatigue in mice. The mice were randomly divided into four groups (n = 16 in each group, i.e. control group, low-dose CSP treated group, intermediate-dose CSP treated group and high-dose CSP treated group. The mice in the treated groups received CSP (100, 200 and 400 mg/kg, ig, and the mice in the control group received drinking water ig. After 28 days, a forced swimming test was performed and some biochemical parameters related to fatigue were examined. The present data suggested that CSP could extend the exhaustive swimming time of mice, as well as increase the hepatic glycogen and muscle glycogen levels, and decrease the blood lactic acid and BUN levels. These results indicated that CSP had anti-fatigue effects.

[Effect of Huanglian Jiedu Decoction on Monocyte Development in apoE Gene Knockout Mice].

Science.gov (United States)

Chen, Bing; Kong, Ya-xian; Ll, Yu-mei; Xue, Xin; Zhang, Jian-ping; Zeng, Hui; Hu, Jing- qing; Ma, Ya-luan

2016-01-01

To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice. Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected. Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P

Bortezomib alters sour taste sensitivity in mice

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Akihiro Ohishi

Full Text Available Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the control level on cessation of its administration. These results suggest that an increase in protein expression of PKD2L1 enhances the sour taste sensitivity in bortezomib-administered mice, and this alteration is reversed on cessation of its administration. Keywords: Taste disorder, Bortezomib, Sour taste, Chemotherapy, Adverse effect

Mitochondrial-nuclear genome interactions in non-alcoholic fatty liver disease in mice.

Science.gov (United States)

Betancourt, Angela M; King, Adrienne L; Fetterman, Jessica L; Millender-Swain, Telisha; Finley, Rachel D; Oliva, Claudia R; Crowe, David R; Ballinger, Scott W; Bailey, Shannon M

2014-07-15

NAFLD (non-alcoholic fatty liver disease) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. In the present study, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, MNX (mitochondrial-nuclear exchange) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6J mice on a C3H/HeN nuclear background and vice versa. Results from MNX mice were compared with wild-type C57BL/6J and C3H/HeN mice fed a control or atherogenic diet. Mice with the C57BL/6J nuclear genome developed more macrosteatosis, inflammation and fibrosis compared with mice containing the C3H/HeN nuclear genome when fed the atherogenic diet. These changes were associated with parallel alterations in inflammation and fibrosis gene expression in wild-type mice, with intermediate responses in MNX mice. Mice with the C57BL/6J nuclear genome had increased State 4 respiration, whereas MNX mice had decreased State 3 respiration and RCR (respiratory control ratio) when fed the atherogenic diet. Complex IV activity and most mitochondrial biogenesis genes were increased in mice with the C57BL/6J nuclear or mitochondrial genome, or both fed the atherogenic diet. These results reveal new interactions between mitochondrial and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD.

Cell-mediated immune suppression effect of rocket kerosene through dermal exposure in mice

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Bing-xin XU

2015-10-01

Full Text Available Objective　To study the effect of cell-mediated immune suppression effect of rocket kerosene (RK through dermal application in mice. Methods　Skin delayed type hypersensitivity (DTH was used to observe the relation of the RK amount the skin exposed and the cellular immune inhibitory function. Different amount of the undiluted fuel was smeared directly onto the dorsal skin of mice. Mice in negative and positive control groups were treated with acetone. After the last exposure, all the mice except those in negative control group were allergized by evenly smearing with 1% dinitrofluorobenzene (DNFB solution on their dorsum. Five days after allergy, 1% DNFB solution was smeared onto right ear of all mice to stimulate the allergic reaction. Twenty-four hours after attack, the auricle swelling, spleen index and thymus index in corresponding mice were determined. In the first series of experiments, different dosages of RK were applied once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 1ml/kg.BW×1 and 2ml/kg.BW×1 group. In the second series of experiments, the certain and same dosage of RK was applied for different times, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 0.5mL/kg.BW×2, 0.5ml/kg.BW×3, 0.5ml/kg.BW×4 and 0.5mL/kg.BW×5 group. In the third series of experiments, the different dosages of RK were applied more than once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×5, 1ml/kg.BW×5 and 2ml/kg.BW×5 group. Lymphocyte proliferation experiment in vitrowas conducted to observe the persistent time of the cell-mediated immune suppression in mice by RK dermal exposure. The lymphocyte proliferation induced by concanavalin A (Con A was analyzed by MTT assay, and T lymphocyte subsets (CD3+, CD4+ and CD

Impaired TFEB-mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-induced Liver Injury and Steatosis in Mice.

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Chao, Xiaojuan; Wang, Shaogui; Zhao, Katrina; Li, Yuan; Williams, Jessica A; Li, Tiangang; Chavan, Hemantkumar; Krishnamurthy, Partha; He, Xi C; Li, Linheng; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing

2018-05-18

Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfeb flox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of chronic ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice were also given injections of torin1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time PCR to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry. Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB, compared with control mice, and hepatocytes had reduced lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting increased mTOR activation. Administration of torin1 increased liver levels of TFEB and reduced steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in liver developed less-severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared to mice carrying a control vector. Mice with knockdown of TFEB, as well as TFEB, TFE3 double-knockout mice, developed more severe liver injury in response to the

Multigene deletions in lung adenocarcinomas from irradiated and control mice

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Zhang, Y.; Woloschak, G.E.

1996-01-01

K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly γ-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF 1 male mice exposed to protracted neutron radiation

Lactation Defect in a Widely Used MMTV-Cre Transgenic Line of Mice

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Yuan, Taichang; Wang, Yongping; Pao, Lily; Anderson, Steve M.; Gu, Haihua

2011-01-01

Background MMTV-Cre mouse lines have played important roles in our understanding about the functions of numerous genes in mouse mammary epithelial cells during mammary gland development and tumorigenesis. However, numerous studies have not included MMTV-Cre mice as controls, and many investigators have not indicated which of the different MMTV-Cre founder lines were used in their studies. Here, we describe a lactation defect that severely limits the use of one of the most commonly used MMTV-Cre founder lines. Methodology/Principal Findings To explore the role of protein tyrosine phosphatase Shp1 in mammary gland development, mice bearing the floxed Shp1 gene were crossed with MMTV-Cre mice and mammary gland development was examined by histological and biochemical techniques, while lactation competency was assessed by monitoring pup growth. Surprisingly, both the Shp1fl/+;MMTV-Cre and MMTV-Cre female mice displayed a severe lactation defect when compared to the Shp1 fl/+ control mice. Histological and biochemical analyses reveal that female mice expressing the MMTV-Cre transgene, either alone or in combination with floxed genes, exhibit defects in lobuloalveolar expansion, presence of large cytoplasmic lipid droplets in luminal alveolar epithelial cells postpartum, and precocious induction of involution. Using a PCR-based genotyping method, the three different founder lines can be distinguished, and we determined that the MMTV-Cre line A, the most widely used MMTV-Cre founder line, exhibits a profound lactation defect that limits its use in studies on mammary gland development. Conclusions/Significance The identification of a lactation defect in the MMTV-Cre line A mice indicates that investigators must use MMTV-Cre alone mice as control in studies that utilize Cre recombinase to excise genes of interest from mammary epithelial cells. Our results also suggest that previous results obtained in studies using the MMTV-Cre line A line should be re-evaluated if the

Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

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Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

2010-01-01

Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

Radiation-induced diploid spermatids in mice

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Hacker-Klom, U; Heiden, Th; Otto, F J; Goehde, W; Mauro, F

1989-05-01

Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute /sup 60/Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author).

Herbicide-induced experimental variegate porphyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs.

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Krijt, J; Stranska, P; Maruna, P; Vokurka, M; Sanitrak, J

1997-01-01

Administration of oxadiazon or oxyfluorfen (1000 ppm in the diet) to male BALB/c mice for 9 days resulted in experimental porphyria, resembling the acute phase of human variegate porphyria. Urinary concentrations of 5-aminolevulinic acid and porphobilinogen reached 1500 and 3000 mumol/L, respectively. Both herbicides caused a decrease of protoporphyrinogen oxidase activity in liver and kidney. Brain protoporphyrinogen oxidase activity was not altered. Liver and kidney porphyrin content increased to 11 and 17 nmol/g, respectively (control mice, 2 nmol/g). Over 50% of liver and kidney porphyrins were in the reduced (porphyrinogen) form. Bile of oxadiazon-treated mice contained 700 nmol/mL of protoporphyrinogen (control mice, 15 nmol/mL). Porphyrin content of the trigeminal nerve increased from 1 nmol/g in control animals to 11 nmol/g in oxadiazon-treated animals, suggesting a possible contribution of peripheral nerve porphyrins to porphyric neuropathy. Mice treated with 125 ppm of oxadiazon in the diet for 9 days excreted moderately elevated levels of porphobilinogen in urine (control mice, less than 50 mumol/L; treated mice, 330 mumol/L). Administration of phenobarbital or phenytoin (single injections on days 7, 8, and 9) increased the urinary porphobilinogen concentration to 3500 mumol/L. This response to porphyrogenic drugs resembles the response observed in human acute porphyrias.

Nesting behavior of house mice (Mus domesticus) selected for increased wheel-running activity.

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Carter, P A; Swallow, J G; Davis, S J; Garland, T

2000-03-01

Nest building was measured in "active" (housed with access to running wheels) and "sedentary" (without wheel access) mice (Mus domesticus) from four replicate lines selected for 10 generations for high voluntary wheel-running behavior, and from four randombred control lines. Based on previous studies of mice bidirectionally selected for thermoregulatory nest building, it was hypothesized that nest building would show a negative correlated response to selection on wheel-running. Such a response could constrain the evolution of high voluntary activity because nesting has also been shown to be positively genetically correlated with successful production of weaned pups. With wheel access, selected mice of both sexes built significantly smaller nests than did control mice. Without wheel access, selected females also built significantly smaller nests than did control females, but only when body mass was excluded from the statistical model, suggesting that body mass mediated this correlated response to selection. Total distance run and mean running speed on wheels was significantly higher in selected mice than in controls, but no differences in amount of time spent running were measured, indicating a complex cause of the response of nesting to selection for voluntary wheel running.

Effect of Jiangzhi tablet on gastrointestinal propulsive function in mice

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Wang, Xiangrong; Geng, Xiuli; Zhao, Jingsheng; Fan, Lili; Zhang, Zhengchen

2018-04-01

This paper aims to study the effect of lipid-lowering tablets on gastric emptying and small intestinal propulsion in mice. Mice were randomly divided into control group, Digestant Pill group, Jiangzhi tablet group, middle dose and small dose, the mice gastric emptying phenolsulfonphthalein, gastric residual rate of phenol red indicator to evaluate the gastric emptying rate, residual rate of detection in mouse stomach; small intestine propulsion and selection of carbon ink as the experimental index. Effects were observed to promote the function of normal mice gastric emptying and intestine. The gastric emptying and small intestinal motor function of normal mice were all promoted by each administration group, and the effect was most obvious in small dose group. The effect of reducing blood lipid on gastrointestinal motility of mice ware obviously enhanced.

Reduced alcohol consumption in mice lacking preprodynorphin.

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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).

High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

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Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

2012-07-01

Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone marrow and spleen.

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Capitano, Maegan L; Chitteti, Brahmananda R; Cooper, Scott; Srour, Edward F; Bartke, Andrzej; Broxmeyer, Hal E

2015-06-01

Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice. Copyright © 2015. Published by Elsevier Inc.

Radioprotection by polyethylene glycol-protein complexes in mice

International Nuclear Information System (INIS)

Gray, B.H.; Stull, R.W.

1983-01-01

Polyethylene glycol of about 5000 D was activated with cyanuric chloride, and the activated compound was complexed to each of three proteins. Polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase were each radioprotectants when administered prophylactically to female B6CBF1 mice before irradiation. The dose reduction factor for these mice was 1.2 when 5000 units of polyethylene glycol-catalase was administered before 60 Co irradiation. Female B6CBF1 mice administered prophylactic intravenous injections of catalase, polyethylene glycol-albumin, or heat-denatured polyethylene glycol-catalase had survival rates similar to phosphate-buffered saline-injected control mice following 60 Co irradiation. Polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase have radioprotective activity in B6CBF1 mice, which appears to depend in part on enzymatic activities of the complex. However, no radioprotective effect was observed in male C57BL/6 mice injected with each polyethylene glycol-protein complex at either 3 or 24 hr before irradiation. The mechanism for radioprotection by these complexes may depend in part on other factors

Effect of Chorda Tympani Nerve Transection on Salt Taste Perception in Mice

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Ishiwatari, Yutaka; Theodorides, Maria L.; Bachmanov, Alexander A.

2011-01-01

Effects of gustatory nerve transection on salt taste have been studied extensively in rats and hamsters but have not been well explored in the mouse. We examined the effects of chorda tympani (CT) nerve transection on NaCl taste preferences and thresholds in outbred CD-1 mice using a high-throughput phenotyping method developed in our laboratory. To measure taste thresholds, mice were conditioned by oral self-administration of LiCl or NaCl and then presented with NaCl concentration series in 2-bottle preference tests. LiCl-conditioned and control NaCl-exposed mice were given bilateral transections of the CT nerve (LiCl-CTX, NaCl-CTX) or were left intact as controls (LiCl-CNT, NaCl-CNT). After recovery from surgery, mice received a concentration series of NaCl (0–300 mM) in 48-h 2-bottle tests. CT transection increased NaCl taste thresholds in LiCl-conditioned mice and eliminated avoidance of concentrated NaCl in control NaCl-exposed mice. This demonstrates that in mice, the CT nerve is important for detection and recognition of NaCl taste and is necessary for the normal avoidance of high concentrations of NaCl. The results of this experiment also show that the method of high-throughput phenotyping of salt taste thresholds is suitable for detecting changes in the taste periphery in mouse genetic studies. PMID:21743094

Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact

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Ting-Lin Yen

2018-04-01

Full Text Available Traumatic brain injury (TBI is one of the leading causes of mortality worldwide and leads to persistent cognitive, sensory, motor dysfunction, and emotional disorders. TBI-caused primary injury results in structural damage to brain tissues. Following the primary injury, secondary injuries which are accompanied by neuroinflammation, microglial activation, and additional cell death subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers, and some types of acute inflammation. In the present study, the neuroprotective effects of platonin against TBI were explored in a controlled cortical impact (CCI injury model in mice. Treatment with platonin (200 µg/kg significantly reduced the neurological severity score, general locomotor activity, and anxiety-related behavior, and improved the rotarod performance of CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin also suppressed messenger (mRNA levels of caspase-3, caspase-1, cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. On the other hand, free radical production after TBI was obviously attenuated in platonin-treated mice. Treatment with platonin exhibited prominent neuroprotective properties against TBI in a CCI mouse model through its anti-inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence collectively indicates that platonin may be a potential therapeutic medicine for use with TBIs.

Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

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Gilly Wolf

2017-06-01

Full Text Available Bilateral common carotid artery stenosis (BCAS models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month and young adult (3 month female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014: on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049, while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05 compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01 and old control mice (p < 0.05. These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

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Goto, Tatsuhiko; Kubota, Yoshifumi; Toyoda, Atsushi

2016-09-01

The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P healthy control mice fed semi-purified and non-purified diets, respectively. These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

The mRNA expression of XRCC repair genes in mice after γ-ray radiation

International Nuclear Information System (INIS)

Wang Qin; Yue Jingyin; Li Jin; Mu Chuanjie; Fan Feiyue

2006-01-01

Objective: To investigate the role of XRCC repair genes in radioresistance of IRM-2 inbred mice. Methods: Northern hybridization was used to measure mRNA expression of XRCC1 and XRCC5 genes in IRM-2 inbred mice. ICR/JCL and 615 after exposure to different doses of γ-ray radiation at different postirradiation time. Results: The levels of XRCC1 and XRCC5 mRNA expression in control IRM-2 mice were higher significantly than those in their control parental mice (P<0.01 and P<0.05). The mRNA expression of XRCC genes in ICR/JCL and 615 mice all increased to some extent after exposure 1, 2 and 4 Gy radiation. But the levels were significantly higher at 2h postirradiation (P<0.05) . The levels of XRCC mRNA expression in IRM-2 mice did not increase significnatly compared with the control mice after exposure 1 and 2 Gy radiation. But the levels of XRCC1 and XRCC5 mRNA expression increased markedly at 4Gy 1h postirradiation (P<0.05 and P<0.01). Conclusion: The basal levels of XRCC1 and XRCC5 mRNA expression in IRM-2 mice were high. The high level of XRCC5 mRNA expression was involved in the repair of DNA double strand breaks induced by higher dose radiation, which perhaps was one of radioresistance causes of IRM-2 mice. (authors)

An anticholinergic reverses motor control and corticostriatal LTD deficits in Dyt1 ΔGAG knock-in mice

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Dang, Mai T.; Yokoi, Fumiaki; Cheetham, Chad C.; Lu, Jun; Vo, Viet; Lovinger, David M.; Li, Yuqing

2011-01-01

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder associated with mutations in DYT1 that codes for torsinA protein. The most common mutation seen in this gene is a trinucleotide deletion of GAG. We previously reported a motor control deficit on a beam-walking task in our Dyt1 ΔGAG knock-in heterozygous mice. In this report we show the reversal of this motor deficit with the anticholinergic trihexyphenidyl (THP), a drug commonly used to treat movement problems in ...

Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With Excess Neuropeptide Y, but Enhances Obesity in Control Mice.

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Ailanen, Liisa; Vähätalo, Laura H; Salomäki-Myftari, Henriikka; Mäkelä, Satu; Orpana, Wendy; Ruohonen, Suvi T; Savontaus, Eriika

2018-01-01

Neuropeptide Y (NPY) plays an important role in the regulation of energy homeostasis in the level of central and sympathetic nervous systems (SNSs). Genetic silencing of peripheral Y 2 -receptors have anti-obesity effects, but it is not known whether pharmacological blocking of peripheral Y 2 -receptors would similarly benefit energy homeostasis. The effects of a peripherally administered Y 2 -receptor antagonist were studied in healthy and energy-rich conditions with or without excess NPY. Genetically obese mice overexpressing NPY in brain noradrenergic nerves and SNS (OE-NPY DβH ) represented the situation of elevated NPY levels, while wildtype (WT) mice represented the normal NPY levels. Specific Y 2 -receptor antagonist, BIIE0246, was administered (1.3 mg/kg/day, i.p.) for 2 or 4.5 weeks to OE-NPY DβH and WT mice feeding on chow or Western diet. Treatment with Y 2 -receptor antagonist increased body weight gain in both genotypes on chow diet and caused metabolic disturbances (e.g., hyperinsulinemia and hypercholesterolemia), especially in WT mice. During energy surplus (i.e., on Western diet), blocking of Y 2 -receptors induced obesity in WT mice, whereas OE-NPY DβH mice showed reduced fat mass gain, hepatic glycogen and serum cholesterol levels relative to body adiposity. Thus, it can be concluded that with normal NPY levels, peripheral Y 2 -receptor antagonist has no potential for treating obesity, but oppositely may even induce metabolic disorders. However, when energy-rich diet is combined with elevated NPY levels, e.g., stress combined with an unhealthy diet, Y 2 -receptor antagonism has beneficial effects on metabolic status.

X-rays and photocarcinogenesis in hairless mice.

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Lerche, Catharina M; Philipsen, Peter A; Wulf, Hans Christian

2013-08-01

It is well known that excessive X-ray radiation can cause non-melanoma skin cancers. With the increased incidence of sun-related skin cancer there is a need to investigate the combination of sunlight and X-rays. Immunocompetent C3.Cg/TifBomTac mice (n = 298) were divided into 12 groups. Mice were irradiated with 12, 29 or 50 kV X-rays. The mice received a total dose of 45 Gy. They were irradiated with 3 SED simulated solar radiation (SSR) either before or after irradiation with X-rays. The groups irradiated with X-rays alone, 0, 3, 9 and 10 mice (0, 12, 29 and 50 kV, respectively) developed squamous cell carcinoma. In the groups irradiated with SSR after X-rays the development of tumours was significantly faster in the 50 kV group than in the corresponding control group (175 vs. 194 days, p X-ray radiation the development of tumours was significantly faster in the 29 and the 50 kV groups than in the corresponding control group (175 vs. 202 days, p X-ray radiation alone is a weak carcinogen in hairless mice. There is an added carcinogenic effect if X-ray radiation is given on prior sun-exposed skin or if the skin is sun-exposed after X-rays. We still believe that X-ray radiation is a safe and effective therapy for various dermatological diseases but caution should be observed if a patient has severely sun-damaged skin or has a high-risk sun behaviour.

Human β-globin locus control region: Analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice

International Nuclear Information System (INIS)

Caterina, J.J.; Ryan, T.M.; Pawlik, K.M.; Townes, T.M.; Brinster, R.L.; Behringer, R.R.; Palmiter, R.D.

1991-01-01

The human β-globin locus control region (LCR) is essential for high-level expression of human var-epsilon-, γ-, and β-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human β-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human β-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletion of both 5' and 3' sequences, a 373-base-pair (BP) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 19-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained

Prenatal effects of ancestral irradiation in inbred mice

International Nuclear Information System (INIS)

Sprackling, L.E.S.

1975-01-01

Mice from 13 inbred strains (S, Z, E, Bab, BaB, BrR, C, K, N, Q, G, CFW, CF1) received continuous cobalt 60 irradiation at low dose rates for varying numbers of consecutive generations. Some Bab and BaB mice had received continuous irradiation for from 24 to 31 generations and the other mice had up to six generations of continuous irradiation in their ancestry. At weaning, the mice were removed from the irradiation room and were mated within strains either to sibs or nonsibs. Ancestral and direct irradiation doses were calculated. The ancestral dose was the effective accumulated dose to the progeny of the mated mice. The direct dose was the amount of irradiation received by any mated female from her conception to her weaning. Each irradiated or control female was scored as fertile or sterile and in utero litter counts were made in pregnant females that were dissected past the tenth day of pregnancy; the sum of moles, dead embryos, and live embryos was the total in utero litter size. A ratio of the living embryos to the total number of embryos in utero was determined for each litter. An increase in ancestral or direct irradiation dose significantly decreased fertility in 11 of the 13 strains. The fertility curves for the pooled data were sigmoid in the area of the doses below those that caused complete sterility. Among the controls, there were significant strain differences in total litter size and in the ratio. Strain X--Y plots, with ancestral or direct doses plotted against total litter size or ratio, revealed the tendency for litter size to decrease as dose increased. The only trend shown for ratio was for the litters with ratios of 0.50 or less to appear more frequently among the irradiated mice. The few corpora lutea counts revealed nothing of significance. Generally, there was a definite trend toward fewer mice alive in utero among the irradiated mice

Rearrangement of Rag-1 recombinase gene in DNA-repair deficient/immunodeficient ``wasted`` mice

Energy Technology Data Exchange (ETDEWEB)

Woloschak, G.E.; Weaver, P.; Churchill, M.; Chang-Liu, C-M. [Argonne National Lab., IL (United States); Libertin, C.R. [Loyola Univ., Maywood, IL (United States)

1992-11-01

Mice recessive for the autosomal gene ``wasted`` (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (Rag-l/Rag-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed that in thymus tissue, a small Rag-I transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{sm_bullet} mice, a two-fold increase in Rag-1 mRNA was evident in thymus tissue. Rag-2 mRNA could only be detected in thymus tissue from wst/{sm_bullet} and not from wst/wst or parental control BCF, mice. Southern blots revealed a rearrangement or deletion within the Rag-1 gene of affected wasted mice that was not evident in known strain-specific parental or littermate controls. These results support the idea that the Rag-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice.

Science.gov (United States)

Niemiec, T; Sikorska, J; Harrison, A; Szmidt, M; Sawosz, E; Wirth-Dzieciolowska, E; Wilczak, J; Pierzynowski, S

2011-02-01

The objective of this study was to evaluate the effect of α-ketoglutarate on redox state parameters and arterial elasticity in elderly mice. Mice in the control group were fed with standard diet, while the experimental animals received the diet supplemented either with calcium (Ca-AKG) or sodium salt of α-ketoglutarate (Na-AKG). The experimental animals were divided into 4 groups with 10 individuals in each: control I (12 months old), control II (2 months old), experimental group I fed with Ca-AKG (12 months old) and experimental group II fed with Na-AKG (12 months old). Mice treated with Ca-AKG as well as the control II animals demonstrated significantly higher level of total antioxidant status (TAS), comparing to the control I animals and those treated with Ca-AKG. Thiobarbituric acid reactive substances (TBARS) level in blood plasma was found significantly lower in young and Ca-AKG treated mice. TBARS liver concentration was significantly different in each examined group. The study also demonstrates the decrease in TBARS level in Ca-AKG treated animals. Treatment with Na-AKG significantly increased glutathione peroxidase activity and decreased the activity of superoxide dismutase. The presented results suggest that Ca-AKG protects the organism against the free radicals related elderly processes. The study presents also the effect of Ca-AKG treatment on arterial elastic characteristics in elderly mice. The beneficial effect of Ca-AKG on ageing organisms was confirmed via redox state stabilization and blood vessel elasticity improvement.

[Study the rudimentary immunoregulatory mechanisms of Ganoderma Spore oil on immunocompromized mice].

Science.gov (United States)

Yi, Youjin; Hu, Shun; Xiong, Xingyao; Liu, Dongbo; Zhong, Yingli

2012-09-01

To study the rudimentary immunoregulatory mechanisms of Ganoderma spore oil on immunocompromized mice model. Thrity KM mice were randomly selected and assigned into three groups (ten animals per group): the model control group, Ganoderma Lucidum spores oil group and the normal control group. The model control group and Ganoderma Lucidum spores oil group were injected intraperitoneally with cyclophosphamide at 40 mg x kg(-1) d to generate a immunocompromized mice model. The normal control group were administered with 0.9% NaCl solution 0.1 ml/10 g BW as placebo. All agents were given orally once a day, given for consecutive 30 days, Ganoderma Lucidum spores oil group 150 mg/kg, the others given maize 0.1 ml/10 g BW. The serum TNF-alpha , IFN-gamma content of the mice through ELISA kit and the expression levels of IL-2, IL-10, IL-12, IL-4, IFN-gamma, TNF-alpha mRNA in mouse spleen and thymus were examined by RT-PCR to rudimentary study its immunoregulatory mechanisms. Ganoderma spore oil can significantly increased the content of TNF-alpha and IFN-gamma in the serum and the expression levels of IL-2, IL-10, IL-12, IL-4, IFN-gamma, TNF-alpha mRNA in spleen and thymus, with obvious difference from the model control (P Ganoderma spore oil can be able to improve the above cytokine ion expression to immunoregulate the immunocompromized mice.

UV-enhanced reactivation of minute-virus-of-mice: stimulation of a late step in the viral life cycle

International Nuclear Information System (INIS)

Rommelaere, J.; Vos, J.-M.; Cornelis, J.J.

1981-01-01

UV-enhanced reactivation of minute-virus-of-mice (MVM), an autonomous parvovirus, was studied in parasynchronous mouse A9 cells. The survival of UV-irradiated MVM is increased in cells which have been UV-irradiated prior to infection. UV-enhanced reactivation can be explained neither by facilitated plaque detection on UV-treated indicator cells, nor by altered kinetics of virus production by UV-irradiated cells. No effect of the multiplicity of infection on virus survival was detected in unirradiated or irradiated cells. The magnitude of UV-enhanced reactivation is a direct exponential function of the UV dose administered to the virus while virus survival is inversely proportional to the UV dosage. The expression of UV-enhanced reactivation can be activated in cells arrested in G 0 , it requires de novo protein synthesis and it is maximal when cells are irradiated 30 h before the onset of viral DNA replication. Early phases of the viral cycle, such as adsorption to cellular receptors, migration to the nucleus and uncoating were not affected by cell irradiation and are unlikely targets of the UV-enhanced reactivation function(s). These results, together with the single-strandedness of the viral genome, strongly suggest that the step stimulated in UV-irradiated cells functions concomitant with, or subsequent to, viral DNA replication. (author)

Influenza Virus-Induced Lung Inflammation Was Modulated by Cigarette Smoke Exposure in Mice

Science.gov (United States)

Han, Yan; Ling, Man To; Mao, Huawei; Zheng, Jian; Liu, Ming; Lam, Kwok Tai; Liu, Yuan; Tu, Wenwei; Lau, Yu-Lung

2014-01-01

Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1) or avian H9N2 (H9N2/G1) virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4+ and CD8+ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed mice, which might

Influenza virus-induced lung inflammation was modulated by cigarette smoke exposure in mice.

Directory of Open Access Journals (Sweden)

Yan Han

Full Text Available Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1 or avian H9N2 (H9N2/G1 virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4+ and CD8+ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed

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

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

Science.gov (United States)

Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

2017-09-05

Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes with age in swimming performance of X-irradiated mice

International Nuclear Information System (INIS)

Norimura, T.; Yoshikawa, I.; Okajima, S.

1980-01-01

The time required to swim 250 cm was determined once weekly for the entire life of fifteen pairs of male dd/K mice. The irradiated group was exposed to a single 224 rad of X-rays at 20 weeks of age. Median survival time (ST 50 ) for the control was 88.9 weeks and that for the irradiated group was 77.4 weeks, and both regression lines relating to death rate and age were parallel. The swimming ability of control mice began to decrease when the mice were 40 weeks of age, after which there was a gradual reduction with age at 0.00646/day. In the irradiated group, the swimming ability decreased from seven weeks after irradiation. The time of 50% reduction of swimming speed (TRS 50 ) for the control was 78.9 weeks and that for the irradiated group was 66.3 weeks, and the slopes of the regression lines relating reduction rate and age were similar. Differences between ST 50 and TRS 50 were 10 weeks in the control and 11 weeks in the irradiated group, respectively. These results indicate that there is no basic difference in the reduction in swimming ability between control and irradiated mice. The X-irradiation may simply mean that the reduction in the swimming ability is displaced to an earlier time with no alteration in the rate of reduction, and that the earlier appearance in the irradiated group is related to premature aging as induced by irradiation. (author)

Mice in Bion-M 1 Space Mission: Training and Selection

Science.gov (United States)

Andreev-Andrievskiy, Alexander; Popova, Anfisa; Boyle, Richard; Alberts, Jeffrey; Shenkman, Boris; Vinogradova, Olga; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Darya; Soldatov, Pavel; Nemirovskaya, Tatyana; Ilyin, Eugeniy; Sychev, Vladimir

2014-01-01

After a 16-year hiatus, Russia has resumed its program of biomedical research in space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19–May 19, 2013). The principal species for biomedical research in this project was the mouse. This paper presents an overview of the scientific goals, the experimental design and the mouse training/selection program. The aim of mice experiments in the Bion-M 1 project was to elucidate cellular and molecular mechanisms, underlying the adaptation of key physiological systems to long-term exposure in microgravity. The studies with mice combined in vivo measurements, both in flight and post-flight (including continuous blood pressure measurement), with extensive in vitro studies carried out shortly after return of the mice and in the end of recovery study. Male C57/BL6 mice group housed in space habitats were flown aboard the Bion-M 1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control groups were used to account for housing effects and possible seasonal differences. Mice training included the co-adaptation in housing groups and mice adaptation to paste food diet. The measures taken to co-adapt aggressive male mice in housing groups and the peculiarities of “space” paste food are described. The training program for mice designated for in vivo studies was broader and included behavioral/functional test battery and continuous behavioral measurements in the home-cage. The results of the preliminary tests were used for the selection of homogenous groups. After the flight, mice were in good condition for biomedical studies and displayed signs of pronounced disadaptation to Earth's gravity. The outcomes of the training program for the mice welfare are discussed. We conclude that our training program was effective and that male mice can be successfully employed in space biomedical research. PMID:25133741

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

International Nuclear Information System (INIS)

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

1990-01-01

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

In Vivo Measurements in Mice in the Bion-M 1 Mission

Science.gov (United States)

Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to

Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice

DEFF Research Database (Denmark)

Buus, Niels Henrik; Hansson, Nicolaj Christopher; Rodriguez-Rodriguez, Rosalia

2011-01-01

were investigated in vitro. Inducible nitric oxide synthase (iNOS) was visualized using immunoblotting. As opposed to WT and fluvastatin- and vehicle-treated mice, OA-fed ApoE(-/-) mice gained no weight during the treatment period. Plasma concentrations of total-cholesterol and triglyceride were...... in combination with OA (100 mg/kg/day), fluvastatin (5 mg/kg/day) or vehicle, with wild type (WT) mice serving as controls. After 8 weeks of treatment atherosclerotic plaque areas in the aortic arch and plasma lipid concentrations were determined. Vasoconstriction and relaxation of the proximal part of aorta...... not significantly reduced by OA- or fluvastatin treatment. Plaque area of vehicle-treated mice was 25%, but only 14% in OA- and 19% in fluvastatin-treated mice. As compared to WT, vasoconstriction to phenylephrine was attenuated in ApoE(-/-) mice. The NOS inhibitor asymmetric dimethylarginine (ADMA) enhanced...

An Object Location Detector Enabling People with Developmental Disabilities to Control Environmental Stimulation through Simple Occupational Activities with Battery-Free Wireless Mice

Science.gov (United States)

Shih, Ching-Hsiang

2011-01-01

This study assessed whether two persons with developmental disabilities would be able to actively perform simple occupational activities by controlling their favorite environmental stimulation using battery-free wireless mice with a newly developed object location detection program (OLDP, i.e., a new software program turning a battery-free…

Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice.

Directory of Open Access Journals (Sweden)

Justin L McCarville

Full Text Available Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg were examined using the novel Mouse Drawer System (MDS aboard the International Space Station (ISS over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2 and transforming growth factor-beta1 (TGF-β1 were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-β1 relative to ground controls. Total colonic TGF-β1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-β1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-β1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

Influence of protein depletion and repletion on lymphocyte activation in adult mice

International Nuclear Information System (INIS)

Elliott, T.S.; Olson, L.M.; Visek, W.J.

1986-01-01

Male 8 month old Balb/c mice were fed 0.5% (Depletion, n = 126) or 6% (Control, n = 16) protein diets for 5 wks. All control and 16 depleted mice were killed (time 0), and the remaining 110 mice were randomly assigned to 1 of 3 diets (3, 6, or 12% protein) and fed for 4, 8, or 32 additional days. Diets were formulated following AIN-76A guidelines with skim milk powder used as the source of protein. Serum albumin and 3 H-thymidine incorporation into splenocytes stimulated by the T-cell mitogens concanavalin A (Con A), or phytohemagglutinin (PHA), and the B-cell mitogen lipopolysaccharide (LPS) were determined. At time 0, mice fed 0.5% protein had lost 32% of their initial body weight and weighed significantly less than controls (19.5 +/- 0.1 g vs 29.9 +/- 0.7 g, p < 0.0001). Protein level did not affect food intake or spleen weight/body weight. Depletion significantly decreased serum albumin concentrations (4.6 +/- 0.1 g/dl vs 6.4 +/- 0.6 g/dl) and responses to PHA and LPS. During repletion mice fed 3% protein weighted significantly less than mice fed 6 or 12% ptn (p < 0.001) despite a significantly higher food intake. The activation of splenocytes by all mitogens increased with time of repletion but was independent of dietary protein concentration

Administration of kefir-fermented milk protects mice against Giardia intestinalis infection.

Science.gov (United States)

Franco, Mariana Correa; Golowczyc, Marina A; De Antoni, Graciela L; Pérez, Pablo F; Humen, Martín; Serradell, María de los Angeles

2013-12-01

Giardiasis, caused by the protozoan Giardia intestinalis, is one of the most common intestinal diseases worldwide and constitutes an important problem for the public health systems of various countries. Kefir is a probiotic drink obtained by fermenting milk with 'kefir grains', which consist mainly of bacteria and yeasts that coexist in a complex symbiotic association. In this work, we studied the ability of kefir to protect mice from G. intestinalis infection, and characterized the host immune response to this probiotic in the context of the intestinal infection. Six- to 8-week-old C75BL/6 mice were separated into four groups: controls, kefir mice (receiving 1 : 100 dilution of kefir in drinking water for 14 days), Giardia mice (infected orally with 4×10(7) trophozoites of G. intestinalis at day 7) and Giardia-kefir mice (kefir-treated G. intestinalis-infected mice), and killed at 2 or 7 days post-infection. Kefir administration was able to significantly reduce the intensity of Giardia infection at 7 days post-infection. An increase in the percentage of CD4(+) T cells at 2 days post-infection was observed in the Peyer's patches (PP) of mice belonging to the Giardia group compared with the control and kefir groups, while the percentage of CD4(+) T cells in PP in the Giardia-kefir group was similar to that of controls. At 2 days post-infection, a reduction in the percentage of B220-positive major histocompatibility complex class II medium cells in PP was observed in infected mice compared with the other groups. At 7 days post-infection, Giardia-infected mice showed a reduction in RcFcε-positive cells compared with the control group, suggesting a downregulation of the inflammatory response. However, the percentages of RcFcε-positive cells did not differ from controls in the kefir and Giardia-kefir groups. An increase in IgA-positive cells was observed in the lamina propria of the kefir group compared with controls at 2 days post-infection. Interestingly, the

The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in Apc Min/+ mice.

Science.gov (United States)

Ono, Junya; Shime, Hiroaki; Takaki, Hiromi; Takashima, Ken; Funami, Kenji; Yoshida, Sumito; Takeda, Yohei; Matsumoto, Misako; Kasahara, Masanori; Seya, Tsukasa

2017-10-17

Intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (MyD88) activation in response to the components of microbiota in Apc Min/+ mice. Microbiota also contains double-stranded RNA (dsRNA), a ligand for TLR3, which activates the toll-like receptor adaptor molecule 1 (TICAM-1, also known as TRIF) pathway. We established Apc Min/+ Ticam1 -/- mice and their survival was compared to survival of Apc Min/+ Myd88 -/- and wild-type (WT) mice. The properties of polyps were investigated using immunofluorescence staining and RT-PCR analysis. We demonstrate that TICAM-1 is essential for suppression of polyp formation in Apc Min/+ mice. TICAM-1 knockout resulted in shorter survival of mice compared to WT mice or mice with knockout of MyD88 in the Apc Min/+ background. Polyps were more frequently formed in the distal intestine of Apc Min/+ Ticam1 -/- mice than in Apc Min/+ mice. Infiltration of immune cells such as CD11b + and CD8α + cells into the polyps was detected histologically. CD11b and CD8α mRNAs were increased in polyps of Apc Min/+ Ticam1 -/- mice compared to Apc Min/+ mice. Gene expression of inducible nitric oxide synthase (iNOS), interferon (IFN)-γ, CXCL9 and IL-12p40 was increased in polyps of Apc Min/+ Ticam1 -/- mice. mRNA and protein expression of c-Myc, a critical transcription factor for inflammation-associated polyposis, were increased in polyps of Apc Min/+ Ticam1 -/- mice. A Lactobacillus strain producing dsRNA was detected in feces of Apc Min/+ mice. These results imply that the TLR3/TICAM-1 pathway inhibits polyposis through suppression of c-Myc expression and supports long survival in Apc Min/+ mice.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

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Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-06-01

The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice

DEFF Research Database (Denmark)

Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

2014-01-01

AIM: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. METHODS...... of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting...... responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar...

Growth restriction, leptin, and the programming of adult behavior in mice.

Science.gov (United States)

Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

2014-12-15

Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, phormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective effects of SGLT2 inhibitor luseogliflozin on pancreatic β-cells in obese type 2 diabetic db/db mice

Energy Technology Data Exchange (ETDEWEB)

Okauchi, Seizo, E-mail: okauchi@med.kawasaki-m.ac.jp; Shimoda, Masashi; Obata, Atsushi; Kimura, Tomohiko; Hirukawa, Hidenori; Kohara, Kenji; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki

2016-02-12

It is well known that Sodium-Glucose Co-transporter 2 (SGLT2) inhibitors, new hypoglycemic agents, improve glycemic control by increasing urine glucose excretion, but it remained unclear how they exert protective effects on pancreatic β-cells. In this study, we examined the effects of SGLT2 inhibitor luseogliflozin on β-cell function and mass using obese type 2 diabetic db/db mice. Ten-week-old male diabetic db/db mice were treated with luseogliflozin 0.0025% or 0.01% in chow (Luse 0.0025% or Luse 0.01%) or vehicle (control) for 4 weeks. Urinary glucose excretion was increased in Luse groups (0.0025% and 0.01%) compared to control mice 3 days after the intervention. Fasting blood glucose levels were significantly lower in mice treated with Luse compared to control mice. Fasting serum insulin concentrations were significantly higher in mice treated with Luse compared to control mice. Triglyceride levels tended to be lower in Luse groups compared to control mice. In immunohistochemical study using pancreas tissues, β-cell mass was larger in Luse groups compared to control group which was due to the increase of β-cell proliferation and decrease of β-cell apoptosis. Furthermore, in gene analysis using isolated islets, insulin 1, insulin 2, MafA, PDX-1 and GLUT2 gene expression levels were significantly higher in Luse groups compared to control group. In contrast, expression levels of fibrosis-related gene such as TGFβ, fibronectin, collagen I and collagen III were significantly lower in Luse groups. In conclusion, SGLT2 inhibitor luseogliflozin ameliorates glycemic control and thus exerts protective effects on pancreatic β-cell mass and function. - Highlights: • SGLT2 inhibitor luseogliflozin ameliorates glycemic control in db/db mice. • Luseogliflozin increases β-cell proliferation and decreases β-cell apoptosis. • Luseogliflozin preserves various β-cell-specific gene expression. • Luseogliflozin decreases various fibrosis-related factors in db

Protective effects of SGLT2 inhibitor luseogliflozin on pancreatic β-cells in obese type 2 diabetic db/db mice

International Nuclear Information System (INIS)

Okauchi, Seizo; Shimoda, Masashi; Obata, Atsushi; Kimura, Tomohiko; Hirukawa, Hidenori; Kohara, Kenji; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki

2016-01-01

It is well known that Sodium-Glucose Co-transporter 2 (SGLT2) inhibitors, new hypoglycemic agents, improve glycemic control by increasing urine glucose excretion, but it remained unclear how they exert protective effects on pancreatic β-cells. In this study, we examined the effects of SGLT2 inhibitor luseogliflozin on β-cell function and mass using obese type 2 diabetic db/db mice. Ten-week-old male diabetic db/db mice were treated with luseogliflozin 0.0025% or 0.01% in chow (Luse 0.0025% or Luse 0.01%) or vehicle (control) for 4 weeks. Urinary glucose excretion was increased in Luse groups (0.0025% and 0.01%) compared to control mice 3 days after the intervention. Fasting blood glucose levels were significantly lower in mice treated with Luse compared to control mice. Fasting serum insulin concentrations were significantly higher in mice treated with Luse compared to control mice. Triglyceride levels tended to be lower in Luse groups compared to control mice. In immunohistochemical study using pancreas tissues, β-cell mass was larger in Luse groups compared to control group which was due to the increase of β-cell proliferation and decrease of β-cell apoptosis. Furthermore, in gene analysis using isolated islets, insulin 1, insulin 2, MafA, PDX-1 and GLUT2 gene expression levels were significantly higher in Luse groups compared to control group. In contrast, expression levels of fibrosis-related gene such as TGFβ, fibronectin, collagen I and collagen III were significantly lower in Luse groups. In conclusion, SGLT2 inhibitor luseogliflozin ameliorates glycemic control and thus exerts protective effects on pancreatic β-cell mass and function. - Highlights: • SGLT2 inhibitor luseogliflozin ameliorates glycemic control in db/db mice. • Luseogliflozin increases β-cell proliferation and decreases β-cell apoptosis. • Luseogliflozin preserves various β-cell-specific gene expression. • Luseogliflozin decreases various fibrosis-related factors in db

Protein restriction does not affect body temperature pattern in female mice.

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Kato, Goro A; Shichijo, Hiroki; Takahashi, Toshihiro; Shinohara, Akio; Morita, Tetsuo; Koshimoto, Chihiro

2017-10-30

Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.

Oxidative dissolution of unirradiated Mimas MOX fuel (U/Pu oxides) in carbonated water under oxic and anoxic conditions

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Odorowski, Mélina [CEA/DEN/DTCD/SECM/LMPA, BP 17171, 30207 Bagnols-sur-Cèze Cedex (France); MINES ParisTech, PSL Research University, Centre de Géosciences, 35 rue St Honoré, 77305 Fontainebleau (France); Jégou, Christophe, E-mail: christophe.jegou@cea.fr [CEA/DEN/DTCD/SECM/LMPA, BP 17171, 30207 Bagnols-sur-Cèze Cedex (France); De Windt, Laurent [MINES ParisTech, PSL Research University, Centre de Géosciences, 35 rue St Honoré, 77305 Fontainebleau (France); Broudic, Véronique; Peuget, Sylvain; Magnin, Magali; Tribet, Magaly [CEA/DEN/DTCD/SECM/LMPA, BP 17171, 30207 Bagnols-sur-Cèze Cedex (France); Martin, Christelle [Agence nationale pour la gestion des déchets radioactifs (Andra), DRD/CM, 1-7 rue Jean-Monnet, 92298 Châtenay-Malabry Cedex (France)

2016-01-15

Few studies exist concerning the alteration of Mimas Mixed-OXide (MOX) fuel, a mixed plutonium and uranium oxide, and data is needed to better understand its behavior under leaching, especially for radioactive waste disposal. In this study, two leaching experiments were conducted on unirradiated MOX fuel with a strong alpha activity (1.3 × 10{sup 9} Bq.g{sub MOX}{sup −1} reproducing the alpha activity of spent MOX fuel with a burnup of 47 GWd·t{sub HM}{sup −1} after 60 years of decay), one under air (oxic conditions) for 5 months and the other under argon (anoxic conditions with [O{sub 2}] < 1 ppm) for one year in carbonated water (10{sup −2} mol L{sup −1}). For each experiment, solution samples were taken over time and Eh and pH were monitored. The uranium in solution was assayed using a kinetic phosphorescence analyzer (KPA), plutonium and americium were analyzed by a radiochemical route, and H{sub 2}O{sub 2} generated by the water radiolysis was quantified by chemiluminescence. Surface characterizations were performed before and after leaching using Scanning Electron Microscopy (SEM), Electron Probe Microanalyzer (EPMA) and Raman spectroscopy. Solubility diagrams were calculated to support data discussion. The uranium releases from MOX pellets under both oxic and anoxic conditions were similar, demonstrating the predominant effect of alpha radiolysis on the oxidative dissolution of the pellets. The uranium released was found to be mostly in solution as carbonate species according to modeling, whereas the Am and Pu released were significantly sorbed or precipitated onto the TiO{sub 2} reactor. An intermediate fraction of Am (12%) was also present as colloids. SEM and EPMA results indicated a preferential dissolution of the UO{sub 2} matrix compared to the Pu-enriched agglomerates, and Raman spectroscopy showed the Pu-enriched agglomerates were slightly oxidized during leaching. Unlike Pu-enriched zones, the UO{sub 2} grains were much more

Immunotoxicological evaluation of wheat genetically modified with TaDREB4 gene on BALB/c mice.

Science.gov (United States)

Liang, Chun Lai; Zhang, Xiao Peng; Song, Yan; Jia, Xu Dong

2013-08-01

To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. Female mice weighing 18-22 g were divided into five groups (10 mice/group), which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat (the proportion is 76%) for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected. No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group. From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Dietary oligofructose and inulin protect mice from enteric and systemic pathogens and tumor inducers.

Science.gov (United States)

Buddington, Karyl K; Donahoo, Jillian B; Buddington, Randal K

2002-03-01

Prebiotics induce changes in the population and metabolic characteristics of the gastrointestinal bacteria, modulate enteric and systemic immune functions, and provide laboratory rodents with resistance to carcinogens that promote colorectal cancer. There is less known about protection from other challenges. Therefore, mice of the B6C3F1 strain were fed for 6 wk a control diet with 100 g/kg cellulose or one of two experimental diets with the cellulose replaced entirely by the nondigestible oligosaccharides (NDO) oligofructose and inulin. From each diet, 25 mice were challenged by a promoter of colorectal cancer (1,2-dimethylhydrazine), B16F10 tumor cells, the enteric pathogen Candida albicans (enterically), or were infected systemically with Listeria monocytogenes or Salmonella typhimurium. The incidences of aberrant crypt foci in the distal colon after exposure to dimethylhdrazine for mice fed inulin (53%) and oligofructose (54%) were lower than in control mice (76%; P 80% for control mice), but fewer of the mice fed inulin died (60%; P dietary NDO was not elucidated, but the findings are consistent with enhanced immune functions in response to changes in the composition and metabolic characteristics of the bacteria resident in the gastrointestinal tract.

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

Science.gov (United States)

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

2015-12-01

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

High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

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Peng Lu

Full Text Available BACKGROUND: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate, the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate, the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF diet and high beta-palmitate fat (HBPF diet on colitis development in Muc2 deficient (Muc2(-/- mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. METHODS: Muc2(-/- mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. RESULTS: Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/- mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1, genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. CONCLUSIONS: This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/- mice by inducing an immunosuppressive Treg cell response.

High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

Science.gov (United States)

Lu, Peng; Bar-Yoseph, Fabiana; Levi, Liora; Lifshitz, Yael; Witte-Bouma, Janneke; de Bruijn, Adrianus C J M; Korteland-van Male, Anita M; van Goudoever, Johannes B; Renes, Ingrid B

2013-01-01

Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate), the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF) diet and high beta-palmitate fat (HBPF) diet on colitis development in Muc2 deficient (Muc2(-/-)) mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. Muc2(-/-) mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/-) mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg) cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1), genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/-) mice by inducing an immunosuppressive Treg cell response.

Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice.

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Vincent Marion

Full Text Available Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass (fl and Villin-Cre mice. Unexpectedly, Ass (fl/fl /VilCre (tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice. Relative to control mice, citrulline production in the splanchnic region of Ass (fl/fl /VilCre (tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass (fl/fl /VilCre (tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2 and transport (Slc25a13, Slc25a15, and Slc3a2, whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver.

Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice.

Science.gov (United States)

Rossi, Emily L; de Angel, Rebecca E; Bowers, Laura W; Khatib, Subreen A; Smith, Laura A; Van Buren, Eric; Bhardwaj, Priya; Giri, Dilip; Estecio, Marcos R; Troester, Melissa A; Hair, Brionna Y; Kirk, Erin L; Gong, Ting; Shen, Jianjun; Dannenberg, Andrew J; Hursting, Stephen D

2016-05-01

Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable with control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL6 levels, expression of proinflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus nonobese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression. Cancer Prev Res; 9(5); 339-48. ©2016 AACR. ©2016 American Association for Cancer Research.

Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure.

Science.gov (United States)

Hill, Cristal M; Fang, Yimin; Miquet, Johanna G; Sun, Liou Y; Masternak, Michal M; Bartke, Andrzej

2016-06-01

Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Antidepressant effects of Mentha pulegium in mice

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Zahra Rabiei

2016-09-01

Full Text Available The aim of this study is to investigate the antidepressant effects of Mentha pulegium essential oil in BALB/c mice. Six experimental groups (7 mice each were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving M. pulegium essential oil (50, 75 and 100 mg/kg, immobility duration significantly decreased compared to the control group. M. pulegium (50 and 75 mg/kg resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. M. pulegium essential oil antidepressant effect that may be due to the inhibition of oxidative stress. The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.

241Am distribution and retention in pregnant mice, in their offspring and in non-pregnant mice: comparison between continuous Am administration and single injection

International Nuclear Information System (INIS)

Huevel, R. Van Den; Vander Plaetse, F.; Leppens, H.; Schoeters, G.

1992-01-01

Pregnant BALB/c mice and age and sex matched nulliparous controls were contaminated with 241 Am (13 kBq per mouse). Five days after the termination of contamination, 241 Am incorporation was measured in the tissues of adults and in the liver an the femur of newborn and one-month-old mice. Pregnancy resulted in higher 241 Am concentrations in bone but lower concentrations in the liver of the mothers. Protracted administration of 241 Am compared to a single injection resulted in a lower concentration of 241 Am in the livers of pregnant mice, their nulliparous controls and from newborn mice. The higher 241 Am concentration in the femur at birth after protected exposure before 14 days of gestation compared to protracted exposure after 14 days of gestation could reflect the increased placental transfer of 241 Am with advancing gestational age. Radiation doses to the femur were estimated between 4 and 20 mGy. Haemopoietic changes were noticed at these dose levels in all groups until at least 6 months after birth. (author)

Release of zinc from the brain of El (epilepsy) mice during seizure induction.

Science.gov (United States)

Takeda, A; Hanajima, T; Ijiro, H; Ishige, A; Iizuka, S; Okada, S; Oku, N

1999-05-15

Brain distribution after i.v. injection of 65ZnCl2 into El mice, an animal model of genetically determined epilepsy, was studied by autoradiography to study the utilization of zinc in the brain. The distribution of 65Zn in the brain of El mice 6 days after injection was almost the same as that of ddY (normal) mice, suggesting that the uptake of zinc by the brain of El mice is normal. To study the movement of zinc in the brain in the course of seizure induction, the concentrations of 65Zn in the brain of seizure-afflicted and untreated control El mice were compared 20 days after 65Zn injection. The concentration of 65Zn in the brain of seized El mice was overall lower than that of control El mice; the concentration of 65Zn was decreased notably in the piriform cortex and amygdaloid nuclei complex during convulsion. These results suggest that the release of zinc from the El mouse brain is enhanced during convulsion. The decrease in actively functioning zinc in the brain may be associated with the increase in susceptibility to seizure in the El mouse. Copyright 1999 Elsevier Science B.V.

Placental and lactating transfer of 147Pm in mice

International Nuclear Information System (INIS)

Tao Feng; Zhu Shoupeng

1990-08-01

The placental and lactating transfer of 147 Pm in late pregnant mice and lactating mice as well as the distribution of 147 Pm in some organs of mother mice were studied and compared. The pregnant mice and lactating mice had intravenous injection with 147 Pm nitrate at the 17th day of gestation and the next day of parturition respectively. The two groups were sacrified at the 1st, 4th, 9th, 14th and 21st day after the injection. The retentions of 147 Pm in the liver, right femur, uterus, spleen, placenta, fetal membrane and litter were determined by the method of liquid scintillation. The results showed that the amount of 147 Pm in litters of both groups was increasing with the days after injection. In the 1st and 4th day of injection the amount of 147 Pm in litters of lactating mice was 20 times higher than those in litters of pregnant mice. The amount of 147 Pm in livers and skeletons and the half-retention time of prenant and lactating dams were much greater than those of control group

In vitro development of embryos from experimentally Kerack-addicted Mice

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Elham Mohammadzadeh

2017-08-01

Full Text Available Background: Prenatal drug exposure, as a common public health concern, is associated with an increased risk of adverse effects on early embryo development. Objective: To investigate the in vitro development of - embryo from experimentally Kerack-addicted mice. Materials and Methods: Twenty-five female mice were studied in five groups: control, vehicle, and three experimental groups of Kerack-dependent mice (I, II, and III which received different doses of Kerack for 14 days. After the establishment of addiction model (7 days, experimental groups I, II, and III were given Kerack intraperitoneally at the doses of 5, 35, and 70 mg/kg, twice a day for a period of 7 days, respectively. The vehicle group received normal saline and lemon juice whilst the control group just received water and food. Morulae were obtained through oviduct flashing. The survived embryos were cultured in T6+ 5mg/ml bovine serum albumin. The developmental rates up to hatched stage daily and embryo quality (differential staining and Tunnel staining were also assessed Results: The developmental potential of embryos obtained from the addicted mother was significantly decreased in comparison with control group. There was a significant reduction in the rate of blastocyst formation in the high dose Kerack dependent group. However, in addicted mice there was reduction in the total cell number (40.92% vs. 65.08% in control and, inner cell mass percentage (17.17% vs. 26.15% in control while apoptotic cells numbers were increased (7.17 vs. 1.46 in control (p<0.05. Conclusion: The Kerack addiction during pregnancy retards preimplantation development and induces apoptosis.

Pelaksanaan Manajemen Mice (Meeting Incentive Convention Exhibition) di Hotel Pangeran Pekanbaru

OpenAIRE

Achmnes, Syofia; Siregar, Damara Saputra

2014-01-01

Implementation of MICE management operationalize theoretical concepts inthe book P.Hasibuan Terry GR (2005) that state that the management process consistsof: planning, organizing, actuating, and controlling.Growing MICE industry in Indonesia, including the city of Pekanbaru. CityGoverment continues to initiate Pekanbaru city as MICE city in Sumatera. One of theleading institutions that have a major role in the realization of this idea is thePangeran hotel Pekanbaru. which is a four-star hote...

Lipid metabolism and body composition in Gclm(-/-) mice

Energy Technology Data Exchange (ETDEWEB)

Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

2011-12-15

In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

Science.gov (United States)

Goetz, Lindsey; Laskowski, Jennifer; Renner, Brandon; Pickering, Matthew C; Kulik, Liudmila; Klawitter, Jelena; Stites, Erik; Christians, Uwe; van der Vlag, Johan; Ravichandran, Kameswaran; Holers, V Michael; Thurman, Joshua M

2018-05-01

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

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Andrea R. Durrant

2012-06-01

Full Text Available The cholinesterases, acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase, are abundant in the nervous system and in other tissues. The role of acetylcholinesterase in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates acetylcholinesterase and butyrylcholinesterase in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While acetylcholinesterase in mdx-sera is elevated, butyrylcholinesterase is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T is a negative modulator of butyrylcholinesterase, but not of acetylcholinesterase, in male mouse sera. T-removal elevated both butyrylcholinesterase activity and the butyrylcholinesterase/acetylcholinesterase ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

Increased Melanoma Growth and Metastasis Spreading in Mice Overexpressing Placenta Growth Factor

Science.gov (United States)

Marcellini, Marcella; De Luca, Naomi; Riccioni, Teresa; Ciucci, Alessandro; Orecchia, Angela; Lacal, Pedro Miguel; Ruffini, Federica; Pesce, Maurizio; Cianfarani, Francesca; Zambruno, Giovanna; Orlandi, Augusto; Failla, Cristina Maria

2006-01-01

Placenta growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in adult pathological angiogenesis. To further investigate PlGF functions in tumor growth and metastasis formation, we used transgenic mice overexpressing PlGF in the skin under the control of the keratin 14 promoter. These animals showed a hypervascularized phenotype of the skin and increased levels of circulating PlGF with respect to their wild-type littermates. Transgenic mice and controls were inoculated intradermally with B16-BL6 melanoma cells. The tumor growth rate was fivefold increased in transgenic animals compared to wild-type mice, in the presence of a similar percentage of tumor necrotic tissue. Tumor vessel area was increased in transgenic mice as compared to controls. Augmented mobilization of endothelial and hematopoietic stem cells from the bone marrow was observed in transgenic animals, possibly contributing to tumor vascularization. The number and size of pulmonary metastases were significantly higher in transgenic mice compared to wild-type littermates. Finally, PlGF promoted tumor cell invasion of the extracellular matrix and increased the activity of selected matrix metalloproteinases. These findings indicate that PlGF, in addition to enhancing tumor angiogenesis and favoring tumor growth, may directly influence melanoma dissemination. PMID:16877362