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Sample records for prenatally irradiated mice

  1. Effects of prenatal irradiation on the development of cerebral cortex and corpus callosum of the mouse

    SciTech Connect

    Schmidt, S.L.; Lent, R.

    1987-10-08

    Defects of the cerebral cortex and corpus callosum of mice subjected prenatally to gamma irradiation were evaluated as a function of dose and of embryonic age at irradiation. Pregnant mice were exposed to a gamma source at 16, 17, and 19 days of gestation (E16, E17, and E19, respectively), with total doses of 2 Gy and 3 Gy, in order to produce brain defects on their progeny. At 60 postnatal days, the brains of the offspring were analyzed qualitatively and quantitatively and compared with those of nonirradiated animals. Mice irradiated at E16 were all acallosal. Those that were exposed to 2 Gy displayed an aberrant longitudinal bundle typical of other acallosals, but this was not the case in those irradiated with 3 Gy. The corpus callosum of animals irradiated at E17 with 3 Gy was pronouncedly hypotrophic, but milder effects were observed in the other groups. Quantitative analysis confirmed a dependence of callosal midsagittal area upon dose and age at irradiation, and, in addition, indicated an interaction between these variables. The neocortex of irradiated animals was hypotrophic: layers II-III were much more affected than layer V, and this was more affected than layer VI. Quantitative analysis indicated that this effect also depended on dose and age at irradiation and that it was due to a loss of cortical neurons. Furthermore, a positive correlation was found between the number of neurons within layers II-III, and V and the midsagittal area of the corpus callosum. Ectopic neurons were found in the white matter and in layer I of animals irradiated at E16 and E17, indicating that fetal exposure to ionizing radiation interfered with the migration of cortical neuroblasts.

  2. Effects of prenatal stress on sexual partner preference in mice.

    PubMed

    Meek, Leslie R; Schulz, Kalynn M; Keith, Courtney A

    2006-09-30

    Three-month old, male Swiss Webster mice were born to either control dams or dams who had been prenatally stressed with light, heat, noise and handling during the last week of gestation. As adults, male offspring were tested on sexual partner preference and sexual behavior (mounting, intromissions and lordosis) with a sexually experienced male stimulus animal and a stimulus estrous female. In comparison to males born to control dams, prenatally stressed males showed a sexual partner preference for the sexually active male as demonstrated by a negative partner preference score, more and longer visits to the male's compartment, fewer and shorter visits to the female's compartment and longer latencies to and lower frequencies of mounts and intromissions of females. In addition, stressed males showed a greater frequency of lordosis and a higher lordosis quotient than did control males. This study is the first to investigate the effects of prenatal stress alone, without hormonal manipulation, on sexual partner preference using both a partner preference paradigm and measures of sexual behavior such as mounting, intromissions and lordosis. These findings support the suggestion that prenatal stress alone is enough to significantly affect sexual partner preference in male mice.

  3. Effects of prenatal stress on sexual partner preference in mice.

    PubMed

    Meek, Leslie R; Schulz, Kalynn M; Keith, Courtney A

    2006-09-30

    Three-month old, male Swiss Webster mice were born to either control dams or dams who had been prenatally stressed with light, heat, noise and handling during the last week of gestation. As adults, male offspring were tested on sexual partner preference and sexual behavior (mounting, intromissions and lordosis) with a sexually experienced male stimulus animal and a stimulus estrous female. In comparison to males born to control dams, prenatally stressed males showed a sexual partner preference for the sexually active male as demonstrated by a negative partner preference score, more and longer visits to the male's compartment, fewer and shorter visits to the female's compartment and longer latencies to and lower frequencies of mounts and intromissions of females. In addition, stressed males showed a greater frequency of lordosis and a higher lordosis quotient than did control males. This study is the first to investigate the effects of prenatal stress alone, without hormonal manipulation, on sexual partner preference using both a partner preference paradigm and measures of sexual behavior such as mounting, intromissions and lordosis. These findings support the suggestion that prenatal stress alone is enough to significantly affect sexual partner preference in male mice. PMID:16844154

  4. Effects of prenatal cocaine exposure on social development in mice

    PubMed Central

    Kabir, Zeeba D.; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet; Kosofsky, Barry E.

    2014-01-01

    Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial PFC (mPFC), specifically BDNF and its downstream signaling molecule, egr1 have been shown to affect the regulation of social interactions (SI). In this study we determined the effects of PCE on SI and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in constitutive expression of BDNF, egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered SI. In prenatal cocaine exposed (PCOC) mice we identified increased SI and USV production at P25, and increased SI but not USVs, at P35. By P45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA in the mPFC of PCOC mice at P30 that normalized by P45. This was concurrent with increased egr1 protein in the mPFC of PCOC mice at P30 suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acH3K9,14, and MeCP2 at the promoters of BDNF exons I and IV, and egr1, our results provide evidence of promoter specific alterations in the mPFC of PCOC juvenile mice with increased association of acH3K9,14 only at the BDNF exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiologic mechanism mediating the altered social development in juvenile mice. PMID:24852757

  5. Disentangling prenatal and postnatal maternal genetic effects reveals persistent prenatal effects on offspring growth in mice.

    PubMed

    Wolf, Jason B; Leamy, Larry J; Roseman, Charles C; Cheverud, James M

    2011-11-01

    Mothers are often the most important determinant of traits expressed by their offspring. These "maternal effects" (MEs) are especially crucial in early development, but can also persist into adulthood. They have been shown to play a role in a diversity of evolutionary and ecological processes, especially when genetically based. Although the importance of MEs is becoming widely appreciated, we know little about their underlying genetic basis. We address the dearth of genetic data by providing a simple approach, using combined genotype information from parents and offspring, to identify "maternal genetic effects" (MGEs) contributing to natural variation in complex traits. Combined with experimental cross-fostering, our approach also allows for the separation of pre- and postnatal MGEs, providing rare insights into prenatal effects. Applying this approach to an experimental mouse population, we identified 13 ME loci affecting body weight, most of which (12/13) exhibited prenatal effects, and nearly half (6/13) exhibiting postnatal effects. MGEs contributed more to variation in body weight than the direct effects of the offsprings' own genotypes until mice reached adulthood, but continued to represent a major component of variation through adulthood. Prenatal effects always contributed more variation than postnatal effects, especially for those effects that persisted into adulthood. These results suggest that MGEs may be an important component of genetic architecture that is generally overlooked in studies focused on direct mapping from genotype to phenotype. Our approach can be used in both experimental and natural populations, providing a widely practicable means of expanding our understanding of MGEs.

  6. Disentangling Prenatal and Postnatal Maternal Genetic Effects Reveals Persistent Prenatal Effects on Offspring Growth in Mice

    PubMed Central

    Wolf, Jason B.; Leamy, Larry J.; Roseman, Charles C.; Cheverud, James M.

    2011-01-01

    Mothers are often the most important determinant of traits expressed by their offspring. These “maternal effects” (MEs) are especially crucial in early development, but can also persist into adulthood. They have been shown to play a role in a diversity of evolutionary and ecological processes, especially when genetically based. Although the importance of MEs is becoming widely appreciated, we know little about their underlying genetic basis. We address the dearth of genetic data by providing a simple approach, using combined genotype information from parents and offspring, to identify “maternal genetic effects” (MGEs) contributing to natural variation in complex traits. Combined with experimental cross-fostering, our approach also allows for the separation of pre- and postnatal MGEs, providing rare insights into prenatal effects. Applying this approach to an experimental mouse population, we identified 13 ME loci affecting body weight, most of which (12/13) exhibited prenatal effects, and nearly half (6/13) exhibiting postnatal effects. MGEs contributed more to variation in body weight than the direct effects of the offsprings’ own genotypes until mice reached adulthood, but continued to represent a major component of variation through adulthood. Prenatal effects always contributed more variation than postnatal effects, especially for those effects that persisted into adulthood. These results suggest that MGEs may be an important component of genetic architecture that is generally overlooked in studies focused on direct mapping from genotype to phenotype. Our approach can be used in both experimental and natural populations, providing a widely practicable means of expanding our understanding of MGEs. PMID:21890739

  7. Subacute exposure to 50-Hz electromagnetic fields affect prenatal and neonatal mice's motor coordination

    NASA Astrophysics Data System (ADS)

    Sakhnini, Lama; Ali, Hassan Al; Qassab, Narjis Al; Arab, Eman Al; Kamal, Amer

    2012-04-01

    In this study, we investigate the possible effect of ELF-EMFs on motor performance in mice (prenatal and neonatal exposed mice). The mice performance is evaluated after 5 days of subacute exposure. Immature mice have been chosen for this study because the immature rodent brain still has the capacity to undergo proliferation, differentiation, and reorganization. Results from the rotarod experiments demonstrated a pronounced deficit in the learning abilities of the prenatal exposed groups, but no pronounced effect was observed for the neonatal exposed group.

  8. Effects of low-dose prenatal irradiation on the central nervous system

    SciTech Connect

    Not Available

    1992-04-01

    Scientists are in general agreement about the effects of prenatal irradiation, including those affecting the central nervous system (CNS). Differing concepts and research approaches have resulted in some uncertainties about some quantitative relationships, underlying interpretations, and conclusions. Examples of uncertainties include the existence of a threshold, the quantitative relationships between prenatal radiation doses and resulting physical and functional lesions, and processes by which lesions originate and develop. A workshop was convened in which scientists with varying backgrounds and viewpoints discussed these relationships and explored ways in which various disciplines could coordinate concepts and methodologies to suggest research directions for resolving uncertainties. This Workshop Report summarizes, in an extended fashion, salient features of the presentations on the current status of our knowledge about the radiobiology and neuroscience of prenatal irradiation and the relationships between them.

  9. Reproductive and genetic effects of continuous prenatal irradiation in the pig

    SciTech Connect

    Erickson, B.H.; Martin, P.G.

    1984-08-01

    The stem germ cells of the prenatal pig are highly vulnerable to the cytotoxic effects of ionizing irradiation. This study was conducted to determine whether sensitivity to killing was also marked by a sensitivity to mutation and how prenatal depletion of the germ-cell population affects reproductive performance. Germ-cell populations were reduced by continuously irradiating sows at dose rates of either 0.25 or 1.0 rad/day for the first 108 days of gestation. The prenatally irradiated boars were tested for sperm-producing ability, sperm abnormalities, dominant lethality, reciprocal translocations, and fertility. Prenatally irradiated females were allowed to bear and nurture one litter, then tested for dominant lethality in a second litter; germ cell survival and follicular development were assessed in their serially sectioned ovaries. Sperm production was not significantly affected in the 0.25-rad boars, but boars irradiated with 1.0 rad per day produced sperm at only 17% of the control level. Incidence of defective sperm was 4.9% and 11.1% in the 0.25 and 1.0 groups, respectively. Four of the 1.0-rad boars were infertile, but prenatal irradiation apparently caused neither dominant lethality nor reciprocal translocations in fertile males. Number of oocytes was reduced to 66 +/- 7% of control in the 0.25-rad gilts, but reproductive performance was unaffected and no dominant lethality was observed. Only 7 +/- 1% of the oocytes survived in the 1.0-rad group. Reproductive performance was normal for the first litter, but four of the 23 sows tested were infertile at the second litter and a significant incidence of dominant lethality was observed.

  10. Prenatal stress induces vulnerability to stress together with the disruption of central serotonin neurons in mice.

    PubMed

    Miyagawa, Kazuya; Tsuji, Minoru; Ishii, Daisuke; Takeda, Kotaro; Takeda, Hiroshi

    2015-01-15

    A growing body of evidence suggests that prenatal stress increases the vulnerability to neuropsychiatric disorders. On the other hand, the ability to adapt to stress is an important defensive function of a living body, and disturbance of this stress adaptability may be related, at least in part, to the pathophysiology of stress-related psychiatric disorders. The aim of the present study was to clarify the relationship between exposure to prenatal stress and the ability to adapt to stress in mice. Naive and prenatally stressed mice were exposed to repeated restraint stress for 60 min/day for 7 days. After the final exposure to restraint stress, the emotionality of mice was evaluated in terms of exploratory activity, i.e., total distance moved as well as the number and duration of rearing and head-dipping behaviors, using an automatic hole-board apparatus. A single exposure to restraint stress for 60 min induced a decrease in head-dipping behavior in the hole-board test. This acute emotional stress response disappeared in naive mice that had been exposed to repeated restraint stress for 60 min/day for 7 days, which confirmed the development of stress adaptation. In contrast, prenatally stressed mice did not develop this stress adaptation, and still showed a decrease in head-dipping behavior after the repeated exposure to restraint stress. Biochemical studies showed that the rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase, was increased in raphe obtained from stress-adapted mice. In contrast, a decrease in tryptophan hydroxylase was observed in stress-maladaptive mice. In addition, the transcription factor Lmx1b, which is essential for differentiation and the maintenance of normal functions in central 5-HT neurons, was decreased in the embryonic hindbrain and adult raphe of prenatally stressed mice. These findings suggest that exposure to excessive prenatal stress may induce a vulnerability to stress and disrupt the development of 5-HT neurons.

  11. Prenatal exposure to phencyclidine produces abnormal behaviour and NMDA receptor expression in postpubertal mice.

    PubMed

    Lu, Lingling; Mamiya, Takayoshi; Lu, Ping; Toriumi, Kazuya; Mouri, Akihiro; Hiramatsu, Masayuki; Kim, Hyoung-Chun; Zou, Li-Bo; Nagai, Taku; Nabeshima, Toshitaka

    2010-08-01

    Several studies have shown the disruptive effects of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists on neurobehavioural development. Based on the neurodevelopment hypothesis of schizophrenia, there is growing interest in animal models treated with NMDA antagonists at developing stages to investigate the pathogenesis of psychological disturbances in humans. Previous studies have reported that perinatal treatment with phencyclidine (PCP) impairs the development of neuronal systems and induces schizophrenia-like behaviour. However, the adverse effects of prenatal exposure to PCP on behaviour and the function of NMDA receptors are not well understood. This study investigated the long-term effects of prenatal exposure to PCP in mice. The prenatal PCP-treated mice showed hypersensitivity to a low dose of PCP in locomotor activity and impairment of recognition memory in the novel object recognition test at age 7 wk. Meanwhile, the prenatal exposure reduced the phosphorylation of NR1, although it increased the expression of NR1 itself. Furthermore, these behavioural changes were attenuated by atypical antipsychotic treatment. Taken together, prenatal exposure to PCP produced long-lasting behavioural deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors in postpubertal mice. It is worth investigating the influences of disrupted NMDA receptors during the prenatal period on behaviour in later life.

  12. Morphological changes in cultures of hippocampus following prenatal irradiation in the rat

    SciTech Connect

    Hamdorf, G.; Shahar, A.; Cervos-Navarro, J.; Scheffler, A.; Sparenberg, A.; Skoberla, A. )

    1990-07-01

    The effect of prenatal irradiation was studied in organotypic cultures of hippocampus, prepared from newborn rats that had been exposed to whole-body irradiation of 1 Gy from a {sup 60}Co-source at day 13 of pregnancy. Light and electron microscopic observations showed remarkable damage to neuronal mitochondria accompanied by extensive swelling, vacuolation of the Golgi complex, and formation of multilamellar bodies and vesicles of the lysosomal type. In contrast to neuronal alterations, no delay in synaptogenesis or onset of myelination was observed based upon the absence of significant morphological changes in synapses and myelin sheaths. Using this tissue culture model it could be confirmed that prenatal exposure to irradiation, even at low doses, induces specific morphological changes in the brain.

  13. Follow-up study on histogenesis of microcephaly associated with ectopic gray matter induced by prenatal {gamma}-irradiation in the mouse

    SciTech Connect

    Sun, Xue-Zhi; Inouye, Monoru; Takagishi, Yoshiko

    1996-03-01

    Brain malformation with ectopic gray matter was visualized with magnetic resonance imaging in small-sized heads of prenatally exposed atomic bomb survivors. The identical brain malformation was reproduced in mice and its histogenesis was studied in the present experiment. Pregnant mice were exposed to {sup 60}Co {gamma}-irradiation at a single dose of 1.5 Gy on embryonic day 13 (E13), and then injected intraperitoneally with 30 mg/kg BrdU on E15. The extensive dead cells appeared throughout the brain mantle at 6 hours (h) after exposure. On E16 cell aggregations formed rosettes. On E18 a high proportion of BrdU-labeled cells reached the superficial layers of the cortical plate with the remaining cells located in the ectopic neuronal masses. The quantitative study showed that labeled cells in layers II to III were fewer and those in layers IV to VI more numerous in the prenatally irradiated adult mice than in controls. The anti-GFAP immunostaining revealed that the glial fibers in the irradiated mice were preserved, but disorganized. These findings suggested that the majority of migrating neurons were able to arrive at their normal layers, but some neurons remained due to the interrupted migratory pathway and eventually formed ectopic neuronal masses beneath the subcortical white matter. 60 refs., 5 figs., 1 tab.

  14. [Effect of alcohol in combination with stress in the prenatal period on adult mice behaviour].

    PubMed

    Morozova, M V; Popova, N K

    2010-11-01

    The aim of the present study was to investigate the effects of the prenatal alcohol and stress on behaviour of adult CBA/LacJ male mice. Pregnant mice were given ethanol 11% from to 21 days of the gestation and were exposed to restraint stress for two hours daily from 15 to 21 days gestation. At 3 months of age, the offspring were tested for behaviour. Alcohol and stress-exposed animals buried more marbles in the marble-burying test, which models obsessive-compulsive disorders (OCD). In addition, the alcohol and stress-exposed males showed increased social activity. No significant effects of the prenatal alcohol and stress exposure on locomotor activity, anxiety, exploring activity of the adult male mice were revealed. Conclusion was made that exposure to the alcohol and stress combination in prenatal period produces predisposition to OCD.

  15. Prenatal irradiation: a major concern for the developing brain.

    PubMed

    Kimler, B F

    1998-04-01

    Irradiation of the mammalian foetus produces a broad spectrum of congenital abnormalities, growth retardations, developmental delays, and functional deficits, depending upon the dose and the specific gestational phase of irradiation. The developing brain is particularly susceptible to production of deleterious effects, with decreased brain size, behavioural alterations, and mental retardation having been documented. Supplementing the limited human data, rodent models have been extensively used to investigate the specific processes by which relatively low doses, with correspondingly minor cellular damage to the developing neocortex, can produce dramatic postnatal consequences in brain structure and function. The effects of a variety of physical (dose, linear energy transfer, dose rate, fractionation) and biological (species, strain, gestational age, time course post-irradiation) parameters have been examined in an attempt to provide much needed information on such critical aspects as dose response, threshold doses for effect, and extrapolation to human risk estimates. Various acute cellular responses (e.g. appearance of pyknotic cells and macrophages) observed in the developing neocortex 0-24 h after in utero irradiation can be associated with postnatal effects. Moreover, it is possible to correlate thinning of specific layers of the cerebral cortex with specific behavioural aberrations, allowing prediction of brain structural changes from functional alterations, and vice versa. Thus, it is possible to speculate as to the mechanisms and targets for extremely sensitive, radiation-induced cellular damage in the developing foetal brain, that will interfere with the orderly and precisely programmed development of the mammalian brain, leading finally to postnatal expression as delays in growth and development, perturbations in behaviour, and alterations in brain structure. PMID:9587081

  16. Prenatal exposure to permethrin influences vascular development of fetal brain and adult behavior in mice offspring.

    PubMed

    Imanishi, Satoshi; Okura, Masahiro; Zaha, Hiroko; Yamamoto, Toshifumi; Akanuma, Hiromi; Nagano, Reiko; Shiraishi, Hiroaki; Fujimaki, Hidekazu; Sone, Hideko

    2013-11-01

    Pyrethroids are one of the most widely used classes of insecticides and show neurotoxic effects that induce oxidative stress in the neonatal rat brain. However, little is still known about effects of prenatal exposure to permethrin on vascular development in fetal brain, central nervous system development, and adult offspring behaviors. In this study, the effects of prenatal exposure to permethrin on the development of cerebral arteries in fetal brains, neurotransmitter in neonatal brains, and locomotor activities in offspring mice were investigated. Permethrin (0, 2, 10, 50, and 75 mg/kg) was orally administered to pregnant females once on gestation day 10.5. The brains of permethrin-treated fetuses showed altered vascular formation involving shortened lengths of vessels, an increased number of small branches, and, in some cases, insufficient fusion of the anterior communicating arteries in the area of circle of Willis. The prenatal exposure to permethrin altered neocortical and hippocampus thickness in the mid brain and significantly increased norepinephrine and dopamine levels at postnatal day 7 mice. For spontaneous behavior, the standing ability test using a viewing jar and open-field tests showed significant decrease of the standing ability and locomotor activity in male mice at 8 or 12 weeks of age, respectively. The results suggest that prenatal exposure to permethrin may affect insufficient development of the brain through alterations of vascular development.

  17. Gender Dependent Evaluation of Autism like Behavior in Mice Exposed to Prenatal Zinc Deficiency

    PubMed Central

    Grabrucker, Stefanie; Boeckers, Tobias M.; Grabrucker, Andreas M.

    2016-01-01

    Zinc deficiency has recently been linked to the etiology of autism spectrum disorders (ASD) as environmental risk factor. With an estimated 17% of the world population being at risk of zinc deficiency, especially zinc deficiency during pregnancy might be a common occurrence, also in industrialized nations. On molecular level, zinc deficiency has been shown to affect a signaling pathway at glutamatergic synapses that has previously been identified through genetic mutations in ASD patients, the Neurexin-Neuroligin-Shank pathway, via altering zinc binding Shank family members. In particular, prenatal zinc deficient but not acute zinc deficient animals have been reported to display autism like behavior in some behavioral tests. However, a full behavioral analysis of a possible autism like behavior has been lacking so far. Here, we performed an extensive behavioral phenotyping of mice born from mothers with mild zinc deficiency during all trimesters of pregnancy. Prenatal zinc deficient animals were investigated as adults and gender differences were assessed. Our results show that prenatal zinc deficient mice display increased anxiety, deficits in nest building and various social interaction paradigm, as well as mild alterations in ultrasonic vocalizations. A gender specific analysis revealed only few sex specific differences. Taken together, given that similar behavioral abnormalities as reported here are frequently observed in ASD mouse models, we conclude that prenatal zinc deficient animals even without specific genetic susceptibility for ASD, already show some features of ASD like behavior. PMID:26973485

  18. Prenatal exposure to allergen, DNA methylation, and allergy in grandoffspring mice

    PubMed Central

    Niedzwiecki, M.; Zhu, H.; Corson, L.; Grunig, G.; Factor, P. H.; Chu, S.; Jiang, H.; Miller, R. L.

    2012-01-01

    Background Prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. We hypothesized that prenatal exposure of mice (F0) to Aspergillus fumigatus (A. fumigatus) would be associated with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in CpG methylation of T-helper genes in third-generation mice (F2). Methods Female BALB/c mice were sensitized to A. fumigatus (62.5, 125, 1250 μg, or saline) and re-exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late) gestation. Grandoffspring were treated with A. fumigatus (62.5 μg) at 9 weeks. IgE, IgG1, and IgG2a levels and cell counts from bronchoalveolar lavage fluid were determined. Lung DNA was pyrosequenced at multiple sites in the interferon (IFN)-γ and interleukin (IL)-4 promoters. Results Grandoffspring of mothers dosed with 1250 μg early during pregnancy developed increased airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed late in pregnancy developed lower IgE (P < 0.05) and airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed early had lower methylation at IL-4 CpG−408 and CpG−393 compared to late dosed mice (P < 0.005 across all doses). Few correlations were found between methylation levels and airway eosinophilia and IgE. Conclusion Prenatal exposure to A. fumigatus late during pregnancy, but not early, was associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal exposure to A. fumigatus was associated with changes in CpG methylation in the IFN-γ and IL-4 promoters that did not correlate consistently with indicators of allergic sensitization. PMID:22583153

  19. Prenatal exposure to low levels of androgen accelerates female puberty onset and reproductive senescence in mice.

    PubMed

    Witham, Emily A; Meadows, Jason D; Shojaei, Shadi; Kauffman, Alexander S; Mellon, Pamela L

    2012-09-01

    Sex steroid hormone production and feedback mechanisms are critical components of the hypothalamic-pituitary-gonadal (HPG) axis and regulate fetal development, puberty, fertility, and menopause. In female mammals, developmental exposure to excess androgens alters the development of the HPG axis and has pathophysiological effects on adult reproductive function. This study presents an in-depth reproductive analysis of a murine model of prenatal androgenization (PNA) in which females are exposed to a low dose of dihydrotestosterone during late prenatal development on embryonic d 16.5-18.5. We determined that PNA females had advanced pubertal onset and a delay in the time to first litter, compared with vehicle-treated controls. The PNA mice also had elevated testosterone, irregular estrous cyclicity, and advanced reproductive senescence. To assess the importance of the window of androgen exposure, dihydrotestosterone was administered to a separate cohort of female mice on postnatal d 21-23 [prepubertal androgenization (PPA)]. PPA significantly advanced the timing of pubertal onset, as observed by age of the vaginal opening, yet had no effects on testosterone or estrous cycling in adulthood. The absence of kisspeptin receptor in Kiss1r-null mice did not change the acceleration of puberty by the PNA and PPA paradigms, indicating that kisspeptin signaling is not required for androgens to advance puberty. Thus, prenatal, but not prepubertal, exposure to low levels of androgens disrupts normal reproductive function throughout life from puberty to reproductive senescence.

  20. Prenatal allergen and diesel exhaust exposure and their effects on allergy in adult offspring mice

    PubMed Central

    2010-01-01

    Background Multiple studies have suggested that prenatal exposure to either allergens or air pollution may increase the risk for the development of allergic immune responses in young offspring. However, the effects of prenatal environmental exposures on adult offspring have not been well-studied. We hypothesized that combined prenatal exposure to Aspergillus fumigatus (A. fumigatus) allergen and diesel exhaust particles will be associated with altered IgE production, airway inflammation, airway hyperreactivity (AHR), and airway remodeling of adult offspring. Methods Following sensitization via the airway route to A. fumigatus and mating, pregnant BALB/c mice were exposed to additional A. fumigatus and/or diesel exhaust particles. At age 9-10 weeks, their offspring were sensitized and challenged with A. fumigatus. Results We found that adult offspring from mice that were exposed to A. fumigatus or diesel exhaust particles during pregnancy experienced decreases in IgE production. Adult offspring of mice that were exposed to both A. fumigatus and diesel exhaust particles during pregnancy experienced decreases in airway eosinophilia. Conclusion These results suggest that, in this model, allergen and/or diesel administration during pregnancy may be associated with protection from developing systemic and airway allergic immune responses in the adult offspring. PMID:20459836

  1. Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice.

    PubMed

    Wang, Lai; Wu, Lin; Wang, Xiaoqing; Deng, Jiexin; Ma, Zhanyou; Fan, Wenjuan; He, Weiya; Deng, Jinbo

    2015-11-01

    In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose-dependent manner (p<0.05) after prenatal alcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (p<0.01). Furthermore, we found that mossy cells were very sensitive to alcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (p<0.05) and decreased with the growing age. Compared with WT pups, the number of apoptotic mossy cells in the hippocampus of SMS2-/- pups increased (p<0.05). Western blotting showed that the expression of activated Caspase 8 and activated Caspase 3 of hippocampal tissue in WT pups and SMS2-/- pups increases after prenatal alcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis.

  2. Cloperastine rescues impairment of passive avoidance response in mice prenatally exposed to diethylstilbestrol.

    PubMed

    Soeda, Fumio; Hirakawa, Emi; Inoue, Masako; Shirasaki, Tetsuya; Takahama, Kazuo

    2014-02-01

    We previously reported that prenatal exposure to diethylstilbestrol (DES) impaired passive avoidance responses in mice. Apart from the above, we also found that cloperastine, a centrally acting antitussive, ameliorated depression-like and anxiety-like behaviors in rodents at antitussive-effective doses. In this study, we investigated whether or not cloperastine rescues impairment of passive avoidance responses in mice prenatally exposed to DES. Male DES-exposed mice were subcutaneously administered cloperastine at 10 or 30 mg/kg twice a day from 32 to 41 days after birth and subjected to behavioral testing 42 to 46 days after birth. Cloperastine at 10 and 30 mg/kg ameliorated DES-induced impairment of passive avoidance responses. In addition, cloperastine affected the levels of 5-HT1A receptors, GIRK and BDNF in the hippocampus of DES-exposed mice. However, the number of BrdU-positive cells in the hippocampus of DES-exposed mice was not changed by chronic administration of cloperastine. These findings suggest that the action of endocrine disruptors in the brain may not always be irreversible, and that the symptoms caused by endocrine disruptors might be curable with drugs such as cloperastine.

  3. Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice

    PubMed Central

    Aung, Kyaw H.; Kyi-Tha-Thu, Chaw; Sano, Kazuhiro; Nakamura, Kazuaki; Tanoue, Akito; Nohara, Keiko; Kakeyama, Masaki; Tohyama, Chiharu; Tsukahara, Shinji; Maekawa, Fumihiko

    2016-01-01

    Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. PMID:27064386

  4. Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice.

    PubMed

    Aung, Kyaw H; Kyi-Tha-Thu, Chaw; Sano, Kazuhiro; Nakamura, Kazuaki; Tanoue, Akito; Nohara, Keiko; Kakeyama, Masaki; Tohyama, Chiharu; Tsukahara, Shinji; Maekawa, Fumihiko

    2016-01-01

    Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. PMID:27064386

  5. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice

    PubMed Central

    Niermann, Sarah; Rattan, Saniya; Brehm, Emily; Flaws, Jodi A.

    2015-01-01

    This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20μg/kg/day-750mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities PMID:25765777

  6. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice.

    PubMed

    Niermann, Sarah; Rattan, Saniya; Brehm, Emily; Flaws, Jodi A

    2015-06-01

    This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20 μg/kg/day-750 mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities. PMID:25765777

  7. Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid.

    PubMed

    Kataoka, Shunsuke; Takuma, Kazuhiro; Hara, Yuta; Maeda, Yuko; Ago, Yukio; Matsuda, Toshio

    2013-02-01

    Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice. Mice exposed to VPA at embryonic day 12.5 (E12.5), but not at E9 and E14.5, displayed social interaction deficits, anxiety-like behaviour and memory deficits at age 4-8 wk. In contrast to male mice, the social interaction deficits (a decrease in sniffing behaviour) were not observed in female mice at age 8 wk. The exposure to VPA at E12.5 decreased the number of Nissl-positive cells in the middle and lower layers of the prefrontal cortex and in the lower layers of the somatosensory cortex at age 8 wk. Furthermore, VPA exposure caused a transient increase in acetylated histone levels in the embryonic brain, followed by an increase in apoptotic cell death in the neocortex and a decrease in cell proliferation in the ganglionic eminence. In contrast, prenatal exposure to valpromide at E12.5 did not affect the behavioural, biochemical and histological parameters. Furthermore, these findings suggest that VPA-induced histone hyperacetylation plays a key role in cortical pathology and abnormal autism-like behaviours in mice.

  8. Dose-related growth deficits in LS but not SS mice prenatally exposed to alcohol.

    PubMed

    Gilliam, D M; Kotch, L E

    1996-01-01

    Genetically based alcohol sensitivity may influence the severity of alcohol-related birth defects. To examine this question, measures of growth and survival were examined in offspring of the alcohol sensitive Long-Sleep (LS) and alcohol-resistant Short-Sleep (SS) mouse lines following prenatal ethanol exposure. Pregnant LS and SS mice received an ethanol dose of either 6 or 8 g/kg/day from days 7 through 18 of pregnancy. Control groups received a maltose-dextran solution made isocaloric to the 8 g/kg/day dose. Ethanol and maltose-dextrin solutions were administered as split doses, 6 h apart, via gavage. Nonintubated lab chow control groups were also included for both mouse lines. Offspring were fostered at birth to lactating mice of an outbred stock. Pregnancy was longer for ethanol-treated LS dams compared to maltose-dextrin and lab chow LS control groups, whereas pregnancy length for ethanol-treated SS dams was similar to SS controls. Prenatal ethanol exposure resulted in dose-related growth deficits in LS but not in SS litters. Line differences in postnatal growth deficits in response to prenatal alcohol exposure suggest maternal or fetal alcohol sensitivity influence alcohol-related birth defects. PMID:8837934

  9. Necrostatin-1 rescues mice from lethal irradiation.

    PubMed

    Huang, Zhentai; Epperly, Michael; Watkins, Simon C; Greenberger, Joel S; Kagan, Valerian E; Bayır, Hülya

    2016-04-01

    There is an emerging need in new medical products that can mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological or nuclear terroristic event. The direct effects of ionizing radiation are realized primarily via apoptotic death pathways in rapidly proliferating cells within the initial 1-2days after the exposure. However later in the course of the radiation disease necrotic cell death may ensue via direct and indirect pathways from increased generation of pro-inflammatory cytokines. Here we evaluated radiomitigative potential of necrostatin-1 after total body irradiation (TBI) and the contribution of necroptosis to cell death induced by radiation. Circulating TNFα levels were increased starting on d1 after TBI and associated with increased plasmalemma permeability in ileum of irradiated mice. Necrostatin-1 given iv. 48h after 9.5Gy TBI attenuated radiation-induced receptor interacting protein kinase 3 (RIPK3) serine phosphorylation in ileum and improved survival vs. vehicle. Utilizing apoptosis resistant cytochrome c(-/-) cells, we showed that radiation can induce necroptosis, which is attenuated by RNAi knock down of RIPK1 and RIPK3 or by treatment with necrostatin-1 or -1s whereas 1-methyl-L-tryptophan, an indoleamine-2,3-dioxygenase inhibitor, did not exhibit radiomitigative effect. This suggests that the beneficial effect of necrostatin-1 is likely through inhibition of RIPK1-mediated necroptotic pathway. Overall, our data indicate that necroptosis, a form of programmed necrosis, may play a significant role in cell death contributing to radiation disease and mortality. This study provides a proof of principle that necrostatin-1 and perhaps other RIPK1 inhibitors are promising therapeutic agents for radiomitigation after TBI. PMID:26802452

  10. Prenatal caffeine exposure modifies behavioural responses in mice.

    PubMed

    Ajarem, J.S.; Brain, P.F.

    1993-10-01

    Caffeine was given to pregnant mice subcutaneously at doses of 10 and 40mg/kg body weight, on the last four days of pregnancy. Subsequently, effects on the behaviour of their cross-fostered male offspring were studied using the "standard opponent" test. Significant decreases in threat, attack, displacement and number of fights, as well as an increase in latency to attack, were observed in the offspring exposed to the higher dose. Thus, excessive consumption of caffeine during pregnancy appears to have a lasting influence on the behaviour of offspring via a direct in utero action. PMID:11224223

  11. Studies on wild house mice. VII. Prenatal maternal environment and aggression.

    PubMed

    Sluyter, F; van der Vlugt, J J; van Oortmerssen, G A; Koolhaas, J M; van der Hoeven, F; de Boer, P

    1996-09-01

    The effect of the maternal environment on intermale aggression was studied by means of embryo transfer of genetically selected aggressive (SAL) and nonaggressive wild house mice (LAL), and their reciprocal F1's, to standard (NMR1) females. No effect was found on the attack latency scores (ALS), i.e., aggression: all genotypes born and raised under natural conditions showed an ALS similar that of genotypes born and raised by NMR1 females. Since previous studies on wild house mice failed to demonstrate postnatal effects on aggression, and the present results indicate the absence of prenatal maternal environmental effects on aggression, the primacy of genetic over maternal variance in the development of adult intermale aggression in wild house mice is indicated.

  12. Effects of Prenatal Irradiation with an Accelerated Heavy-Ion Beam on Postnatal Development in Rats

    NASA Astrophysics Data System (ADS)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Fujita, K.; Coffigny, H.; Hayata, I.

    Effects on postnatal neurophysiological development in offspring were studied following exposure of pregnant Wistar rats to accelerated neon-ion beams with a LET value of about 30 keV mu m at a dose range from 0 1 Gy to 2 0Gy on the 15th day of gestation The age at which four physiologic markers appeared and five reflexes were acquired was examined prior to weaning Gain in body weight was monitored until the offspring were 3 months old Male offspring were evaluated as young adults using two behavioral tests The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison Our previous study on carbon-ion beams with a LET value of about 13 keV mu m was also cited to elucidate a possible LET-related effect For most of the endpoints at early age significant alteration was even observed in offspring prenatally received 0 1 Gy of accelerated neon ions while neither X rays nor carbon-ions under the same dose resulted in such a significant alteration compared to that from the sham-irradiated dams All offspring whose mothers received 2 0 Gy died prior to weaning Offspring from dams irradiated with accelerated neon ions generally showed higher incidences of prenatal death and preweaning mortality markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to those exposed to X-rays or carbon ions at doses of 0 1 to 1 5 Gy Significantly reduced ratios of main organ weight to body weight at postnatal ages of 30 60 and 90 days were also observed

  13. Prenatal SSRI alters the hormonal and behavioral responses to stress in female mice: Possible role for glucocorticoid resistance.

    PubMed

    Avitsur, Ronit; Grinshpahet, Rachel; Goren, Naama; Weinstein, Ido; Kirshenboim, Or; Chlebowski, Noa

    2016-08-01

    Life time prevalence of major depression disorder (MDD) is higher in women compared to men especially during the period surrounding childbirth. Women suffering from MDD during pregnancy use antidepressant medications, particularly Selective Serotonin Reuptake Inhibitors (SSRI). These drugs readily cross the placental barrier and impact the developing fetal brain. The present study assessed the effects of prenatal exposure to fluoxetine (FLX), an SSRI antidepressant drug, on corticosterone and behavioral responses to stress in female mice. In young females, prenatal FLX significantly elevated corticosterone response to continuous stress. In adults, prenatal FLX augmented corticosterone response to acute stress and suppressed the response to continuous stress. Additionally, prenatal FLX significantly augmented stress-induced increase in locomotion and reduced anxiety- and depressive-like behaviors in adult, but not young mice. The dexamethasone suppression test revealed that prenatal FLX induced a state of glucocorticoid resistance in adult females, indicating that the negative feedback control of the hypothalamic-pituitary-adrenal axis response to stress was disrupted. These findings provide the first indication of altered hormonal and behavioral responses to continuous stress and suggest a role for the development of glucocorticoid resistance in these effects. According to these findings, prenatal environment may have implications for stress sensitivity and responsiveness to life challenges. Furthermore, this study may assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy. PMID:27283378

  14. Prenatal immune activation in mice blocks the effects of environmental enrichment on exploratory behavior and microglia density.

    PubMed

    Buschert, Jens; Sakalem, Marna E; Saffari, Roja; Hohoff, Christa; Rothermundt, Matthias; Arolt, Volker; Zhang, Weiqi; Ambrée, Oliver

    2016-06-01

    Adverse environmental factors including prenatal maternal infection are capable of inducing long-lasting behavioral and neural alterations which can enhance the risk to develop schizophrenia. It is so far not clear whether supportive postnatal environments are able to modify such prenatally-induced alterations. In rodent models, environmental enrichment influences behavior and cognition, for instance by affecting endocrinologic, immunologic, and neuroplastic parameters. The current study was designed to elucidate the influence of postnatal environmental enrichment on schizophrenia-like behavioral alterations induced by prenatal polyI:C immune stimulation at gestational day 9 in mice. Adult offspring were tested for amphetamine-induced locomotion, social interaction, and problem-solving behavior as well as expression of dopamine D1 and D2 receptors and associated molecules, microglia density and adult neurogenesis. Prenatal polyI:C treatment resulted in increased dopamine sensitivity and dopamine D2 receptor expression in adult offspring which was not reversed by environmental enrichment. Prenatal immune activation prevented the effects of environmental enrichment which increased exploratory behavior and microglia density in NaCl treated mice. Problem-solving behavior as well as the number of immature neurons was affected by neither prenatal immune stimulation nor postnatal environmental enrichment. The behavioral and neural alterations that persist into adulthood could not generally be modified by environmental enrichment. This might be due to early neurodevelopmental disturbances which could not be rescued or compensated for at a later developmental stage.

  15. Effects of prenatal stress and neonatal handling on anxiety, spatial learning and serotonergic system of male offspring mice.

    PubMed

    Akatsu, Shigemi; Ishikawa, Chihiro; Takemura, Kaori; Ohtani, Akiko; Shiga, Takashi

    2015-12-01

    Environmental factors during perinatal period have various effects on behavior. The present study examined the effects of prenatal stress and neonatal handling on anxiety and spatial learning of offspring. Prenatal stress increased anxiety-related behavior of adult offspring, whereas neonatal handling had no effect. In contrast, spatial learning was not affected by prenatal stress, but improved by neonatal handling in both prenatally stressed and non-stressed mice. Next, to elucidate possible brain mechanisms mediating effects of environmental factors on behavior, we focused on serotonin (5-HT) system in the frontal cortex and hippocampus which is involved in anxiety and learning. We examined effects of environmental factors on the mRNA expression of 5-HT1A, 5-HT2A and 5-HT2C receptors in the frontal cortex and hippocampus during postnatal period and adulthood. Both prenatal stress and neonatal handling altered the mRNA expression of 5-HT receptors. These effects were dependent on environmental factors, brain regions and developmental stages. In summary, the present study revealed that prenatal stress and neonatal handling had differential effects on anxiety and spatial learning of offspring, and concomitantly the expression of 5-HT receptors. It was also shown that the effects of prenatal stress on 5-HT system were recovered partially by neonatal handling.

  16. Prenatal exposure to selective serotonin reuptake inhibitors (SSRI) increases aggression and modulates maternal behavior in offspring mice.

    PubMed

    Svirsky, Natali; Levy, Sigal; Avitsur, Ronit

    2016-01-01

    Selective serotonin reuptake inhibitors (SSRI) are commonly prescribed antidepressant drugs in pregnant women. SSRIs cross the placental barrier and affect serotonergic neurotransmission in the fetus. Although no gross SSRI-related teratogenic effects were reported, infants born following prenatal exposure to SSRIs are at higher risk for various developmental abnormalities. The aim of this study was to examine the effects of prenatal SSRI on social and maternal behavior in mice. To this end, pregnant female dams were exposed to saline or fluoxetine (FLX) throughout pregnancy, and the behavior of the offspring was examined. The results indicate that in utero FLX increased aggression in adult males and delayed emergence of maternal behavior in adult females. Social exploration and recognition memory were not affected by prenatal FLX exposure. These findings support the notion that alterations in the development of serotonergic pathways following prenatal exposure to SSRIs are associated with changes in social and maternal behavior throughout life.

  17. BDNF epigenetic modifications associated with schizophrenia-like phenotype induced by prenatal stress in mice

    PubMed Central

    Dong, Erbo; Dzitoyeva, Svetlana G.; Matrisciano, Francesco; Tueting, Patricia; Grayson, Dennis R.; Guidotti, Alessandro

    2014-01-01

    Background Prenatal stress is considered a risk factor for several neurodevelopmental disorders including schizophrenia (SZ). An animal model involving restraint stress of pregnant mice suggests that prenatal stress (PRS) induces epigenetic changes in specific GABAergic and glutamatergic genes likely to be implicated in SZ including the gene for brain derived neurotrophic factor (BDNF). Methods Studying adult offspring of pregnant mice subjected to PRS, we explored the long-term effect of PRS on behavior and on the expression of key chromatin remodeling factors including DNA methyltransferase 1 (DNMT1), ten-eleven translocation hydroxylases (TETs), methyl CpG binding protein 2 (MeCP2), histone deacetylases (HDACs), histone methyltransferases (MLL1, SETD1, G9A and EZH1) and demethylase (LSD1) in the frontal cortex (FC) and hippocampus (HP). We also measured the expression of BDNF. Results Adult PRS offspring demonstrate behavioral abnormalities suggestive of SZ and molecular changes similar to SZ postmortem brain: a significant increase in DNMT1 and TET1 in the FC and HP but not in cerebellum, no changes in HDACs, histone methytransferases/demethylases or MeCP2, and a significant decrease in BDNF variants measured in the FC and HP. The decrease of the corresponding BDNF transcript level was paralleled by an enrichment of 5-methylcytosine and 5-hydroxylmethylcytosine levels at Bdnf gene regulatory regions. In addition, the expression of BDNF transcripts (IV and IX) was positively correlated with social approach in both PRS and non-stressed mice. Conclusions Since patients with psychosis and PRS mice show similar epigenetic signature, PRS offspring may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in SZ patients. PMID:25444166

  18. Aqueductal stenosis and development of hydrocephalus in prenatal methylmercury poisoning in mice

    SciTech Connect

    Choi, B.H.; Caple, M.; Espinosa, T.; Kim, D.; Song, D.

    1986-03-01

    Methylmercury (MeHg) is a ubiquitous environmental pollutant that can cause irreparable CNS damage, particularly upon the developing fetal CNS. As an ongoing study of the effects of MeHg upon the developing CNS, timed-pregnant C57BL/6J mice were poisoned by intraperitoneal injections of methylmercuric chloride (MMC), 12 mg/kg, in divided doses on E-14, 15 and 16. In another experiment, the pregnant animals were fed MMC (2 mg/kg/day) in their drinking water, starting on E-2 and continuing throughout gestation. The animals were allowed to come to term and the offspring sacrificed on postnatal days 5, 10, and 20. In both of these experiments, up to 9% of the offspring affected by prenatal MeHg poisoning developed marked hydrocephalus. Serial on ..mu..m sections of the aqueductus revealed severe stenosis associated with marked edema and spongy changes of ependymal cells and surrounding neuropil. No inflammatory or gliotic reactions of the periaqueductal tissue was seen. These changes are very similar to those observed in congenital hydrocephalus in humans and suggest that toxic damage to developing ependymal cells due to prenatal exposures of agents such as MeHg may have etiological role in some of the human congenital hydrocephalus. The details of the scanning and transmission electron microscopy along with demonstration of mercury grains in tissues will be presented.

  19. Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice.

    PubMed

    Xu, Yajun; Tang, Yunan; Li, Yong

    2008-03-01

    Maternal alcohol consumption during pregnancy can induce central nervous system abnormalities in the fetus, and folic acid supplementation can reverse some of the effects. The objective of the present study was to investigate prenatal alcohol exposure-induced fetal brain proteome alteration and the protective effect of folic acid using proteomic techniques. Alcohol (5.0 g/kg) was given intragastrically from gestational day (GD) 6 to 15, with or without 60.0 mg folic acid/kg given intragastrically during GD 1-16 to pregnant Balb/c mice. The control group received distilled water only. Results of litter evaluation on GD 18 showed that supplementation of folic acid reversed the prevalence of microcephaly induced by alcohol. Proteomic analysis indicated that, under the dosage of the present investigation, folic acid mainly reversed the alcohol-altered proteins involved in energy production, signal pathways and protein translation, which are all important for central nervous system development. PMID:17697403

  20. Behavior and Brain Gene Expression Changes in Mice Exposed to Preimplantation and Prenatal Stress

    PubMed Central

    Strata, Fabrizio; Giritharan, Gnanaratnam; Sebastiano, Francesca Di; Piane, Luisa Delle; Kao, Chia-Ning; Donjacour, Annemarie

    2015-01-01

    Preimplantation culture of mouse embryos has been suggested to result in reduced anxiety-like behavior in adulthood. Here, we investigated the effects of in vitro fertilization (IVF), embryo culture, and different diets on anxiety-like behavior using the elevated plus maze (EPM). We hypothesized that exposure to suboptimal conditions during the preimplantation stage would interact with the suboptimal diet to alter behavior. The expression of genes related to anxiety was then assessed by quantitative real-time polymerase chain reaction in various brain regions. When fed a normal diet during gestation and a moderately high-fat Western diet (WD) postnatally, naturally conceived (NC) and IVF mice showed similar anxiety-like behavior on the EPM. However, when fed a low-protein diet prenatally and a high-fat diet postnatally (LP/HF), NC mice showed a modest increase in anxiety-like behavior, whereas IVF mice showed the opposite: a strongly reduced anxiety-like behavior on the EPM. The robust reduction in anxiety-like behavior in IVF males fed the LP/HF diets was, intriguingly, associated with reduced expression of MAO-A, CRFR2, and GABA markers in the hypothalamus and cortex. These findings are discussed in relation to the developmental origin of health and disease hypothesis and the 2-hit model, which suggests that 2 events, occurring at different times in development, can act synergistically with long-term consequences observed during adulthood. PMID:25398605

  1. Effects of tetrabromobisphenol A, brominated flame retardant, in ICR mice after prenatal and postnatal exposure.

    PubMed

    Tada, Y; Fujitani, T; Yano, N; Takahashi, H; Yuzawa, K; Ando, H; Kubo, Y; Nagasawa, A; Ogata, A; Kamimura, H

    2006-08-01

    Tetrabromobisphenol A (TBBPA), brominated flame retardant, is produced in the largest amounts globally for use in plastics or building materials. TBBPA has been detected in sediment, air at the dismantling plant or human serum samples. In the present study, we examined the effects of prenatal and postnatal exposure to TBBPA in mice. TBBPA (99.1% pure) in diet was administered to pregnant ICR mice at doses of 0% (control), 0.01%, 0.1% or 1.0% from gestational day 0 to weaning at postnatal day 27. The average daily food intake and body weight of dams showed no significant differences between the control and treated groups. There were no dose-related effects on reproductive data. Serum concentrations of total-cholesterol and liver weights of treated dams and offspring were higher than those of the control mice. Histological findings in treated dams or offspring showed the increase of focal necrosis of hepatocytes and inflammatory cell infiltration in the liver, and increase of dilation or atrophy of renal tubules and cyst in the kidney. TBBPA was developed as a new, safe class of flame retardant and was not highly toxic. However, the present data suggested that TBBPA caused a lipid metabolic disorder and hepatic or kidney lesion, under these conditions. PMID:16716481

  2. Immunization of mice with Trypanosoma rhodesiense exposed to ultraviolet irradiation

    SciTech Connect

    Charoenvit, Y.; Campbell, G.H.

    1981-11-01

    Exposure time of Trypanosoma rhodesiense as short as 1 minute to ultraviolet (uv) light prevents the organisms from causing infection. Live trypanosome challenge of mice immunized with uv-irradiated trypanosomes results in sterile immunity. This allows a method for the induction of protective immunity to experimental trypanosomiasis which can be performed in most laboratories using uv germicidal lamps found in sterile hoods.

  3. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism.

    PubMed

    Al-Amin, Md Mamun; Rahman, Md Mahbubur; Khan, Fazlur Rahman; Zaman, Fahmida; Mahmud Reza, Hasan

    2015-06-01

    Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behavior in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2mg/kg) was given to the experimental group (VPA_AST, n=10) while saline was given to the control group (VPA, n=10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity.

  4. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism.

    PubMed

    Al-Amin, Md Mamun; Rahman, Md Mahbubur; Khan, Fazlur Rahman; Zaman, Fahmida; Mahmud Reza, Hasan

    2015-06-01

    Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behavior in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2mg/kg) was given to the experimental group (VPA_AST, n=10) while saline was given to the control group (VPA, n=10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity. PMID:25732953

  5. Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses.

    PubMed

    Davis, David A; Bortolato, Marco; Godar, Sean C; Sander, Thomas K; Iwata, Nahoko; Pakbin, Payam; Shih, Jean C; Berhane, Kiros; McConnell, Rob; Sioutas, Constantinos; Finch, Caleb E; Morgan, Todd E

    2013-01-01

    Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM). In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m(3)) or control filtered ambient air for 10 weeks (3×5 hour exposures per week), encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml) to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.

  6. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke

    PubMed Central

    Amos-Kroohs, Robyn M.; Williams, Michael T.; Braun, Amanda A.; Graham, Devon L; Webb, Cynthia L.; Birtles, Todd S.; Greene, Robert M.; Vorhees, Charles V.; Pisano, M. Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of ‘active’ maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6 h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1 h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function. PMID

  7. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

    PubMed

    Amos-Kroohs, Robyn M; Williams, Michael T; Braun, Amanda A; Graham, Devon L; Webb, Cynthia L; Birtles, Todd S; Greene, Robert M; Vorhees, Charles V; Pisano, M Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function. PMID:23314114

  8. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

    PubMed

    Amos-Kroohs, Robyn M; Williams, Michael T; Braun, Amanda A; Graham, Devon L; Webb, Cynthia L; Birtles, Todd S; Greene, Robert M; Vorhees, Charles V; Pisano, M Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function.

  9. Maternal exercise during pregnancy ameliorates the postnatal neuronal impairments induced by prenatal restraint stress in mice.

    PubMed

    Bustamante, Carlos; Henríquez, Ricardo; Medina, Felipe; Reinoso, Carmen; Vargas, Ronald; Pascual, Rodrigo

    2013-06-01

    Clinical and preclinical studies have demonstrated that prenatal stress (PS) induces neuronal and behavioral disturbances in the offspring. In the present study, we determined whether maternal voluntary wheel running (VWR) during pregnancy could reverse the putative deleterious effects of PS on the neurodevelopment and behavior of the offspring. Pregnant CF-1 mice were randomly assigned to control, restraint stressed or restraint stressed+VWR groups. Dams of the stressed group were subjected to restraint stress between gestational days 14 and delivery, while control pregnant dams remained undisturbed in their home cages. Dams of the restraint stressed+VWR group were subjected to exercise between gestational days 1 and 17. On postnatal day 23 (P23), male pups were assigned to one of the following experimental groups: mice born from control dams, stressed dams or stressed+VWR dams. Locomotor behavior and pyramidal neuronal morphology were evaluated at P23. Animals were then sacrificed, and Golgi-impregnated pyramidal neurons of the parietal cortex were morphometrically analyzed. Here, we present two major findings: first, PS produced significantly diminished dendritic growth of parietal neurons without altered locomotor behavior of the offspring; and second, maternal VWR significantly offset morphological impairments.

  10. Protective effect of early prenatal stress on the induction of asthma in adult mice: Sex-specific differences.

    PubMed

    Vargas, Mauro Henrique Moraes; Campos, Natália Evangelista; de Souza, Rodrigo Godinho; da Cunha, Aline Andrea; Nuñez, Nailê Karine; Pitrez, Paulo Márcio; Donadio, Márcio Vinícius Fagundes

    2016-10-15

    Adversities faced during the prenatal period can be related to the onset of diseases in adulthood. However, little is known about the effects on the respiratory system. This study aimed to evaluate the effects of prenatal stress in two different time-points during pregnancy on pulmonary function and on the inflammatory profile of mice exposed to an asthma model. Male and female BALB/c mice were divided into 3 groups: control (CON), prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last week of pregnancy (PNS2). Both PNS1 and PNS2 pregnant females were submitted to restraint stress. As adults, fear/anxiety behaviors were assessed, and animals were subjected to an asthma model induced by ovalbumin. Pulmonary function, inflammatory parameters in bronchoalveolar lavage (BAL) and histology were evaluated. There was a significant decrease in the number of entries and time spent in the central quadrant on the open field test for the PNS1 animals. Females (PNS1) showed improved pulmonary function (airway resistance, tissue damping and pulmonary elastance), significant increase in the percentage of neutrophils and lymphocytes and a decrease in eosinophils when compared to controls. There was a significant decrease in inflammatory cytokines in BAL of both males (IL-5 and IL-13) and females (IL-4, IL-5 and IL-13) from PNS1 and PNS2 when compared to the CON group. Prenatal stress starting from the beginning of pregnancy reduces the impact of asthma development in adult female mice, showing an improved pulmonary function and a lower inflammatory response in the lungs. PMID:27568231

  11. Protective effect of early prenatal stress on the induction of asthma in adult mice: Sex-specific differences.

    PubMed

    Vargas, Mauro Henrique Moraes; Campos, Natália Evangelista; de Souza, Rodrigo Godinho; da Cunha, Aline Andrea; Nuñez, Nailê Karine; Pitrez, Paulo Márcio; Donadio, Márcio Vinícius Fagundes

    2016-10-15

    Adversities faced during the prenatal period can be related to the onset of diseases in adulthood. However, little is known about the effects on the respiratory system. This study aimed to evaluate the effects of prenatal stress in two different time-points during pregnancy on pulmonary function and on the inflammatory profile of mice exposed to an asthma model. Male and female BALB/c mice were divided into 3 groups: control (CON), prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last week of pregnancy (PNS2). Both PNS1 and PNS2 pregnant females were submitted to restraint stress. As adults, fear/anxiety behaviors were assessed, and animals were subjected to an asthma model induced by ovalbumin. Pulmonary function, inflammatory parameters in bronchoalveolar lavage (BAL) and histology were evaluated. There was a significant decrease in the number of entries and time spent in the central quadrant on the open field test for the PNS1 animals. Females (PNS1) showed improved pulmonary function (airway resistance, tissue damping and pulmonary elastance), significant increase in the percentage of neutrophils and lymphocytes and a decrease in eosinophils when compared to controls. There was a significant decrease in inflammatory cytokines in BAL of both males (IL-5 and IL-13) and females (IL-4, IL-5 and IL-13) from PNS1 and PNS2 when compared to the CON group. Prenatal stress starting from the beginning of pregnancy reduces the impact of asthma development in adult female mice, showing an improved pulmonary function and a lower inflammatory response in the lungs.

  12. Neonatal Irradiation Sensitizes Mice to Delayed Pulmonary Challenge

    PubMed Central

    Johnston, Carl J.; Manning, Casey M.; Rangel-Moreno, Javier; Randall, Troy D.; Hernady, Eric; Finkelstein, Jacob N.; Williams, Jacqueline P.

    2013-01-01

    Significant differences exist between the physiology of the immature, neonatal lung compared to that of the adult lung that may affect acute and late responses to irradiation. Identifying these differences is critical to developing successful mitigation strategies for this special population. Our current hypothesis proposes that irradiation during the neonatal period will alter developmental processes, resulting in long-term consequences, including altered susceptibility to challenge with respiratory pathogens. C57BL/6J mice, 4 days of age, received 5 Gy whole-body irradiation. At subsequent time points (12, 26 and 46 weeks postirradiation), mice were intranasally infected with 120 HAU of influenza A virus. Fourteen days later, mice were sacrificed and tissues were collected for examination. Morbidity was monitored following changes in body weight and survival. The magnitude of the pulmonary response was determined by bronchoalveolar lavage, histological examination and gene expression of epithelial and inflammatory markers. Viral clearance was assessed 7 days post-influenza infection. Following influenza infection, irradiated animals that were infected at 26 and 46 weeks postirradiation lost significantly more weight and demonstrated reduced survival compared with those infected at 12 weeks postirradiation, with the greatest deleterious effect seen at the late time point. The results of these experiments suggest that radiation injury during early life may affect the lung’s response to a subsequent pathogenic aerial challenge, possibly through a chronic and progressive defect in the immune system. This finding may have implications for the development of countermeasures in the context of systemic radiation exposure. PMID:23496054

  13. Long-Term Effects of Prenatal Hypoxia on Schizophrenia-Like Phenotype in Heterozygous Reeler Mice.

    PubMed

    Howell, Kristy R; Pillai, Anilkumar

    2016-07-01

    Prenatal hypoxia (PHX) is a well-known environmental factor implicated in the pathophysiology of schizophrenia. However, the long-term effects of PHX on schizophrenia-related neuroplasticity are poorly understood. Using behavioral tasks, MRI imaging, and biochemical studies, we examined the long-term effects of PHX in heterozygous reeler mice (HRM; mice deficient for reelin, a candidate gene for schizophrenia). PHX at E17 failed to induce any significant deficits in prepulse inhibition, spatial memory, anxiety-like behavior, or blood flow in wild type (WT) and HRM at 6 months of age. However, PHX induced a significant increase in frontal cortex volume in WT whereas the higher frontal cortical volume found in HRM was significantly reduced by PHX. A significant decrease in reelin levels was observed in frontal cortex of WT and HRM and hippocampus of HRM following PHX. In addition, PHX induced significant reductions in hypoxia inducible factor-1α (HIF-1α) levels in frontal cortex and hippocampus of HRM. Although no significant effect of PHX was observed in vascular endothelial growth factor (VEGF) protein levels in frontal cortex and hippocampus of WT and HRM, serum VEGF levels were found higher in HRM following PHX. Moreover, glucocorticoid receptor (GR) protein levels were significantly lower in frontal cortex of WT and HRM and hippocampus of HRM following PHX. We found a significant reduction in serum corticosterone levels of PHX-treated WT mice. These findings suggest that future experiments addressing gene-environment interaction in schizophrenia should consider age-dependent effects of the environmental factor, in addition to the specificity of the gene of interest. PMID:26059812

  14. Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development.

    PubMed

    Schambra, Uta B; Goldsmith, Jeff; Nunley, Kevin; Liu, Yali; Harirforoosh, Sam; Schambra, Heidi M

    2015-01-01

    Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about

  15. Trehalose dimycolate enhances survival of fission neutron-irradiated mice and Klebsiella pneumoniae-challenged irradiated mice

    SciTech Connect

    McChesney, D.G.; Ledney, G.D.; Madonna, G.S. )

    1990-01-01

    The survival of B6D2F1 female mice exposed to lethal doses of fission neutron radiation is increased when trehalose dimycolate (TDM) preparations are given either 1 h after exposure or 1 day before exposure to radiation. TDM in an emulsion of squalene, Tween 80, and saline was the most effective formulation for increasing the 30-day survival of mice when given 1 day before (90%) or 1 h after (88%) exposure to radiation. An aqueous suspension of a synthetic analog of TDM was less effective at increasing 30-day survival (60%) when given 1 day prior to radiation exposure and not effective when given 1 h after radiation. Mice receiving a sublethal dose (3.5 Gy) of fission neutron radiation and either the TDM emulsion or synthetic TDM 1 h after irradiation were substantially more resistant to challenge with 10, 100, 1000, or 5000 times the LD50/30 dose of Klebsiella pneumoniae than untreated mice.

  16. Prenatal stress and peripubertal stimulation of the endocannabinoid system differentially regulate emotional responses and brain metabolism in mice.

    PubMed

    Macrì, Simone; Ceci, Chiara; Canese, Rossella; Laviola, Giovanni

    2012-01-01

    The central endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal-axis mediate individual responses to emotionally salient stimuli. Their altered developmental adjustment may relate to the emergence of emotional disturbances. Although environmental influences regulate the individual phenotype throughout the entire lifespan, their effects may result particularly persistent during plastic developmental stages (e.g. prenatal life and adolescence). Here, we investigated whether prenatal stress--in the form of gestational exposure to corticosterone supplemented in the maternal drinking water (100 mg/l) during the last week of pregnancy--combined with a pharmacological stimulation of the ECS during adolescence (daily fatty acid amide hydrolase URB597 i.p. administration--0.4 mg/kg--between postnatal days 29-38), influenced adult mouse emotional behaviour and brain metabolism measured through in vivo quantitative magnetic resonance spectroscopy. Compared to control mice, URB597-treated subjects showed, in the short-term, reduced locomotion and, in the long term, reduced motivation to execute operant responses to obtain palatable rewards paralleled by reduced levels of inositol and taurine in the prefrontal cortex. Adult mice exposed to prenatal corticosterone showed increased behavioural anxiety and reduced locomotion in the elevated zero maze, and altered brain metabolism (increased glutamate and reduced taurine in the hippocampus; reduced inositol and N-Acetyl-Aspartate in the hypothalamus). Present data further corroborate the view that prenatal stress and pharmacological ECS stimulation during adolescence persistently regulate emotional responses in adulthood. Yet, whilst we hypothesized these factors to be interactive in nature, we observed that the consequences of prenatal corticosterone administration were independent from those of ECS drug-induced stimulation during adolescence.

  17. Effects of feeding lactobacillus GG on lethal irradiation in mice

    SciTech Connect

    Dong, M.Y.; Chang, T.W.; Gorbach, S.L.

    1987-05-01

    Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls.

  18. Gene Expression Changes in C57BL/6J and DBA/2J Mice Following Prenatal Alcohol Exposure

    PubMed Central

    Downing, Chris; Flink, Stephen; Florez-McClure, Maria L.; Johnson, Thomas E.; Tabakoff, Boris; Kechris, Katerina J.

    2012-01-01

    Background Prenatal alcohol exposure can result in Fetal Alcohol Spectrum Disorder (FASD). Not all women who consume alcohol during pregnancy have children with FASD and studies have shown that genetic factors can play a role in ethanol teratogenesis. We examined gene expression in embryos and placentae from C57BL/6J (B6) and DBA/2J (D2) mice following prenatal alcohol exposure. B6 fetuses are susceptible to morphological malformations following prenatal alcohol exposure while D2 are relatively resistant. Methods Male and female B6 and D2 mice were mated for two hours in the morning, producing four embryonic genotypes: true-bred B6B6 and D2D2, and reciprocal B6D2 and D2B6. On gestational day 9dams were intubated with either 5.8 g/kg ethanol, an is caloric amount of maltose-dextrin, or nothing Four hours later dams were sacrificed and embryos and placentae were harvested. RNA was extracted, labeled and hybridized to Affymetrix Mouse Genome 430 v2 microarray chips. Data were normalized, subjected to analysis of variance and tested for enrichment of gene ontology (GO) molecular function and biological process using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results Several gene classes were differentially expressed in B6 and D2 regardless of treatment, including genes involved in polysaccharide binding and mitosis. Prenatal alcohol exposure altered expression of a subset of genes, including genes involved in methylation, chromatin remodeling, protein synthesis and mRNA splicing. Very few genes were differentially expressed between maltose-exposed tissues and tissues that received nothing, so we combined these groups for comparisons with ethanol. While we observed many expression changes specific to B6 following prenatal alcohol exposure, none were specific for D2. Gene classes up-or down regulated in B6 following prenatal alcohol exposure included genes involved in mRNA splicing, transcription and translation. Conclusions Our study

  19. Prenatal Exposure to Silver Nanoparticles Causes Depression Like Responses in Mice

    PubMed Central

    Tabatabaei, S. R. F.; Moshrefi, M.; Askaripour, M.

    2015-01-01

    Despite increasing studies on silver nanoparticles, their mechanism of action is not so clear, especially their probable toxicity on reproduction procedure, developmental process and offspring behavior. Therefore in the present study the effect of silver nanoparticles exposure during gestational period on offspring's depression behavior was assessed. Thirty virgin female mice were divided into three groups (n=10 for each group) including: one control and two experimental groups, which received an equal volume (0.2 ml) of suspension containing 0, 0.2 and 2 mg/kg of silver nanoparticles, respectively. After mating, the suspension was injected and repeated every 3 days till accouchement. Depression behaviors were assessed by tail suspension test and forced swimming test, in 45-day-old male and female progenies (6 groups, n=10). In males, both dose of silver nanoparticles (0.2 and 2 mg/kg) decreased mobility and increased immobility time in forced swimming test (P<0.05), but in female no effects were observed in mobility and immobility time. In tail suspension test, 2 mg/kg of silver nanoparticles lead to decrease of mobility time (P<0.05) and increase of immobility time (P<0.05) in female offspring but in males no significant effect was observed on mobility and immobility time. We may concluded that the prenatal exposure to silver nanoparticles probably cause gender-specific depression like behaviors in offspring, possibly through neurotoxic effect during neuronal development. PMID:26997695

  20. Compartmental responses after thoracic irradiation of mice: Strain differences

    SciTech Connect

    Chiang, C.-S.; Liu, W.-C.; Jung, S.-M.; Chen, F.-H.; Wu, C.-R.; McBride, William H.; Lee, C.-C.; Hong, J.-H. . E-mail: jihong@adm.cgmh.org.tw

    2005-07-01

    Purpose: To examine and compare the molecular and cellular processes leading to radiation fibrosis and pneumonitis in C57BL/6J and C3H/HeN mice. Methods and Materials: At indicated times after various doses of thoracic irradiation, the cell populations obtained by bronchoalveolar lavage of C57BL/6J mice were differentially analyzed by cytology and assessed by RNase protection (RPA) assay for levels of cytokines and related genes. The molecular responses in bronchial alveolar lavage (BAL) populations were compared with those in whole lung of C57BL/6J mice and with those of C3H/HeN mice. The former strain develops late radiation fibrosis, whereas the latter develop subacute radiation pneumonitis. Results: In C57BL/6J mice, a decrease in the total number of BAL cells was found 1 week after 6, 12, or 20 Gy thoracic irradiation with a subsequent dose-dependent increase up to 6 months. After 12 and 20 Gy, large, foamy macrophages and multinucleated cells became evident in BAL at 3 weeks, only to disappear at 4 months and reappear at 6 months. This biphasic response was mirrored by changes expression of mRNA for proinflammatory cytokines and the Mac-1 macrophage-associated antigen. As with BAL, whole lung tissue also showed biphasic cytokine and Mac-1 mRNA responses, but there were striking temporal differences between the two compartments, with changes in whole lung tissue correlating better than BAL with the onset of fibrosis in this strain. The radiation-induced proinflammatory mRNA responses had strain-dependent and strain-independent components. Thoracic irradiation of C3H/HeN induced similar increases in tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{alpha}/{beta}, and interferon (IFN)-{gamma} mRNA expression in lung as it did in C57BL/6J mice during the 'presymptom' phase at 1-2 months. However, immediately preceding and during the pneumonitic time period at 3-4 months, TNF-{alpha} and IL-1{alpha}/{beta} mRNAs were highly upregulated in C3H/HeN mice, which

  1. Prenatal Polycyclic Aromatic Hydrocarbon, Adiposity, Peroxisome Proliferator-Activated Receptor (PPAR) γ Methylation in Offspring, Grand-Offspring Mice

    PubMed Central

    Yan, Zhonghai; Zhang, Hanjie; Maher, Christina; Arteaga-Solis, Emilio; Champagne, Frances A.; Wu, Licheng; McDonald, Jacob D.; Yan, Beizhan; Schwartz, Gary J.; Miller, Rachel L.

    2014-01-01

    Rationale Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH) have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear. Objectives We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected. Materials and Methods Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND) 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding proteins (C/EBP) α, cyclooxygenase (Cox)-2, fatty acid synthase (FAS) and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue. Findings Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice. Conclusions Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny. PMID:25347678

  2. [Radiobiological effects of total mice irradiation with Bragg's peak protons].

    PubMed

    Ivanov, A A; Molokanov, A G; Ushakov, I B; Bulynina, T M; Vorozhtsova, S V; Abrosimova, A N; Kryuchkova, D M; Gaevsky, V N

    2013-01-01

    Outbred CD-1 female mice were irradiated in a proton beam (171 MeV, 5 Gy) on the phasotron at the Joint Institute of Nuclear Research (Dubna, Russia). Radiation was delivered in two points of the depth dose distribution: at the beam entry and on Bragg's peak. Technical requirements for studying the effects of Bragg's peak protons on organism of experimental animals were specified. It was recognized that protons with high linear energy transfer (mean LET = 1.6 keV/microm) cause a more severe damaging effect to the hemopoietic system and cytogenetic apparatus in bone marrow cells as compared with entry protons and 60Co gamma-quanta. It was shown that recovery of the main hemopoietic organs and immunity as well as elimination of chromosomal aberrations take more time following irradiation with Bragg's peak protons but not protons with the energy of 171 MeV.

  3. Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

    PubMed

    Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

    2015-05-01

    The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner.

  4. Dynamics of Delayed p53 Mutations in Mice Given Whole-Body Irradiation at 8 Weeks

    SciTech Connect

    Okazaki, Ryuji; Ootsuyama, Akira; Kakihara, Hiroyo; Mabuchi, Yo; Matsuzaki, Yumi; Michikawa, Yuichi; Imai, Takashi; Norimura, Toshiyuki

    2011-01-01

    Purpose: Ionizing irradiation might induce delayed genotoxic effects in a p53-dependent manner. However, a few reports have shown a p53 mutation as a delayed effect of radiation. In this study, we investigated the p53 gene mutation by the translocation frequency in chromosome 11, loss of p53 alleles, p53 gene methylation, p53 nucleotide sequence, and p53 protein expression/phosphorylation in p53{sup +/+} and p53{sup +/-} mice after irradiation at a young age. Methods and Materials: p53{sup +/+} and p53{sup +/-} mice were exposed to 3 Gy of whole-body irradiation at 8 weeks of age. Chromosome instability was evaluated by fluorescence in situ hybridization analysis. p53 allele loss was evaluated by polymerase chain reaction, and p53 methylation was evaluated by methylation-specific polymerase chain reaction. p53 sequence analysis was performed. p53 protein expression was evaluated by Western blotting. Results: The translocation frequency in chromosome 11 showed a delayed increase after irradiation. In old irradiated mice, the number of mice that showed p53 allele loss and p53 methylation increased compared to these numbers in old non-irradiated mice. In two old irradiated p53{sup +/-} mice, the p53 sequence showed heteromutation. In old irradiated mice, the p53 and phospho-p53 protein expressions decreased compared to old non-irradiated mice. Conclusion: We concluded that irradiation at a young age induced delayed p53 mutations and p53 protein suppression.

  5. Effect of low frequency low energy pulsing electromagnetic field (PEMF) on X-ray-irradiated mice

    SciTech Connect

    Cadossi, R.; Hentz, V.R.; Kipp, J.; Eiverson, R.; Ceccherelli, G.; Zucchini, P.; Emilia, G.; Torelli, G.; Franceschi, C.; Cossarizza, A.

    1989-02-01

    C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PEMF 24 h a day, we observed a more rapid decline in white blood cells (WBC) in the peripheral blood of mice exposed to PEMF at all the x-ray dosages used. No effect of exposure to PEMF was observed on the survival of the mice irradiated with 6.3 Gy and 8.5 Gy; in mice irradiated with 6.8 Gy, 2 out of 12 survived when exposed to PEMF as compared to 10 out of 12 control mice that were irradiated only. At day 4 after irradiation autoradiographic studies performed on bone marrow and spleen of 8.5-Gy-irradiated mice showed no difference between controls and mice exposed to PEMF, whereas on 6.8-Gy mice the bone marrow labeling index was lower in mice exposed to PEMF. In mice irradiated to 6.3 Gy we observed that the recovery of WBC in the peripheral blood was slowed in mice exposed to PEMF and their body weight was significantly lower than in control mice that were irradiated only. The spleen and bone marrow of the mice irradiated to 6.3 Gy and sacrificed at days 4, 14, 20, and 25 after irradiation were analyzed by autoradiography to evaluate the labeling index. Half of the spleens from mice sacrificed at day 25 after irradiation were used to evaluate the RNA content. Autoradiography showed that in the spleen and bone marrow of control mice, there were more cells labeled with (3H)thymidine at days 4 and 14 and less at days 20 and 25 after irradiation in comparison with mice irradiated and exposed to PEMF.

  6. Prenatal exposure to bisphenol A interferes with the development of cerebellar granule neurons in mice and chicken.

    PubMed

    Mathisen, Gro H; Yazdani, Mazyar; Rakkestad, Kirsten E; Aden, Petra K; Bodin, Johanna; Samuelsen, Mari; Nygaard, Unni C; Goverud, Ingeborg L; Gaarder, Mona; Løberg, Else Marit; Bølling, Anette K; Becher, Rune; Paulsen, Ragnhild E

    2013-12-01

    In mice, prenatal exposure to low doses of bisphenol A has been shown to affect neurogenesis and neuronal migration in cortex, resulting in disturbance of both neuronal positioning and the network formation between thalamus and cortex in the offspring brain. In the present study we investigated whether prenatal exposure to bisphenol A disturbs the neurodevelopment of the cerebellum. Two different model systems were used; offspring from two strains of mice from mothers receiving bisphenol A in the drinking water before mating, during gestation and lactation, and chicken embryos exposed to bisphenol A (in the egg) on embryonic day 16 for 24h before preparation of cerebellar granule cell cultures. In the cerebellum, tight regulation of the level of transcription factor Pax6 is critical for correct development of granule neurons. During the development, the Pax6 level in granule neurons is high when these cells are located in the external granule layer and during their migration to the internal granule layer, and it is then reduced. We report that bisphenol A induced an increase in the thickness of the external granule layer and also an increase in the total cerebellar Pax6 level in 11 days old mice offspring. In cultured chicken cerebellar granule neurons from bisphenol A injected eggs the Pax6 level was increased day 6 in vitro. Together, these findings indicate that bisphenol A may affect the granule neurons in the developing cerebellum and thereby may disturb the correct development of the cerebellum.

  7. Emotional Contagion is not Altered in Mice Prenatally Exposed to Poly (I:C) on Gestational Day 9

    PubMed Central

    Gonzalez-Liencres, Cristina; Juckel, Georg; Esslinger, Manuela; Wachholz, Simone; Manitz, Marie-Pierre; Brüne, Martin; Friebe, Astrid

    2016-01-01

    Prenatal immune activation has been associated with increased risk of developing schizophrenia. The polyinosinic-polycytidylic acid (Poly(I:C)) mouse model replicates some of the endophenotype characteristic of this disorder but the social deficits observed in schizophrenia patients have not been well studied in this model. Therefore we aimed to investigate social behavior, in particular emotional contagion for pain, in this mouse model. We injected pregnant mouse dams with Poly(I:C) or saline (control) on gestation day 9 (GD9) and we evaluated their offspring in the pre-pulse inhibition (PPI) test at age 50–55 days old to confirm the reliability of our model. Mice were then evaluated in an emotional contagion test immediately followed by the light/dark test to explore post-test anxiety-like behavior at 10 weeks of age. In the emotional contagion test, an observer (prenatally exposed to Poly(I:C) or to saline) witnessed a familiar wild-type (WT) mouse (demonstrator) receiving electric foot shocks. Our results replicate the sensory gating impairments in the Poly(I:C) offspring but we only observed minor group differences in the social tasks. One of the differences we found was that demonstrators deposited fewer feces in the presence of control observers than of observers prenatally exposed to Poly(I:C), which we suggest could be due to the observers’ behavior. We discuss the findings in the context of age, sex and day of prenatal injection, suggesting that Poly(I:C) on GD9 may be a valuable tool to assess other symptoms or symptom clusters of schizophrenia but perhaps not comprising the social domain. PMID:27445729

  8. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    NASA Astrophysics Data System (ADS)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  9. Prenatal Tests

    MedlinePlus

    ... X Home > Pregnancy > Prenatal care > Prenatal tests Prenatal tests E-mail to a friend Please fill in ... if you’re feeling fine. What are prenatal tests? Prenatal tests are medical tests you get during ...

  10. Prenatal Care

    MedlinePlus

    ... Our ePublications > Prenatal care fact sheet ePublications Prenatal care fact sheet Print this fact sheet Health Care ... More information on prenatal care What is prenatal care? Prenatal care is the health care you get ...

  11. Neuropeptide Y Overexpressing Female and Male Mice Show Divergent Metabolic but Not Gut Microbial Responses to Prenatal Metformin Exposure

    PubMed Central

    Salomäki-Myftari, Henriikka; Vähätalo, Laura H.; Ailanen, Liisa; Pietilä, Sami; Laiho, Asta; Hänninen, Arno; Pursiheimo, Juha-Pekka; Munukka, Eveliina; Rintala, Anniina; Savontaus, Eriika; Pesonen, Ullamari; Koulu, Markku

    2016-01-01

    Background Prenatal metformin exposure has been shown to improve the metabolic outcome in the offspring of high fat diet fed dams. However, if this is evident also in a genetic model of obesity and whether gut microbiota has a role, is not known. Methods The metabolic effects of prenatal metformin exposure were investigated in a genetic model of obesity, mice overexpressing neuropeptide Y in the sympathetic nervous system and in brain noradrenergic neurons (OE-NPYDβH). Metformin was given for 18 days to the mated female mice. Body weight, body composition, glucose tolerance and serum parameters of the offspring were investigated on regular diet from weaning and sequentially on western diet (at the age of 5–7 months). Gut microbiota composition was analysed by 16S rRNA sequencing at 10–11 weeks. Results In the male offspring, metformin exposure inhibited weight gain. Moreover, weight of white fat depots and serum insulin and lipids tended to be lower at 7 months. In contrast, in the female offspring, metformin exposure impaired glucose tolerance at 3 months, and subsequently increased body weight gain, fat mass and serum cholesterol. In the gut microbiota, a decline in Erysipelotrichaceae and Odoribacter was detected in the metformin exposed offspring. Furthermore, the abundance of Sutterella tended to be decreased and Parabacteroides increased. Gut microbiota composition of the metformin exposed male offspring correlated to their metabolic phenotype. Conclusion Prenatal metformin exposure caused divergent metabolic phenotypes in the female and male offspring. Nevertheless, gut microbiota of metformin exposed offspring was similarly modified in both genders. PMID:27681875

  12. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  13. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals. PMID:26465197

  14. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

    USGS Publications Warehouse

    Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

    2015-01-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  15. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue. [Mice

    SciTech Connect

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-04-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy.

  16. Effects of prenatal irradiation with accelerated heavy-ion beams on postnatal development in rats: III. Testicular development and breeding activity

    NASA Astrophysics Data System (ADS)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

    With a significant increase in human activities dealing with space missions, potential teratogenic effects on the mammalian reproductive system from prenatal exposure to space radiation have become a hot topic that needs to be addressed. However, even for the ground experiments, such effects from exposure to high LET ionizing radiation are not as well studied as those for low LET ionizing radiations such as X-rays. Using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, effects on gonads in prenatal male fetuses, on postnatal testicular development and on breeding activity of male offspring were studied following exposure of the pregnant animals to either accelerated carbon-ion beams with a LET value of about 13 keV/μm or neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on gestation day 15. The effects of X-rays at 200 kVp estimated for the same biological end points were studied for comparison. A significantly dose-dependent increase of apoptosis in gonocytes appeared 6 h after irradiations with a dose of 0.5 Gy or more. Measured delayed testis descent and malformed testicular seminiferous tubules were observed to be significantly different from the control animals at a dose of 0.5 Gy. These effects are observed to be dose- and LET-dependent. Markedly reduced testicular weight and testicular weight to body weight ratio were scored at postnatal day 30 even in the offspring that were prenatally irradiated with neon-ions at a dose of 0.1 Gy. A dose of 0.5 Gy from neon-ion beams induced a marked decrease in breeding activity in the prenatally irradiated male rats, while for the carbon-ion beams or X-rays, the significantly reduced breeding activity was observed only when the prenatal dose was at 1.0 Gy or more. These findings indicated that prenatal irradiations with heavy-ion beams on gestation day 15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male

  17. A BIOASSAY THAT IDENTIFIES POSTNATAL FUNCTIONAL DEFICITS IN MICE PRENATALLY EXPOSED TO XENOBIOTICS

    EPA Science Inventory

    Experimental strategies to evaluate adverse postnatal effects due to prenatal exposure exist for many organ systems. Often, however, there is insufficient information to suggest that a particular organ system(s) may be sensitive to the test agent. A single bioassay to identify ...

  18. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1996-06-01

    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 {gamma}-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{sub 1} male mice exposed to protracted neutron radiation.

  19. A Longitudinal Evaluation of Partial Lung Irradiation in Mice by Using a Dedicated Image-Guided Small Animal Irradiator

    SciTech Connect

    Granton, Patrick V.; Dubois, Ludwig; Elmpt, Wouter van; Hoof, Stefan J. van; Lieuwes, Natasja G.; De Ruysscher, Dirk

    2014-11-01

    Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging. Methods and Materials: C57BL/6 adult male mice (n=76) were divided into 6 groups: a control group (0 Gy) and groups irradiated with a single fraction of 4, 8, 12, 16, or 20 Gy using 5-mm circular parallel-opposed fields targeting the upper right lung. A Monte Carlo model of the small animal irradiator was used for dose calculations. Following irradiation, all mice were imaged at regular intervals over 39 weeks (10 time points total). Nonrigid deformation was used to register the initial micro-CT scan to all subsequent scans. Results: Significant differences could be observed between the 3 highest (>10 Gy) and 3 lowest irradiation (<10 Gy) dose levels. A mean difference of 120 ± 10 HU between the 0- and 20-Gy groups was observed at week 39. RILF was found to be spatially limited to the irradiated portion of the lung. Conclusions: The data suggest that the severity of RILF in partial lung irradiation compared to large field irradiation in mice for the same dose is reduced, and therefore higher doses can be tolerated.

  20. Genetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice

    SciTech Connect

    Galvan, Antonella; Noci, Sara; Mancuso, Mariateresa; Pazzaglia, Simonetta; Saran, Anna; Dragani, Tommaso A.

    2008-12-01

    Purpose: Ptch1 germ-line mutations in mice predispose to radiation-induced basal cell carcinoma of the skin, with tumor incidence modulated by the genetic background. Here, we examined the possible mechanisms underlying skin response to radiation in F1 progeny of Ptch1{sup neo67/+} mice crossed with either skin tumor-susceptible (Car-S) or -resistant (Car-R) mice and X-irradiated (3 Gy) at 2 days of age or left untreated. Methods and Materials: We conducted a gene expression profile analysis in mRNA samples extracted from the skin of irradiated or control mice, using Affymetrix whole mouse genome expression array. Confirmation of the results was done using real-time reverse-transcriptase polymerase chain reaction. Results: Analysis of the gene expression profile of normal skin of F1 mice at 4 weeks of age revealed a similar basal profile in the nonirradiated mice, but alterations in levels of 71 transcripts in irradiated Ptch1{sup neo67/+} mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1{sup neo67/+} mice of the Car-S cross. Conclusions: These results indicate that neonatal irradiation causes a persistent change in the gene expression profile of the skin. The tendency of mice genetically resistant to skin tumorigenesis to show a more complex pattern of transcriptional response to radiation than do genetically susceptible mice suggests a role for this response in genetic resistance to basal cell tumorigenesis.

  1. Effect of ultraviolet irradiation on mast cell-deficient W/Wv mice

    SciTech Connect

    Ikai, K.; Danno, K.; Horio, T.; Narumiya, S.

    1985-07-01

    The effect of UV irradiation on the skin was investigated in (WB-W/+) X (C57BL/6J-Wv/+)F1-W/Wv mice, which are genetically deficient in tissue mast cells. Their congenic littermates (+/+) and normal albino mice (ICR or BALB/c) were used as controls. Mice were irradiated with 500 mJ/cm2 of UVB and the increment of ear thickness was measured before and 6, 12, and 24 h after irradiation. Ear swelling in W/Wv mice at 12 and 24 h after irradiation was significantly smaller than that in +/+ and ICR mice. In contrast, the number of sunburn cells formed 24 h after UVB irradiation (200 or 500 mJ/cm2) was similar in W/Wv, +/+ and ICR mice. On the other hand, when mice were treated with 8-methoxy-psoralen (0.5%) plus UVA irradiation (4 J/cm2) (topical PUVA), ears of W/Wv and BALB/c mice, which were both white in color, were thickened similarly 72 h after treatment, but less swelling was observed in +/+ mice, which were black in skin color. The amount of prostaglandin D2 (PGD2) in ears, determined by radioimmunoassay specific for PGD2, was elevated 3-fold in +/+ and ICR mice at 3 h after irradiation with 500 mJ/cm2 of UVB in comparison with basal level without irradiation. However, such elevation was not observed in W/Wv mice. These results suggest that mast cells play an important role in UVB-induced inflammation, and PGs from mast cells are responsible at least in part for the development of this reaction. However, neither mast cells nor PGs contribute to the sunburn cell formation and ear swelling response by PUVA treatment.

  2. Transcriptome Analysis in Prenatal IGF1-Deficient Mice Identifies Molecular Pathways and Target Genes Involved in Distal Lung Differentiation

    PubMed Central

    Hernández-Porras, Isabel; López, Icíar Paula; De Las Rivas, Javier; Pichel, José García

    2013-01-01

    Background Insulin-like Growth Factor 1 (IGF1) is a multifunctional regulator of somatic growth and development throughout evolution. IGF1 signaling through IGF type 1 receptor (IGF1R) controls cell proliferation, survival and differentiation in multiple cell types. IGF1 deficiency in mice disrupts lung morphogenesis, causing altered prenatal pulmonary alveologenesis. Nevertheless, little is known about the cellular and molecular basis of IGF1 activity during lung development. Methods/Principal Findings Prenatal Igf1−/− mutant mice with a C57Bl/6J genetic background displayed severe disproportional lung hypoplasia, leading to lethal neonatal respiratory distress. Immuno-histological analysis of their lungs showed a thickened mesenchyme, alterations in extracellular matrix deposition, thinner smooth muscles and dilated blood vessels, which indicated immature and delayed distal pulmonary organogenesis. Transcriptomic analysis of Igf1−/− E18.5 lungs using RNA microarrays identified deregulated genes related to vascularization, morphogenesis and cellular growth, and to MAP-kinase, Wnt and cell-adhesion pathways. Up-regulation of immunity-related genes was verified by an increase in inflammatory markers. Increased expression of Nfib and reduced expression of Klf2, Egr1 and Ctgf regulatory proteins as well as activation of ERK2 MAP-kinase were corroborated by Western blot. Among IGF-system genes only IGFBP2 revealed a reduction in mRNA expression in mutant lungs. Immuno-staining patterns for IGF1R and IGF2, similar in both genotypes, correlated to alterations found in specific cell compartments of Igf1−/− lungs. IGF1 addition to Igf1−/− embryonic lungs cultured ex vivo increased airway septa remodeling and distal epithelium maturation, processes accompanied by up-regulation of Nfib and Klf2 transcription factors and Cyr61 matricellular protein. Conclusions/Significance We demonstrated the functional tissue specific implication of IGF1 on fetal lung

  3. Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

    PubMed

    Fang, Y-W; Yang, S-S; Chau, T; Nakamura, M; Yamazaki, O; Seki, G; Yamada, H; Hsu, H-M; Cheng, C-J; Lin, S-H

    2015-05-01

    We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

  4. The pyramidal neuron in cerebral cortex following prenatal X-irradiation

    SciTech Connect

    Donoso, J.A.; Norton, S.

    1982-07-01

    Pregnant rats were subjected to whole body X-irradiation amounting to 125 R, on gestational day 15. Cortical pyramidal neurons were examined in irradiated and control offspring at 4 weeks and 4 to 6 months postnatally. All gestationally irradiated rats developed ectopic cortex located below the corpus callosum adjacent to the caudate nucleus in the forebrain. With the rapid Golgi stain, counts were made of dendritic spines on the apical dendrites of layer 5 pyramidal cells in the normally-located cortex and compared with similar neurons in the ectopias. Dendritic spines were present on all pyramidal cells but spines were more sparse on ectopic pyramidal cells. Electron microscopic examination of ectopic and layered cortex in irradiated rats showed axodendritic synapses on the spines and shafts of the dendrites and axosomatic synapses, all of which were indistinguishable morphologically from synapses in control cortex. As a result of the observations made with the light and electron microscopes, it is concluded that the ectopic cortex may contain functional cells in spite of the abnormal location of the tissue.

  5. Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene.

    PubMed

    Zhao, Q; Behringer, R R; de Crombrugghe, B

    1996-07-01

    The paired-class homeobox-containing gene, Cart1, is expressed in forebrain mesenchyme, branchial arches, limb buds and cartilages during embryogenesis. Here, we show that Cart1-homozygous mutant mice are born alive with acrania and meroanencephaly but die soon after birth-a phenotype that strikingly resembles a corresponding human syndrome caused by a neural tube closure defect. Developmental studies suggest that Cart1 is required for forebrain mesenchyme survival and that its absence disrupts cranial neural tube morphogenesis by blocking the initiation of closure in the midbrain region that ultimately leads to the generation of lethal craniofacial defects. Prenatal treatment of Cart1 homozygous mutants with folic acid suppresses the development of the acrania/meroanencephaly phenotype. PMID:8673125

  6. Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors

    PubMed Central

    Kang, Jaeseung; Kim, Eunjoon

    2015-01-01

    Animals prenatally exposed to valproic acid (VPA), an antiepileptic agent, have been used as a model for autism spectrum disorders (ASDs). Previous studies have identified enhanced NMDA receptor (NMDAR) function in the brain of VPA rats, and demonstrated that pharmacological suppression of NMDAR function normalizes social deficits in these animals. However, whether repetitive behavior, another key feature of ASDs, can be rescued by NMDAR inhibition remains unknown. We report here that memantine, an NMDAR antagonist, administered to VPA mice rescues both social deficits and repetitive behaviors such as self-grooming and jumping. These results suggest that suppression of elevated NMDAR function in VPA animals normalizes repetitive behaviors in addition to social deficits. PMID:26074764

  7. Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet

    PubMed Central

    Orellana, Juan A.; Busso, Dolores; Ramírez, Gigliola; Campos, Marlys; Rigotti, Attilio; Eugenín, Jaime; von Bernhardi, Rommy

    2014-01-01

    Nicotine, the most important neuroteratogen of tobacco smoke, can reproduce brain and cognitive disturbances per se when administered prenatally. However, it is still unknown if paracrine signaling among brain cells participates in prenatal nicotine-induced brain impairment of adult offspring. Paracrine signaling is partly mediated by unopposed channels formed by connexins hemichannels (HCs) and pannexins serving as aqueous pores permeable to ions and small signaling molecules, allowing exchange between the intra- and extracellular milieus. Our aim was to address whether prenatal nicotine exposure changes the activity of those channels in adult mice offspring under control conditions or subjected to a second challenge during young ages: high-fat/cholesterol (HFC) diet. To induce prenatal exposure to nicotine, osmotic minipumps were implanted in CF1 pregnant mice at gestational day 5 to deliver nicotine bitartrate or saline (control) solutions. After weaning, offspring of nicotine-treated or untreated pregnant mice were fed ad libitum with chow or HFC diets for 8 weeks. The functional state of connexin 43 (Cx43) and pannexin 1 (Panx1) unopposed channels was evaluated by dye uptake experiments in hippocampal slices from 11-week-old mice. We found that prenatal nicotine increased the opening of Cx43 HCs in astrocytes, and Panx1 channels in microglia and neurons only if offspring mice were fed with HFC diet. Blockade of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2) and prostaglandin E receptor 1 (EP1), ionotropic ATP receptor type 7 (P2X7) and NMDA receptors, showed differential inhibition of prenatal nicotine-induced channel opening in glial cells and neurons. Importantly, inhibition of the above mentioned enzymes and receptors, or blockade of Cx43 and Panx1 unopposed channels greatly reduced adenosine triphosphate (ATP) and glutamate release from hippocampal slices of prenatally nicotine-exposed offspring. We propose that unregulated gliotransmitter

  8. Prenatal ontogeny of the dopamine-dependent neurobehavioral phenotype in Pitx3 deficient mice

    PubMed Central

    Kleven, Gale A.; Joshi, Priyanka; Voogd, Marco; Ronca, April E.

    2013-01-01

    Mouse models with prenatal alterations in dopaminergic functioning can provide new opportunities to identify fetal behavioral abnormalities and the underlying neural substrates dependent on dopamine. In this study, we tested the hypothesis that prenatal loss of nigrostriatal function is associated with fetal akinesia, or difficulty initiating movement. Specific behaviors were analyzed in fetal offspring derived from pregnant Pitx3ak/2J and C57BL/6J dams on the last four days before birth (E15–18 of a 19-day gestation). Using digital videography, we analyzed: (a) Behavioral State, by quantification of high and low amplitude movements, (b) Interlimb Movement Synchrony, a measure of the temporal relationship between spontaneous movements of limb pairs, (c) Facial Wiping, a characteristic response to perioral tactile stimulation similar to the defensive response in human infants, and (d) Oral Grasp of a non-nutritive nipple, a component of suckling in the human infant. Pitx3 mutants showed a selective decrease in Interlimb Movement Synchrony rates at the shortest (0.1s) temporal interval coupled with significantly increased latencies to exhibit Facial Wiping and Oral Grasp. Collectively, our findings provide evidence that the primary fetal neurobehavioral deficit of the Pitx3 mutation is akinesia related to nigrostriatal damage. Other findings of particular interest were the differences in neurobehavioral functioning between C57BL/6J and Pitx3 heterozygous subjects, suggesting the two groups are not equivalent controls. These results further suggest that fetal neurobehavioral assessments are sensitive indicators of emerging neural dysfunction, and may have utility for prenatal diagnosis. PMID:23489835

  9. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice

    PubMed Central

    2010-01-01

    Background Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physico-chemical properties. Consequently, also toxicological properties may change compared to the parent compound. We examined developmental and neurobehavioral effects following maternal exposure to a nanoparticulate UV-filter (UV-titan L181). Methods Time-mated mice (C57BL/6BomTac) were exposed by inhalation 1h/day to 42 mg/m3 aerosolized powder (1.7·106 n/cm3; peak-size: 97 nm) on gestation days 8-18. Endpoints included: maternal lung inflammation; gestational and litter parameters; offspring neurofunction and fertility. Physicochemical particle properties were determined to provide information on specific exposure and deposition. Results Particles consisted of mainly elongated rutile titanium dioxide (TiO2) with an average crystallite size of 21 nm, modified with Al, Si and Zr, and coated with polyalcohols. In exposed adult mice, 38 mg Ti/kg was detected in the lungs on day 5 and differential cell counts of bronchoalveolar lavage fluid revealed lung inflammation 5 and 26-27 days following exposure termination, relative to control mice. As young adults, prenatally exposed offspring tended to avoid the central zone of the open field and exposed female offspring displayed enhanced prepulse inhibition. Cognitive function was unaffected (Morris water maze test). Conclusion Inhalation exposure to nano-sized UV Titan dusts induced long term lung inflammation in time-mated adult female mice. Gestationally exposed offspring displayed moderate neurobehavioral alterations. The results are discussed in the light of the observed particle size distribution in the exposure atmosphere and the potential pathways by which nanoparticles may impart changes in fetal development. PMID:20546558

  10. Prenatal diethylstilbestrol induces malformation of the external genitalia of male and female mice and persistent second-generation developmental abnormalities of the external genitalia in two mouse strains

    PubMed Central

    Mahawong, Phitsanu; Sinclair, Adriane; Li, Yi; Schlomer, Bruce; Rodriguez, Esequiel; Max, Ferretti M.; Liu, Baomei; Baskin, Laurence S.; Cunha, Gerald R.

    2014-01-01

    Potential trans-generational influence of diethylstilbestrol (DES) exposure emerged with reports of effects in grandchildren of DES-treated pregnant women and of reproductive tract tumors in offspring of mice exposed in utero to DES. Accordingly, we examined the trans-generational influence of DES on development of external genitalia (ExG) and compared effects of in utero DES exposure in CD-1 and C57BL/6 mice injected with oil or DES every other day from gestational days 12 to 18. Mice were examined at birth, and on 5 to 120 days postnatal to evaluate ExG malformations. Of 23 adult (≥60 days) prenatally DES-exposed males, features indicative of urethral meatal hypospadias (see text for definitions) ranged from 18 to 100% in prenatally DES-exposed CD-1 males and 31 to 100% in prenatally DES-exposed C57BL/6 males. Thus, the strains differed in the incidence of male urethral hypospadias. Ninety-one percent of DES-exposed CD-1 females and 100% of DES-exposed C57BL/6 females had urethral-vaginal fistula. All DES-exposed CD-1 and C57BL/6 females lacked an os clitoris. None of the prenatally oil-treated CD-1 and C57BL/6 male and female mice had ExG malformations. For the second-generation study, 10 adult CD-1 males and females, from oil- and DES-exposed groups, respectively, were paired with untreated CD-1 mice for 30 days, and their offspring evaluated for ExG malformations. None of the F1 DES-treated females were fertile. Nine of 10 prenatally DES-exposed CD-1 males sired offspring with untreated females, producing 55 male and 42 female pups. Of the F2 DES-lineage adult males, 20% had exposed urethral flaps, a criterion of urethral meatal hypospadias. Five of 42 (11.9%) F2 DES lineage females had urethral-vaginal fistula. In contrast, all F2 oil-lineage males and all oil-lineage females were normal. Thus, prenatal DES exposure induces malformations of ExG in both sexes and strains of mice, and certain malformations are transmitted to the second-generation. PMID

  11. Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays

    PubMed Central

    Nishimura, Yoshikazu; Homma-Takeda, Shino; Kim, Hee-Sun; Kakuta, Izuru

    2014-01-01

    The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage. PMID:24508645

  12. Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays.

    PubMed

    Nishimura, Yoshikazu; Homma-Takeda, Shino; Kim, Hee-Sun; Kakuta, Izuru

    2014-03-01

    The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage.

  13. Prenatal and Lactational Exposure to Bisphenol A in Mice Alters Expression of Genes Involved in Cortical Barrel Development without Morphological Changes

    PubMed Central

    Han, Longzhe; Itoh, Kyoko; Yaoi, Takeshi; Moriwaki, Sanzo; Kato, Shingo; Nakamura, Keiko; Fushiki, Shinji

    2011-01-01

    It has been reported that premature infants in neonatal intensive care units are exposed to a high rate of bisphenol A (BPA), an endocrine disrupting chemical. Our previous studies demonstrated that corticothalamic projection was disrupted by prenatal exposure to BPA, which persisted even in adult mice. We therefore analyzed whether prenatal and lactational exposure to low doses of BPA affected the formation of the cortical barrel, the barreloid of the thalamus, and the barrelette of the brainstem in terms of the histology and the expression of genes involved in the barrel development. Pregnant mice were injected subcutaneously with 20 µg/kg of BPA daily from embryonic day 0 (E0) to postnatal 3 weeks (P3W), while the control mice received a vehicle alone. The barrel, barreloid and barrelette of the adult mice were examined by cytochrome C oxidase (COX) staining. There were no significant differences in the total and septal areas and the patterning of the posterior medial barrel subfield (PMBSF), barreloid and barrelette, between the BPA-exposure and control groups in the adult mice. The developmental study at postnatal day 1 (PD1), PD4 and PD8 revealed that the cortical barrel vaguely appeared at PD4 and completely formed at PD8 in both groups. The expression pattern of some genes was spatiotemporally altered depending on the sex and the treatment. These results suggest that the trigeminal projection and the thalamic relay to the cortical barrel were spared after prenatal and lactational exposure to low doses of BPA, although prenatal exposure to BPA was previously shown to disrupt the corticothalamic projection. PMID:21448315

  14. Prenatal and Lactational Exposure to Bisphenol A in Mice Alters Expression of Genes Involved in Cortical Barrel Development without Morphological Changes.

    PubMed

    Han, Longzhe; Itoh, Kyoko; Yaoi, Takeshi; Moriwaki, Sanzo; Kato, Shingo; Nakamura, Keiko; Fushiki, Shinji

    2011-02-26

    It has been reported that premature infants in neonatal intensive care units are exposed to a high rate of bisphenol A (BPA), an endocrine disrupting chemical. Our previous studies demonstrated that corticothalamic projection was disrupted by prenatal exposure to BPA, which persisted even in adult mice. We therefore analyzed whether prenatal and lactational exposure to low doses of BPA affected the formation of the cortical barrel, the barreloid of the thalamus, and the barrelette of the brainstem in terms of the histology and the expression of genes involved in the barrel development. Pregnant mice were injected subcutaneously with 20 µg/kg of BPA daily from embryonic day 0 (E0) to postnatal 3 weeks (P3W), while the control mice received a vehicle alone. The barrel, barreloid and barrelette of the adult mice were examined by cytochrome C oxidase (COX) staining. There were no significant differences in the total and septal areas and the patterning of the posterior medial barrel subfield (PMBSF), barreloid and barrelette, between the BPA-exposure and control groups in the adult mice. The developmental study at postnatal day 1 (PD1), PD4 and PD8 revealed that the cortical barrel vaguely appeared at PD4 and completely formed at PD8 in both groups. The expression pattern of some genes was spatiotemporally altered depending on the sex and the treatment. These results suggest that the trigeminal projection and the thalamic relay to the cortical barrel were spared after prenatal and lactational exposure to low doses of BPA, although prenatal exposure to BPA was previously shown to disrupt the corticothalamic projection. PMID:21448315

  15. NRF2 deficiency reduces life span of mice administered thoracic irradiation.

    PubMed

    Travis, Elizabeth L; Rachakonda, Girish; Zhou, Xinhui; Korhonen, Katrina; Sekhar, Konjeti R; Biswas, Swati; Freeman, Michael L

    2011-09-15

    Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-β and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-β-mediated signaling, assessed by measuring expression of a surrogate TGF-β1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2(-/-) mice resulted in rapid expression of PAI-1 and FSP-1 compared to irradiated wild-type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2(-/-) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild-type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2(+/-) and Nfe2l2(-/-) mice exhibited a mean life span of 176 days compared to wild-type mice, which lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for the development of late tissue injury.

  16. Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice

    PubMed Central

    Schraut, K G; Jakob, S B; Weidner, M T; Schmitt, A G; Scholz, C J; Strekalova, T; El Hajj, N; Eijssen, L M T; Domschke, K; Reif, A; Haaf, T; Ortega, G; Steinbusch, H W M; Lesch, K P; Van den Hove, D L

    2014-01-01

    The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/− offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0 R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/− mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt

  17. High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

    NASA Astrophysics Data System (ADS)

    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

  18. Effects of prenatal stress and exercise on dentate granule cells maturation and spatial memory in adolescent mice.

    PubMed

    Bustamante, Carlos; Bilbao, Pamela; Contreras, William; Martínez, Mauricio; Mendoza, Antonio; Reyes, Alvaro; Pascual, Rodrigo

    2010-11-01

    Exposure to prenatal stress (PS) increases the risk of developing neurobehavioral disturbances later in life. Previous work has shown that exercise can exert beneficial effects on brain damage; however, it is unknown whether voluntary wheel running (VWR) can ameliorate the neurobehavioral impairments induced by PS in adolescent offspring. Pregnant CF-1 mice were randomly assigned to control (n=5) or stressed (n=5) groups. Pregnant dams were subjected to restraint stress between gestational days 14 and 21 (G14-21), whereas controls remained undisturbed in their home cages. On postnatal day 21 (P21), male pups were randomly assigned to the following experimental groups: control (n=5), stressed (n=5), and stressed mice+daily submitted to VWR (n=4). At P52, all groups were behaviorally evaluated in the Morris water maze. Animals were then sacrificed, and Golgi-impregnated granule cells were morphometrically analyzed. The results indicate that PS produced significant behavioral and neuronal impairments in adolescent offspring and that VWR significantly offset these deleterious effects.

  19. Hepatic mitochondrial alteration in CD1 mice associated with prenatal exposures to low doses of perfluorooctanoic acid (PFOA)

    PubMed Central

    Quist, Erin M.; Filgo, Adam J.; Cummings, Connie A.; Kissling, Grace E.; Hoenerhoff, Mark J.; Fenton, Suzanne E.

    2014-01-01

    Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3 and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number, but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA. PMID:25326589

  20. Facilitation of allogeneic bone marrow engraftment in mice by total lymphoid irradiation combined with total-body irradiation

    SciTech Connect

    Ang, K.K.; Waer, M.; van der Schueren, E.; Vandeputte, M.

    1983-07-01

    Different groups of C57BL/Ka mice received daily fractions of 2 Gy total lymphoid irradiation (TLI) in a total dose of 34, 24, or 14 Gy. On the day after the last irradiation, 30 X 10(6) allogeneic (BALB/c) nucleated bone marrow cells were infused into the irradiated animals. When the last one or two fractions of the radiation schedule were given to the whole body (combined total lymphoid-total-body irradiation, TLBI): (1) stable bone marrow chimerism with a higher number of donor-type cells in the peripheral blood was induced in a higher percentage of mice that had received 34 Gy TLBI compared with mice that received 34 Gy TLI. (2) bone marrow chimerism could also be induced after 24 Gy or 14 Gy TLBI, whereas 24 and 14 Gy TLI alone were ineffective. The tolerance to the TLBI schedules was excellent and no clinical signs of graft-versus-host disease were noticed. It is concluded that the addition of TBI can facilitate bone marrow engraftment after TLI and drastically reduce the number of radiation fractions needed to obtain successful chimerism after allogeneic bone marrow transplantation in mice.

  1. Prenatal stress and ethanol exposure produces inversion of sexual partner preference in mice.

    PubMed

    Popova, Nina K; Morozova, Maryana V; Amstislavskaya, Tamara G

    2011-02-01

    The presence of a sexually receptive female behind perforated transparent partition induced sexual arousal and specific behavior in male mice so they spent more time near partition in an attempt to make their way to the female. Three-chambered free-choice model was used to evaluate sexual partner preference. The main pattern of sexual preference was the time spent by a male mouse at the partition dividing female (F-partition time) versus a partition dividing male (M-partition time). Pregnant mice were given ethanol (11vol.%) for 1-21 gestational days, and were exposed to restraint stress (2h daily for 15-21 day of the gestation). Control pregnant mice had free access to water and food and were not stressed. Adult male offspring of ethanol and stress exposed dams (E+S) showed decreased F-partition time and increased M-partition time. Whereas F-partition time in all control mice prevailed over M-partition time, 78% E+S mice demonstrated prevailed M-partition time. E+S mice were more active in social interaction with juvenile male. No significant differences between E+S and control mice in the open field and novelty tests were revealed. Therefore, E+S exposure during dam gestation inverted sexual partner preference in male offspring, suggesting that stress and alcohol in pregnancy produces predisposition to homosexuality.

  2. Prenatal administration of the cytochrome P4501A inducer, {Beta}-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: Implications for bronchopulmonary dysplasia (BPD) in premature infants

    SciTech Connect

    Couroucli, Xanthi I.; Liang Yanhong Wei; Jiang Weiwu; Wang Lihua; Barrios, Roberto; Yang Peiying; Moorthy, Bhagavatula

    2011-10-15

    Supplemental oxygen contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this investigation, we tested the hypothesis that prenatal treatment of pregnant mice (C57BL/6J) with the cytochrome P450 (CYP)1A1 inducer, ss-napthoflavone (BNF), will lead to attenuation of lung injury in newborns (delivered from these dams) exposed to hyperoxia by mechanisms entailing transplacental induction of hepatic and pulmonary CYP1A enzymes. Pregnant mice were administered the vehicle corn oil (CO) or BNF (40 mg/kg), i.p., once daily for 3 days on gestational days (17-19), and newborns delivered from the mothers were either maintained in room air or exposed to hyperoxia (> 95% O{sub 2}) for 1-5 days. After 3-5 days of hyperoxia, the lungs of CO-treated mice showed neutrophil infiltration, pulmonary edema, and perivascular inflammation. On the other hand, BNF-pretreated neonatal mice showed decreased susceptibility to hyperoxic lung injury. These mice displayed marked induction of ethoxyresorufin O-deethylase (EROD) (CYP1A1) and methoxyresorufin O-demethylase (MROD) (CYP1A2) activities, and levels of the corresponding apoproteins and mRNA levels until PND 3 in liver, while CYP1A1 expression alone was augmented in the lung. Prenatal BNF did not significantly alter gene expression of pulmonary NAD(P)H quinone reductase (NQO1). Hyperoxia for 24-72 h resulted in increased pulmonary levels of the F{sub 2}-isoprostane 8-iso-PGF{sub 2{alpha}}, whose levels were decreased in mice prenatally exposed to BNF. In conclusion, our results suggest that prenatal BNF protects newborns against hyperoxic lung injury, presumably by detoxification of lipid hydroperoxides by CYP1A enzymes, a phenomenon that has implications for prevention of BPD in infants. - Highlights: > Supplemental oxygen is routinely administered to premature infants. > Hyperoxia causes lung injury in experimental animals. > Prenatal treatment of mice with beta-naphthoflavone attenuates oxygen

  3. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    SciTech Connect

    Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

    2013-11-15

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

  4. Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    NASA Astrophysics Data System (ADS)

    Takahashi, A.; Kondo, N.; Inaba, H.; Uotani, K.; Kiyohara, Y.; Ohnishi, K.; Ohnishi, T.

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr +/ + were irradiated with X-ray at 3.0 C3y at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/ + mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

  5. Haplosufficient genomic androgen receptor signaling is adequate to protect female mice from induction of polycystic ovary syndrome features by prenatal hyperandrogenization.

    PubMed

    Caldwell, A S L; Eid, S; Kay, C R; Jimenez, M; McMahon, A C; Desai, R; Allan, C M; Smith, J T; Handelsman, D J; Walters, Kirsty A

    2015-04-01

    Polycystic ovary syndrome (PCOS) is associated with reproductive, endocrine, and metabolic abnormalities. Because hyperandrogenism is the most consistent PCOS feature, we used wild-type (WT) and androgen receptor (AR) knockout (ARKO) mice, together with a mouse model of PCOS, to investigate the contribution of genomic AR-mediated actions in the development of PCOS traits. PCOS features were induced by prenatal exposure to dihydrotestosterone (250 μg) or oil vehicle (control) on days 16-18 of gestation in WT, heterozygote, and homozygote ARKO mice. DHT treatment of WT mice induced ovarian cysts (100% vs 0%), disrupted estrous cycles (42% vs 100% cycling), and led to fewer corpora lutea (5.0±0.4 vs 9.8±1.8). However, diestrus serum LH and FSH, and estradiol-induced-negative feedback as well as hypothalamic expression of kisspeptin, neurokinin B, and dynorphin, were unaffected by DHT treatment in WT mice. DHT-treated WT mice exhibited a more than 48% increase in adipocyte area but without changes in body fat. In contrast, heterozygous and homozygous ARKO mice exposed to DHT maintained comparable ovarian (histo)morphology, estrous cycling, and corpora lutea numbers, without any increase in adipocyte size. These findings provide strong evidence that genomic AR signaling is an important mediator in the development of these PCOS traits with a dose dependency that allows even AR haplosufficiency to prevent induction by prenatal androgenization of PCOS features in adult life.

  6. Enhanced hematopoietic recovery in irradiated mice pretreated with interleukin-1 (IL-1)2,3

    SciTech Connect

    Schwartz, G.N.; MacVittie, T.J.; Vigneulle, R.M.; Patchen, M.L.; Douches, S.D.

    1987-01-01

    Data in this report compare the number of colony-forming cells (CFC) in bone marrow from irradiated and pre-irradiated C57B1/6J mice injected with saline or recombinant interleukin-1-alpha (rIL-1). Eight to 12 days after sublethal or lethal irradiation, there were more CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units erythroid), GM-CFC (granulocyte-macrophage colony-forming cells), and 8 CFU-S (colony-forming units-spleen) in bone marrow from rIL-1 injected mice than from saline injected mice. Prior to irradiation, there was no increase in number of CFC in bone marrow from rIL-1 injected mice. However, as determined by sensitivity to hydroxyurea, rIL-1 injection stimulated GM-CFC into cell cycle. These results demonstrate that rIL-1 injection increases the number of CFC that survive in irradiated mice and may be a consequence of the stimulation of CFC into cell cycle prior to irradiation.

  7. Recovery of hematopoietic colony-forming cells in irradiated mice pretreated with interleukin 1 (IL-1)

    SciTech Connect

    Schwartz, G.N.; Neta, R.; Vigneulle, R.M.; Patchen, M.L.; MacVittie, T.J.

    1988-10-01

    Data in this report determined the effect of a single injection of recombinant interleukin 1 alpha (rIL-1) prior to irradiation of B6D2F1 mice on the recovery of colony-forming cells (CFC) at early and late times after sublethal and lethal doses of radiation. Injection of rIL-1 promoted an earlier recovery of mature cells in the blood and CFC in the bone marrow and spleen. For example, 8 days after 6.5 Gy irradiation, the number of CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units-erythroid), and GM-CFC (granulocyte-macrophage colony-forming cells) per femur was approximately 1.5-fold higher in rIL-1-injected mice than in saline-injected mice. Also, 5, 9, and 12 days after irradiation, the number of both day 8 and day 12 CFU-S (colony-forming units-spleen) was almost twofold greater in bone marrow from rIL-1-injected mice. The earlier recovery of CFU-S in rIL-1-injected mice was not associated with an increase in the number of CFU-S that survived immediately after irradiation. Also, 7 months after irradiation, the number of CFU-S per femur of both saline- and rIL-1-injected mice was still less than 50% of normal values. Data in this report demonstrate that a single injection of rIL-1 prior to irradiation accelerates early hematopoietic recovery in irradiated mice, but does not prevent expression of radiation-induced frontend damage or long-term damage to hematopoietic tissues.

  8. Attenuating effects of omega-3 fatty acids (Omegaven) on irradiation-induced intestinal injury in mice.

    PubMed

    Sun, Mingli; Pang, Lei; Ju, Xuepeng; Sun, Haigang; Yu, Jiankun; Zhao, Haishan; Yao, Weifan; Wei, Minjie

    2014-02-01

    Gastrointestinal injury is a major cause of death following exposure to high levels of irradiation, and no effective treatments are currently available. In this study, we examined the effect of omega-3 fatty acids (Omegaven) on intestinal injury of BALB/c mice induced by irradiation. Intravenously administered 3 days prior to irradiation for 7 consecutive days, Omegaven was shown to improve survival, intestinal morphology including villous height, crypt height and mucosal thickness and the intestinal proliferation compared with saline control. Omegaven also normalized the levels of circulating tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), attenuated the increase of diamino oxidase (DAO) activity and malondialdehyde (MDA) level and recovered the decrease of superoxide dismutase (SOD) activity. Meanwhile, Omegaven attenuated the myelosuppression caused by irradiation. In conclusion, our results suggest that Omegaven enhanced the survival of irradiated mice and minimized the effects of radiation on gastrointestinal injury. PMID:24316316

  9. Voluntary Exercise Improves Estrous Cyclicity in Prenatally Androgenized Female Mice Despite Programming Decreased Voluntary Exercise: Implications for Polycystic Ovary Syndrome (PCOS).

    PubMed

    Homa, Lori D; Burger, Laura L; Cuttitta, Ashley J; Michele, Daniel E; Moenter, Suzanne M

    2015-12-01

    Prenatal androgen (PNA) exposure in mice produces a phenotype resembling lean polycystic ovary syndrome. We studied effects of voluntary exercise on metabolic and reproductive parameters in PNA vs vehicle (VEH)-treated mice. Mice (8 wk of age) were housed individually and estrous cycles monitored. At 10 weeks of age, mice were divided into groups (PNA, PNA-run, VEH, VEH-run, n = 8-9/group); those in the running groups received wheels allowing voluntary running. Unexpectedly, PNA mice ran less distance than VEH mice; ovariectomy eliminated this difference. In ovary-intact mice, there was no difference in glucose tolerance, lower limb muscle fiber types, weight, or body composition among groups after 16 weeks of running, although some mitochondrial proteins were mildly up-regulated by exercise in PNA mice. Before running, estrous cycles in PNA mice were disrupted with most days in diestrus. There was no change in cycles during weeks 1-6 of running (10-15 wk of age). In contrast, from weeks 11 to 16 of running, cycles in PNA mice improved with more days in proestrus and estrus and fewer in diestrus. PNA programs reduced voluntary exercise, perhaps mediated in part by ovarian secretions. Exercise without weight loss improved estrous cycles, which if translated could be important for fertility in and counseling of lean women with polycystic ovary syndrome. PMID:26360506

  10. Allogeneic bone marrow transplantation in mice after total lymphoid irradiation: influence of breeding conditions and strain of recipient mice

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-02-01

    Different groups of C57BL/ka or BALB/c mice received a dose of 34 Gy or 42 Gy of fractionated total lymphoid irradiation (TLI) before bone marrow transplantation with 30 x 10/sup 6/ BALB/c or C57BL nucleated bone marrow cells, respectively. BALB/c mice that were not bred in specific pathogen-free conditions before TLI showed a high morbidity and mortality rate after 34 Gy of TLI and allogeneic bone marrow transplantation as compared with BALB/c or C57BL that were bred in pathogen-free conditions before irradiation. Many of the conventionally bred BALB/c mice had clinical and histologic signs of graft-vs-host disease after TLI and allogeneic bone marrow infusion. Although leucocytosis and lymphocytosis and the immunologic competence as measured with in vitro tests were equally depressed after 34 Gy TLI in BALB/c and C57BL mice, chimerism was nevertheless significantly easier to obtain in BALB/c mice. The incidence of chimerism after TLI could be enhanced in C57BL mice by increasing the total radiation dose from 34 to 42 Gy. This augmentation of chimerism was paralleled by the induction of more suppressor cells after 42 Gy of TLI in C57BL mice.

  11. Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation.

    PubMed

    Sumita, Yoshinori; Liu, Younan; Khalili, Saeed; Maria, Ola M; Xia, Dengsheng; Key, Sharon; Cotrim, Ana P; Mezey, Eva; Tran, Simon D

    2011-01-01

    Treatment for most patients with head and neck cancers includes ionizing radiation. A consequence of this treatment is irreversible damage to salivary glands (SGs), which is accompanied by a loss of fluid-secreting acinar-cells and a considerable decrease of saliva output. While there are currently no adequate conventional treatments for this condition, cell-based therapies are receiving increasing attention to regenerate SGs. In this study, we investigated whether bone marrow-derived cells (BMDCs) can differentiate into salivary epithelial cells and restore SG function in head and neck irradiated mice. BMDCs from male mice were transplanted into the tail-vein of 18Gy-irradiated female mice. Salivary output was increased in mice that received BMDCs transplantation at week 8 and 24 post-irradiation. At 24 weeks after irradiation (IR), harvested SGs (submandibular and parotid glands) of BMDC-treated mice had greater weights than those of non-treated mice. Histological analysis shows that SGs of treated mice demonstrated an increased level of tissue regenerative activity such as blood vessel formation and cell proliferation, while apoptotic activity was increased in non-transplanted mice. The expression of stem cell markers (Sca-1 or c-kit) was detected in BMDC-treated SGs. Finally, we detected an increased ratio of acinar-cell area and approximately 9% of Y-chromosome-positive (donor-derived) salivary epithelial cells in BMDC-treated mice. We propose here that cell therapy using BMDCs can rescue the functional damage of irradiated SGs by direct differentiation of donor BMDCs into salivary epithelial cells.

  12. Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy.

    PubMed

    Waddington, Simon N; Nivsarkar, Megha S; Mistry, Ajay R; Buckley, Suzanne M K; Kemball-Cook, Geoffrey; Mosley, Karen L; Mitrophanous, Kyriacos; Radcliffe, Pippa; Holder, Maxine V; Brittan, Mairi; Georgiadis, Anastasios; Al-Allaf, Faisal; Bigger, Brian W; Gregory, Lisa G; Cook, H Terence; Ali, Robin R; Thrasher, Adrian; Tuddenham, Edward G D; Themis, Mike; Coutelle, Charles

    2004-11-01

    Hemophilia B, also known as Christmas disease, arises from mutations in the factor IX (F9) gene. Its treatment in humans, by recombinant protein substitution, is expensive, thus limiting its application to intermittent treatment in bleeding episodes and prophylaxis during surgery; development of inhibitory antibodies is an associated hazard. This study demonstrates permanent therapeutic correction of his disease without development of immune reactions by introduction of an HIV-based lentiviral vector encoding the human factor IX protein into the fetal circulation of immunocompetent hemophiliac and normal outbred mice. Plasma factor IX antigen remained at around 9%, 13%, and 16% of normal in the 3 hemophilia B mice, respectively, until the last measurement at 14 months. Substantial improvement in blood coagulability as measured by coagulation assay was seen in all 3 mice and they rapidly stopped bleeding after venipuncture. No humoral or cellular immunity against the protein, elevation of serum liver enzymes, or vector spread to the germline or maternal circulation were detected.

  13. Comparative effects of centrophenoxine on the picrotoxin convulsive-seizure threshold in non-irradiated and irradiated mice.

    PubMed

    Georgiev, V P; Petkova, B P

    1978-01-01

    A comparative study is made of the effect of centrophenoxine (CP) on the picrotoxin convulsive-seizure threshold (PCST) in non-irradiated and irradiated 3 and 7 days previously male mice. It is found that the CP appliked intracerebroventricularly in doses of 200 and 400 micrograms/mouse (weight 18-22 g), increases PCST. In non-irradiated mice the PCST-increasing effect of CP occurs rapidly (5 min) and it is brief (it can be observed until the 15th min). When the irradiation is performed three days previously, the PCST-increasing effect of CP is prolonged (it is observed until the 6th hour after its application). When the irradiation is performed seven days previously the characteristic features of the PCST-increasing effect of CP are similar to those in the early stage (3 days), the only difference being that the duration of the effect is prolonged to 120 min. Generally, these specificities of the CP effect are valid for all three phases of the convulsive seizure (general excitation, clonic convulsive seizure and tonic convulsive seizure.

  14. Alterations to eye structures in hairless mice by long-term ultraviolet irradiation. A histopathological study.

    PubMed

    Vangsted, P

    1985-04-01

    The eyes of 75 Hr/Hr hairless mice were irradiated with one minimal erythema dose/day of UV light for a period of 12 months, and then observed for a further 6 months. The mice were divide into 3 subgroups, - one without protectans, - one protected by the sun protection lotion Sea and Ski, factor 5, - and one by Piz Buin, Factor 6. The eyes of 75 non-irradiated mice of the same type, subdivided into 3 comparable groups, served as controls. Animals which died during the test period were examined immediately. After the 18 months period, eyes and adnexa of the surviving animals were examined macroscopically and by light microscopy. The lifespan of unprotected, irradiated mice was significantly shorter than the protected groups. The eyelids of irradiated mice presented hyperplasia, actinic keratosis and invasive carcinoma, the latter in 20%. No melanotic tumours were recorded. Since the sun lotion protected animals had a significantly longer lifespan they showed a higher number of palpebral tumours. No irradiation lesions could be demonstrated in the lens, the vitreous or the retina.

  15. NICOTINE EFFECTS ON THE ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

    EPA Science Inventory

    Considerable research has shown long-lasting effects of early exposure in experimental animals to nicotine. Anatoxin-a is produced by cyanobacteria and has been shown to be a potent nicotinic agonist. This experiment evaluated the motor activity of adult mice, and their respons...

  16. 16Oxygen irradiation enhances cued fear memory in B6D2F1 mice

    NASA Astrophysics Data System (ADS)

    Raber, Jacob; Marzulla, Tessa; Kronenberg, Amy; Turker, Mitchell S.

    2015-11-01

    The space radiation environment includes energetic charged particles that may impact cognitive performance. We assessed the effects of 16O ion irradiation on cognitive performance of C57BL/6J × DBA/2J F1 (B6D2F1) mice at OHSU (Portland, OR) one month following irradiation at Brookhaven National Laboratory (BNL, Upton, NY). Hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory of B6D2F1 mice were tested. 16O ion exposure enhanced cued fear memory. This effect showed a bell-shaped dose response curve. Cued fear memory was significantly stronger in mice irradiated with 16O ions at a dose of 0.4 or 0.8 Gy than in sham-irradiated mice or following irradiation at 1.6 Gy. In contrast to cued fear memory, contextual fear memory was not affected following 16O ion irradiation at the doses used in this study. These data indicate that the amygdala might be particularly susceptible to effects of 16O ion exposure.

  17. Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation

    SciTech Connect

    Fushiki, M.; Ono, K.; Sasai, K.; Shibamoto, Y.; Tsutsui, K.; Nishidai, T.; Takahashi, M.; Abe, M. )

    1990-02-01

    We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases.

  18. Prenatal exposure to anti-HIV drugs. long-term neurobehavioral effects of lamivudine (3TC) in CD-1 mice.

    PubMed

    Calamandrei, G; Venerosi, A; Branchi, I; Valanzano, A; Alleva, E

    2000-01-01

    The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (NaCl 0. 9%) from pregnancy day 10 to delivery. Offspring behavior was examined on postnatal day 35 in a 20-min social interaction test. At adulthood different behavioral endpoints were analyzed, including locomotor activity and exploration in an open field following administration of the muscarinic antagonist scopolamine (2 mg/kg), spatial learning in either radial arm or Morris water maze, virgin female behavior in a maternal induction test, and pain sensitivity in a hot-plate test (52 +/- 0.1 degrees C). Our findings confirm the low neurotoxicity of 3TC in comparison to AZT. However some significant behavioral alterations were found, namely (1) a decrease in immobility in the open field test, (2) an increase in the responsiveness to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in the open field, and (3) a longer escape latency in the first day of the reversal phase in the Morris task (particularly marked in the 250-mg/kg treatment group). No significant changes in either pain sensitivity, social/affiliative, or maternal behavior were found, although a higher occurrence of aggressive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females.

  19. Effect of semiconductor GaAs laser irradiation on pain perception in mice

    SciTech Connect

    Zarkovic, N.; Manev, H.; Pericic, D.; Skala, K.; Jurin, M.; Persin, A.; Kubovic, M.

    1989-01-01

    The influence of subacute exposure (11 exposures within 16 days) of mice to the low power (GaAs) semiconductive laser-stimulated irradiation on pain perception was investigated. The pain perception was determined by the latency of foot-licking or jumping from the surface of a 53 degrees C hot plate. Repeated hot-plate testing resulted in shortening of latencies in both sham- and laser-irradiated mice. Laser treatment (wavelength, 905 nm; frequency, 256 Hz; irradiation time, 50 sec; pulse duration, 100 nsec; distance, 3 cm; peak irradiance, 50 W/cm2 in irradiated area; and total exposure, 0.41 mJ/cm2) induced further shortening of latencies, suggesting its stimulatory influence on pain perception. Administration of morphine (20 mg/kg) prolonged the latency of response to the hot plate in both sham- and laser-irradiated mice. This prolongation tended to be lesser in laser-irradiated animals. Further investigations are required to elucidate the mechanism of the observed effect of laser.

  20. Protection of swiss albino mice against whole-body gamma irradiation by Mentha piperita (Linn.).

    PubMed

    Samarth, R M; Goyal, P K; Kumar, Ashok

    2004-07-01

    The radioprotective effects of Mentha oil (Mentha piperita Linn.) against radiation induced haematological alterations in peripheral blood and the survival of Swiss albino mice were studied. Mentha oil 40 micro L/animal/day for 3 consecutive days when fed orally prior to whole-body gamma irradiation (8 Gy) showed protection of the animals in terms of the survival percentage and haematological parameters in mice. Fifty per cent of the animals died within 20 days and 100% mortality was observed up to 30 days post-irradiation in the control irradiated group. Whereas only 17% of the mice died within 30 days in the experimental group (Mentha oil pretreated irradiated). The total RBC count decreased maximally at 24 h (3.45 +/- 0.20 x 10(12)/L, p < 0.001), similar observations were obtained for the WBC count, haemoglobin content and haematocrit percentage in the irradiated control animals. However, in irradiated animals pretreated with Mentha oil, although the initial values of haematological components were lower they later showed a remarkable recovery reaching normal at 30 days post-irradiation compared with the irradiated control animals. In general, the recovery of the blood cell number in irradiated animals depends on the survival of stem cells and their derivatives. The results from the present study suggest that the oil of Mentha piperita (Linn.) has a radioprotective role in stimulating/protecting the haematopoietic system. Hence, enhanced survival and an increase in the haematological constituents of peripheral blood of mice against lethal gamma radiation was observed.

  1. Long-term ultraviolet A irradiation of the eye induces photoaging of the skin in mice.

    PubMed

    Hiramoto, Keiichi; Yamate, Yurika; Kobayashi, Hiromi; Ishii, Masamitsu

    2012-01-01

    Irradiation by long-term ultraviolet (UV) A initiates the induction of photoaging. However, the mechanisms responsible for the structural changes of skin induced by UVA irradiation of the eye are still unknown. Male hairless mice were used in this study. The eye or dorsal skin was locally exposed to UVA after covering the remaining body surface with aluminum foil at a dose of 110 kJ/m(2) using a FL20SBLB-A lamp for 60 days. The plasma α-melanocyte stimulating hormone (α-MSH), nitrogen oxides (NO(2)/NO(3)), tumor necrosis factor-α (TNF-α), and the prostaglandin E(2) (PGE(2)) content all increased after UVA irradiation. The levels of NO(2)/NO(3), TNF-α, and PGE(2) also increased more after UVA skin irradiation than after UVA eye irradiation. However, the level of α-MSH increased more by eye irradiation than skin irradiation. In addition, UVA irradiation of the eye and dorsal skin increased the number of mast cells and fibroblasts. Furthermore, the expression of the melanocortin-1 receptor (MC1R) was increased on the fibroblast surface by UVA irradiation of the eye. These results indicate that the signal evoked by UVA irradiation of the eye, through the hypothalamo-pituitary proopiomelanocortin system, up-regulated the production of α-MSH. This hormone controls the collagen generation from fibroblasts, thus suggesting that photoaging was induced by UVA irradiation of the eye.

  2. Evaluation of reduced allergenicity of irradiated peanut extract using splenocytes from peanut-sensitized mice

    NASA Astrophysics Data System (ADS)

    Oh, Sejo; Jang, Da-In; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Myung-Woo; Lee, Soo-Young

    2009-07-01

    Peanut (PN) allergy is one of the most serious forms of IgE-mediated food hypersensitivity. Gamma irradiation has been widely used for the preservation of food. The results of our previous studies showed that the IgE-binding capacity to several antigens were profoundly reduced after gamma irradiation. In this study, we evaluated the changes of allergenecity and cytokine production profiles after exposure of irradiated PN extract in a PN-allergy mouse model. Mice were sensitized to PN extract by intragastric administration on days 0, 1, 2, and 7, and then challenged on day 21. Four weeks later, we evaluated the cytokine production patterns and proliferation responses of splenocytes that were stimulated with intact PN extract, compared to 10 and 50 kGy irradiated PN extract. When the cells were stimulated with 10 kGy of irradiated PN extract, a higher level of production of IFN-γ and IL-10 cytokines was observed. However, stimulation with 50 kGy of irradiated PN extract resulted in a higher level of production of only IFN-γ cytokines. In addition, the Th1/Th2 ratio increased in response to treatment with gamma-irradiated PNs. The results of this study show that the allergenicity of PN extracts could be reduced by gamma irradiation which caused downregulation of Th2 lymphocyte activity in the PN-sensitized mice.

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

    SciTech Connect

    Lin, T.P.

    1980-07-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    1996-06-01

    The radiation protective activity of intraperitoneally 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. 6 Gy 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 gmM/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.

  5. Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

    NASA Astrophysics Data System (ADS)

    Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Eui-Baek; Lee, Soo-Young; Kang, Il-Jun; Byun, Myung-Woo

    2007-11-01

    Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN- γ level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice.

  6. Radioprotection of mice by a single subcutaneous injection of heat-killed Lactobacillus casei after irradiation

    SciTech Connect

    Nomoto, K.; Yokokura, T.; Tsuneoka, K.; Shikita, M. )

    1991-03-01

    Treatment of whole-body gamma-irradiated mice with a preparation of Lactobacillus casei (LC 9018) immediately after irradiation caused a sustained increase in serum colony-stimulating activity which was followed by an enhanced repopulation of granulocyte-macrophage colony-forming cells in the femoral marrow and spleen. Numbers of blood leukocytes, erythrocytes, and platelets were increased earlier in the treated mice than in the controls, and the survival rate was elevated significantly. The radioprotective effect was dependent on the dose of LC 9018 as well as on the dose of radiation. These results demonstrate the value of LC 9018 for the treatment of myelosuppression after radiotherapy or radiation accidents.

  7. Ocular sensitization of mice by live (but not irradiated) Chlamydia trachomatis serovar A

    SciTech Connect

    Colley, D.G.; Goodman, T.G.; Barsoum, I.S.

    1986-10-01

    Ocular exposure of mice to live elementary bodies of Chlamydia trachomatis serovar A results in immunological sensitization of the mice. This reactivity is manifested by the development of early (5 h) and delayed-type (24 h) dermal reactivity and serovar-specific antibody formation against either live or irradiated (100 kilorads) elementary bodies. Parallel ocular exposure of mice to irradiated elementary bodies does not result in this sensitization. The early and late dermal immune responses induced by ocular exposure to live organisms can be transferred to unexposed mice by serum and lymphoid cell transfers, respectively. It appears that successful murine ocular sensitization by human C. trachomatis serovar A elementary bodies is an ability manifested by live organisms and not by inactivated but antigenic organisms.

  8. Studies of the effect of 0. 4-Gy and 0. 6-Gy prenatal X-irradiation on postnatal adult behavior in the Wistar rat

    SciTech Connect

    Jensh, R.P.; Brent, R.L.; Vogel, W.H.

    1987-02-01

    Thirty-four pregnant Wistar rats were X-irradiated on the 9th or 17th day of gestation at a dosage level 0.4 Gy or 0.6 Gy or were sham-irradiated. All mothers were allowed to deliver their offspring, and litters were limited to a maximum of eight on day 2. On day 30, 224 offspring were weaned and raised until 60 days of age, at which time testing began. Each rat randomly received, in random order, three of the following six behavioral tests: Water T-maze, Conditioned Avoidance Response, Forelimb Hanging, Activity Wheel, Swimming, and Open Field. There were no statistically significant differences between the irradiated and control groups for maternal weight or weight gain or mean litter size, although the litter size of the 17th day 0.6-Gy group was slightly lower. Among offspring irradiated with 0.6 Gy on the 17th day, 3-day-old neonates' weights were significantly reduced. Offspring irradiated on the 17th day with 0.6 Gy exhibited higher Conditioned Avoidance Response 5th-day and retest avoidance scores than did the controls. There were also significant sex differences in responses within the irradiated and control groups for several tests, which were unrelated to radiation exposure. The results of this study indicate that low-level X-irradiation during the fetal period of rat gestation results in neonatal growth retardation and subtle behavioral alterations that may be manifested in adult life. Growth retardation may be the most sensitive indicator of subtle effects that result from low-level prenatal exposure to X-rays.

  9. Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

    NASA Astrophysics Data System (ADS)

    Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

    1994-10-01

    Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

  10. Radioprotective effects of troxerutin against gamma irradiation in V79 cells and mice.

    PubMed

    Ping, Xu; Junqing, Jia; Junfeng, Jia; Enjin, Jiang

    2011-01-01

    The purpose of this study was to determine radioprotective effects of troxerutin. Cell experiments were carried out to test the cytotoxicity of troxerutin on V79 cells and to observe effects on apoptosis caused by 60CO γ rays. A model of 8 Gy ray-caused damage of mice was established to observe the effect that troxerutin has on the physical symptom of irradiated mice and to calculate the 30-day survival rate. It showed that troxerutin had no obvious cytotoxicity at the level of less than 20 μg/ml; but had a redioprotective effect in dose-dependence on viability of V79 cells at the range of 0.2-5 μg/mL irradiated by 5 Gy ray of 60CO γ ray. After the 8 Gy irradiation, the mice lost some weight, were dried up in fur and feather, low spirit, awkward in movement, shrinking in body and handicapped in sight, while mice with troxerutin were much better. So it was clear that troxerutin could increase the 30-day survival rates of irradiated mice dramatically. These results collectively indicate that troxerutin is an effective radioprotective agent.

  11. Cutaneous metallothionein induction by ultraviolet B irradiation in interleukin-6 null mice.

    PubMed

    Nishimura, N; Reeve, V E; Nishimura, H; Satoh, M; Tohyama, C

    2000-02-01

    The mediators of cutaneous metallothionein induction by ultraviolet radiation have not been defined. In this study we sought to identify cytokines that might be involved. We examined the role of interleukin-6, using the IL-6 null (IL-6-/-) mouse, which has been observed to be highly sensitive to ultraviolet radiation damage. Whereas cutaneous metallothionein concentration, measured by radioimmunoassay, began to rise in wild-type (IL-6+/+) mice by 12 h after ultraviolet irradiation, there was a significant delay in the IL-6-/- mice until 48 h after UV irradiation. Immunohistologically, metallothionein appeared in IL-6+/+ mice at 24 h in dermal fibroblasts, and then by 48 h in epidermal basal keratinocytes, with intensity increasing until 72 h, and was coincident with proliferating cell nuclear antigen-positive staining. Corresponding metallothionein expression in IL-6-/- mouse skin was significantly delayed. Serum interleukin-6 was elevated in IL-6+/+ mice following ultraviolet irradiation, with peak concentration at 4 h, but no increase in serum interleukin-1beta was found in either IL-6+/+ or IL-6-/- mice. Interestingly, tumor necrosis factor alpha concentration in serum was elevated at 12 h postirradiation in IL-6+/+ mice, but there was an earlier (at 4 and 8 h) time-dependent increase in tumor necrosis factor alpha in serum of the IL-6-/- mice. Skin zinc and copper concentrations were not altered by ultraviolet irradiation in either IL-6+/+ or IL-6-/- mice. The results suggest that interleukin-6 may be a very early mediator of cutaneous metallothionein induction by ultraviolet radiation, but that this role is possibly assumed by alternative cytokines like tumor necrosis factor alpha when interleukin-6 is deficient. PMID:10651996

  12. Oral ofloxacin therapy of Pseudomonas aeruginosa sepsis in mice after irradiation

    SciTech Connect

    Brook, I.; Ledney, G.D. )

    1990-07-01

    Death subsequent to whole-body irradiation is associated with gram-negative bacterial sepsis. The effect of oral therapy with the new quinolone ofloxacin for orally acquired Pseudomonas aeruginosa infection was tested in B6D2F1 mice exposed to 7.0 Gy of bilateral radiation from 60Co. A dose of 10(7) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Only 4 of 20 untreated mice (20%) survived for at least 30 days compared with 19 of 20 mice (95%) treated with ofloxacin (P less than 0.005). P. aeruginosa was isolated from the livers of 21 to 28 untreated mice (75%), compared with only 2 of 30 treated mice (P less than 0.005). Ofloxacin reduced colonization of the ileum by P. aeruginosa; 24 of 28 untreated mice (86%) harbored the organisms, compared with only 5 of 30 (17%) with ofloxacin (P less than 0.005). This experiment was replicated twice, and similar results were obtained. These data illustrate the efficacy of the quinolone ofloxacin for oral therapy of orally acquired P. aeruginosa infection in irradiated hosts.

  13. Potentiation of chemically induced lung fibrosis by thorax irradiation. [Mice

    SciTech Connect

    Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Witschi, H.P.

    1980-04-01

    Intraperitoneal injection of butylated hydroxytoluene (BHT) causes epithelial cell death, followed 2 to 4 days later by extensive proliferation of type II alveolar cells in mouse lung. Five to 8 days after BHT, most dividing cells are capillary endothelial cells or interstitial cells. In animials that were exposed to 200 rad thorax irradiation immediately or 1 day after BHT, lung hydroxyproline was increased 2 weeks later. The response was dose dependent, and the interaction between BHT and thorax irradiation was synergistic. Light microscopy showed abnormal accumulation of collagen in the alveolar septa. Lung hydroxyproline was not increased in animals that were irradiated 6 days after BHT, compared to animals treated with BHT alone. We concluded that fibrosis develops if lung is damaged by a blood-borne agent and radiation to the thorax occurs at a time when it may compromise alveolar reepithelialization. Exposure to x-rays during proliferation of capillary endothelial cells or interstitial cells does not enhance development of fibrosis.

  14. Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice

    PubMed Central

    Robinson, Dean M; Peebles, Karen C; Kwok, Henry; Adams, Brandon M; Clarke, Lan-Ling; Woollard, Gerald A; Funk, Gregory D

    2002-01-01

    We examined the effects of in utero nicotine exposure on postnatal development of breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole-body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42. Nicotine delayed early postnatal changes in breathing pattern. During normoxia, control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (fA) which declined by P3 in control animals (from 6.7 ± 0.7 to 2.2 ± 0.7 min−1) but persisted in P3 nicotine-exposed animals (5.4 ± 1.3 min−1). Hypoxia induced a rapid and sustained reduction in fA except in P0 nicotine-exposed animals where it fell initially and then increased throughout the hypoxic period. During recovery, fA increased above control levels in both groups at P0. By P3 this increase was reduced in control but persisted in nicotine-exposed animals. To examine the origin of differences in respiratory behaviour, we compared the activity of hypoglossal (XII) nerves and motoneurons in medullary slice preparations. The frequency and variability of the respiratory rhythm and the envelope of inspiratory activity in XII nerves and motoneurons were indistinguishable between control and nicotine-exposed animals. Activation of postsynaptic nicotine receptors caused an inward current in XII motoneurons that potentiated XII nerve burst amplitude by 25 ± 5 % in control but only 14 ± 3 % in nicotine-exposed animals. Increased apnoea following nicotine exposure does not appear to reflect changes in basal activity of rhythm or pattern-generating networks, but may result, in part, from reduced nicotinic modulation of XII motoneurons. PMID:11826179

  15. Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

    PubMed Central

    Zhang, Junye; Cui, Lei; Xu, Minhua; Zheng, Yuanli

    2014-01-01

    Objectives One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice. Methods DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations. Results The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR. Conclusions Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and

  16. Loss of Metabotropic Glutamate Receptor 5 Function on Peripheral Benzodiazepine Receptor in Mice Prenatally Exposed to LPS

    PubMed Central

    Arsenault, Dany; Coulombe, Katherine; Zhu, Aijun; Gong, Chunyu; Kil, Kun-Eek; Choi, Ji-Kyung; Poutiainen, Pekka; Brownell, Anna-Liisa

    2015-01-01

    Parental microglial induced neuroinflammation, triggered by bacterial- or viral infections, can induce neuropsychiatric disorders like schizophrenia and autism to offspring in animal models. Recent investigations suggest that microglia, the resident immune cells of the brain, provides a link between neurotransmission, immune cell activation, brain inflammation and neuronal dysfunction seen with the offspring. Relatively little is known about how reduction of brain inflammation and restoration of glial function are associated with diminution of brain degeneration and behavioral deficits in offspring. Increased mGluR5 expression and the long-lasting excitotoxic effects of the neurotoxin during brain development are associated with the glial dysfunctions. We investigated the relationship of mGluR5 and PBR and how they regulate glial function and inflammatory processes in mice prenatally exposed to LPS (120μg/kg, between gestational days 15 and 17), an inflammatory model of a psychiatric disorder. Using PET imaging, we showed that pharmacological activation of mGluR5 during 5 weeks reduced expression of classic inflammation marker PBR in many brain areas and that this molecular association was not present in LPS-exposed offspring. The post-mortem analysis revealed that the down regulation of PBR was mediated through activation of mGluR5 in astrocytes. In addition, we demonstrated that this interaction is defective in a mouse model of the psychiatric deficit offering a novel insight of mGluR5 involvement to brain related disorders and PBR related imaging studies. In conclusion, mGluR5 driven glutamatergic activity regulates astrocytic functions associated with PBR (cholesterol transport, neurosteroidogenesis, glial phenotype) during maturation and could be associated with neuropsychiatric disorders in offspring. PMID:26536027

  17. Low Dose Cranial Irradiation-Induced Cerebrovascular Damage Is Reversible in Mice

    PubMed Central

    Bocsik, Alexandra; Sántha, Petra; Schilling-Tóth, Boglárka; Léner, Violetta; Varga, Zoltán; Kahán, Zsuzsanna; Deli, Mária A.; Sáfrány, Géza; Hegyesi, Hargita

    2014-01-01

    Background High-dose radiation-induced blood-brain barrier breakdown contributes to acute radiation toxicity syndrome and delayed brain injury, but there are few data on the effects of low dose cranial irradiation. Our goal was to measure blood-brain barrier changes after low (0.1 Gy), moderate (2 Gy) and high (10 Gy) dose irradiation under in vivo and in vitro conditions. Methodology Cranial irradiation was performed on 10-day-old and 10-week-old mice. Blood-brain barrier permeability for Evans blue, body weight and number of peripheral mononuclear and circulating endothelial progenitor cells were evaluated 1, 4 and 26 weeks postirradiation. Barrier properties of primary mouse brain endothelial cells co-cultured with glial cells were determined by measurement of resistance and permeability for marker molecules and staining for interendothelial junctions. Endothelial senescence was determined by senescence associated β-galactosidase staining. Principle Findings Extravasation of Evans blue increased in cerebrum and cerebellum in adult mice 1 week and in infant mice 4 weeks postirradiation at all treatment doses. Head irradiation with 10 Gy decreased body weight. The number of circulating endothelial progenitor cells in blood was decreased 1 day after irradiation with 0.1 and 2 Gy. Increase in the permeability of cultured brain endothelial monolayers for fluorescein and albumin was time- and radiation dose dependent and accompanied by changes in junctional immunostaining for claudin-5, ZO-1 and β-catenin. The number of cultured brain endothelial and glial cells decreased from third day of postirradiation and senescence in endothelial cells increased at 2 and 10 Gy. Conclusion Not only high but low and moderate doses of cranial irradiation increase permeability of cerebral vessels in mice, but this effect is reversible by 6 months. In-vitro experiments suggest that irradiation changes junctional morphology, decreases cell number and causes senescence in brain

  18. Effects of prenatal X-irradiation on postnatal testicular development and function in the Wistar rat: development/teratology/behavior/radiation

    SciTech Connect

    Jensh, R.P.; Brent, R.L.

    1988-11-01

    It is evident that significant permanent tissue hypoplasia can be produced following radiation exposure late in fetal development. Because two organs, brain and testes, are developmentally and functionally interrelated, it was of interest to determine whether fetal testicular hypoplasia was a primary or a secondary effect of fetal brain irradiation. Twenty-four pregnant Wistar strain rats were randomly assigned to one of four groups, and a laparotomy was performed on day 18 of gestation. The fetuses received sham irradiation, whole body irradiation, or only head/thorax or pelvic body irradiation at a dosage level of 1.5 Gy. Mothers were allowed to deliver and raise their offspring until postnatal day 30, when the offspring were weaned. At 60 days of age, 74 male offspring were allowed to mate with colony control females of similar age until successful insemination or until the males reached 90 days of age, when they were killed. Testes were weighed and processed for histologic examination. Direct radiation of testes, due to whole body or pelvic exposure, resulted in testicular growth retardation and significantly reduced spermatogenesis. Breeding activity of the males and the percent of positive inseminations were also slightly reduced. However, a significant percentage of male offspring receiving direct testicular radiation did produce offspring. Head/thorax-only irradiation did not adversely affect testicular growth or spermatogenesis. Therefore, the use of histologic analysis as the sole determinant of infertility may be misleading. This study indicates that testicular growth retardation and an increased infertility rate result from direct prenatal exposure of rat testes to X-radiation and are not necessarily mediated via X-irradiation effects on the central nervous system.

  19. Induction of acute brain injury in mice by irradiation with high-LET charged particles

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Hong

    The present study was performed to evaluate the induction of acute brain injury in mice after 235 Mev/u carbon ion irradiation. In our study, young outbred Kunming mice were divided into four treatment groups according to the penetration depth of carbon ions. Animals were irradiated with a sublethal dose of carbon ion beams prior to the Bragg curve. An experiment was performed to evaluate the acute alterations in histology, DNA double-strand breaks (DNA DSBs) as well as p53and Bax expression in the brain 96 h post-irradiation. The results demonstrated that various histopathological changes, a significant number of DNA DSBs and elevated p53 and Bax protein expression were induced in the brain following exposure to carbon ions. This was particularly true for mice irradiated with ions having a 9.1 cm-pentration depth, indicating that carbon ions can led to deleterious lesions in the brain of young animals within 96 h. Moreover, there was a remarkable increase in DNA DSBs and in the severity of histopathological changes as the penetration depths of ions increased, which may be associated with the complex track structure of heavy ions. These data reveal that carbon ions can promote serious neuropathological degeneration in the cerebral cortex of young mice. Given that damaged neurons cannot regenerate, these findings warrant further investigation of the adverse effects of the space radiation and the passage of a therapeutic heavy ion beam in the plateau region of the Bragg curve through healthy brain tissue.

  20. Effects of prenatal irradiation with an accelerated heavy-ion beam on postnatal development in rats: II. Further study on neurophysiologic alterations

    NASA Astrophysics Data System (ADS)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

    Organogenesis is a highly radiosensitive period, study of prenatal exposure to high LET heavy ion beams on postnatal development is important for clarifying the radiation risk in space and promoting the evidence-based mechanism research. The effects from heavy ion irradiations are not well studied as those for low LET radiations such as X-rays in this field, even the ground-based investigations remain to be addressed. Using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, postnatal neurophysiological development in offspring was investigated following exposure of pregnant rats to accelerated neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on the 15th day of gestation. The age for appearance of four physiologic markers and attainment of five neonatal reflexes, and gain in body weight were monitored. Male offspring were evaluated as young adults using two behavioral tests including open field and hole-board dipping tests. The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison. For most of the endpoints at early age, significant neurophysiological alteration was observed even in offspring receiving 0.1 Gy of accelerated neon ions but not X-rays. All offspring receiving 2.0 Gy of accelerated neon ions died prior to weaning. Offspring prenatally irradiated with neon ions generally showed higher incidences of prenatal death, increased preweaning mortality, markedly delayed accomplishment in physiological markers and reflexes, significantly lower body weight and reduced ratios of main organ weight to body weight, and altered behavior compared to those exposed to X-rays at doses of 0.1 1.5 Gy. These findings indicate that irradiations with neon ions at 0.1 1.5 Gy on day 15 of gestation caused varied developmental alterations in offspring, and efficient dose leading to the detrimental effects seemed to be lower than that of X-rays.

  1. Parp-2 is required to maintain hematopoiesis following sublethal γ-irradiation in mice

    PubMed Central

    Farrés, Jordi; Martín-Caballero, Juan; Martínez, Carlos; Lozano, Juan J.; Llacuna, Laura; Ampurdanés, Coral; Ruiz-Herguido, Cristina; Dantzer, Françoise; Schreiber, Valérie; Villunger, Andreas; Bigas, Anna; Yélamos, José

    2016-01-01

    Hematopoietic stem cells self-renew for life to guarantee the continuous supply of all blood cell lineages. Here we show that Poly(ADP-ribose) polymerase-2 (Parp-2) plays an essential role in hematopoietic stem/progenitor cells (HSPC) survival under steady-state conditions and in response to stress. Increased levels of cell death were observed in HSPC from untreated Parp-2−/− mice, but this deficit was compensated by increased rates of self-renewal, associated with impaired reconstitution of hematopoiesis upon serial bone marrow transplantation. Cell death after γ-irradiation correlated with an impaired capacity to repair DNA damage in the absence of Parp-2. Upon exposure to sublethal doses of γ-irradiation, Parp-2−/− mice exhibited bone marrow failure that correlated with reduced long-term repopulation potential of irradiated Parp-2−/− HSPC under competitive conditions. In line with a protective role of Parp-2 against irradiation-induced apoptosis, loss of p53 or the pro-apoptotic BH3-only protein Puma restored survival of irradiated Parp-2−/− mice, whereas loss of Noxa had no such effect. Our results show that Parp-2 plays essential roles in the surveillance of genome integrity of HSPC by orchestrating DNA repair and restraining p53-induced and Puma-mediated apoptosis. The data may affect the design of drugs targeting Parp proteins and the improvement of radiotherapy-based therapeutic strategies. PMID:23678004

  2. Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen

    PubMed Central

    Röck, Katharina; Joosse, Simon Andreas; Müller, Julia; Heinisch, Nina; Fuchs, Nicola; Meusch, Michael; Zipper, Petra; Reifenberger, Julia; Pantel, Klaus; Fischer, Jens Walter

    2016-01-01

    Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice. Half of the mice received estradiol substitution. Mice were UVB-irradiated for 20 weeks and afterwards kept for 10 weeks without irradiation. The collagen-, hyaluronan- and proteoglycan- (versican, biglycan, lumican) matrix, collagen cleavage products and functional skin parameters were analyzed. The intrinsic aging process was characterized by increased collagen fragmentation and accumulation of biglycan. Chronic UVB-irradiation additionally augmented the lumican, versican and hyaluronan content of the dermis. In the absence of further UVB-irradiation the degradation of collagen and accumulation of biglycan in the extrinsically aged group was perpetuated in an excessive matter. Whereas estradiol increased the proteoglycan content, it reversed the effects of the perpetuated extrinsic response on collagen degradation. Suspension of the intrinsic pathway might therefore be sufficient to antagonize UVB-evoked long-term damage to the dermal ECM. PMID:27460287

  3. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

    PubMed Central

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

  4. Influence of nandrolone decanoate on the repopulation of the thymus after total body irradiation of mice

    SciTech Connect

    Plum, J.; Huys, J.; De Scheerder, Y.; Dhont, E.; De Smedt, M.

    1982-10-01

    It has been reported that nandrolone decanoate is helpful in overcoming the neutropenic phase following irradiation. In the present study the influence of nandrolone decanoate on the thymus' cellularity after total body irradiation was investigated. In comparison with a placebo-treated group, mice receiving nandrolone decanoate showed a similar pattern of thymus repopulation, but a significantly lower number of thymocytes over the whole period of treatment was found. Nonirradiated mice also had a significantly lower number of thymocytes when treated with nandrolone decanoate. In addition, the number of circulating leukocytes was also evaluated over a period of 1 month after total body irradiation. On 11 of the 21 days investigated, a significantly higher number of leukocytes was found in the nandrolone decanoate-treated group. We conclude that the action of nandrolone decanoate was not clearly distinct from that of testosterone regarding either granulopoiesis or thymic involution.

  5. The effect of gamma-rays on the hemoglobin of whole-body irradiated mice

    NASA Astrophysics Data System (ADS)

    Ashry, H. A.; Selim, N. S.; El-Behay, A. Z.

    1994-07-01

    Changes in the UV-visible absorption spectrum of mouse hemoglobin as a result of whole body irradiation were studied. White albino adult mice were exposed to a Cs-137 γ-source at a dose rate of 47.5 Gy/h to different absorbed dose values ranging from 1 to 8 Gy. Blood specimens were taken 24 h after irradiation. The UV-visible absorption spectra of hemoglobin of irradiated and control mice were measured in the wavelength range from 200 to 700 nm. The obtained results showed significant changes in the bands measured at 340 nm, in the Soret band measured at 410 nm, also, the α- and β-bands measured at 537 and 572 nm showed significant decrease in intensity with the absorbed dose increase. The absorbance measured at 630 nm showed no significant changes. The radiation effect on the animal hemoglobin was discussed on the basis of the obtained results.

  6. Effect of UV irradiation on lethal infection of mice with Candida albicans.

    PubMed

    Denkins, Y M; Kripke, M L

    1993-02-01

    Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID:8451288

  7. Podophyllum hexandrum-Mediated Survival Protection and Restoration of Other Cellular Injuries in Lethally Irradiated Mice.

    PubMed

    Sankhwar, Sanghmitra; Gupta, Manju Lata; Gupta, Vanita; Verma, Savita; Suri, Krishna Avtar; Devi, Memita; Sharma, Punita; Khan, Ehsan Ahmed; Alam, M Sarwar

    2011-01-01

    This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg(-1) body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD(100), has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.

  8. Prolonged expression of senescence markers in mice exposed to gamma-irradiation

    PubMed Central

    Seol, Min-A; Eom, Hyeon Soo; Kim, Seol-Hwa; Park, Hae-Ran; Jo, Sung-Kee

    2012-01-01

    Although ionizing radiation is known to induce cellular senescence in vitro and in vivo, its long-term in vivo effects are not well defined. In this study, we examined the prolonged expression of senescence markers in mice irradiated with single or fractionated doses. C57BL/6 female mice were exposed to 5 Gy of γ-rays in single or 5, 10, 25 fractions. At 2, 4, and 6 months after irradiation, senescence markers including mitochondrial DNA (mtDNA) common deletion, p21, and senescence-associated β-galactosidase (SA β-gal) were monitored in the lung, liver, and kidney. Increases of mtDNA deletion were detected in the lung, liver, and kidney of irradiated groups. p21 expression and SA β-gal staining were also increased in the irradiated groups compared to the non-irradiated control group. Increases of senescence markers persisted up to 6 months after irradiation. Additionally, the extent of mtDNA deletion and the numbers of SA β-gal positive cells were greater as the number of radiation fractions increased. In conclusion, our results showed that ionizing radiation, especially that delivered in fractions, can cause the persistent upregulation of senescence marker expression in vivo. This should be considered when dealing with chronic normal tissue injuries caused by radiation therapy or radiation accidents. PMID:23271173

  9. Pharmacological activation of group-II metabotropic glutamate receptors corrects a schizophrenia-like phenotype induced by prenatal stress in mice.

    PubMed

    Matrisciano, Francesco; Tueting, Patricia; Maccari, Stefania; Nicoletti, Ferdinando; Guidotti, Alessandro

    2012-03-01

    Prenatal exposure to restraint stress causes long-lasting changes in neuroplasticity that likely reflect pathological modifications triggered by early-life stress. We found that the offspring of dams exposed to repeated episodes of restraint stress during pregnancy (here named 'prenatal restraint stress mice' or 'PRS mice') developed a schizophrenia-like phenotype, characterized by a decreased expression of brain-derived neurotrophic factor and glutamic acid decarboxylase 67, an increased expression of type-1 DNA methyl transferase (DNMT1) in the frontal cortex, and a deficit in social interaction, locomotor activity, and prepulse inhibition. PRS mice also showed a marked decrease in metabotropic glutamate 2 (mGlu2) and mGlu3 receptor mRNA and protein levels in the frontal cortex, which was manifested at birth and persisted in adult life. This decrease was associated with an increased binding of DNMT1 to CpG-rich regions of mGlu2 and mGlu3 receptor promoters and an increased binding of MeCP2 to the mGlu2 receptor promoter. Systemic treatment with the selective mGlu2/3 receptor agonist LY379268 (0.5 mg/kg, i.p., twice daily for 5 days), corrected all the biochemical and behavioral abnormalities shown in PRS mice. Our data show for the first time that PRS induces a schizophrenia-like phenotype in mice, and suggest that epigenetic changes in mGlu2 and mGlu3 receptors lie at the core of the pathological programming induced by early-life stress.

  10. Pharmacological activation of group-II metabotropic glutamate receptors corrects a schizophrenia-like phenotype induced by prenatal stress in mice.

    PubMed

    Matrisciano, Francesco; Tueting, Patricia; Maccari, Stefania; Nicoletti, Ferdinando; Guidotti, Alessandro

    2012-03-01

    Prenatal exposure to restraint stress causes long-lasting changes in neuroplasticity that likely reflect pathological modifications triggered by early-life stress. We found that the offspring of dams exposed to repeated episodes of restraint stress during pregnancy (here named 'prenatal restraint stress mice' or 'PRS mice') developed a schizophrenia-like phenotype, characterized by a decreased expression of brain-derived neurotrophic factor and glutamic acid decarboxylase 67, an increased expression of type-1 DNA methyl transferase (DNMT1) in the frontal cortex, and a deficit in social interaction, locomotor activity, and prepulse inhibition. PRS mice also showed a marked decrease in metabotropic glutamate 2 (mGlu2) and mGlu3 receptor mRNA and protein levels in the frontal cortex, which was manifested at birth and persisted in adult life. This decrease was associated with an increased binding of DNMT1 to CpG-rich regions of mGlu2 and mGlu3 receptor promoters and an increased binding of MeCP2 to the mGlu2 receptor promoter. Systemic treatment with the selective mGlu2/3 receptor agonist LY379268 (0.5 mg/kg, i.p., twice daily for 5 days), corrected all the biochemical and behavioral abnormalities shown in PRS mice. Our data show for the first time that PRS induces a schizophrenia-like phenotype in mice, and suggest that epigenetic changes in mGlu2 and mGlu3 receptors lie at the core of the pathological programming induced by early-life stress. PMID:22089319

  11. Effects of chronic postnatal opioid receptor blockade by naltrexone upon proliferation capacity in the prenatally x-irradiated brain of the rat

    SciTech Connect

    Schmahl, W.; Miaskowski, U. )

    1991-01-01

    We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. Nx led to an intermittent augmentation of the mitotic index of the x-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon Nx treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic x-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by Nx, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern.

  12. Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr. ) Karst after X-ray irradiation in mice

    SciTech Connect

    Hsu, H.Y.; Lian, S.L.; Lin, C.C. )

    1990-01-01

    Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).

  13. Altered prostate growth and daily sperm production in male mice exposed prenatally to subclinical doses of 17alpha-ethinyl oestradiol.

    PubMed

    Thayer, K A; Ruhlen, R L; Howdeshell, K L; Buchanan, D L; Cooke, P S; Preziosi, D; Welshons, W V; Haseman, J; vom Saal, F S

    2001-05-01

    Approximately 2 million women in the USA and Europe continue taking oral contraceptives each year during undetected pregnancy due primarily to non-compliance and also to individual variation in sensitivity to hormones in the contraceptives. Prenatal exposure to oral contraceptives containing 17alpha-ethinyl oestradiol (EE) has generally not been associated with an increased incidence of externally observable malformations at birth. The purpose of this study was to assess effects on reproductive organs in adult male mice that had been exposed during gestation day 0 through 17 (equivalent to gestation week 16 in humans) to clinically relevant (approximately 0.5 microg/kg/day) and lower doses of EE. Doses used in this study ranged from 0.002 to 2 microg/kg/day. By 5 months of age, prostate weight was significantly (P < 0.05) higher than controls in most treatment groups of EE (0.02-2 microg/kg). Prostatic androgen receptor populations were significantly elevated only in the 0.02 microg/kg group, suggesting different mechanisms for the increase in prostate weight at different doses. Daily sperm production (DSP) and DSP per gramme of testis were reduced in all treatment groups during adolescence, but not later in adulthood. These findings are consistent with prior studies showing that prenatal exposure of mice to very low doses of a number of oestrogenic chemicals can alter the adult male reproductive system without causing gross external malformations.

  14. Behavioral responses to acute and sub-chronic administration of the synthetic cannabinoid JWH-018 in adult mice prenatally exposed to corticosterone.

    PubMed

    Macrì, Simone; Lanuzza, Lara; Merola, Gustavo; Ceci, Chiara; Gentili, Stefano; Valli, Antonella; Macchia, Teodora; Laviola, Giovanni

    2013-07-01

    Recent data indicate that both availability and consumption of synthetic and natural psychoactive substances, marketed under the name of "legal highs", has increased. Among them, the aminoalkylindole-derivative JWH-018 is widely distributed due to its capability of binding the cannabinoid receptors CB1 and CB2 thereby mimicking the effects of classical drug agonists. To address whether the behavioral effects of the synthetic compound JWH-018 are similar to those induced by classical cannabinoid agonists, we investigated, in outbred CD1 mice, the consequences of its acute and sub-chronic administration (0, 0.03, 0.1, or 0.3 mg/kg, IP) at the level of body temperature, pain perception, general locomotion, and anxiety. In order to address whether the exposure to precocious stressors-modified individual reactivity to this psychoactive substance, we also investigated its effects in adult mice previously exposed to prenatal stress in the form of corticosterone supplementation in the maternal drinking water (33 or 100 mg/L). In the absence of major effects on motor coordination, JWH-018-reduced body temperature, locomotion and pain reactivity, and increased indices of anxiety. Prenatal corticosterone administration-reduced individual sensitivity to the effects of JWH-018 administration in all the aforementioned parameters. This altered response is not due to variations in JWH-018 metabolism. Present data support the hypothesis that precocious stress may affect, in the long-term, the functional status, and reactivity of the endocannabinoid system.

  15. Reconstruction of hematopoietic function in irradiated mice promoted by polysacc haride peptide.

    PubMed

    Wang, Tao; Wang, Hao; Zou, Zhenghui; Gu, Zhenlun

    2000-08-15

    OBJECTIVE: To study the effect of polysaccharide peptide (PSP) on the reconstruction of the hematopoietic function in mice irrad iated by lethal dose. METHODS: The characteristics of proliferation of colony forming unit-granulocyte macrophage (CFU-GM) and colony forming unit-spleen (CFU-S) were measured after continuous injection of PSP in mice for seven days with different doses. RESULTS: Injection of 25 mg/kg PSP in mice could promote and in crease CFU-GM proliferation and cell mitosis, markedly enhance survival ratio, survival time and CFU-S. CONCLUSIONS: PSP has significant regulative effects on the reco nstruction of the hematopoietic and the immunologic functions in mice irradiated by lethal dose. PMID:11874671

  16. 28Silicon Irradiation Impairs Contextual Fear Memory in B6D2F1 Mice.

    PubMed

    Raber, Jacob; Marzulla, Tessa; Stewart, Blair; Kronenberg, Amy; Turker, Mitchell S

    2015-06-01

    The space radiation environment consists of multiple species of charged particles, including (28)Si, (48)Ti and protons that may impact cognition, but their damaging effects have been poorly defined. In mouse studies, C57Bl6/J homozygous wild-type mice and genetic mutant mice on a C57Bl6/J background have typically been used for assessing effects of space radiation on cognition. In contrast, little is known about the radiation response of mice on a heterozygous background. Therefore, in the current study we tested the effects of (28)Si, (48)Ti and proton radiation on hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory in C57Bl6/J × DBA2/J F1 (B6D2F1) mice three months after irradiation. Contextual fear memory was impaired at a 1.6 Gy dose of (28)Si radiation, but not cued fear memory. (48)Ti or proton irradiation did not affect either type of memory. Based on earlier space radiation cognitive data in C57Bl6/J mice, these data highlight the importance of including different genetic backgrounds in studies aimed at assessing cognitive changes after exposure to space radiation.

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

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1997-08-01

    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{sub 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) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} 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.

  18. Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body. gamma. irradiation

    SciTech Connect

    Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

    1981-11-01

    The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body ..gamma.. irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice.

  19. Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice

    SciTech Connect

    Jerrells, T.R.; Palmer, B.A.; Osterman, J.V.

    1983-01-01

    Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice.

  20. Influence of conditioned psychological stress on immunological recovery in mice exposed to low-dose x irradiation

    SciTech Connect

    Sato, K.; Flood, J.F.; Makinodan, T.

    1984-05-01

    A study was initiated to determine the effects of psychological stress on the immune response in BALB/c mice recovering from exposure to a low dose of ionizing radiation. Mice were first subjected to conditioning training for 12 days, then exposed to 200 R, subjected to psychological stress for 14 days, and assessed for peak anti-sheep RBC response. The seven treatment groups included two unirradiated groups and five irradiated groups. Mice exposed to 200 R and then subjected to conditioned psychological stress responded less vigorously to antigenic stimulation than those of the other irradiated groups. The psychological stress imposed upon these mice did not influence the antibody-forming capacity of unirradiated mice. These results indicate that a psychological stress which did not affect the immunological activity of unirradiated mice can curtail the immunological recovery of mice exposed to low doses of ionizing radiation.

  1. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  2. Irradiation of protoporphyric mice induces down-regulation of epidermal eicosanoid metabolism

    SciTech Connect

    He, D.; Lim, H.W. )

    1991-09-01

    This study investigated the effect of radiation on clinical and histologic changes, and on cutaneous eicosanoid metabolism, in Skh:HR-1 hairless albino mice rendered protoporphyric by the administration of collidine. At 0.1-18 h after exposure to 12 kJ/m2 of 396-406 nm irradiation, thicknesses of back skin and ears were measured, and histologic changes were evaluated by using hematoxylin and eosin (H-E) and Giemsa's stains. Activities of eicosanoid-metabolizing enzymes in epidermal and dermal homogenates were assessed by incubating the tissue homogenates with 3H-AA, followed by quantitation of the eicosanoids generated by radio-TLC. In irradiated protoporphyric mice, an increase of back-skin thickness was noted at 0.1 h, reaching a peak at 18 h, whereas maximal increase in ear thickness was observed at 12 h. Histologic changes included dermal edema, increased mast cell degranulation, and mononuclear cells in the dermis. In these irradiated protoporphyric animals, generations of 6 keto-PGF1a, PGF2a, PGE2, PGD2, and HETE by epidermal eicosanoid-metabolizing enzymes were markedly suppressed at all the timepoints studied. Dermal eicosanoid-metabolizing enzymes of irradiated protoporphyric mice generated increased amounts of PGE2 and HETE at 18 h, probably reflecting the presence of dermal cellular infiltrates. The suppression of the activities of epidermal eicosanoid-metabolizing enzymes was prevented by intraperitoneal injection of WR-2721, a sulfhydryl group generator, prior to irradiation, suggesting that the suppression was secondary to photo-oxidative damage of the enzymes during the in vivo phototoxic response. These results suggest that the effect of protoporphyrin and radiation on cutaneous eicosanoid metabolism in this animal model in vivo is that of a down regulation of the activities of epidermal eicosanoid-metabolizing enzymes.

  3. Oral administration of hyaluronan prevents skin dryness and epidermal thickening in ultraviolet irradiated hairless mice.

    PubMed

    Kawada, Chinatsu; Kimura, Mamoru; Masuda, Yasunobu; Nomura, Yoshihiro

    2015-12-01

    Hyaluronan is a component of the extracellular matrix that plays a role in water retention in tissues. In this study, we orally administered hyaluronans of varying molecular weights (300k and less than 10k) repeatedly to hairless mice exposed to ultraviolet (UV) irradiation and examined their effects on the skin of these mice. UV irradiation induces a marked increase in the epidermal thickness of the dorsal skin and a marked decrease in the skin moisture content; however, orally administered hyaluronan, particularly that with a molecular weight of less than 10k, markedly reversed the increase and decrease in the epidermal thickness and skin moisture content, respectively. Furthermore, on analyzing the mice skin, orally administered hyaluronan with a molecular weight of less than 10k increased the levels of the HAS2 gene expression in the skin. Based on these findings, it is assumed that orally administered hyaluronans, with molecular weight of 300k and less than 10k, reversed UV irradiation-induced skin disturbance. In particular, it was considered that the increase in the skin moisture content by orally administered hyaluronan, with a molecular weight of less than 10k, was related to the effect on skin cells.

  4. Endpoint Refinement for Total Body Irradiation of C57BL/6 Mice

    PubMed Central

    Nunamaker, Elizabeth A; Artwohl, James E; Anderson, Robert J; Fortman, Jeffrey D

    2013-01-01

    Acute radiation syndrome is a life-threatening condition that has the potential to affect large populations of humans. Although several animal models of this syndrome are available, the total-body–irradiated mouse has emerged as an important tool to evaluate the efficacy of prospective prophylaxis, mitigation, and treatment compounds. Despite the widespread use of this model, humane endpoints have not been clearly identified. To address this issue, we developed a cageside observation-based scoring system specifically for total-body–irradiated mice to assess the progression of clinical signs associated with acute radiation syndrome. Male C57BL/6 mice (n = 175; age, 8 to 9 wk) received an anticipated LD50 dose of radiation and were observed for progression of clinical signs of acute radiation syndrome for 30 d. All mice were scored individually through cageside observation of their body posture (score, 0 to 3), eye appearance (0 to 3), and activity level (0 to 3). Retrospective analysis of the score data indicated that death could be predicted accurately by using increasing cumulative scores (0 to 9). Total scores of 6, 7, 8, and 9 were associated with mortality rates of 78.6%, 86.4%, 93.3%, and 100%, respectively. Furthermore, scores of 6, 7, and 8 predicted death within 3, 1.5, and 0.5 d, respectively. The use of this scoring system provides investigators and IACUCs with predictive humane, surrogate endpoints for total-body–irradiated mice. This system allows preemptive euthanasia of mice before they become moribund, thereby minimizing pain and distress associated with acute radiation syndrome and improving animal welfare. PMID:23561934

  5. Alternative types of duodenal ulcer induced in mice by partial x irradiation of the thorax

    SciTech Connect

    Michalowski, A.; Uehara, S.; Yin, W.B.; Burgin, J.; Silvester, J.A.

    1983-07-01

    The present study extends our earlier observations on gastrointestinal pathology in thorax-irradiated female CFLP mice. It shows that exposure of the lower mediastinum to single doses of 14 to 30 Gy x rays results in the formation of the proximal duodenal ulcer accompanied frequently by erosion of the antral gastric mucosa. X irradiation of the lateral thoracic fields is responsible for single ulcers in the proximity of duodenal papilla, often associated with a circumscribed area of degeneration of the fundic mucosa of the stomach. In view of the small amount of radiation received by the subdiaphragmatic parts of the alimentary tract, these gastro-duodenal lesions represent abscopal effects of thoracic irradiation.

  6. Alternative types of duodenal ulcer induced in mice by partial X irradiation of the thorax

    SciTech Connect

    Michalowski, A.; Uehara, S.; Yin, W.B.; Burgin, J.; Silvester, J.A.

    1983-07-01

    The present study extends our earlier observations on gastrointestinal pathology in thorax-irradiated female CFLP mice. It shows that exposure of the lower mediastinum to single doses of 14-30 Gy X rays results in the formation of the proximal duodenal ulcer accompanied frequently by erosion of the antral gastric mucosa. X irradiation of the lateral thoracic fields is responsible for single ulcers in the proximity of duodenal papilla, often associated with a circumscribed area of degeneration of the fundic mucosa of the stomach. In view of the small amount of radiation received by the subdiaphragmatic parts of the alimentary tract, these gastro-duodenal lesions represent abscopal effects of thoracic irradiation.

  7. Effect of intrasplenic injection of allogeneic bone marrow cells on the survival of lethally X-irradiated mice

    SciTech Connect

    Imamura, M.; Miyazaki, T.; Okabe, M.; Sakurada, K.; Musashi, M.; Kawamura, K.; Hatakeyama, M.

    1983-01-01

    Radiation chimeras in mice were induced by intrasplenic injection of allogeneic bone marrow cells instead of intravenous injection. Interestingly, the survival time in X-irradiated BALB/c mice inoculated intrasplenically (i.s.) with bone marrow cells from C3H/He mice was markedly prolonged as compared with that in X-irradiated BALB/c mice inoculated i.v. with bone marrow cells from C3H/He mice. However, when C57BL/6 mice were used as donors, a significant difference between i.s. injection and i.v. injection has not been found in survival time at 60 days after X irradiation. On the contrary, when bone marrow cells from BALB/c or C57BL/6 mice were injected into X-irradiated C3H/He mice, i.s. injection gave longer survival days to recipients than did i.v. injection. Based on testing their chimerism, it was suggested that lymphoid cells of donor origin were predominantly identified in almost all BALB/c or C3H/He recipients which were inoculated i.s. with bone marrow cells from C57BL/6 mice. However, somewhat incomplete chimerism was observed when the C3H/He to BALB/c donor-recipient combination was used and vice versa.

  8. Delayed induction of pigmented spots on UVB-irradiated hairless mice.

    PubMed

    Naganumaa, M; Yagi, E; Fukuda, M

    2001-01-01

    Human skin exposed to solar radiation for a long time subsequently develops pigmented spots, which are named solar lentigines. Since no animal model of this process is currently available, we attempted to induce similar spots in pigmented hairless mice. The mice were irradiated at 38 or 94 mJ/cm(2) three times/week for various periods of time (1-8 weeks) under an ultraviolet light source (Toshiba FL-SE; UVB). Skin pigmentation of irradiated mice was visually observed and skin color was determined with a colorimeter for 78 weeks. Uniform pigmentation was induced, but persisted only during exposure, disappearing completely within 2 weeks after cessation of exposure. At about 28 weeks after the first exposure, pigmented spots suddenly began to appear. These pigmented spots were less than 2 mm in diameter and light brown in color. The length of the latent period until appearance and the extent of development of these spots were dependent on the exposure period. Histological examination revealed increased numbers of active melanocytes and melanin granules in the affected epidermis. These pigmented spots closely resemble solar lentigines in humans, and the mice should be useful as an animal model of solar lentigines.

  9. Whole-Body Proton Irradiation Causes Long-Term Damage to Hematopoietic Stem Cells in Mice

    PubMed Central

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Luo, Yi; Allen, Antiño R.; Koturbash, Igor; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH

  10. Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice.

    PubMed

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Luo, Yi; Allen, Antiño R; Koturbash, Igor; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2015-02-01

    Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH

  11. Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice.

    PubMed

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Luo, Yi; Allen, Antiño R; Koturbash, Igor; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2015-02-01

    Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH

  12. Prenatal immunotoxicant exposure and postnatal autoimmune disease.

    PubMed Central

    Holladay, S D

    1999-01-01

    Reports in humans and rodents indicate that immune development may be altered following perinatal exposure to immunotoxic compounds, including chemotherapeutics, corticosteroids, polycyclic hydrocarbons, and polyhalogenated hydrocarbons. Effects from such exposure may be more dramatic or persistent than following exposure during adult life. For example, prenatal exposure to the insecticide chlordane or to the polycyclic aromatic hydrocarbon benzo[(italic)a(/italic)]pyrene produces what appears to be lifelong immunosuppression in mice. Whether prenatal immunotoxicant exposure may predispose the organism to postnatal autoimmune disease remains largely unknown. In this regard, the therapeutic immunosuppressant cyclosporin A (CsA) crosses the placenta poorly. However, lethally irradiated rodents exposed to CsA postsyngeneic bone marrow transplant (i.e., during re-establishment of the immune system) develop T-cell-mediated autoimmune disease, suggesting this drug may produce a fundamental disruption in development of self-tolerance by T cells. The environmental contaminant 2,3,7, 8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD) crosses the placenta and produces fetal thymic effects (italic)in vivo(/italic) similar to effects of CsA in fetal thymic organ culture, including inhibited thymocyte maturation and reduced expression of thymic major histocompatability complex class II molecules. These observations led to the suggestion that gestational exposure to TCDD may interfere with normal development of self-tolerance. Possibly supporting this hypothesis, when mice predisposed to development of autoimmune disease were treated with TCDD during gestation, postnatal autoimmunity was exacerbated. Similar results have been reported for mice exposed to diethylstilbestrol during development. These reports suggest that prenatal exposure to certain immunotoxicants may play a role in postnatal expression of autoimmunity. PMID:10502532

  13. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Barbosa, Décio S; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-24

    Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress-dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-β and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease.

  14. Schistosoma mansoni: interactive effects of irradiation and cryopreservation on parasite maturation and immunization of mice

    SciTech Connect

    James, E.R.; Dobinson, A.R.

    1984-06-01

    Mechanically transformed schistosomula of Schistosoma mansoni were irradiated with levels of 60Co irradiation between 2.5 and 54 krad, cryopreserved by the two-step addition of ethanediol and rapid cooling technique, and were injected intramuscularly into groups of mice which were perfused 40 days later. The schistosomula were either irradiated and then cryopreserved (IC) or cryopreserved and then irradiated in the frozen state (CI). Development into adult worms was prevented with 4 krad for IC schistosomula, but for CI schistosomula a small number of worms (1.6%) was recovered using 8.8 krad. A dose of 4 krad was sufficient to prevent development of unfrozen controls (I), but for schistosomula irradiated while exposed to ethanediol (EI), a dose of 7 krad was required. Using the different protocols, the peak levels of protection against a challenge infection were achieved with 9 (IC) and 16 krad (CI), compared to 20 krad for unfrozen schistosomula (I) reported previously. The highest level of protection (65%) was achieved with CI schistosomula. Possible interactions between the radioprotective and damaging effects of cryopreservation are discussed.

  15. A study of the effect of sequential injection of 5-androstenediol on irradiation-induced myelosuppression in mice.

    PubMed

    Kim, Joong Sun; Jang, Won Suk; Lee, Sunjoo; Son, Yeonghoon; Park, Sunhoo; Lee, Seung Sook

    2015-06-01

    Herein, we aimed at examining the therapeutic effects of 5-androstenediol (5-AED), a natural hormone produced in the adrenal cortex, on radiation-induced myelosuppression in C3H/HeN mice. The mice were subjected to whole-body irradiation with a sublethal dose of 5 Gy gamma-irradiation to induce severe myelosuppression, and 5-AED (50 mg/kg) was administered subcutaneously. 5-AED was administrated 1 day before irradiation (pre-treatment) or twice weekly for 3 weeks starting from 1 h after irradiation (post-treatment). Treatment with 5-AED significantly ameliorated the decrease in the peripheral blood neutrophil and platelet populations in irradiated myelosuppressive mice, but had no effect on the lymphocyte population. It also ameliorated hypocellularity and disruption of bone marrow induced by irradiation and led to rapid recovery of myeloid cells. Further, it attenuated the decrease in spleen weight and megakaryocyte and myeloid cell populations in the spleen and promoted multilineage hematopoietic recovery. We found that a single injection of 5-AED produced only a temporary therapeutic effect, while sequential injection of 5-AED after irradiation had a more pronounced and prolonged therapeutic effect and reduced myelosuppression by irradiation. Thus, sequential injection of 5-AED after irradiation has therapeutic potential for radiation-induced myelosuppression when administered continuously and can be a significant therapeutic candidate for the management of acute radiation syndrome, particularly in a mass casualty scenario where rapid and economic intervention is important. PMID:25234002

  16. Haematopoietic, Antioxidant and Membrane Stabilizing Property of Diallyl Disulphide in Irradiated Mice

    PubMed Central

    Tenkanidiyoor, Yogish Somayaji; Vasudeva, Vidya; Rao, Shama; Gowda, Damodara; Rao, Chandrika; Sanjeev, Ganesh

    2016-01-01

    Introduction Diallyl disulphide is an organo-sulphur compound which is present in garlic and responsible for the characteristic odor of garlic. It is known for its anticancer and invitro membrane stabilizing properties. Aim The main aim was to evaluate the haematopoietic, antioxidant and membrane stabilizing property of diallyl disulfide in irradiated mice. Materials and Methods Mice were grouped into 6 groups as control, drug control, radiation control and drug pre-treatment groups (i.e. drug administration + radiation group) The mice were fed orally for 15 consecutive days and on the 15th day, one hour after drug administration, the mice were irradiated with 6Gy electron beam radiation. The changes in blood cell count, total antioxidant levels, malondialdehyde and reduced glutathione levels were determined. The immunomodulatory response of DADS to the radiological effects was determined by the estimation of IL-6 levels. Results A significant improvement in pre-drug treatment group when compared to control groups in the haemoglobin, red blood cell count, white blood cell count, haematocrit and platelet counts was observed. There is an increased level of interleukin-6 in the drug treated groups compared to the radiation control. An increase in the malondialdehyde levels and decrease in the glutathione levels in the irradiated group indicate increased lipid peroxidation and oxidative stress, whereas, there is a significant reduction in the malondialdehyde levels and increased glutathione levels in the drug pre-treatment groups showing membrane stabilization. Conclusion Thus DADS proves to be an effective haematopoietic and antioxidative agent to counter radiation induced haematopoietic suppression and oxidative stress. PMID:27042448

  17. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  18. Sensory dynamics of intense microwave irradiation: A comparative study of aversive behaviors by mice and rats

    SciTech Connect

    Justesen, D.R.

    1981-10-01

    The results of two experiments are reported, the first on 24 mice and 14 rats, all experimentally naive, that were observed for evidence of adventitious escape from faradic shock or from a potentially lethal, 2450-MHz microwave field in a multi-mode cavity. All of ten rats irradiated at a whole-body-averaged dose rate of 60 mW/g convulsed and expired, presumably from radiation-induced hyperpyrexia. Eight of ten mice irradiated at 60 mW/g survived the four sessions of irradiation, but reliable evidence of escape learning was not observed. The data of the second experiment, which was a pilot study of four rats with an extensive history of exposure to intense but intermittently applied microwave fields, revealed that the animals learned to thermoregulate behaviorally by locomoting in and out of the safe-area circle. A strong relation between dose rate (30, 60, and 120 mW/g) and proportion of time spent in the safe area was observed (r = .97). Post-exposure means of colonic temperature during three sets of sessions under the different rates of energy dosing were highly stable and averaged 39.6 deg C.

  19. Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules

    SciTech Connect

    Lewis, F.A.; Stirewalt, M.A.; Leef, J.L.

    1984-06-01

    Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at least 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals.

  20. Life-shortening and carcinogenesis in mice irradiated neonatally with x rays

    SciTech Connect

    Sasaki, S.; Kasuga, T.

    1981-11-01

    The characteristics of life-shortening and carcinogenesis were investigated in x-irradiated neonatal B6WFr mice. Animals were irradiated with 24 hr after birth and allowed to complete their normal life span. Mean life span was shortened linearly with doses at a rate of 9.1% per 100 R for females and 9.8% for males. The spectrum of neoplastic diseases was apparently modulated by x irradiation, showing neonatal B6WFr mice to be highly susceptible to the induction of thymic lymphoma, liver tumor, and pituitary tumor. The dose-response relationship for thymice lymphoma could be described by a linear-quadratic model, and linearity could be rejected. Thymic lymphoma developed after a short latent period, resulting in death between 100 and 450 days of age. Liver and pituitary tumors increased with increasing dose up to 400 R and decreased thereafter. The latent period for liver tumor development was apparently shortened with increasing doses. Pituitary tumor developed in excess only in females after a long latent period.

  1. Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)

    SciTech Connect

    Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I. )

    1991-03-01

    Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area (TBSA)) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma.

  2. Developmental disturbance of rat cerebral cortex following prenatal low-dose gamma-irradiation: a quantitative study

    SciTech Connect

    Fukui, Y.; Hoshino, K.; Hayasaka, I.; Inouye, M.; Kameyama, Y. )

    1991-06-01

    Pregnant rats were exposed to a single whole-body gamma-irradiation on Day 15 of gestation at a dose of 0.27, 0.48, 1.00, or 1.46 Gy. They were allowed to give birth and the offspring were killed at 6 or 12 weeks of age for microscopic and electron microscopic examinations of the cerebrum. Their body weight, brain weight, cortical thickness, and numerical densities of whole cells and synapses in somatosensory cortex were examined. Growth of the dendritic arborization of layer V pyramidal cells was also examined quantitatively with Golgi-Cox specimens. A significant dose-related reduction in brain weight was found in all irradiated groups. Neither gross malformation nor abnormality of cortical architecture was observed in the groups exposed to 0.27 Gy. A significant change was found in thickness of cortex in the groups exposed to 0.48 Gy or more. Cell packing density increased significantly in the group exposed to 1.00 Gy. Significant reduction in the number of intersections of dendrites with the zonal boundaries were found in the groups exposed to 0.27 Gy or more. There was no difference in the numerical density of synapses in layer I between the control and irradiated groups. These results suggested that doses as low as 0.27 Gy could cause a morphologically discernible change in the mammalian cerebrum.

  3. Long-Term Effects of {sup 56}Fe Irradiation on Spatial Memory of Mice: Role of Sex and Apolipoprotein E Isoform

    SciTech Connect

    Villasana, Laura E.; Benice, Theodore S.; Raber, Jacob

    2011-06-01

    Purpose: To assess whether the effects of cranial {sup 56}Fe irradiation on the spatial memory of mice in the water maze are sex and apolipoprotein E (apoE) isoform dependent and whether radiation-induced changes in spatial memory are associated with changes in the dendritic marker microtubule-associated protein 2 (MAP-2) and the presynaptic marker synaptophysin. Methods and Materials: Two-month-old male and female mice expressing human apoE3 or apoE4 received either a 3-Gy dose of cranial {sup 56}Fe irradiation (600 MeV/amu) or sham irradiation. Mice were tested in a water maze task 13 months later to assess effects of irradiation on spatial memory retention. After behavioral testing, the brain tissues of these mice were analyzed for synaptophysin and MAP-2 immunoreactivity. Results: After irradiation, spatial memory retention of apoE3 female, but not male, mice was impaired. A general genotype deficit in spatial memory was observed in sham-irradiated apoE4 mice. Strikingly, irradiation prevented this genotype deficit in apoE4 male mice. A similar but nonsignificant trend was observed in apoE4 female mice. Although there was no change in MAP-2 immunoreactivity after irradiation, synaptophysin immunoreactivity was increased in irradiated female mice, independent of genotype. Conclusions: The effects of {sup 56}Fe irradiation on the spatial memory retention of mice are critically influenced by sex, and the direction of these effects is influenced by apoE isoform. Although in female mice synaptophysin immunoreactivity provides a sensitive marker for effects of irradiation, it cannot explain the apoE genotype-dependent effects of irradiation on the spatial memory retention of the mice.

  4. Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis.

    PubMed

    Hofer, M; Pospísil, M; Tkadlecek, L; Viklická, S; Pipalová, I; Holá, J

    1992-01-01

    An impairment of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of prostaglandin synthesis inhibitors (PGSIs), indomethacin or diclofenac, was observed. Morphological examination of the gastrointestinal tract and the estimation of blood loss into its lumen in animals treated with diclofenac did not show serious damage such as haemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation.

  5. Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice.

    PubMed

    Kumar, Arun; Selvan, Tamizh G; Tripathi, Akanchha M; Choudhary, Sandeep; Khan, Shahanshah; Adhikari, Jawahar S; Chaudhury, Nabo K

    2015-09-01

    Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30 min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only (P < 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice. PMID:25863274

  6. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans. PMID:26254283

  7. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans.

  8. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

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

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  9. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice

    PubMed Central

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

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  10. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

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

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  11. Prenatal exposure of mice to the human liver carcinogen Aflatoxin B1 reveals a critical window of susceptibility to genetic change

    PubMed Central

    Chawanthayatham, Supawadee; Thiantanawat, Apinya; Egner, Patricia A.; Groopman, John D.; Wogan, Gerald N.; Croy, Robert G.; Essigmann, John M.

    2014-01-01

    It has become axiomatic that critical windows of susceptibility to genotoxins exist and that genetic damage in utero may be a trigger for later life cancers. Data supporting this critical window hypothesis are remarkably few. This study provides a quantitative bridge between DNA damage by the liver carcinogen aflatoxin B1 (AFB1) during prenatal development and the risk of later life genetic disease. AFB1 was given to pregnant C57BL/6J mice, carrying F1 gestation day 14 (GD14) embryos of the B6C3F1 genotype. Ultra-high performance liquid chromatography and mass spectrometry (UPLC-MS) using aflatoxin-15N5-guanine adduct standards afforded measurement of the AFB1-N7-Gua and AFB1-FAPY adducts six hours post dosing in liver DNA of mothers and embryos. A parallel cohort gave birth and the livers of the F1 were analyzed for mutations in the gpt gene at three and ten weeks of age. The data revealed mutational spectra dominated by G:C to T:A mutations in both the mother and offspring that are characteristic of AFB1 and distinct from background. It was shown that adducts in GD14 embryos were 20-fold more potent inducers of mutagenesis than adducts in parallel-dosed adults. This sensitivity enhancement correlated with Ki67 staining of the liver, reflecting the proliferative potential of the tissue. Taken together, these data provide insight into the relative genetic risks of prenatal and adult exposures to AFB1. Early life exposure, especially during the embryonic period, is strikingly more mutagenic than treatment later in life. Moreover the data provide a baseline against which risk prevention strategies can be evaluated. PMID:25070670

  12. Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice.

    PubMed

    Kripke, M L; Cox, P A; Alas, L G; Yarosh, D B

    1992-08-15

    Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage. PMID:1502162

  13. Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

    PubMed

    Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

    2010-01-01

    We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia. PMID:20016249

  14. Chloroquine Engages the Immune System to Eradicate Irradiated Breast Tumors in Mice

    SciTech Connect

    Ratikan, Josephine Anna; Sayre, James William

    2013-11-15

    Purpose: This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system. Methods and Materials: Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death. Results: Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected. Conclusions: This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy.

  15. Thread Embedding Acupuncture Inhibits Ultraviolet B Irradiation-Induced Skin Photoaging in Hairless Mice

    PubMed Central

    Kim, Yoon-Jung; Kim, Ha-Neui; Shin, Mi-Sook; Choi, Byung-Tae

    2015-01-01

    Thread embedding acupuncture (TEA) is an acupuncture treatment applied to many diseases in Korean medical clinics because of its therapeutic effects by continuous stimulation to tissues. It has recently been used to enhance facial skin appearance and antiaging, but data from evidence-based medicine are limited. To investigate whether TEA therapy can inhibit skin photoaging by ultraviolet B (UVB) irradiation, we performed analyses for histology, histopathology, in situ zymography and western blot analysis in HR-1 hairless mice. TEA treatment resulted in decreased wrinkle formation and skin thickness (Epidermis; P = 0.001 versus UV) in UVB irradiated mice and also inhibited degradation of collagen fibers (P = 0.010 versus normal) by inhibiting proteolytic activity of gelatinase matrix-metalloproteinase-9 (MMP-9). Western blot data showed that activation of c-Jun N-terminal kinase (JNK) induced by UVB (P = 0.002 versus normal group) was significantly inhibited by TEA treatment (P = 0.005 versus UV) with subsequent alleviation of MMP-9 activation (P = 0.048 versus UV). These results suggest that TEA treatment can have anti-photoaging effects on UVB-induced skin damage by maintenance of collagen density through regulation of expression of MMP-9 and related JNK signaling. Therefore, TEA therapy may have potential roles as an alternative treatment for protection against skin damage from aging. PMID:26185518

  16. The contribution of late-generated neurons to the callosal projection in rat: a study with prenatal x-irradiation

    SciTech Connect

    Jensen, K.F.; Altman, J.

    1982-08-01

    Studies utilizing horseradish peroxidase tracing methods have suggested that there are species differences in the relative contribution of the different neocortical layers to the callosal projection. The present investigation utilized x-irradiation at different gestational ages to eliminate the late-generated neurons in the rat neocortex. The caudorostral gradient of reduction in the neuronal population of the supragranular layers is closely correlated with the gradient of reduction in the size of the corpus callosum. Furthermore, the callosal projection is absent in anteroposterior cortical segments in which the development of the supragranular layers was prevented without a reduction of the number of neurons in the infragranular layers of the neocortex. These results indicate that late-generated neurons residing primarily in the supragranular layers are essential for the formation of the corpus callosum.

  17. [CYTOGENETIC EFFECTS IN MICE BONE MARROW AFTER IRRADIATION BY FAST NEUTRONS].

    PubMed

    Vorozhtsova, S V; Bulynina, T M; Ivanov, A A

    2016-01-01

    Mechanisms of damaging mice bone marrow cells by 1.5 MeV neutrons at the dose of 25-250 cGy, dose rate of 23.9 cGy/s and γ-quants ⁶⁰Co as a standard radiation were studied. The mitotic index and aberrant mitoses in marrow preparations were counted in 24 and 72 hours after irradiation. Coefficients of relative biological effectiveness (RBE) of fast neutrons 24 and 72 hours post irradiation calculated from mitotic index reduction and aberrant mitoses formation were within the range from 4.1 ± 0.1 to 7.3 ± 0.1. Mean time of the existence of chromosomal aberrations in marrow cells was determined. For the specified doses from γ-rays, the period of aberrations existence was 1.4-1.1 cycles and for neutrons, 1.0-0.6 cycles. Morphologic analysis of neutron-induced damages and ratio of the most common breaks demonstrated a high production of bridges, which outnumbered cells with fragments in 3 to 4 times suggesting a more destructive effect on the genetic structures of cells. RBE of fast neutrons is a variable that grows with a radiation dose. Moreover, RBE estimated after 72 hours exceeded values it had 24 hours after irradiation. PMID:27347593

  18. [CYTOGENETIC EFFECTS IN MICE BONE MARROW AFTER IRRADIATION BY FAST NEUTRONS].

    PubMed

    Vorozhtsova, S V; Bulynina, T M; Ivanov, A A

    2016-01-01

    Mechanisms of damaging mice bone marrow cells by 1.5 MeV neutrons at the dose of 25-250 cGy, dose rate of 23.9 cGy/s and γ-quants ⁶⁰Co as a standard radiation were studied. The mitotic index and aberrant mitoses in marrow preparations were counted in 24 and 72 hours after irradiation. Coefficients of relative biological effectiveness (RBE) of fast neutrons 24 and 72 hours post irradiation calculated from mitotic index reduction and aberrant mitoses formation were within the range from 4.1 ± 0.1 to 7.3 ± 0.1. Mean time of the existence of chromosomal aberrations in marrow cells was determined. For the specified doses from γ-rays, the period of aberrations existence was 1.4-1.1 cycles and for neutrons, 1.0-0.6 cycles. Morphologic analysis of neutron-induced damages and ratio of the most common breaks demonstrated a high production of bridges, which outnumbered cells with fragments in 3 to 4 times suggesting a more destructive effect on the genetic structures of cells. RBE of fast neutrons is a variable that grows with a radiation dose. Moreover, RBE estimated after 72 hours exceeded values it had 24 hours after irradiation.

  19. Candidate vaccine antigens identified by antibodies from mice vaccinated with 15- or 50-kilorad-irradiated cercariae of Schistosoma mansoni.

    PubMed Central

    Richter, D; Harn, D A

    1993-01-01

    In murine schistosomiasis, the highest levels of resistance to cercarial challenge are obtained by vaccination with radiation-attenuated cercariae. To identify candidate vaccine antigens relevant to the vaccine model, we examined parasite antigens recognized by antibodies from mice vaccinated with irradiated cercariae of Schistosoma mansoni. To optimize recognition of a wide spectrum of antigens, several factors that influence the level of protection in this model were varied; specifically, we examined the effect of (i) single versus multiple vaccinations with irradiated cercariae, (ii) the dose of irradiation (15 or 50 kilorads) administered to the cercariae, and (iii) the genetic background of mouse strains, high-responder (C57BL/6J) versus moderate-responder (CBA/J) mice. We found that the number of vaccinations did not alter antibody specificity but modified the relative antibody titers against particular antigens. The dose of irradiation used to attenuate the immunizing cercariae had a similar effect on antibody titers but in addition influenced antibody specificity. Only mice that had been vaccinated with moderately irradiated cercariae recognized cathepsin B (Sm31) and Sm32. Interestingly, when vaccinated mice of the two strains, C57BL/6J and CBA/J, were compared, differences in antibody responses to particular antigens were observed. Both strains recognized the integral membrane protein Sm23, glutathione S-transferase, and cathepsin B, whereas Sm32 and paramyosin were recognized only by CBA/J mice, and heat shock protein 70 was recognized exclusively by C57BL/6J mice. In this study, we conclusively identified six distinct antigens that are specifically recognized by the humoral immune response of vaccinated mice. Images PMID:8418037

  20. Protection against Whole Body γ-Irradiation Induced Oxidative Stress and Clastogenic Damage in Mice by Ginger Essential Oil.

    PubMed

    Jeena, Kottarapat; Liju, Vijayasteltar B; Ramanath, Viswanathan; Kuttan, Ramadasan

    2016-01-01

    Radioprotective effects of ginger essential oil (GEO) on mortality, body weight alteration, hematological parameters, antioxidant status and chromosomal damage were studied in irradiated mice. Regression analysis of survival data in mice exposed to radiation yielded LD50/30 as 7.12 and 10.14 Gy for control (irradiation alone) and experimental (GEO-treated irradiated) mice, respectively, with a dose reduction factor (DRF) of 1.42. In mice exposed to whole-body gamma-irradiation (6 Gy), GEO pre-treatment at 100 and 500 mg/kg b.wt (orally) significantly ameliorated decreased hematological and immunological parameters. Radiation induced reduction in intestinal tissue antioxidant enzyme levels such as superoxide dismutase, catalase, glutathione peroxidase and glutathione was also reversed following administration of GEO. Tissue architecture of small intestine which was damaged following irradiation was improved upon administration of GEO. Anticlastogenic effects of GEO were studied by micronuclei assay, chromosomal aberration and alkaline gel electrophoresis assay. GEO significantly decreased the formation of micronuclei, increased the P/N ratio, inhibited the formation of chromosomal aberrations and protected agaisnt cellular DNA damage in bone marrow cells as revealed by comet assay. These results are supportive of use of GEO as a potential radioprotective compound. PMID:27039766

  1. Prenatal Care

    MedlinePlus

    ... many problems and prevent others. Your doctor or midwife will give you a schedule for your prenatal ... diabetes or high blood pressure, your doctor or midwife will probably want to see you more often. ...

  2. Rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice

    SciTech Connect

    Afifi, M.S.H.

    1985-01-01

    The objective of this study was to investigate the mechanisms of rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice, in part by investigating the hypothesis that two or more cell types are involved in recognition and rejection of hemopoietic cells. Interferon (IFN) was used as a tool for investigating such mechanisms. IFN alpha/beta stimulated the rejection of normal hemopoietic marrow cell grafts in Fl hybrid and in allogeneic host mice but did not affect the growth of cells in syngeneic mice. IFN alpha/beta was effective in hosts pretreated with silica but not in hosts pretreated with cyclophosphamide (Cy) or with anti-asialoGMI serum. Rabbit anti-IFN alpha/beta, but not anti-IFN gamma, serum inhibited genetic resistance to bone marrow cells. These results indicated that IFN alpha/beta was acting indirectly during the rejection of normal hemopoietic cells. It is proposed that four events occur in succession: a host cell recognizes the hemopoietic histocompatibility (Hh) antigens expressed on the surface of incompatible stem cells; this recognition leads to secretion of IFN; IFN activates natural killer (NK) cells; NK cells lyse donor stem cells. Silica interrupts one or both of the first two events. i.e., recognition and/or interrupts one or both of the first two events, i.e. recognition and/or IGN secretion.

  3. Electrophisiological signatures linked to particle irradiation on rodents within ALTEA-MICE

    NASA Astrophysics Data System (ADS)

    Narici, L.; Altea-Mice Team

    After several dry and test runs we performed in July 2004 a full scale electrophysiological experiment on normal mice that provided a first objective functional measure of heavy ions effect on the visual system Twentytwo mice was studied Electrophysiological signals were recorded from the retina and visual cortex during and with time information with luminance stimulation and beam bursts Repeated bursts of 12 C ions at 200 MeV i e below the Cerenkov threshold were delivered to the retina of dark-adapted mice In particular three- to five hundred 12 C bursts with nominal length of 1-5 ms intensity of 10 3 -10 4 particles burst 200 MeV n and 3 s interval between consecutive bursts were delivered by beam Light stimulation light flashes of 1 ms was performed before and after irradiation Ion bursts evoked a transient electrophysiological signal from the retina with waveform comparable to the response to light but longer latencies and smaller amplitude Variability among animals was high and may be accounted for by differences due to e g anaesthesia in the sensitivity saturation threshold of the cone rod systems contributing to the response or by effects on photoreceptors of the energy locally supplemented by the heat The amplitude of the retinal signal was correlated with the number of particles burst in one mouse with a signal-to-noise ratio and amplitude allowing measurements on the responses to single ion bursts

  4. Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

    PubMed

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.

  5. Treatment of Irradiated Mice with High-Dose Ascorbic Acid Reduced Lethality

    PubMed Central

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure. PMID:25651298

  6. Prevention and Mitigation of Acute Death of Mice after Abdominal Irradiation by the Antioxidant N-Acetyl-cysteine (NAC)

    PubMed Central

    Jia, Dan; Koonce, Nathan A.; Griffin, Robert J.; Jackson, Cassie; Corry, Peter M.

    2010-01-01

    Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.c. injection of N-acetyl-l-cysteine (NAC) or vehicle for 7 days starting either 4 h before or 2 h after irradiation, and monitored for up to 30 days. Separately, mice from each group were assayed 6 days after irradiation for bone marrow reactive oxygen species (ROS), ex vivo colony formation of bone marrow stromal cells, and histological changes in the duodenum. Irradiation of the abdomen caused dose-dependent weight loss and mortality. Radiation-induced acute death was preceded not only by a massive loss of duodenal villi but also, surprisingly, abscopal suppression of stromal cells and elevation of ROS in the nonirradiated bone marrow. NAC diminished these radiation-induced changes and improved 10- and 30-day survival rates to >50% compared with <5% in vehicle-treated controls. Our data establish a central role for abscopal stimulation of bone marrow ROS in acute death in mice after abdominal irradiation. PMID:20426657

  7. Behavioral and molecular neuroepigenetic alterations in prenatally stressed mice: relevance for the study of chromatin remodeling properties of antipsychotic drugs

    PubMed Central

    Dong, E; Tueting, P; Matrisciano, F; Grayson, D R; Guidotti, A

    2016-01-01

    We have recently reported that mice born from dams stressed during pregnancy (PRS mice), in adulthood, have behavioral deficits reminiscent of behaviors observed in schizophrenia (SZ) and bipolar (BP) disorder patients. Furthermore, we have shown that the frontal cortex (FC) and hippocampus of adult PRS mice, like that of postmortem chronic SZ patients, are characterized by increases in DNA-methyltransferase 1 (DNMT1), ten-eleven methylcytosine dioxygenase 1 (TET1) and exhibit an enrichment of 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) at neocortical GABAergic and glutamatergic gene promoters. Here, we show that the behavioral deficits and the increased 5MC and 5HMC at glutamic acid decarboxylase 67 (Gad1), reelin (Reln) and brain-derived neurotrophic factor (Bdnf) promoters and the reduced expression of the messenger RNAs (mRNAs) and proteins corresponding to these genes in FC of adult PRS mice is reversed by treatment with clozapine (5 mg kg−1 twice a day for 5 days) but not by haloperidol (1 mg kg−1 twice a day for 5 days). Interestingly, clozapine had no effect on either the behavior, promoter methylation or the expression of these mRNAs and proteins when administered to offspring of nonstressed pregnant mice. Clozapine, but not haloperidol, reduced the elevated levels of DNMT1 and TET1, as well as the elevated levels of DNMT1 binding to Gad1, Reln and Bdnf promoters in PRS mice suggesting that clozapine, unlike haloperidol, may limit DNA methylation by interfering with DNA methylation dynamics. We conclude that the PRS mouse model may be useful preclinically in screening for the potential efficacy of antipsychotic drugs acting on altered epigenetic mechanisms. Furthermore, PRS mice may be invaluable for understanding the etiopathogenesis of SZ and BP disorder and for predicting treatment responses at early stages of the illness allowing for early detection and remedial intervention. PMID:26756904

  8. Variable maturation and oviposition by female Schistosoma japonicum in mice: the effects of irradiation of the host prior to infection

    SciTech Connect

    Cheever, A.W.; Duvall, R.H.

    1987-11-01

    The maturation of female Schistosoma japonicum was found to vary greatly within each of two Philippine strains of this parasite and some females did not contain uterine eggs 7 to 15 weeks after infection while others contained numerous eggs before the fifth week of infection. It was found that female worms containing less than 20 uterine eggs contributed little to the accumulation of eggs in the tissues of infected mice. Such worms also generally appeared to be immature. The variable rate of maturation of worms is likely to have profound effects on the immune reactions of mice as well as on the pathologic response to infection. Systematic delay in oviposition was serendipitously found in worms from mice which had been irradiated for other purposes prior to exposure to S. japonicum, and from the fourth to the sixth week after infection egg production by worms in irradiated mice lagged well behind that in intact mice. Seven to 10 weeks after infection these worms were laying normal numbers of eggs, as judged by egg passage per worm pair in the feces and the accumulation of eggs in the tissues. S. mansoni developed normally in irradiated mice.

  9. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    SciTech Connect

    Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki; Botaitis, Sotirios; Torvinen, Sira; Simopoulos, Constantinos; Kortsaris, Alexandros; Sivridis, Efthimios; Koukourakis, Michael I.

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function

  10. Circadian cycle dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation

    PubMed Central

    Adler, Daniel A; Ammanuel, Simon; Lei, Jun; Dada, Tahani; Borbiev, Talaibek; Johnston, Michael.V.; Kadam, Shilpa.D.; Burd, Irina

    2014-01-01

    Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term EEG biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video-EEG-EMG analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was performed blind to treatment group, on each 10 second EEG epochs using synchronous video, EMG and EEG trace signatures to generate individual hypnograms. Automated EEG power spectrums were analyzed for delta and theta-beta power ratios during wake vs. sleep cycles. Both control and LPS hypnograms showed an ultradian wake/sleep cycling. Since rodents are nocturnal animals, control mice showed the expected diurnal variation with significantly longer time spent in wake states during the dark cycle phase. In contrast, the LPS treated mice lost this circadian rhythm. Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average NREM cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian cycle and activity state dependent. PMID:24954445

  11. Biodistribution of gold nanoparticles synthesized by γ-irradiation after intravenous administration in mice

    NASA Astrophysics Data System (ADS)

    Luan Le, Quang; Phuong Linh Do, Thi; Phuong Uyen Nguyen, Huynh; Phu Dang, Van; Hien Nguyen, Quoc

    2014-06-01

    In the present research work we evaluate the in vivo distribution of gold nanoparticles (AuNPs) at different time durations after intravenous administration in mice. AuNPs with size of about 20 nm and concentration of 1 mM were synthesized by gamma irradiation method using 0.5% alginate as a stabilizer. AuNPs were characterized by UV-Vis spectrum and transmission electron microscope (TEM) image. The as-synthesized AuNPs solution was centrifuged to concentrate to 2 mg AuNPs/1 ml solution. Intravenous administration of AuNPs in mice was done at the tail with 1 mg AuNPs (0.5 ml). After 1, 3, 6 and 12 h of injection, blood was collected, mice were sacrificed and various tissues/organs were removed. The blood haematology and serum clinical chemistry indexes of mice intravenously injected with AuNPs were not significantly different compared to those of the control ones. In addition, gold content in the samples was quantitatively determined by k0-neutron activation analysis (k0-NAA) at nuclear research reactor, Da Lat Vietnam. Results showed that after 1 h of administration, AuNPs were mainly accumulated in blood (41.56%), in liver (51.60.%), in lung (6.16%) and in kidney (0.53%). After that the content of AuNPs in blood was decreased to nearly normal at 6 h while the content of AuNPs in liver, lung and kidney was accumulatively increased. After 6 h of administration AuNPs were mainly accumulated in organs like liver (76.33%), lung (11.86%) and kidney (2.23%). Thus, the obtained results are practically useful for using AuNPs as x-ray contrast agent, especially for blood and liver.

  12. Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice.

    PubMed

    Ng, Royce L X; Scott, Naomi M; Bisley, Jackie L; Lambert, Misty J; Gorman, Shelley; Norval, Mary; Hart, Prue H

    2013-12-01

    When antigen-loaded dendritic cells (DCs) differentiated from the bone marrow (BM) of UV-irradiated mice (UV-BMDCs) were adoptively transferred into naive mice or mice pre-sensitized with that antigen, the recipients exhibited a reduced immune response following antigen challenge. Hence, UV-BMDCs are poorly immunogenic and can suppress pre-existing immunity. The UV-induced effect on BM-derived DCs was rapid (observed 1 day after UV radiation), long-lasting (observed 10 days after UV radiation) and UV dose-dependent. The mechanism by which UV-BMDCs could regulate immunity was investigated. The CD11c(+) cells, differentiated using granulocyte-macrophage colony-stimulating factor + interleukin-4, were confirmed to be DCs because they did not express the myeloid-derived suppressor cell marker, Gr1. UV-BMDCs did not display altered antigen uptake, processing or ability to activate T cells in vitro. When gene expression in UV-BMDCs and DCs differentiated from the BM of non-irradiated mice (control-BMDCs) was examined, Ccl7, Ccl8 and CSF1R (CD115) mRNA transcripts were up-regulated in UV-BMDCs compared with control-BMDCs. However, neutralizing antibodies for Ccl7 and Ccl8 did not abrogate the reduced immunogenicity of UV-BMDCs in vivo. Moreover, the up-regulation of CSF1R transcript did not correspond with increased receptor expression on UV-BMDCs. The phenotypes of UV-BMDCs and control-BMDCs were similar, with no difference in the expression of CD4, CD8α, CD103, B220 or F4/80, or the regulatory molecules CCR7 (CD197), FasL (CD95L), B7H3 (CD276) and B7H4. However, PDL1 (CD274) expression was reduced in UV-BMDCs compared with control-BMDCs following lipopolysaccharide stimulation. In summary, UV-BMDCs do not express the classical phenotypic or gene expression properties of DCs reported by others as 'regulatory' or 'tolerogenic'. PMID:23826713

  13. NICOTINE EFFECTS ON THE MOTOR ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

    EPA Science Inventory

    Several studies in the literature have shown that exposure of mice and rats to nicotine early in development alters its effects when the rodents are subsequently challenged with nicotine. Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria, and has caus...

  14. Developmental Abnormalities of Neuronal Structure and Function in Prenatal Mice Lacking the Prader-Willi Syndrome Gene Necdin

    PubMed Central

    Pagliardini, Silvia; Ren, Jun; Wevrick, Rachel; Greer, John J.

    2005-01-01

    Necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome (PWS). Ndntm2Stw mutant mice die shortly after birth because of abnormal respiratory rhythmogenesis generated by a key medullary nucleus, the pre-Bötzinger complex (preBötC). Here, we address two fundamental issues relevant to its pathogenesis. First, we performed a detailed anatomical study of the developing medulla to determine whether there were defects within the preBötC or synaptic inputs that regulate respiratory rhythmogenesis. Second, in vitro studies determined if the unstable respiratory rhythm in Ndntm2Stw mice could be normalized by neuromodulators. Anatomical defects in Ndntm2Stw mice included defasciculation and irregular projections of axonal tracts, aberrant neuronal migration, and a major defect in the cytoarchitecture of the cuneate/gracile nuclei, including dystrophic axons. Exogenous application of neuromodulators alleviated the long periods of slow respiratory rhythms and apnea, but some instability of rhythmogenesis persisted. We conclude that deficiencies in the neuromodulatory drive necessary for preBötC function contribute to respiratory dysfunction of Ndntm2Stw mice. These abnormalities are part of a more widespread deficit in neuronal migration and the extension, arborization, and fasciculation of axons during early stages of central nervous system development that may account for respiratory, sensory, motor, and behavioral problems associated with PWS. PMID:15972963

  15. Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: A review of current work. (Reannouncement with new availability information)

    SciTech Connect

    Ledney, G.D.; Madonna, G.S.; Elliott, T.B.; Moore, M.M.; Jackson, W.E.

    1991-12-31

    When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, the authors developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60 (Co sources). Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections.

  16. Effects of low-dose carbon ion irradiation on the proliferation of splenocytes and the concentration of interferon in mice

    NASA Astrophysics Data System (ADS)

    Li, Ning

    AIM: To investigate the changes in the proliferation response of splenic lymphocytes and the concentration of serum interferon (IFN-γ) in mice induced by low doses carbon ion irradiation. METHODS: The experiment was carried out in the laboratory of physical medicine, Institute of Modern Physics, Chinese Academy of Sciences in November 2006. 1. Thirty Kunming mice were randomly divided into five groups with six animals in each group and irradiated with 0, 0.01, 0.03, 0.05 and 0.10 Gy carbon ion at Heavy Ion Research Facility Laboratory of Lanzhou. Twenty-four hours after irradiation, the eyeballs of mice were taken out under anesthesia and blood was harvested. 2. The concentration of IFN-γ in serum was detected by ELISA kit. After the mice were executed, the spleen was harvested under sterile condition to prepare spleen mononuclear cell suspension. The effects of concanavalin A(ConA) and lipopolysaccharide(LPS) on the proliferations of mononuclear cells was tested by MTT assay. RESULTS: All thirty mice were involved in the result analysis. 1. The concentration of IFN-γ in serum remarkably increased after irradiation with 0.01 Gy and 0.03 Gy compared with that in controls (p<0.05). However, the concentration of IFN-γ decreased after irradiation with 0.05 Gy and 0.1 Gy. 2. Compared with control group, the proliferation of T lymphocytes induced by ConA and B lymphocytes induced by LPS remarkably increased after irradiation with 0.01 Gy (p<0.001) and the effect was of significant difference compared with that of 0.03 Gy (p<0.01). The irradiation with 0.05 Gy presented an inhibition to the proliferation of splenic lymphocytes. This inhibition was also obvious when irradiated with 0.10 Gy. CONCLUSION: 0.01 Gy and 0.03 Gy carbon ion irradiation can stimulate the proliferation of splenocytes, induce the secretion of IFN-γ and, in consequence, enhance the immune function.

  17. Effects of Lipopolysaccharide on the response of C57BL/6J mice to whole thorax irradiation

    PubMed Central

    Zaidi, Asif; Jelveh, Salomeh; Mahmood, Javed; Hill, Richard P

    2013-01-01

    Background and Purpose Inflammatory and fibrogenic processes play a crucial role in the radiation-induced injury in the lung. The aim of the present study was to examine whether additive LPS exposure in the lung (to simulate respiratory infection) would affect pneumonitis or fibrosis associated with lung irradiation. Material and Methods Wildtype C57Bl/6J (WT-C57) and TNFα, TNFR1 and TNFR2 knockout (−/−) mice, in C57Bl/6J background, were given whole thorax irradiation (10Gy) with or without post-irradiation intratracheal administration of LPS (50μg/mice). Functional deficit was examined by measuring breathing rate at various times after treatment. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry were used to analyse the protein expression and m-RNA of Interleukin-1 alpha (IL-1α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumour Necrosis Factor alpha (TNFα) and Transforming Growth Factor beta (TGFβ) in the lung at various times after treatment. Inflammatory cells were detected by Mac-3 (macrophages) and Toluidine Blue (mast cells) staining. Collagen content was estimated by hydroxyproline (total collagen) and Sircol assay (soluble collagen). Levels of oxidative damage were assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG) staining. Results LPS exposure significantly attenuated the breathing rate increases following irradiation of WT-C57, TNFR1−/− and TNFR2−/− mice and to a lesser extent in TNFα−/− mice. Collagen content was significantly reduced after LPS treatment in WT-C57, TNFR1−/− and TNFα−/− mice and there was a trend in TNFR2−/− mice. Similarly there were lower levels of inflammatory cells and cytokines in the LPS treated mice. Conclusions This study reveals a mitigating effect of early exposure to LPS on injury caused by irradiation on lungs of C57Bl mice. The results suggest that immediate infection post irradiation may not impact lung response negatively in radiation

  18. [DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE].

    PubMed

    Ivanov, A A; Bulynina, T M; Molokanov, A G; Vorozhtsova, S V; Utina, D M; Severyukhin, Yu S; Ushakov, I B

    2015-01-01

    The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/μm to 1.6 keV/μm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect.

  19. Topical Administration of Manuka Oil Prevents UV-B Irradiation-Induced Cutaneous Photoaging in Mice

    PubMed Central

    Kwon, Oh Sook; Yang, Beom Seok

    2013-01-01

    Manuka tree is indigenous to New Zealand, and its essential oil has been used as a traditional medicine to treat wounds, fever, and pain. Although there is a growing interest in the use of manuka oil for antiaging skin care products, little is known about its bioactivity. Solar ultraviolet (UV) radiation is the primary environmental factor causing skin damage and consequently premature aging. Therefore, we evaluated manuka oil for its effects against photoaging in UV-B-irradiated hairless mice. Topical application of manuka oil suppressed the UV-B-induced increase in skin thickness and wrinkle grading in a dose-dependent manner. Application of 10% manuka oil reduced the average length, depth, and % area of wrinkles significantly, and this was correlated with inhibition of loss of collagen fiber content and epidermal hyperplasia. Furthermore, we observed that manuka oil could suppress UV-B-induced skin inflammation by inhibiting the production of inflammatory cytokines. Taken together, this study provides evidence that manuka oil indeed possesses antiphotoaging activity, and this is associated with its inhibitory activity against skin inflammation induced by UV irradiation. PMID:23762170

  20. [DEMONSTRATION OF LIKELIHOOD OF THE NEGATIVE EFFECT OF PHYSICAL PROTECTION DURING TOTAL PROTON IRRADIATION OF MICE].

    PubMed

    Ivanov, A A; Bulynina, T M; Molokanov, A G; Vorozhtsova, S V; Utina, D M; Severyukhin, Yu S; Ushakov, I B

    2015-01-01

    The experiments were performed with outbred CD-1 male mice (SPF category). Total irradiation at 1.0; 2.5 and 5.0 Gy by protons with the average energy of 170 MeV was conducted in a level medical beam of the phasotron at the Joint Institute of Nuclear Investigations. Targets were 2 points of in-depth dose distribution, i.e. beam entrance of the object, and modified Bragg peak. As a physical protector, the comb filter increases linear energy transfer (LET) of 170 MeV entrance protons from 0.49 keV/μm to 1.6 keV/μm and, according to the bone marrow test, doubles the biological effectiveness of protons when comparing radiation doses that cause 37% inhibition of blood cell formation in the bone marrow. Physical protection increases dose rate from 0.37 Gy/min for entrance protons to 0.8 Gy/min for moderated protons which more than in thrice reduces time of irradiation needed to reach an equal radiobiological effect. PMID:26554131

  1. Differential effects of prenatal stress in female 5-HTT-deficient mice: towards molecular mechanisms of resilience.

    PubMed

    Jakob, Sissi; Schraut, Karla-Gerlinde; Schmitt, Angelika G; Scholz, Claus-Jürgen; Ortega, Gabriela; Steinbusch, Harry W; Lesch, Klaus-Peter; van den Hove, Daniel L A

    2014-01-01

    Prenatal stress (PS) exposure is known to increase the risk of developing emotional disorders like major depression in later life. However, some individuals do not succumb to adversity following developmental stress exposure, a phenomenon referred to as resilience. To date, the molecular mechanisms explaining why some subjects are vulnerable and others more resilient to PS are far from understood. Recently, we have shown that the serotonin transporter (5-HTT) gene may play a modulating role in rendering individuals susceptible or resilient to PS. However, it is not clear which molecular players are mediating the interaction between PS and the 5-Htt genotype in the context of vulnerability and resilience to PS. For this purpose, we performed a microarray study with the help of Affymetrix GeneChip® Mouse Genome 430 2.0 Array, in which we separated wild-type and heterozygous 5-Htt-deficient (5-Htt+/-) PS offspring into susceptible and resilient offspring according to their performance in the forced swim test. Performance-oriented LIMMA analysis on the mRNA expression microarray data was followed by subsequent Spearman's correlation analysis linking the individual qRT-PCR mRNA expression data to various anxiety- and depression-related behavioral and neuroendocrine measures. Results indicate that, amongst others, Fos-induced growth factor (Figf), galanin receptor 3 (Galr3), growth hormone (Gh) and prolactin (Prl) were differentially expressed specifically in resilient offspring when compared to controls, and that the hippocampal expression of these genes showed several strong correlations with various measures of the hypothalamus-pituitary-adrenal axis (re)activity. In conclusion, there seems to be an intricate interplay between the expression of Figf, Galr3, Gh and Prl and neuroendocrine regulation, which may be critical in mediating resilience to PS exposure. More insight into the exact role of these molecular players may significantly enhance the development of new

  2. Early micro-rheological consequences of single fraction total body low-dose photon irradiation in mice.

    PubMed

    Szluha, Kornelia; Lazanyi, Kornelia; Furka, Andrea; Kiss, Ferenc; Szabo, Imre; Pintye, Eva; Miko, Iren; Nemeth, Norbert

    2014-01-01

    Despite of the studies on widespread biological effects of irradiation, surprisingly only little number of papers can be found dealing with its in vivo hemorheological impact. Furthermore, other studies suggested that low-dose irradiation might differ from high-dose in more than linear ways. On Balb/c Jackson female adult mice hematological and hemorheological impacts of total body irradiation were investigated 1 hour following 0.002, 0.005, 0.01, 0.02, 0.05 and 0.1 Gy dose irradiation. In case of 0.01 Gy further groups were analyzed 30 minutes, 2, 4, 6, 24 and 48 h after irradiation. According to the results, it seems that the dose-dependent changes of blood micro-rheological parameters are not linear. The irradiation dose of 0.01 Gy acted as a point of 'inflexion', because by this dose we found the most expressed changes in hematological parameters, as well as in red blood cell aggregation, deformability and osmoscan data. The time-dependent changes showed progressive decrease in pH, rise in lactate concentration, further decrease in erythrocyte aggregation index and deformability, with moderate shifting of the optimal osmolarity point and modulation in membrane stability. As conclusion, low-dose total body irradiation may cause micro-rheological changes, being non-linearly correlated with the irradiation dose.

  3. Jeju ground water containing vanadium induced immune activation on splenocytes of low dose γ-rays-irradiated mice.

    PubMed

    Ha, Danbee; Joo, Haejin; Ahn, Ginnae; Kim, Min Ju; Bing, So Jin; An, Subin; Kim, Hyunki; Kang, Kyung-goo; Lim, Yoon-Kyu; Jee, Youngheun

    2012-06-01

    Vanadium, an essential micronutrient, has been implicated in controlling diabetes and carcinogenesis and in impeding reactive oxygen species (ROS) generation. γ-ray irradiation triggers DNA damage by inducing ROS production and causes diminution in radiosensitive immunocytes. In this study, we elucidate the immune activation capacities of Jeju water containing vanadium on immunosuppression caused by γ-ray irradiation, and identify its mechanism using various low doses of NaVO(3). We examined the intracellular ROS generation, DNA damage, cell proliferation, population of splenocytes, and cytokine/antibody profiles in irradiated mice drinking Jeju water for 180 days and in non-irradiated and in irradiated splenocytes both of which were treated with NaVO(3). Both Jeju water and 0.245 μM NaVO(3) attenuated the intracellular ROS generation and DNA damage in splenocytes against γ-ray irradiation. Splenocytes were significantly proliferated by the long-term intake of Jeju water and by 0.245 μM NaVO(3) treatment, and the expansion of B cells accounted for the increased number of splenocytes. Also, 0.245 μM NaVO(3) treatment showed the potency to amplify the production of IFN-γ and total IgG in irradiated splenocytes, which correlated with the expansion of B cells. Collectively, Jeju water containing vanadium possesses the immune activation property against damages caused by γ-irradiation.

  4. Differential expression of cancer pathway-related genes in low-versus high-dose-rate-irradiated AKR/J mice

    NASA Astrophysics Data System (ADS)

    Jong Bong, Jin; Kang, Yu Mi; Shin, Suk Chul; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun

    2012-11-01

    To understand the biological effects of ionizing radiation on lymphomagenesis, we reared AKR/J mice for 130 days with exposure to either high-dose-rate (HDR, 0.8 Gy/min, a single dose of 4.5 Gy) or low-dose-rate (LDR, 0.7 mGy/h, a cumulative dose of 2.1 Gy) irradiation. After 130 days, we compared the mean thymus weight, analyzed the histological changes, and measured apoptotic cell numbers using the terminal deoxynucleotidyl transferase-mediated dUTP-end labeling (TUNEL) assay. We also used microarrays and quantitative polymerase chain reaction analysis (qPCR) to analyze the expression profiles of cancer pathway-related genes in the thymuses of the mice. The mean thymus weight of the LDR-irradiated mice decreased relative to Sham- and HDR-irradiated mice. Histopathological examination revealed that the neoplastic cells in the thymuses of the Sham- and HDR-irradiated mice were pleomorphic, with marked anisocytosis and anisokaryosis, whereas the cells and their nuclei were relatively small and uniform in size in the LDR-irradiated mice. Furthermore, TUNEL assays showed that the number of apoptotic cells was higher in the LDR-irradiated mice than in the Sham- and HDR-irradiated mice. Microarray analysis showed differentially expressed genes according to carcinogenic stage (DNA repair/genomic instability, DNA damage signaling pathway, cell cycle, cancer pathway, p53 signaling pathway, apoptosis, and T- and B-cell activation). qPCR data for cancer pathway-related genes showed that Cds1 gene expression was upregulated in the LDR-irradiated mice, whereas expression of the Itga4, Myc, and Itgb1 genes was upregulated in the irradiated mice. However, the functions of cancer pathway-related genes require further study and validation.

  5. Cell cycle of primitive hematopoietic progenitors decelerated in senescent mice is reactively accelerated after 2-Gy whole-body irradiation

    PubMed Central

    Tsuboi, Isao; Kuramoto, Kazunao; Kusunoki, Yoichiro; Inoue, Tohru

    2016-01-01

    Aging is considered to be a functional retardation of continuous xenobiotic responses over a lifetime after the developmental period; thus, the effects of ionizing radiation over a lifetime may be somewhat accounted for by a modifier of aging effects. This study was conducted to evaluate the possible/synergic effects of radiation during aging by determining cell-cycle parameters of hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs), such as the percent of cells in cycling, the generation doubling time, and the cumulative cycling-cell fraction, by bromodeoxyuridine-ultraviolet assay, which enables the determination of their cycling capacity in vivo. Colony-forming progenitor cells, such as colony-forming unit (CFU)-granulocyte/macrophage (GM), CFU in the spleen on day 9 (CFU-S9), and CFU-S on day 13 (CFU-S13) for mature, less mature, and immature HPCs, respectively, were evaluated in young and old mice (6 weeks and 21 months of age, respectively) with or without 2-Gy whole-body irradiation and a 4-week recovery period. Then, cell-cycle parameters were evaluated and compared. As a result, the generation doubling time of all types of HPC was prolonged by the irradiation in both young and old mouse groups, except that of CFU-S13 in old mice, which showed acceleration of the cell cycle following the irradiation. In addition, only CFU-S13 in irradiated old mice showed a significant increase in the cumulative cycling-cell-fraction ratio. Significant changes due to the effects of aging and irradiation on HPCs were observed only in the immature HPCs, i.e., the cell cycle of immature HPCs was suppressed by aging without irradiation and was, in contrast, accelerated as the cells recovered from radiation-induced damage. This suggests that the mechanisms of peripheral blood recovery after 2-Gy whole-body irradiation are markedly different between young and old mice, although 21-month-old mice showed almost the same level of recovery as the young mice. PMID

  6. Androgens Attenuate Vitamin D Production Induced by UVB Irradiation of the Skin of Male Mice by an Enzymatic Mechanism.

    PubMed

    Xue, Yingben; Ying, Lee; Horst, Ronald L; Watson, Gordon; Goltzman, David

    2015-12-01

    Cutaneous exposure to UVB irradiation is an important source of vitamin D. Here, we examined sex-specific differences in cutaneous vitamin D production in mice. Both male and female mice on a vitamin D-deficient diet manifested vitamin D deficiency, with mineral abnormalities, secondary hyperparathyroidism, and osteomalacia. UVB irradiation significantly increased vitamin D levels in the skin of female mice and normalized serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, as well as mineral and skeletal abnormalities. However, in male mice, the vitamin D response to UVB was attenuated and mineral and skeletal abnormalities were not normalized. The vitamin D precursor, 7-dehydrocholesterol (7DHC), was significantly lower in the skin of male than female mice. This reduction was due to local androgen action in the skin as demonstrated by castration studies and skin-specific androgen receptor deletion in male mice, both of which reversed the male phenotype. Local androgen regulation in the skin of the CYP11A1 gene, which encodes a crucial enzyme that metabolizes cholesterol, 7DHC, and vitamin D, appeared to contribute to the gender differences in UVB-induced vitamin D production and to its reversal of vitamin D deficiency. Sex-specific, enzymatically regulated differences in cutaneous production of vitamin D may therefore be of importance to ensure vitamin D sufficiency.

  7. Transient infiltration of neutrophils into the thymus following whole-body X-ray irradiation in IL-10 knockout mice

    SciTech Connect

    Fujiwara, Hiroya; Yamazaki, Takahiro; Uzawa, Akiko; Nagata, Kisaburo; Kobayashi, Yoshiro

    2008-05-02

    IL-10 is known to suppress the inflammatory responses in a variety of experimental models. Because we previously found that whole-body X-irradiation causes massive apoptosis in the thymus and transient infiltration of neutrophils, in this study, we examined whether or not IL-10 is involved in the regulation of neutrophil infiltration upon whole-body X-ray irradiation using IL-10 knockout mice. Although IL-10 was induced in the thymus on whole-body X-ray irradiation, apoptosis of thymocytes, neutrophil infiltration, and MIP-2 and KC production in the thymus were not affected by an IL-10 deficiency. Coculturing of bone marrow-derived macrophages with late apoptotic cells caused MIP-2 production, which was also not affected by an IL-10 deficiency. These results suggest the uniqueness of the inflammatory response induced by whole-body X-ray irradiation, which does not seem to be regulated by IL-10.

  8. Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice

    PubMed Central

    Hougaard, Karin S; Jensen, Keld A; Nordly, Pernille; Taxvig, Camilla; Vogel, Ulla; Saber, Anne T; Wallin, Håkan

    2008-01-01

    Background Results from epidemiological studies indicate that particulate air pollution constitutes a hazard for human health. Recent studies suggest that diesel exhaust possesses endocrine activity and therefore may affect reproductive outcome. This study in mice aimed to investigate whether exposure to diesel exhaust particles (DEP; NIST 2975) would affect gestation, postnatal development, activity, learning and memory, and biomarkers of transplacental toxicity. Pregnant mice (C57BL/6; BomTac) were exposed to 19 mg/m3 DEP (~1·106 particles/cm3; mass median diameter ≅ 240 nm) on gestational days 9–19, for 1 h/day. Results Gestational parameters were similar in control and diesel groups. Shortly after birth, body weights of DEP offspring were slightly lower than in controls. This difference increased during lactation, so by weaning the DEP exposed offspring weighed significantly less than the control progeny. Only slight effects of exposure were observed on cognitive function in female DEP offspring and on biomarkers of exposure to particles or genotoxic substances. Conclusion In utero exposure to DEP decreased weight gain during lactation. Cognitive function and levels of biomarkers of exposure to particles or to genotoxic substances were generally similar in exposed and control offspring. The particle size and chemical composition of the DEP and differences in exposure methods (fresh, whole exhaust versus aged, resuspended DEP) may play a significant role on the biological effects observed in this compared to other studies. PMID:18331653

  9. Protective efficacy of semi purified fraction of high altitude podophyllum hexandrum rhizomes in lethally irradiated Swiss albino mice.

    PubMed

    Gupta, M L; Tyagi, S; Flora, S J S; Agrawala, P K; Choudhary, P; Puri, S C; Sharma, A; Devi, M; Haksar, A; Qazi, G N; Tripathi, R P

    2007-05-30

    A fraction of high altitude Podophyllum hexandrum rhizome, REC-2006, was evaluated for its radioprotective efficacy against lethal gamma-irradiation (10 Gy, whole body) in Swiss albino mice. The maximum tolerated dose (MTD) and LD50 of this fraction were found to be 45 mg/kg b.w. and 74 mg/kg b.w. respectively. Pre-irradiation (- 2 h, ) administration (i.p.) of 6 or 8 mg/kg b.w. of REC-2006 rendered > 90% survival in lethally irradiated mice. The dose reduction factor was calculated to be 1.62 considering survival as the end point. REC-2006 treatment marked in significant increase in endogenous spleen colony forming units. In REC-2006 treated group, super oxide dismutase activity was increased significantly compared to the radiation control group (Liver, p = 0.00, Jejunum p = 0.00). The extract also inhibited radiation induced lipid peroxidation in liver (p = 0.00) at 24 h. REC-2006 administration (100-200 microg/ml) significantly reduced the halo diameter in mice thymocytes. Nearly 10 fold difference between the effective dose (6 mg/kg b.w.) and LD50 and the high degree of whole body survival (> 90% against 10 Gy irradiation) indicates REC-2006 to be safe and highly promising to achieve significant radioprotection against lethal radiation. Further purification and identification of active molecules and their efficacy studies in higher animals therefore demand attention.

  10. Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation

    PubMed Central

    Oba, Chisato; Morifuji, Masashi; Ichikawa, Satomi; Ito, Kyoko; Kawahata, Keiko; Yamaji, Taketo; Asami, Yukio; Itou, Hiroyuki; Sugawara, Tatsuya

    2015-01-01

    Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM) improved the water content of the stratum corneum (SC) in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation. PMID:26302442

  11. Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation.

    PubMed

    Oba, Chisato; Morifuji, Masashi; Ichikawa, Satomi; Ito, Kyoko; Kawahata, Keiko; Yamaji, Taketo; Asami, Yukio; Itou, Hiroyuki; Sugawara, Tatsuya

    2015-01-01

    Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM) improved the water content of the stratum corneum (SC) in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation. PMID:26302442

  12. Prenatal Care.

    ERIC Educational Resources Information Center

    Office of Child Development (DHEW), Washington, DC.

    Initially published by the Children's Bureau in 1913, this pamphlet has been revised frequently. Its purpose is to point out the importance of medical care during pregnancy. Comfortable pregnancies, easy labor, and better care for their new infants are the usual concerns of prospective mothers. Consequently, this 1962 edition of "Prenatal Care"…

  13. Prenatal Care.

    ERIC Educational Resources Information Center

    Health Resources and Services Administration (DHHS/PHS), Rockville, MD. Office for Maternal and Child Health Services.

    This booklet is the first in a series of publications designed to provide parents with useful information about childrearing. Contents are organized into three parts. Part I focuses on the pregnancy, prenatal care, development of the baby, pregnant lifestyles, nutrition, common discomforts, and problems of pregnancy. Part II provides information…

  14. Neurochemical effects of a 20 kHz magnetic field on the central nervous system in prenatally exposed mice

    SciTech Connect

    Dimberg, Y.

    1995-09-01

    C57/B1 mice were exposed during pregnancy (gestation days 0--19) to a 20 kHz magnetic field (MF). The asymmetric sawtooth-waveform magnetic field in the exposed racks had a flux density of 15 {micro}T (peak to peak). After 19 days, the exposure was terminated, and the mice were housed individually under normal laboratory conditions. On postnatal day (PD) 1, PD21, and PD308, various neurochemical markers in the brains of the offspring were investigated and the brains weighed. No significant difference was found in the whole brain weight at PD1 or PD21 between exposed offspring and control animals. However, on PD308, a significant decrease in weight of the whole brain was detected in exposed animals. No significant differences were found in the weight of cortex, hippocampus, septum, or cerebellum on nay of the sampling occasions, nor were any significant differences detected in protein-, DNA-level, nerve growth factor (NGF), acetylcholine esterase- (AChE), or 2{prime},3{prime}-cyclic nucleotide 3{prime}-phosphodiesterase- (CNP; marker for oligodendrocytes) activities on PD21 in cerebellum. Cortex showed a more complex pattern of response to MF: MF treatment resulted in a decrease in DNA level and increases in the activities of CNP, AChE, and NGF protein. On PD308, the amount of DNA was significantly reduced in MF-treated cerebellum and CNP activity was still enhanced in MF-treated cortex compared to controls. Most of the effect of MF treatment during the embryonic period were similar to those induced by ionizing radiation but much weaker. However, the duration of the exposure required to elucidate the response of different markers to MF seems to be greater and effects appear later during development compared to responses to ionizing radiation.

  15. Abrogation of resistance to Theiler's virus-induced demyelination in C57BL mice by total body irradiation.

    PubMed

    Rodriguez, M; Patick, A K; Pease, L R

    1990-03-01

    Theiler's murine encephalitis virus (TMEV) produces an unusual biphasic disease in susceptible mice characterized by poliomyelitis with early viral replication in neurons, followed by chronic demyelination with viral antigen expression in spinal cord white matter. In addition, infectious virus persists in the central nervous system (CNS) throughout the chronic phase of disease. Previous studies have indicated an important role for major histocompatibility complex (MHC)-gene products in determining resistance/susceptibility to disease. In particular, certain class I gene products of the D region of the H-2 gene complex render mice of the C57BL lineage resistant to induction of demyelination. Intracerebral infection of B10.S(DS) mice results in demyelination in the spinal cord while infection of C57BL/10(Db) or B10.S(9R)(Dd) fails to produce white matter destruction. In this study we showed that immunosuppression with gamma irradiation renders normally resistant B10.S(9R) and C57BL/10 mice susceptible to TMEV-induced demyelination and allowed for increased viral replication. In addition, the majority of irradiated C57BL/10 mice infected with virus showed extensive areas of CNS remyelination by oligodendrocytes beginning at 63 days post-infection. In contrast, immunosuppression of normally susceptible B10.S mice resulted in acute disease and high mortality accompanied by overwhelming destruction of neurons. The study supports the hypothesis that MHC-conferred resistance in C57BL mice is associated with MHC D region products and indicate an important active role for the immune system early in infection in limiting vital infection during disease induction in nonimmunosuppressed mice.

  16. RBE for late somatic effects in mice irradiated with 60 MeV protons relative to X-rays.

    NASA Technical Reports Server (NTRS)

    Darden, E. B., Jr.; Clapp, N. K.; Bender, R. S.; Jernigan, M. C.; Upton, A. C.

    1971-01-01

    Investigation of the relative biological effectiveness of energetic protons for the induction of somatic effects in a mammal (mice) following whole body irradiation. The proton energy used approximates the mean energy for proton spectra accompanying solar events. The effects on longevity and the incidence of major neoplastic diseases are summarized. The results obtained suggest that medium energy proton irradiation is no more effective, and on the whole, probably less effective, than conventional X radiation for the induction of late radiation effects in the mouse.

  17. Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice

    SciTech Connect

    Hakkinen, P.J.; Whiteley, J.W.; Witschi, H.R.

    1982-08-01

    The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity.

  18. M cells and granular mononuclear cells in Peyer's patch domes of mice depleted of their lymphocytes by total lymphoid irradiation

    SciTech Connect

    Ermak, T.H.; Steger, H.J.; Strober, S.; Owen, R.L.

    1989-03-01

    The cytoarchitecture of Peyer's patches that were depleted of their lymphocytes by total lymphoid irradiation (TLI) was examined with particular attention to the effects on M cells in the follicle epithelium and on mononuclear cells in follicle domes underlying the epithelium. Five-month-old, specific pathogen-free Balb/c mice were irradiated with 200-250 rad/day, five times a week to a total dose of 3400-4250, and their Peyer's patches were either fixed for electron microscopy or frozen for immunohistochemistry 1-4 days after completion of irradiation. Control mice were examined at the same time intervals. Follicle domes of TLI mice had approximately one fourth the epithelial surface area of domes of control mice. Within the epithelium, lymphoid cells were virtually depleted after TLI, and yet the epithelium contained M cells. In control mice, most M cells were accompanied by lymphoid cells in invaginations of the apical-lateral cell membrane. In TLI mice, most M cells did not have such apical-lateral invaginations and were columnar shaped. Other than lacking lymphocytes, these cells appeared to be mature M cells. Some M cells did have lymphoid cells or granular mononuclear cells below their basal membranes, adjacent to the basal lamina. Below the epithelium, the proportion of granular mononuclear cells was greatly increased following TLI. The retention of M cells and the increase in proportion of granular mononuclear cells in follicle domes are consistent with selective depletion of lymphocytes following TLI. Persistence of M cells without lymphocytic invaginations after TLI suggests that M cells can differentiate in the absence of, or at least in the presence of very few, lymphocytes, and that invagination by lymphocytes is not necessary to maintain mature M cell morphology.

  19. 2.45 GHz microwave irradiation-induced oxidative stress affects implantation or pregnancy in mice, Mus musculus.

    PubMed

    Shahin, Saba; Singh, Vineet Prakash; Shukla, Ritesh K; Dhawan, Alok; Gangwar, Ravi Kumar; Singh, Surya Pal; Chaturvedi, Chandra Mohini

    2013-03-01

    The present experiment was designed to study the 2.45 GHz low-level microwave (MW) irradiation-induced stress response and its effect on implantation or pregnancy in female mice. Twelve-week-old mice were exposed to MW radiation (continuous wave for 2 h/day for 45 days, frequency 2.45 GHz, power density=0.033549 mW/cm(2), and specific absorption rate=0.023023 W/kg). At the end of a total of 45 days of exposure, mice were sacrificed, implantation sites were monitored, blood was processed to study stress parameters (hemoglobin, RBC and WBC count, and neutrophil/lymphocyte (N/L) ratio), the brain was processed for comet assay, and plasma was used for nitric oxide (NO), progesterone and estradiol estimation. Reactive oxygen species (ROS) and the activities of ROS-scavenging enzymes- superoxide dismutase, catalase, and glutathione peroxidase-were determined in the liver, kidney and ovary. We observed that implantation sites were affected significantly in MW-irradiated mice as compared to control. Further, in addition to a significant increase in ROS, hemoglobin (p<0.001), RBC and WBC counts (p<0.001), N/L ratio (p<0.01), DNA damage (p<0.001) in brain cells, and plasma estradiol concentration (p<0.05), a significant decrease was observed in NO level (p<0.05) and antioxidant enzyme activities of MW-exposed mice. Our findings led us to conclude that a low level of MW irradiation-induced oxidative stress not only suppresses implantation, but it may also lead to deformity of the embryo in case pregnancy continues. We also suggest that MW radiation-induced oxidative stress by increasing ROS production in the body may lead to DNA strand breakage in the brain cells and implantation failure/resorption or abnormal pregnancy in mice.

  20. Resistance induced by normal and irradiated Schistosoma mansoni: ability of various worm stages to serve as inducers and targets in mice

    SciTech Connect

    Dean, D.A.; Cioli, D.; Bukowski, M.A.

    1981-09-01

    Lung stage schistosomula exposed to 50 kilorads of gamma irradiation induced significant resistance to challenge infection with Schistosoma mansoni following intravenous (tail or mesenteric vein), intramuscular, or intraperitoneal injection into mice. Similar or higher levels were induced with irradiated cercariae, while irradiated 3- or 4-week-old worms induced little resistance. Non-irradiated day 6 and day 12 lung schistosomula injected into mice immunized with irradiated cercariae were susceptible to elimination, though to a lesser extent than a challenge infection administered at the cercarial stage. Day 20 liver worms injected into a mesenteric vein were not susceptible to irradiated cercaria-induced resistance. In contrast, cercariae, day 6 lung schistosomula, day 12 lung schistosomula and day 20 liver worms were all susceptible to the resistance induced by a chronic (non-irradiated) infection.

  1. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-05-15

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  2. Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice.

    PubMed

    Murakami, Hitoshi; Shimbo, Kazutaka; Inoue, Yoshiko; Takino, Yoshinobu; Kobayashi, Hisamine

    2012-06-01

    Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that chronic UV irradiation decreases collagen amounts and induces wrinkle formation. Amino acids are generally known to regulate protein metabolism. Therefore, we investigated the effects of UV irradiation and various orally administered amino acids on skin collagen synthesis rates. Groups of 4-5 male, 8-week-old HR-1 hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen was evaluated by incorporating L-[ring-2H5]-phenylalanine. We confirmed that the FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal tropocollagen was measured 30 min after a single oral administration of amino acids (1 g/kg) to groups of 5-16 UVB-irradiated mice. Branched-chain amino acids (BCAA, 1.34±0.32), arginine (Arg, 1.66±0.39), glutamine (Gln, 1.75±0.60), and proline (Pro, 1.48±0.26) did not increase the FSR of skin tropocollagen compared with distilled water, which was used as a control (1.56±0.30). However, essential amino acids mixtures (BCAA+Arg+Gln, BCAA+Gln, and BCAA+Pro) significantly increased the FSR (2.07±0.58, 2.04±0.54, 2.01±0.50 and 2.07±0.59, respectively). This result suggests that combinations of BCAA and glutamine or proline are important for restoring dermal collagen protein synthesis impaired by UV irradiation.

  3. Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

    SciTech Connect

    Edmondson, Elijah F.; Hunter, Nancy R.; Weil, Michael M.; Mason, Kathryn A.

    2015-07-15

    Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor

  4. Full reconstitution of the immune deficiency in scid mice with normal stem cells requires low-dose irradiation of the recipients

    SciTech Connect

    Fulop, G.M.; Phillips, R.A.

    1986-06-15

    Mice homozygous for an autosomal recessive mutation for the scid gene exhibit a defect that specifically impairs lymphoid differentiation but not myelopoiesis. Such mice can be cured of their lymphoid deficiency by grafts with normal bone marrow, although full reconstitution of lymphoid function is seldom obtained. Long-term bone marrow cultures (LTBMC) are devoid of all mature B and pre-B cells but contain lymphoid stem cells. We therefore reconstituted scid mice with LTBMC cells to study the kinetics of B lymphocyte reconstitution in normal and irradiated (4 Gy) scid recipients and in irradiated (9.5 Gy) co-isogenic C.B-17 mice. Detectable colony-forming B cells rapidly increased in the spleen and bone marrow of irradiated C.B-17 and irradiated scid recipients, reaching normal levels between 4 and 6 wk post-grafting. Unirradiated scid recipients showed limited reconstitution in spleen and very poor reconstitution in bone marrow. Unirradiated scid recipients also had relatively few surface Ig+ cells in spleen or bone marrow, whereas both groups of irradiated recipients had normal numbers between 4 and 6 wk post-reconstitution. Normal levels of cytotoxic T cell activity by 8 wk after reconstitution were observed only in the irradiated C.B-17 and irradiated scid recipients. Analysis of mice reconstituted with cells from LTBMC indicates that these cultures contain lymphoid stem cells with significant proliferative and self-renewal potential, and that full reconstitution of lymphoid function requires prior irradiation of the scid recipient.

  5. Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice

    PubMed Central

    Gutiérrez-Torres, Daniela Sarahí; González-Horta, Carmen; Del Razo, Luz María; Infante-Ramírez, Rocío; Ramos-Martínez, Ernesto; Levario-Carrillo, Margarita; Sánchez-Ramírez, Blanca

    2015-01-01

    Inorganic arsenic (iAs) exposure induces a decrease in glucose type 4 transporter (GLUT4) expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2) exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n = 15) were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P < 0.01) and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P < 0.05) in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups. PMID:26339590

  6. Effects of prenatal exposure to extremely low electro-magnetic field on in vivo derived blastocysts of mice

    PubMed Central

    Bayat, Parvin-Dokht; Darabi, Mohmmad Reza; Ghanbari, Ali; Amiri, Sara; Sohouli, Pardis

    2012-01-01

    Background: Indisputable population exposure to widespread electromagnetic fields, has grown concerns over the probable health effects of these fields. Objective: The present study was aimed to examine the possible effects of 50 Hz extremely low frequency electromagnetic field (ELF-EMF) exposure on the number and quality of mice blastocysts. Materials and Methods: In present study, 66 NMRI pregnant females divided into two treated and non-treated groups. The treated group exposed to ELF-EMF (50 Hz and 6×10-3 T). Subsequently, embryos were collected by flushing the uterine horn and Fallopian tubes on the day 3 of gestation. Number of trophoectoderm (TE) and Inner Cell Mass (ICM) cells in blastocysts were determined after differential nuclei staining using a modified method. Furthermore, number of all flushed blastocysts calculated in each group. Results: There was no significant difference in mean number of blastocysts in treated (6.64±1.34) and none treated (8.22±1.59) groups. In treated group, there were significant decreased in total cell number of blastocysts (p=0.000), number of ICM cells (p=0.000), and number of TE cells (p=0.001) whereas the ratio of ICM/TE cells increased (p=0.002). Conclusion: The data indicate that ELF-EMF is able to affect cellular composition of blastocysts, but it can't omit total volume of blastocysts. PMID:25246926

  7. Effect of whole-body irradiation of mice on the number of background plaque-forming cells

    SciTech Connect

    Anderson, R.E.; Lefkovits, I.; Soeederberg, A.

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  8. Effect of whole-body irradiation of mice on the number of background plaque-forming cells.

    PubMed

    Anderson, R E; Lefkovits, I; Söederberg, A

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  9. Anti-inflammatory activities of light emitting diode irradiation on collagen-induced arthritis in mice (a secondary publication)

    PubMed Central

    Ohta, Mitsuhiro; Sato, Yusuke; Abiko, Yoshimitsu

    2014-01-01

    Background and aims: Rheumatoid arthritis (RA) is an auto-immune disease afflicting multiple joints of the body, where as a result of the increase in inflammatory cytokines and tissue destructive factors such as matrix metalloproteinase (MMP)-3, deterioration of the bones and cartilages of the joints occurs. The present investigation was carried out to study the anti-inflammatory activities of light emitting diode (LED) irradiation on hind paw inflammation in collagen-induced arthritis (CIA) mice models. Materials and method: RA in the CIA mouse model was induced by immunization of DBA/1J mice with intradermal injections of an emulsion of bovine type II collagen and complete Freund's adjuvant. A total of 20 CIA mice were subdivided into the following groups: control group, CIA group and 2 groups of LED irradiated CIA mice (LED groups) (n=5 per group). The mouse knee joint area in the LED groups (the 570 nm and 940 nm groups) was irradiated with LED energy, three times a week for 500 s per session over 8 weeks at a dose of 5 J/cm2. The hind paw swelling was assessed by the increase in hind paw thickness. The serum levels of the inflammatory cytokines and arthritic factor MMP-3 were determined with an enzyme-linked immunosorbent assay (ELISA). Results: In the LED-570 and LED-940 groups at 4 weeks after arthritis induction, the swelling inhibition index was 18.1±4.9 and 29.3±4.0 respectively. Interleukin (IL)-1β, IL-6 and MMP-3 serum levels were significantly lower in the LED-940 group. Conclusions: LED irradiation, particularly in the near-infrared was effective for inhibition of the inflammatory reactions caused by RA. PMID:25368445

  10. Pilot-Scale Pulsed UV Light Irradiation of Experimentally Infected Raspberries Suppresses Cryptosporidium parvum Infectivity in Immunocompetent Suckling Mice.

    PubMed

    Le Goff, L; Hubert, B; Favennec, L; Villena, I; Ballet, J J; Agoulon, A; Orange, N; Gargala, G

    2015-12-01

    Cryptosporidium spp., a significant cause of foodborne infection, have been shown to be resistant to most chemical food disinfectant agents and infective for weeks in irrigation waters and stored fresh vegetal produce. Pulsed UV light (PL) has the potential to inactivate Cryptosporidium spp. on surfaces of raw or minimally processed foods or both. The present study aimed to evaluate the efficacy of PL on viability and in vivo infectivity of Cryptosporidium parvum oocysts present on raspberries, a known source of transmission to humans of oocyst-forming apicomplexan pathogens. The skin of each of 20 raspberries was experimentally inoculated with five 10-μl spots of an oocyst suspension containing 6 × 10(7) oocysts per ml (Nouzilly isolate). Raspberries were irradiated by PL flashes (4 J/cm(2) of total fluence). This dose did not affect colorimetric or organoleptic characteristics of fruits. After immunomagnetic separation from raspberries, oocysts were bleached and administered orally to neonatal suckling mice. Seven days after infection, mice were euthanized, and the number of oocysts in the entire small intestine was individually assessed by immunofluorescence flow cytometry. Three of 12 and 12 of 12 inoculated mice that received 10 and 100 oocysts isolated from nonirradiated raspberries, respectively, were found infected. Four of 12 and 2 of 12 inoculated mice that received 10(3) and 10(4) oocysts from irradiated raspberries, respectively, were found infected. Oocyst counts were lower in animals inoculated with 10(3) and 10(4) oocysts from irradiated raspberries (92 ± 144 and 38 ± 82, respectively) than in animals infected with 100 oocysts from nonirradiated raspberries (35,785 ± 66,221, P = 0.008). PL irradiation achieved oocyst reductions of 2 and 3 log for an inoculum of 10(3) and 10(4) oocysts, respectively. The present pilot-scale evaluation suggests that PL is an effective mode of decontamination for raspberries and prompts further applicability

  11. Pilot-Scale Pulsed UV Light Irradiation of Experimentally Infected Raspberries Suppresses Cryptosporidium parvum Infectivity in Immunocompetent Suckling Mice.

    PubMed

    Le Goff, L; Hubert, B; Favennec, L; Villena, I; Ballet, J J; Agoulon, A; Orange, N; Gargala, G

    2015-12-01

    Cryptosporidium spp., a significant cause of foodborne infection, have been shown to be resistant to most chemical food disinfectant agents and infective for weeks in irrigation waters and stored fresh vegetal produce. Pulsed UV light (PL) has the potential to inactivate Cryptosporidium spp. on surfaces of raw or minimally processed foods or both. The present study aimed to evaluate the efficacy of PL on viability and in vivo infectivity of Cryptosporidium parvum oocysts present on raspberries, a known source of transmission to humans of oocyst-forming apicomplexan pathogens. The skin of each of 20 raspberries was experimentally inoculated with five 10-μl spots of an oocyst suspension containing 6 × 10(7) oocysts per ml (Nouzilly isolate). Raspberries were irradiated by PL flashes (4 J/cm(2) of total fluence). This dose did not affect colorimetric or organoleptic characteristics of fruits. After immunomagnetic separation from raspberries, oocysts were bleached and administered orally to neonatal suckling mice. Seven days after infection, mice were euthanized, and the number of oocysts in the entire small intestine was individually assessed by immunofluorescence flow cytometry. Three of 12 and 12 of 12 inoculated mice that received 10 and 100 oocysts isolated from nonirradiated raspberries, respectively, were found infected. Four of 12 and 2 of 12 inoculated mice that received 10(3) and 10(4) oocysts from irradiated raspberries, respectively, were found infected. Oocyst counts were lower in animals inoculated with 10(3) and 10(4) oocysts from irradiated raspberries (92 ± 144 and 38 ± 82, respectively) than in animals infected with 100 oocysts from nonirradiated raspberries (35,785 ± 66,221, P = 0.008). PL irradiation achieved oocyst reductions of 2 and 3 log for an inoculum of 10(3) and 10(4) oocysts, respectively. The present pilot-scale evaluation suggests that PL is an effective mode of decontamination for raspberries and prompts further applicability

  12. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice

    PubMed Central

    Kim, Ha Neui; Gil, Chan Hee; Kim, Yu Ri; Shin, Hwa Kyoung; Choi, Byung Tae

    2016-01-01

    We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation. PMID:27484958

  13. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice.

    PubMed

    Kim, Ha Neui; Gil, Chan Hee; Kim, Yu Ri; Shin, Hwa Kyoung; Choi, Byung Tae

    2016-01-01

    We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation. PMID:27484958

  14. Incidence of acute myeloid leukemia and hepatocellular carcinoma in mice irradiated with 1 GeV/nucleon (56)Fe ions.

    PubMed

    Weil, Michael M; Bedford, Joel S; Bielefeldt-Ohmann, Helle; Ray, F Andrew; Genik, Paula C; Ehrhart, Eugene J; Fallgren, Christina M; Hailu, Fitsum; Battaglia, Christine L R; Charles, Brad; Callan, Matthew A; Ullrich, Robert L

    2009-08-01

    Abstract Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the leukemogenic efficacy of one such HZE species, 1 GeV (56)Fe ions, a component of space radiation, in a mouse model for radiation-induced acute myeloid leukemia. CBA/CaJ mice were irradiated with 1 GeV/nucleon (56)Fe ions or (137)Cs gamma rays and followed until they were moribund or to 800 days of age. We found that 1 GeV/nucleon (56)Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia (AML). However, (56)Fe-ion-irradiated mice had a much higher incidence of hepatocellular carcinoma (HCC) than gamma-irradiated mice, with an estimated RBE of approximately 50. These data suggest a difference in the effects of HZE iron ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. PMID:19630525

  15. Prenatal alcohol exposure retards the migration and development of serotonin neurons in fetal C57BL mice.

    PubMed

    Zhou, F C; Sari, Y; Zhang, J K; Goodlett, C R; Li, T

    2001-02-28

    Incomplete neural tube fusion (iNTF), induced by alcohol, in midline floor and roof plates was found in our recent study. In this study, serotonin (5-HT) neurons, known to be born entirely in the midline raphe at brainstem, were examined during their development with fetal alcohol exposure. Weight-matched C57BL mice pregnant dams were divided into three groups on E8: one received ethanol via a chocolate Sustacal liquid diet providing 20% ethanol-derived calories as the sole source of nutrients (ALC); the second received an isocaloric Sustacal liquid diet and was pair-fed to individual dams in the ethanol-fed group (PF); the third was fed ad lib rat chow (Chow). Fetal brains were obtained on E15 and were processed for immunostaining of 5-HT and its trophic factor, S100 beta. The ascending 5-HT neurons, in normal development, appear bilaterally near midline on E12, and by E15, as seen in chow and PF groups, migrate from the midline germinal zone laterally and dorsally to their final position with rich fibers. In contrast, in the E15 ALC group, many 5-HT-im neurons were found remaining in the midline germinal region or had migrated, but with under-differentiated, sparse fibers. There were 20--30% fewer 5-HT-im neurons in ALC as compared to PF and Chow. In addition, the number of S100 beta cells was less in ALC as compared with PF and Chow groups. No difference was found between PF and Chow in number of 5-HT-im or S100 beta-im cells. The 5-HT neurons found compromised in migration and differentiation may, in part, stem from failure of access to floor plate or midline tissue induction and the insufficient support by S100 beta. As 5-HT neurons have been implicated for signaling brain maturation, fewer 5-HT neurons may have lasting effects on the development of brain or, if persistent in the adult, profoundly affect adult brain function.

  16. Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body γ-irradiation in mice via restoration of hematopoietic tissues

    PubMed Central

    Ghoneum, Mamdooh; Badr El-Din, Nariman K.; Abdel Fattah, Salma M.; Tolentino, Lucilene

    2013-01-01

    The aim of the current study is to examine the protective effect of MGN-3 on overall maintenance of hematopoietic tissue after γ-irradiation. MGN-3 is an arabinoxylan from rice bran that has been shown to be a powerful antioxidant and immune modulator. Swiss albino mice were treated with MGN-3 prior to irradiation and continued to receive MGN-3 for 1 or 4 weeks. Results were compared with mice that received radiation (5 Gy γ rays) only, MGN-3 (40 mg/kg) only and control mice (receiving neither radiation nor MGN-3). At 1 and 4 weeks post-irradiation, different hematological, histopathological and biochemical parameters were examined. Mice exposed to irradiation alone showed significant depression in their complete blood count (CBC) except for neutrophilia. Additionally, histopathological studies showed hypocellularity of their bone marrow, as well as a remarkable decrease in splenic weight/relative size and in number of megakaryocytes. In contrast, pre-treatment with MGN-3 resulted in protection against irradiation-induced damage to the CBC parameters associated with complete bone marrow cellularity, as well as protection of the aforementioned splenic changes. Furthermore, MGN-3 exerted antioxidative activity in whole-body irradiated mice, and provided protection from irradiation-induced loss of body and organ weight. In conclusion, MGN-3 has the potential to protect progenitor cells in the bone marrow, which suggests the possible use of MGN-3/Biobran as an adjuvant treatment to counteract the severe adverse side effects associated with radiation therapy. PMID:23287771

  17. Sequential appearance of T-cell receptor gamma delta- and alpha beta-bearing intestinal intra-epithelial lymphocytes in mice after irradiation.

    PubMed

    Yoshikai, Y; Ishida, A; Murosaki, S; Ando, T; Nomoto, K

    1991-12-01

    We have previously reported that T-cell receptor (TcR) gamma delta-bearing T cells precede TcR alpha beta-bearing T cells in appearance in the thymus after whole-body irradiation. In the present study, the kinetics of appearance of intestinal intra-epithelial lymphocytes (IEL) was examined in mice after whole-body irradiation with a lethal dose of 9.5 Gy or with a sublethal dose of 6 Gy. The number of CD3+ IEL decreased to the lowest value 4 days after irradiation with 9.5 Gy, and thereafter increased to half as many as the normal level by day 7. Thy-1+TcR alpha beta- IEL and Thy-TcR alpha beta- IEL recovered considerably by day 7 after the irradiation, whereas Thy-1+TcR alpha beta+ IEL and Thy-1+TcR alpha beta+ IEL hardly recovered at this stage. All mice died within 12 days after irradiation with a lethal dose of 9.5 Gy. On the other hand, when irradiation dose was decreased to 6 Gy, all mice survived beyond 40 days after irradiation. The number of CD3+ IEL recovered to the normal level by 10 days after irradiation with 6 Gy. Consistently with the results in mice irradiated with a lethal dose, the first cells to increase in IEL of mice irradiated with a sublethal dose were TcR gamma delta+ IEL expressing Thy-1 antigen. The number of Thy-1+TcR gamma delta+ IEL increased to approximately two-fold as many as that in normal mice by day 10, while TcR alpha beta+ IEL began to increase in number from day 20 after irradiation and recovered to the normal level by day 40 after irradiation. Thus, sequential appearance of TcR gamma delta+ and TcR alpha beta+ IEL was evident after irradiation, similar to that seen in the thymus after irradiation. The IEL on day 10 after a sublethal irradiation, which is composed mainly of Thy-1+TcR gamma delta+ IEL, exhibited a strong cytolytic activity against P815 in the presence of anti-CD3 mAb, suggesting that the early appearing Thy-1+TcR gamma delta+ IEL may play important roles in epithelial immunity at an early stage after irradiation.

  18. Localization of DNA damage and its role in altered antigen-presenting cell function in ultraviolet-irradiated mice

    PubMed Central

    1996-01-01

    Prior ultraviolet (UV) irradiation of the site of application of hapten on murine skin reduces contact sensitization, impairs the ability of dendritic cells in the draining lymph nodes (DLN) to present antigen, and leads to development of hapten-specific suppressor T lymphocytes. We tested the hypothesis that UV-induced DNA damage plays a role in the impaired antigen-presenting activity of DLN cells. First, we assessed the location and persistence of cells containing DNA damage. A monoclonal antibody specific for cyclobutyl pyrimidine dimers (CPD) was used to identify UV-damaged cells in the skin and DLN of C3H mice exposed to UV radiation. Cells containing CPD were present in the epidermis, dermis, and DLN and persisted, particularly in the dermis, for at least 4 d after UV irradiation. When fluorescein isothiocyanate (FITC) was applied to UV-exposed skin, the DLN contained cells that were Ia+, FITC+, and CPD+; such cells from mice sensitized 3 d after UV irradiation exhibited reduced antigen-presenting function in vivo. We then assessed the role of DNA damage in UV-induced modulation of antigen-presenting cell (APC) function by using a novel method of increasing DNA repair in mouse skin in vivo. Liposomes containing T4 endonuclease V (T4N5) were applied to the site of UV exposure immediately after irradiation. This treatment prevented the impairment in APC function and reduced the number of CPD+ cells in the DLN of UV- irradiated mice. Treatment of unirradiated skin with T4N5 in liposomes or treatment of UV-irradiated skin with liposomes containing heat- inactivated T4N5 did not restore immune function. These studies demonstrate that cutaneous immune cells sustain DNA damage in vivo that persists for several days, and that FITC sensitization causes the migration of these to the DLN, which exhibits impaired APC function. Further, they support the hypothesis that DNA damage is an essential initiator of one or more of the steps involved in impaired APC function

  19. Panax ginseng prevents apoptosis in hair follicles and accelerates recovery of hair medullary cells in irradiated mice.

    PubMed

    Kim, S H; Jeong, K S; Ryu, S Y; Kim, T H

    1998-01-01

    We studied the effect of the water fraction of Panax ginseng, one of traditional oriental medicine herbs on apoptosis and the formation of medullary cell in the hair follicles of irradiated mice. The hair follicle or its differentiated product, the hair, which represents a linear historical record of follicular proliferative activity, could provide a biological indicator of the effect of radioprotective drugs. Adult N:GP(s) mice with hair follicles synchronously in the middle of the hair growth cycle received whole-body doses of gamma-radiation. The hair follicles were analysed either 12 hours after irradiation with 2 Gy in the experiment on the apoptosis, or 3 days after irradiation with 3 Gy in the experiment on the forming medulla. The number of medullary cells per unit length (100 microns) were measured by H and E staining. Apoptosis was detected by a nonisotopic in situ DNA end-labeling (ISEL) technique and H and E stain applied to the serial histologic sections. Ginseng administration before irradiation resulted in a suppression of apoptosis, as shown by a reduced number of cells stained with ISEL for fragmented DNA, both i.p. (0.3 mg/head, p < 0.05) and p.o. (2 mg/ml of drinking water, p < 0.05) treatment. In addition, ginseng treatment was associated with an increase in the number of medullary cell per unit length as compared with the vehicle treated mice (p < 0.001, i.p.; p < 0.05, p.o.). These results indicate that the water fraction of ginseng can exert a potent effect on the recovery of the hair follicles by its combined effects on proliferation and apoptosis of the cells in the hair follicle. PMID:9627805

  20. Monoallelic Loss of the Imprinted Gene Grb10 Promotes Tumor Formation in Irradiated Nf1+/- Mice

    PubMed Central

    Mroue, Rana; Huang, Brian; Braunstein, Steve; Firestone, Ari J.; Nakamura, Jean L.

    2015-01-01

    Imprinted genes are expressed from only one parental allele and heterozygous loss involving the expressed allele is sufficient to produce complete loss of protein expression. Genetic alterations are common in tumorigenesis but the role of imprinted genes in this process is not well understood. In earlier work we mutagenized mice heterozygous for the Neurofibromatosis I tumor suppressor gene (NF1) to model radiotherapy-associated second malignant neoplasms that arise in irradiated NF1 patients. Expression analysis of tumor cell lines established from our mouse models identified Grb10 expression as widely absent. Grb10 is an imprinted gene and polymorphism analysis of cell lines and primary tumors demonstrates that the expressed allele is commonly lost in diverse Nf1 mutant tumors arising in our mouse models. We performed functional studies to test whether Grb10 restoration or loss alter fundamental features of the tumor growth. Restoring Grb10 in Nf1 mutant tumors decreases proliferation, decreases soft agar colony formation and downregulates Ras signaling. Conversely, Grb10 silencing in untransformed mouse embryo fibroblasts significantly increased cell proliferation and increased Ras-GTP levels. Expression of a constitutively activated MEK rescued tumor cells from Grb10-mediated reduction in colony formation. These studies reveal that Grb10 loss can occur during in vivo tumorigenesis, with a functional consequence in untransformed primary cells. In tumors, Grb10 loss independently promotes Ras pathway hyperactivation, which promotes hyperproliferation, an early feature of tumor development. In the context of a robust Nf1 mutant mouse model of cancer this work identifies a novel role for an imprinted gene in tumorigenesis. PMID:26000738

  1. Polysaccharide isolated from Parmelia tinctorum ameliorates ionizing irradiation-induced damage in mice

    PubMed Central

    Xu, Wenqing; Yang, Fujun; Shen, Xiu; Fan, Saijun; Liu, Qiang; Wang, Dezhi

    2014-01-01

    In this study, WPT-A, a type of water-soluble homogeneous lichen polysaccharide, was isolated and purified from Parmelia tinctorum. We investigated whether WPT-A has radioprotective effects when administered before total-body irradiation (TBI). Mice were treated with WPT-A via intraperitoneal injection (i.p.) once per day for three consecutive days prior to 7, 7.5, 8.5, 10 or 10.5-Gy TBI. Our results indicated that the survival rate was enhanced at a range of levels of TBI. The calculated dose reduction factor (DRF) was 1.2. White blood cell (WBC) counts, spleen colony forming units (CFU-S) and bone marrow nucleated cell (BMNC) counts were used to investigate the radioprotective effects of WPT-A on the hematopoietic system. The treatment groups received WPT-A at 20, 50 and 80 mg/kg b.w. doses before 6.5-Gy TBI and showed significantly higher BMNC and WBC counts compared with the radiation-only group. The groups administered 50 and 80 mg/kg b.w. WPT-A showed a significant increase in CFU-S compared with the radiation-only group. We also carried out a single cell gel electrophoresis assay to explore the radioprotective effects of WPT-A on DNA damage. The results from single-cell gel electrophoresis of peripheral blood leukocytes showed that WPT-A attenuated radiation-induced DNA damage. These results indicate a potential use for WPT-A as a radioprotector. PMID:24722682

  2. Induction of transplantation tolerance in mice across major histocompatibility barrier by using allogeneic thymus transplantation and total lymphoid irradiation

    SciTech Connect

    Waer, M.; Palathumpat, V.; Sobis, H.; Vandeputte, M. )

    1990-07-15

    The use of allogeneic thymus transplantation as a means of inducing tolerance across MHC barriers was investigated in thymectomized, total lymphoid irradiated BALB/c mice. In 90% of the animals long term outgrowth of histologically normal C57BL thymus grafts was observed. None of the latter animals was chimeric. All thymus graft-bearing mice showed specific nonresponsiveness for C57BL MHC Ag in mixed lymphocyte reaction and cell-mediated lympholysis. Spleen cells of the C57BL thymus-bearing mice were unable to induce lethal graft-vs-host disease in neonatal (BALB/c X C57BL) F1 mice but provoked a vigorous graft-vs-host disease reaction in (BALB/c x C3H) F1 neonates. Tolerant mice permanently accepted C57BL heart and pancreas grafts, but all rejected C3H grafts. Induction of tolerance of BALB/c pre-T cells through allogeneic thymus graft and/or specific suppressor cells seems to be involved. The present model offers new opportunities to study thymocyte maturation in a fully allogeneic environment and may yield applications for clinical organ transplantation.

  3. Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI)

    SciTech Connect

    Moscovitch, M.; Rosenmann, E.; Neeman, Z.; Slavin, S.

    1983-02-01

    The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders.

  4. TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice.

    PubMed

    Edin, Nina Jeppesen; Altaner, Čestmír; Altanerova, Veronica; Ebbesen, Peter

    2015-01-01

    Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation. PMID:26673923

  5. TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice

    PubMed Central

    Altaner, Čestmír; Altanerova, Veronica; Ebbesen, Peter

    2015-01-01

    Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation. PMID:26673923

  6. A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

    SciTech Connect

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.

    1989-05-01

    Male mice were divided into three experimental groups and a control group. Mice in the experimental groups received one of three doses of acute X irradiation (1.73, 0.29, and 0.05 Gy) and together with the control unirradiated mice were then mated weekly to unirradiated female mice for a 9-week experimental period. Embryos were recovered from the weekly matings at the four-cell stage and examined by the chimera assay for proliferative disadvantage. Aggregation chimeras were constructed of embryos from female mice mated to irradiated males (experimental embryos) and embryos from females mated to unexposed males (control embryos) and contained either one experimental embryo and one control embryo (heterologous chimera) or two control embryos (control chimera). The control embryo in heterologous chimeras and either embryo in control chimeras were prelabeled with the vital dye fluorescein isothiocyanate (FITC), and the chimeras were cultured for 40 h and viewed under phase-contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution from the FITC-labeled embryo. Experimental and control embryos that were cultured singly were also examined for embryo cell number at the end of the 40-h culture period. In control chimeras, the mean ratio of the unlabeled cells:total chimera cell number (henceforth referred to as ''mean ratio'') was 0.50 with little or no weekly variation over the 9-week experimental period. During Weeks 4-7, the mean ratios of heterologous chimeras differed significantly from the mean ratio of control chimeras with the greatest differences occurring during Week 7 (0.41 for chimeras of 0.05 Gy dose group, 0.40 for chimeras of the 0.29 Gy dose group, and 0.17 for chimeras of the 1.73 Gy dose group).

  7. Effects of cyclophosphamide and irradiation singly and in combination upon SaI growth in A/J mice

    SciTech Connect

    Anderson, R.E.; Williams, W.L.; Tokuda, S.

    1987-05-01

    The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed.

  8. Boswellic acid disables signal transduction of IL-6-STAT-3 in Ehrlich ascites tumor bearing irradiated mice.

    PubMed

    Moustafa, Enas Mahmoud; Thabet, Noura Magdy; Azab, Khaled Shaaban

    2016-08-01

    Boswellic acid (BA) is known for its ability to trigger apoptosis as well as to inhibit angiogenesis in tumor tissue. In this study, we investigated the effect of BA on the IL-6-STAT-3 signalling pathway in irradiated mice bearing solid tumors of Ehrlich ascites carcinoma (EAC). For this, we administered BA (25 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection) to mice with EAC, and then exposed them to 4 Gy of gamma radiation. Data analyses of the results revealed a specific impact from BA on IL-6R mRNA and survivin mRNA in EACs and irradiated EAC-bearing mice. Also, significant improvements were observed in the protein expression of JAK-1, P-JAK-1, STAT-3, P-STAT-3, and caspase-3, as well as VEGF and IL-6 levels. We propose that BA interfered with IL-6-STAT-3 signal transduction, thereby preventing the activation of caspase-3 and subsequently triggering the process of apoptosis. However, the alternative angiogenesis pathway, which includes the over-expression of VEGF and which depends on IL-6-STAT-3 signalling, was inhibited by the action of BA. Thus, we recommend that therapeutic strategies for cancer should include treatment with BA.

  9. Effect of prenatal X irradiation on chemical components of DNA and DNA-protein crosslinks in rat cerebrum in the perinatal periods

    SciTech Connect

    Iwasaki, S.; Tanaka, H.; Arima, M.

    1987-04-01

    Wistar rats were X-irradiated in utero with 100 or 200 R on Day 13 of gestation. X Irradiation resulted in decreases not only in cerebral weight up to 15 days old but also in DNA content from Day 19 of gestation to 5 days old, and in a tendency to increase the ratio of protein to DNA in the perinatal period. The DNA contents of the homogenate, isolated nuclei, and chromatin of the cerebrum in the irradiated group were significantly lower than those in the control group. The ratio of protein to DNA at the nuclei, chromatin, and isolated DNA steps increased on irradiation. The total nucleoside content of isolated DNA determined by high-performance liquid chromatography was higher in the irradiated group than that in the control group on Day 21 of gestation but not on Day 19 of gestation. No new peaks were observed and no change in the guanine-cytosine content was seen on irradiation. X Irradiation resulted in decreases in the cytosine and deoxycytidine contents and an increase in the deoxyadenosine content. The formation of DNA-protein crosslinks in the cerebral chromatin as determined by a filter binding assay tended to increase in the irradiated groups.

  10. Identification of Schistosoma mansoni glycoproteins recognized by protective antibodies from mice immunized with irradiated cercariae

    SciTech Connect

    Dalton, J.P.; Strand, M.; Mangold, B.L.; Dean, D.A.

    1986-06-15

    The humoral immune response of mice patently infected with Schistosoma mansoni and of mice vaccinated with radiation-attenuated cercariae were compared by radioimmunoassays and one-and two-dimensional polyacrylamide gel analyses of radioimmunoprecipitates. The binding observed with antibodies of mice vaccinated twice with radiation-attenuated cercariae over a period of 7 to 11 wk was less than 50% of the binding observed with antibodies of mice patently infected for 20 wk, but three to four times greater than that obtained with antibodies of mice infected for 6 wk, irrespective of whether the test extracts were derived from schistosomula or adult worms. Sera of vaccinated mice precipitated a restricted number of predominantly high m.w. glycoproteins of both schistosomula and adult worms metabolically labeled with sulfur-35 methionine. Each of the glycoproteins of 36 hr in vitro-cultured schistosomula that was precipitated by the sera of vaccinated mice was also precipitated by the sera of infected mice. Although radiation-attenuated larvae do not reach the adult stage, mice vaccinated with these still elicit a strong immune response against egg glycoproteins. These results show that the antibody response in mice vaccinated with radiation-attenuated larvae differs qualitatively and quantitatively from that of infected mice.

  11. Comparison of Cesium-137 and X-ray Irradiators by Using Bone Marrow Transplant Reconstitution in C57BL/6J Mice

    PubMed Central

    Gibson, Brian W; Boles, Nathan C; Souroullas, George P; Herron, Alan J; Fraley, Joe K; Schwiebert, Rebecca S; Sharp, John J; Goodell, Margaret A

    2015-01-01

    Mice are used extensively in transplantation studies involving bone marrow ablation. Due to the increasing security issues and expenses involved with γ irradiators, self-contained X-ray irradiators have been increasing in popularity. We hypothesized that bone marrow ablation by irradiation of mice with a 137Cs irradiator would be comparable to that from an X-ray source irradiator. A lethal-dose curve was obtained by irradiating C57BL/6J mice with 500, 700, 900, and 1100 cGy from either source. These data were used to determine the lethal radiation exposure range for a noncompetitive bone marrow engraftment curve for each source. At 90 d after reconstitution, the bone marrow engraftment curves revealed significant differences between the 2 sources in the establishment of B cell, myeloid, and T cell lineages. Murine B cell reconstitution after exposure to a 137Cs source was greater than that after X-ray exposure at each dose level, whereas the converse was true for myeloid cell reconstitution. At the 1050- and 1100-cGy doses, mice irradiated by using the X-ray source demonstrated higher levels of T cell reconstitution but decreased survival compared with mice irradiated with the 137Cs source. We concluded that although both sources ablated endogenous bone marrow sufficiently to enable stem cell engraftment, there are distinct physiologic responses that should be considered when choosing the optimal source for use in a study and that irradiation from the 137Cs source was associated with lower overall morbidity due to opportunistic infection. PMID:26141441

  12. Comparison of Cesium-137 and X-ray Irradiators by Using Bone Marrow Transplant Reconstitution in C57BL/6J Mice.

    PubMed

    Gibson, Brian W; Boles, Nathan C; Souroullas, George P; Herron, Alan J; Fraley, Joe K; Schwiebert, Rebecca S; Sharp, John J; Goodell, Margaret A

    2015-06-01

    Mice are used extensively in transplantation studies involving bone marrow ablation. Due to the increasing security issues and expenses involved with γ irradiators, self-contained X-ray irradiators have been increasing in popularity. We hypothesized that bone marrow ablation by irradiation of mice with a (137)Cs irradiator would be comparable to that from an X-ray source irradiator. A lethal-dose curve was obtained by irradiating C57BL/6J mice with 500, 700, 900, and 1100 cGy from either source. These data were used to determine the lethal radiation exposure range for a noncompetitive bone marrow engraftment curve for each source. At 90 d after reconstitution, the bone marrow engraftment curves revealed significant differences between the 2 sources in the establishment of B cell, myeloid, and T cell lineages. Murine B cell reconstitution after exposure to a (137)Cs source was greater than that after X-ray exposure at each dose level, whereas the converse was true for myeloid cell reconstitution. At the 1050- and 1100-cGy doses, mice irradiated by using the X-ray source demonstrated higher levels of T cell reconstitution but decreased survival compared with mice irradiated with the (137)Cs source. We concluded that although both sources ablated endogenous bone marrow sufficiently to enable stem cell engraftment, there are distinct physiologic responses that should be considered when choosing the optimal source for use in a study and that irradiation from the (137)Cs source was associated with lower overall morbidity due to opportunistic infection. PMID:26141441

  13. Effect of Artocarpus communis Extract on UVB Irradiation-Induced Oxidative Stress and Inflammation in Hairless Mice.

    PubMed

    Lee, Chiang-Wen; Ko, Horng-Huey; Chai, Chee-Yin; Chen, Wan-Tzu; Lin, Chun-Ching; Yen, Feng-Lin

    2013-01-01

    Administration of antioxidants and anti-inflammatory agents is an effective strategy for preventing ultraviolet (UV) irradiation-induced skin damage. Artocarpus communis possesses several pharmacological activities, such as antioxidant, anticancer and anti-inflammation. However, the photoprotective activity of methanol extract of A. communis heartwood (ACM) in ultraviolet irradiation-induced skin damage has not yet been investigated. The present study was performed using ultraviolet absorption, histopathological observation, antioxidant and anti-inflammation assays to elucidate the mechanism of the photoprotective activity of ACM. Our results indicated that ACM displayed a UVA and UVB absorption effect and then effectively decreased scaly skin, epidermis thickness and sunburn cells during ultraviolet irradiation in hairless mice. ACM not only decreased ultraviolet irradiation-mediated oxidative stress, including lowering the overproduction of reactive oxygen species and lipid peroxidation (p < 0.05), but also reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin 1β. Additionally, ACM can decrease the synthesis of cytosolic phospholipase A2, cyclooxygenase, inducible nitric oxide synthase and vascular cell adhesion molecular-1 via inhibiting TNF-α-independent pathways (p < 0.05) in UVB-mediated inflammation and formation of sunburn cells. Consequently, we concluded that ACM extract has a photoprotective effect against UVB-induced oxidative stress and inflammation due to its sunscreen property, and its topical formulations may be developed as therapeutic and/or cosmetic products in further studies.

  14. Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression

    SciTech Connect

    Kotzin, B.L.; Arndt, R.; Okada, S.; Ward, R.; Thach, A.B.; Strober, S.

    1986-05-01

    We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.

  15. Encapsulation of antigen in poly(D,L-lactide-co-glycolide) microspheres protects from harmful effects of γ-irradiation as assessed in mice.

    PubMed

    Mohanan, Deepa; Gander, Bruno; Kündig, Thomas M; Johansen, Pål

    2012-02-01

    During the last two decades, synthetic polymers such as poly(lactide-co-glycolide) (PLGA) have been investigated for the development of nano- or microparticles as adjuvants or antigen vehicles. To enable transfer of this technology to human settings, the issue of sterilisation is of central importance. Since most polymers are heat-sensitive, sterilisation of polymeric microspheres for parenteral administration is assured either by costly and laborious aseptical preparation or the more preferred γ-irradiation. Many studies have investigated the effect of γ-irradiation on various physiochemical properties of the microspheres, but investigations on immunological effects are rare. We prepared poly(lactide-co-glycolide) (PLGA) microspheres containing ovalbumin (OVA) and tested the effect of γ-irradiation on the various immunological properties in mice. For reference, OVA was γ-irradiated and tested equivalently. The ability of encapsulated or non-encapsulated OVA to trigger activation of dendritic cells (DCs) was not affected by irradiation. However, while γ-irradiation of free OVA strongly influenced the antigen presentation, encapsulated OVA was not affected by irradiation. γ-Irradiation of OVA also reduced the immunogenicity in mice with regard to OVA-specific IgG1 production. In contrast, the antibody and the T-cell responses in mice immunised with PLGA-encapsulated OVA were similar irrespective of the γ-irradiation status. Hence, encapsulation of antigen into PLGA microspheres protects antigen from the potential detrimental effect of γ-irradiation leading to inactivation or altered immunogenicity. Sterilisation by γ-irradiation therefore enables a cost-effective production of PLGA-based antigen-delivery systems as compared to the more laborious and expensive aseptical production of such vaccines. PMID:22024408

  16. Purple grape juice as a protector against acute x-irradiation induced alterations on mobility, anxiety, and feeding behaviour in mice.

    PubMed

    Soares, Félix A A; Dalla Corte, Cristiane L; Andrade, Edson R; Marina, Raquel; González, Paquita; Barrio, Juan P

    2014-04-01

    The aim of this work was to test the hypothesis that a moderate intake of organic purple grape juice shows a positive radiomodifier effect over early behavioural damage following acute X-irradiation in mice. Anxiety-, locomotion-, and feeding-related responses to 6 Gy total body X-irradiation (TBI) were studied via open field, Rotarod, and feeding/drinking recording. Thirty-two male mice weighing 25-30 g were grouped according grape juice (J) or water (W) ad libitum drinking and either non-irradiated (N) or irradiated (R). 24 h post-TBI the access frequency to the center and corners of the open field was decreased, and the total stay in the corners increased, in RW vs. NW mice. Anxiety-related parameters decreased in RJ vs. RW mice. Rotarod latency times increased 72 h post-TBI in RJ vs RW mice. No overall changes in food and drink intake were observed along the experimental period. On the irradiation day, bout number was increased and bout duration was decreased in RW mice. The changes were reversed by purple grape juice intake. Grape juice intake before and after TBI can overcome several radiation-induced changes in behaviour within 24-72 hours after sub-lethal X-irradiation. This beneficial effect on short-term anxiety and mobilityrelated activities could probably be included in the list of flavonoid bio-effects. The present findings could be relevant in designing preventive interventions aimed to enhance body defense mechanisms against short-term irradiation damage.

  17. The effect of irradiation in air or in hyperbaric oxygen on the Fib/T tumor in WHT mice pretreated with a hypoxic gas mixture

    SciTech Connect

    Hendrikse, A.; Blekkenhorst, G. )

    1991-01-01

    The effect of exposing WHT mice bearing the Fib/T tumor to a low-oxygen environment (8, 10, and 15% oxygen) for 48 h or 72 h before irradiation was compared, using an in vitro colony-forming excision assay, to the effect obtained when mice were pretreated with air. The response of the Fib/T tumor to radiation delivered in air was improved both by a 48-h and by a 72-h exposure of the animals to 8, 10, and 15% oxygen. However, the greatest tumor sensitization was achieved when mice were kept in 8% oxygen for 48 h before irradiation. These results are interpreted and discussed in relation to increases in the 2,3-DPG concentration, which were shown to occur when mice were exposed to a reduced oxygen environment. The relative importance of two models proposed to explain these findings is assessed. If mice pretreated with air were irradiated in hyperbaric oxygen, a similar tumor response was observed compared to that when mice were exposed to 8% oxygen for 48 h and then irradiated in air.

  18. Melanin production through novel processing of proopiomelanocortin in the extracellular compartment of the auricular skin of C57BL/6 mice after UV-irradiation.

    PubMed

    Yamamoto, Hiroyuki; Yamane, Tomohiro; Iguchi, Kazuaki; Tanaka, Kiyotaka; Iddamalgoda, Arunasiri; Unno, Keiko; Hoshino, Minoru; Takeda, Atsushi

    2015-09-29

    The production of melanin is regulated by α-melanocyte-stimulating hormone (α-MSH), which is produced from proopiomelanocortin (POMC). Keratinocytes release POMC along with lower levels of α-MSH and ACTH. To clarify the mechanism of melanogenesis after ultraviolet (UV)-irradiation, this study focused on the expression of POMC and POMC-derived peptides after UV-irradiation. Western blot analysis and immunoassays indicated that both POMC and α-MSH-like immunoreactivity (α-MSH-LI) increased after UV-irradiation. However, other POMC-derived products were very low. In hypophysectomized mice, α-MSH-LI increased to the same level as in control mice after UV-irradiation. Structural analysis revealed that the major α-MSH-LI product was ACTH(1-8). Furthermore, ACTH(1-8) competed with [(125)I]-α-MSH for receptor binding and increased melanin production via a melanocortin-1 receptor. These results suggested that melanin was produced through ACTH(1-8) after UV-irradiation. Trypsin-like enzymatic activity, which is responsible for POMC activation, increased after UV-irradiation and was identified as tryptase. In mast cell-deficient mice, which do not produce tryptase, α-MSH-LI levels were unchanged after UV-irradiation. The present study demonstrates the production of ACTH(1-8) from POMC by tryptase, which is a novel peptide-processing mechanism in the extracellular compartment of the skin.

  19. Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

    PubMed

    Moon, Ju-Yeon; Shin, Hee-June; Son, Hyun-Hwa; Lee, Jeongae; Jung, Uhee; Jo, Sung-Kee; Kim, Hyun Sik; Kwon, Kyung-Hoon; Park, Kyu Hwan; Chung, Bong Chul; Choi, Man Ho

    2014-05-01

    The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5β-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points.

  20. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Silva, Thais C C; Caviglione, Carla V; Bottura, Carolina; Fonseca, Maria J V; Vicentini, Fabiana T M C; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:26741806

  1. Gamma-Irradiated Influenza A Virus Provides Adjuvant Activity to a Co-Administered Poorly Immunogenic SFV Vaccine in Mice

    PubMed Central

    Babb, Rachelle; Chan, Jennifer; Khairat, Jasmine E.; Furuya, Yoichi; Alsharifi, Mohammed

    2014-01-01

    Many currently available inactivated vaccines require “adjuvants” to maximize the protective immune responses generated against the antigens of interest. Recent studies in mice with gamma-irradiated influenza A virus (γ-FLU) have shown its superior efficacy compared to other forms of inactivated FLU vaccines and its ability to induce both potent interferon type-I (IFN-I) responses and the IFN-I-associated partial lymphocyte activation. Commonly, IFN-I responses induced by adjuvants, combined in vaccine preparations, have been shown to effectively enhance the immunogenicity of the antigens of interest. Therefore, we investigated the potential adjuvant activity of γ-FLU and the possible effect on antibody responses against co-administrated antigens, using gamma-irradiated Semliki Forest virus (γ-SFV) as the experimental vaccine in mice. Our data show that co-vaccination with γ-FLU and γ-SFV resulted in enhanced SFV-specific antibody responses in terms of increased titers by sixfold and greater neutralization efficacy, when compared to vaccination with γ-SFV alone. This study provides promising evidence related to the possible use of γ-FLU as an adjuvant to poorly immunogenic vaccines without compromising the vaccine efficacy of γ-FLU. PMID:24959166

  2. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Silva, Thais C C; Caviglione, Carla V; Bottura, Carolina; Fonseca, Maria J V; Vicentini, Fabiana T M C; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

  3. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice

    PubMed Central

    Martinez, Renata M.; Pinho-Ribeiro, Felipe A.; Steffen, Vinicius S.; Silva, Thais C. C.; Caviglione, Carla V.; Bottura, Carolina; Fonseca, Maria J. V.; Vicentini, Fabiana T. M. C.; Vignoli, Josiane A.; Baracat, Marcela M.; Georgetti, Sandra R.; Verri, Waldiceu A.; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2′-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:26741806

  4. Prenatal Treatment of Mosaic Mice (Atp7a mo-ms) Mouse Model for Menkes Disease, with Copper Combined by Dimethyldithiocarbamate (DMDTC)

    PubMed Central

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Koteja, Paweł; Chrząścik, Katarzyna; Møller, Lisbeth Birk

    2012-01-01

    Menkes disease is a fatal neurodegenerative disorder in infants caused by mutations in the gene ATP7A which encodes a copper (Cu) transporter. Defects in ATP7A lead to accumulated copper in the small intestine and kidneys and to copper deficiencies in the brain and the liver. The copper level in the kidney in postnatal copper-treated Menkes patients may reach toxic levels. The mouse model, mosaic Atp7a mo-ms recapitulates the Menkes phenotype and die about 15.75±1.5 days of age. In the present study we found that prenatal treatment of mosaic murine fetuses throughout gestation days 7, 11, 15 and 18 with a combination of CuCl2 (50 mg/kg) and dimethyldithiocarbamate (DMDTC) (280 mg/kg) leads to an increase in survival to about 76±25.3 days, whereas treatment with CuCl2 alone (50 mg/kg) only leads to survival for about 21 days ±5 days. These copper-DMDTC treated mutants showed an improved locomotor activity performance and a gain in body mass. In contrast to treatment with CuCl2 alone, a significant increase in the amount of copper was observed in the brain after prenatal copper-DMDTC treatment as well as a decrease in the amount of accumulated copper in the kidney, both leading towards a normalization of the copper level. Although copper-DMDTC prenatal treatment only leads to a small increase in the sub-normal copper concentration in the liver and to an increase of copper in the already overloaded small intestine, the combined results suggest that prenatal copper-DMDTC treatment also should be considered for humans. PMID:22815746

  5. Prenatal treatment of mosaic mice (Atp7a mo-ms) mouse model for Menkes disease, with copper combined by dimethyldithiocarbamate (DMDTC).

    PubMed

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Koteja, Paweł; Chrząścik, Katarzyna; Møller, Lisbeth Birk

    2012-01-01

    Menkes disease is a fatal neurodegenerative disorder in infants caused by mutations in the gene ATP7A which encodes a copper (Cu) transporter. Defects in ATP7A lead to accumulated copper in the small intestine and kidneys and to copper deficiencies in the brain and the liver. The copper level in the kidney in postnatal copper-treated Menkes patients may reach toxic levels. The mouse model, mosaic Atp7a (mo-ms) recapitulates the Menkes phenotype and die about 15.75±1.5 days of age. In the present study we found that prenatal treatment of mosaic murine fetuses throughout gestation days 7, 11, 15 and 18 with a combination of CuCl(2) (50 mg/kg) and dimethyldithiocarbamate (DMDTC) (280 mg/kg) leads to an increase in survival to about 76±25.3 days, whereas treatment with CuCl(2) alone (50 mg/kg) only leads to survival for about 21 days ±5 days. These copper-DMDTC treated mutants showed an improved locomotor activity performance and a gain in body mass. In contrast to treatment with CuCl(2) alone, a significant increase in the amount of copper was observed in the brain after prenatal copper-DMDTC treatment as well as a decrease in the amount of accumulated copper in the kidney, both leading towards a normalization of the copper level. Although copper-DMDTC prenatal treatment only leads to a small increase in the sub-normal copper concentration in the liver and to an increase of copper in the already overloaded small intestine, the combined results suggest that prenatal copper-DMDTC treatment also should be considered for humans. PMID:22815746

  6. [The epididymal adipose tissue of mice after nanosecond pulse-periodic microwave irradiation].

    PubMed

    Kereya, A V; Bolshakov, M A; Zharkova, L P; Ivanov, V V; Knyazeva, I R; Kutenkov, O P; Rostov, V V; Semjonova, Yu N

    2014-01-01

    The effect of pulse-periodic microwave radiation (PPMR) of the pulse repetition frequency of 8-25 pulseper second, the peak power density of 1500 W/cm2 on the epididymal adipose tissue of micewas investigated. The effect was assessed by the changes in the fat mass and size of the irradiated adipocytes. It was found that the fat mass and size distribution of adipocytes are affected by irradiation. The effects depend on the pulse repetition frequency and intensity of exposure.

  7. Immunohistochemical quantitation of three collagen isotypes in perfused areas and nonperfused foci of the lungs of irradiated mice

    SciTech Connect

    Miller, G.G.; Sharplin, J.; Franko, A.J. )

    1989-07-01

    Collagen isotypes I, III, and IV were quantitated by video image analysis of fluorescent-antibody-stained lung tissue sections from control and irradiated C57L/J and BALB/c mice. The perfusion status of lungs was determined by injecting colloidal carbon into the hepatic vein immediately prior to sacrificing the animals. Well-perfused parenchymal regions turned black, whereas nonperfused areas remained pale. Previous histological studies indicated substantial differences in the types of lesions found in the lungs of these two strains. C57L/J mice develop extensive and persistent contracted fibrosis. In lung sections of C57L/J mice examined 28 weeks after a dose of 11 Gy X rays, all three collagen isotypes were significantly elevated to levels 37-51% higher than age-matched control values in perfused regions of lung. In nonperfused areas, which had the histological appearance of contracted scar tissue, the three collagen isotype levels were further elevated to values 83-90% greater than controls. This finding suggests that in C57L/J mice, an elevation of each or all of the three collagen isotypes to levels approximately 45% greater than controls is consistent with continued pulmonary function during the intermediate phase of lung damage, whereas areas of parenchyma containing isotype levels in excess of 185% of control values coincide with functionally deficient regions. BALB/cCr Alt. mice examined 28 weeks subsequent to 14.5 Gy X rays had a variety of visible lesion, most of which were nonperfused. In addition, one-quarter of nonperfused acini had no visible lesion. In perfused areas, the three isotypes were increased to 119-132% of control levels, with a further, significant (P less than 0.05) increase to 128-144% of control values in nonperfused parenchyma.

  8. Embryonic effects transmitted by male mice irradiated with 512 MeV/u {sup 56}Fe nuclei

    SciTech Connect

    Wiley, L.M.; Van Beek, M.E.A.B.; Raabe, O.G.

    1994-06-01

    High-energy, high-charge nuclei may contribute substantially to the yearly equivalent dose in space flight from galactic cosmic radiation (GCR) at solar minimum. The largest single heavy-ion component is {sup 56}Fe. We used the mouse embryo chimera assay to test 512 MeV/u {sup 56}Fe nuclei for effects on the rate of proliferation of embryonic cells transmitted by sperm from irradiated mice. Male CD1 mice were acutely irradiated with 0.01, 0.05, or 0.1 Gy (LET, 184 keV/{mu}m; fluence, 3.5 x 10{sup 4}-3.3 x 10{sup 5} nuclei/cm{sup 2}; average dose rate, 0.02 Gy/min) at the Lawrence Berkeley Laboratory BEVATRON/BEVALAC Facility in Berkeley, CA. Irradiated males were bred weekly for 7 weeks to nonirradiated females and their four-cell embryos were paired with control embryos, forming aggregation chimeras. After 30-35 h of culture, chimeras were dissociated to obtain {open_quotes}proliferation ratios{close_quotes} (number of cells contributed by the embryo from the irradiated male/total number of cells in the chimera). Significant dose-dependent decreases in proliferation ratios were obtained across all three dose groups for postirradiation week 2 (P < 0.05 to P < 0.003). The 0.01- and 0.05-Gy dose groups also produced significant decreases in proliferation ratios for postirradiation week 1 (P < 0.05 to P < 0.01) and the 0.05-Gy dose group produced significant decreases in proliferation ratios for postirradiation week 6 (P < 0.05). Postirradiation weeks 1, 2 and 6 correspond to irradiation of epididymal sperm, testicular spermatids and spermatogonia, respectively. We calculate that only about 5% of sperm in the 0.1-Gy, 2.5% in the 0.05-Gy and 0.5% in the 0.01-Gy dose groups sustained direct hits from {sup 56}Fe nuclei. However, up to 47% of sperm during postirradiation weeks 1 and 2 transmitted proliferation ratios that were at or below one standard deviation from control mean proliferation ratios. 26 refs., 4 figs., 10 tabs.

  9. [Radiation effects of exposure during prenatal development].

    PubMed

    Streffer, C

    1995-03-01

    The embryo and fetus are very radiosensitive during the total prenatal development period. The quality and extent of radiation effects depend strongly on the developmental stage at which the exposure occurs. During the preimplantation period radiation exposure can cause death of the embryo after radiation doses of 0.2 Gy and higher. Malformations are only observed in very rare cases when genetic predispositions exist. Macroscopic-anatomical malformations are induced only after irradiation during the major organogenesis. On the basis of experimental data with mammals it is assumed that a radiation dose of about 0.2 Gy doubles the malformation risk. Studies in humans give rise to the assumption that the human embryo is more radioresistant than the embryos of mice and rats. Radiation exposure during the major organogenesis and the early fetal period lead to disturbances in the growth and developmental processes. During early fetogenesis (week 8-15 post corruption) high radiosensitivity exists for the development of the central nervous system. Radiation doses of 1 Gy cause severe mental retardation in about 50% of exposed fetuses. Analysis of the dose-effect curves shows that there is probably a dose-effect curve with a threshold for this effect. It must be taken into account that radiation exposure during the fetal period also induces cancer. The studies, however, do not allow quantitative estimate of this radiation risk at present. It is therefore generally assumed that the risk is about the same level as for children.

  10. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Yuan, Hong; Burk, Laurel M.; Inscoe, Christy R.; Hadsell, Michael J.; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-03-01

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

  11. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array.

    PubMed

    Zhang, Lei; Yuan, Hong; Burk, Laurel M; Inscoe, Christy R; Hadsell, Michael J; Chtcheprov, Pavel; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-03-01

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

  12. Potential Beneficial Effects of Si-Wu-Tang on White Blood Cell Numbers and the Gastrointestinal Tract of γ-Ray Irradiated Mice.

    PubMed

    Ni, Jin; Romero-Weaver, Ana L; Kennedy, Ann R

    2014-09-01

    Si-Wu-Tang (SWT) is a decoction consisting of a mixture of ingredients of Rehmanniae Radix, Angelica Radix, Chuanxiong Rhizoma and Paeoniae Radix. As a traditional Chinese herbal decoction, SWT has been widely used for the treatment of diseases characterized as blood and/or energy deficit. The present study was performed to evaluate the effects of SWT on the different populations of circulating white blood cells (WBCs) and gastrointestinal changes in γ-ray irradiated mice. Female mice were treated daily with orally administered SWT seven days before irradiation, until one day before irradiation or until one day before sample collection. WBC counts were determined from peripheral blood samples taken from the mice at different times post-irradiation. Hematoxylin and eosin (H&E) staining, as well as immunohistochemical analysis of fibrinogen, were utilized to evaluate the effects of SWT in the intestines of mice after radiation exposure. The results of the present studies demonstrate that SWT has protective effects against radiation damage to circulating WBCs, specifically to lymphocytes, and to the gastrointestinal tract of the irradiated animals. PMID:25324699

  13. Potential Beneficial Effects of Si-Wu-Tang on White Blood Cell Numbers and the Gastrointestinal Tract of γ-Ray Irradiated Mice.

    PubMed

    Ni, Jin; Romero-Weaver, Ana L; Kennedy, Ann R

    2014-09-01

    Si-Wu-Tang (SWT) is a decoction consisting of a mixture of ingredients of Rehmanniae Radix, Angelica Radix, Chuanxiong Rhizoma and Paeoniae Radix. As a traditional Chinese herbal decoction, SWT has been widely used for the treatment of diseases characterized as blood and/or energy deficit. The present study was performed to evaluate the effects of SWT on the different populations of circulating white blood cells (WBCs) and gastrointestinal changes in γ-ray irradiated mice. Female mice were treated daily with orally administered SWT seven days before irradiation, until one day before irradiation or until one day before sample collection. WBC counts were determined from peripheral blood samples taken from the mice at different times post-irradiation. Hematoxylin and eosin (H&E) staining, as well as immunohistochemical analysis of fibrinogen, were utilized to evaluate the effects of SWT in the intestines of mice after radiation exposure. The results of the present studies demonstrate that SWT has protective effects against radiation damage to circulating WBCs, specifically to lymphocytes, and to the gastrointestinal tract of the irradiated animals.

  14. Potential Beneficial Effects of Si-Wu-Tang on White Blood Cell Numbers and the Gastrointestinal Tract of γ-Ray Irradiated Mice

    PubMed Central

    Ni, Jin; Romero-Weaver, Ana L.; Kennedy, Ann R.

    2014-01-01

    Si-Wu-Tang (SWT) is a decoction consisting of a mixture of ingredients of Rehmanniae Radix, Angelica Radix, Chuanxiong Rhizoma and Paeoniae Radix. As a traditional Chinese herbal decoction, SWT has been widely used for the treatment of diseases characterized as blood and/or energy deficit. The present study was performed to evaluate the effects of SWT on the different populations of circulating white blood cells (WBCs) and gastrointestinal changes in γ-ray irradiated mice. Female mice were treated daily with orally administered SWT seven days before irradiation, until one day before irradiation or until one day before sample collection. WBC counts were determined from peripheral blood samples taken from the mice at different times post-irradiation. Hematoxylin and eosin (H&E) staining, as well as immunohistochemical analysis of fibrinogen, were utilized to evaluate the effects of SWT in the intestines of mice after radiation exposure. The results of the present studies demonstrate that SWT has protective effects against radiation damage to circulating WBCs, specifically to lymphocytes, and to the gastrointestinal tract of the irradiated animals. PMID:25324699

  15. Dystrophic Changes in Extraocular Muscles after Gamma Irradiation in mdx:utrophin+/− Mice

    PubMed Central

    McDonald, Abby A.; Kunz, Matthew D.; McLoon, Linda K.

    2014-01-01

    Extraocular muscles (EOM) have a strikingly different disease profile than limb skeletal muscles. It has long been known that they are spared in Duchenne (DMD) and other forms of muscular dystrophy. Despite many studies, the cause for this sparing is not understood. We have proposed that differences in myogenic precursor cell properties in EOM maintain normal morphology over the lifetime of individuals with DMD due to either greater proliferative potential or greater resistance to injury. This hypothesis was tested by exposing wild type and mdx:utrophin+/− (het) mouse EOM and limb skeletal muscles to 18 Gy gamma irradiation, a dose known to inhibit satellite cell proliferation in limb muscles. As expected, over time het limb skeletal muscles displayed reduced central nucleation mirrored by a reduction in Pax7-positive cells, demonstrating a significant loss in regenerative potential. In contrast, in the first month post-irradiation in the het EOM, myofiber cross-sectional areas first decreased, then increased, but ultimately returned to normal compared to non-irradiated het EOM. Central nucleation significantly increased in the first post-irradiation month, resembling the dystrophic limb phenotype. This correlated with decreased EECD34 stem cells and a concomitant increase and subsequent return to normalcy of both Pax7 and Pitx2-positive cell density. By two months, normal het EOM morphology returned. It appears that irradiation disrupts the normal method of EOM remodeling, which react paradoxically to produce increased numbers of myogenic precursor cells. This suggests that the EOM contain myogenic precursor cell types resistant to 18 Gy gamma irradiation, allowing return to normal morphology 2 months post-irradiation. This supports our hypothesis that ongoing proliferation of specialized regenerative populations in the het EOM actively maintains normal EOM morphology in DMD. Ongoing studies are working to define the differences in the myogenic precursor cells

  16. T lymphocytes from mice immunized with irradiated sporozoites eliminated malaria from hepatocytes

    SciTech Connect

    Hoffman, S.L.; Isenbarger, D.; Long, G.W.; Sedegah, M.; Szarfman, A.

    1990-01-01

    When mice are immunized with radiation-attenuated sporozoites they are solidly protected against sporozoite challenge by an immune response that has been shown to require CD8+ lymphocytes in several strains of mice. The target of this CD8+ T-cell-dependent immunity has not been established. Immune BALB/c mice were shown to develop malaria-specific. CD8+ T-cell-dependent inflammatory infiltrates in their livers after challenge with Plasmodium berghei sporozoites. Spleen cells from immune BALB/c and C57BL/6 mice eliminated hepatocytes infected with the liver stage of P. berghei in vitro. The activity against infected hepatocytes is not inhibited by antibodies to interferon-y and is not present in culture supernatants. It is generally restricted, an indication that malaria antigens on the hepatocyte surface are recognized by immune T-effector cells.

  17. Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice.

    PubMed

    Teruya, Kiichiro; Myojin-Maekawa, Yuki; Shimamoto, Fumio; Watanabe, Hiromitsu; Nakamichi, Noboru; Tokumaru, Koichiro; Tokumaru, Sennosuke; Shirahata, Sanetaka

    2013-01-01

    Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15 d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent.

  18. The peripheral chimerism of bone marrow-derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice.

    PubMed

    Filip, Stanislav; Mokrý, Jaroslav; Vávrová, Jiřina; Sinkorová, Zuzana; Mičuda, Stanislav; Sponer, Pavel; Filipová, Alžběta; Hrebíková, Hana; Dayanithi, Govindan

    2014-05-01

    Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.

  19. Recombinant human manganese superoxide dismutase (rMnSOD): a positive effect on the immunohematological state of mice irradiated with protons

    NASA Astrophysics Data System (ADS)

    Ambesi-Impiombato, Francesco Saverio; Belov, Oleg; Bulinina, Taisia; Ivanov, Alexander; Mancini, Aldo; Borrelli, Antonella; Krasavin, Eugene A.

    Protons represent the largest component of space radiation. In this regard screening of radioprotective drugs capable of increasing radioresistance of astronauts obligatory includes studying these compounds using proton radiation injury models. The recombinant human manganese superoxide dismutase (rMnSOD) had previously demonstrated its efficacy on an in vivo X-ray induced injury model, when multiple intraperitoneal treatments allowed the survival of mice irradiated with doses which were lethal for the control animals (Borrelli A et al. “A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells”. Free Radic Biol Med. 2009, 46, 110-6). Using the model of sublethal whole-body irradiation with protons available at Phasotron of Joint Institute for Nuclear Research (Dubna, Russia), we reconstruct the bone-marrow form of the acute radiation sickness to test the radioprotective effect of rMnSOD. Male (CBAxC57Bl6) F1 hybrid SPF mice weighting approximately 24 g were exposed to 171 MeV protons at the dose of 4 Gy. After irradiation, the sixfold daily subcutaneous treatment with rMnSOD has provided a statistically significant acceleration of the recovery of thymus and spleen mass and of the number of leukocytes in mice peripheral blood. In the control, untreated and irradiated mice, these positive effects were not observed even on day 7 after exposure. The number of karyocytes in bone marrow of irradiated mice has even exceeded its basal level in the control group 7 days after irradiation. The rMnSOD-treated group has thus demonstrated a significant hyper-restoration of this characteristic. In the presentation, several possibilities of using of rMnSOD in space medicine will be discussed, taking into account various biomedically relevant effects of this enzyme.

  20. p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice

    PubMed Central

    Lu, Lu; Wang, Yue-Ying; Zhang, Jun-Ling; Li, De-Guan; Meng, Ai-Min

    2016-01-01

    Senescent hematopoietic stem cells (HSCs) accumulate with age and exposure to stress, such as total-body irradiation (TBI), which may cause long-term myelosuppression in the clinic. However, the methods available for long-term myelosuppression remain limited. Previous studies have demonstrated that sustained p38 mitogen-activated protein kinases (p38 MAPK) activation in HSCs following exposure to TBI in mice and the administration of its inhibitor twenty-four hours after TBI may partially prevent long-term myelosuppression. However, long-term myelosuppression is latent and identified long after the administration of radiation. In this study, we investigated the effects of SB203580 (a small molecule inhibitor of p38 MAPK) on long-term myelosuppression induced by TBI. Mice with hematopoietic injury were injected intraperitoneally with SB203580 every other day five times beginning 70 days after 6 Gy of 137Cs γ ray TBI. Our results at 80 days demonstrated that SB203580 did not significantly improve the TBI-induced long-term reduction of peripheral blood cell and bone marrow nucleated cell (BMNC) counts, or defects in hematopoietic progenitor cells (HPCs) and HSC clonogenic function. SB203580 reduced reactive oxygen species (ROS) production and p-p38 expression; however, SB203580 had no effect on p16 expression in the HSCs of mice. In conclusion, these findings suggest that treatment with SB203580 70 days after TBI in mice inhibits the ROS-p38 oxidative stress pathway; however, it has no therapeutic effect on long-term myelosuppression induced by TBI. PMID:27338355

  1. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

    SciTech Connect

    Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori . E-mail: kuwabara@vetmed.hokudai.ac.jp

    2007-05-01

    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-{beta}-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth.

  2. Prenatal and neonatal radiation injury and lymphohematopoietic development in the dog

    SciTech Connect

    Nold, J.B.

    1985-01-01

    Immunologic and hematopoietic responses were studied in beagle dogs following prenatal or neonatal irradiation to evaluate the effects of ionizing radiation on the developing lymphohematopoietic system. In prenatally-irradiated dogs thymic medullary volumes were significantly reduced at birth, but had returned to control levels by 12 weeks of age. Irradiated dogs exhibited a significant reduction in primary humoral antibody responses and showed a concurrent decrease in T helper lymphocytes in the peripheral blood. In neonatally-irradiated dogs lymphocyte blastogenic responses were sharply decreased at 8 weeks, but returned to control levels by 12 weeks of age. Contact sensitivity to dinitrochlorobenzene was decreased, indicating reduced cell-mediated immune responses. Alterations in peripheral blood lymphocyte subpopulations included decreases in B cells and increases in T cells, possibly due to increased numbers of T suppressor cells. There were significant reductions in body size and body tissue weights in all irradiated dogs, although these were more severe and persistent in the prenatally-irradiated dogs. These data show that prenatally or neonatally-irradiated dogs have significantly postnatal immunologic and hematopoietic defects. The effect on bone marrow function in prenatally-irradiated dogs was more severe and persistent than in neonatally-irradiated animals; however, the neonatally-irradiated dogs exhibited more severe alterations in lymphocyte subpopulations than did the prenatally-irradiated dogs. The observation of altered lymphocyte subpopulations suggests altered immunoregulation and raises some important questions relating to radiation-induced immunodeficiency and increased susceptibility to clinical disease, including neoplasia.

  3. Assessing Cardiac Injury in Mice With Dual Energy-MicroCT, 4D-MicroCT, and MicroSPECT Imaging After Partial Heart Irradiation

    SciTech Connect

    Lee, Chang-Lung; Min, Hooney; Befera, Nicholas; Clark, Darin; Qi, Yi; Das, Shiva; Johnson, G. Allan; Badea, Cristian T.; Kirsch, David G.

    2014-03-01

    Purpose: To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT). Methods and Materials: To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53{sup FL/+} and Tie2Cre; p53{sup FL/−} mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion. Results: After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53{sup FL/−} mice. In Tie2Cre; p53{sup FL/−} mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53{sup FL/+} mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R{sup 2} = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53{sup FL/−} mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated. Conclusions: Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches

  4. WISP-1 contributes to fractionated irradiation-induced radioresistance in esophageal carcinoma cell lines and mice.

    PubMed

    Li, Wen-Feng; Zhang, Li; Li, Hai-Ying; Zheng, Si-Si; Zhao, Liang

    2014-01-01

    Cancer cells that survive fractionated irradiation can be radioresistant and cause tumor recurrence. However, the molecular mechanisms underlying the development of radioresistance in cancer cells remain elusive. The aim of this study was to investigate the role of WISP-1 in the development of radioresistance in esophageal carcinoma during fractionated irradiation. Radioresistant esophageal cancer cells were generated from normal esophageal cancer cells via fractionated irradiation, and expression levels of related proteins were determined by Western blot. Radiosensitivity of cells was established by clonogenic cell survival assays, and cell cycle distribution was evaluated by flow cytometry. Protein distributions were determined by immunofluorescence, and cell toxicity was evaluated by cell counting kit-8 assays. In vivo validations were performed in a xenograft transplantation mouse model. Our data indicate that WISP-1 plays an important role in the development of radioresistance in esophageal cancer cells during fractionated irradiation. The overexression of WISP-1 in esophageal cancer cells was associated with radioresistance. Depletion of extracellular WISP-1 by antibody neutralizing reversed radioresistance and directly induced mitotic catastrophe resulting in cell death. WISP-1 may be a candidate therapeutic target in the treatment of recurrent esophageal carcinoma after radiotherapy.

  5. Survival of irradiated recipient mice after transplantation of bone marrow from young, old and “early aging” mice

    PubMed Central

    Guest, Ian; Ilic, Zoran; Sell, Stewart

    2015-01-01

    Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16–18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best. PMID:26796640

  6. Survival of irradiated recipient mice after transplantation of bone marrow from young, old and "early aging" mice.

    PubMed

    Guest, Ian; Ilic, Zoran; Scrable, Heidi; Sell, Stewart

    2015-12-01

    Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16-18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best.

  7. Prolonged bone marrow and skin allograft survival after pretransplant conditioning with cyclophosphamide and total lymphoid irradiation. [Mice

    SciTech Connect

    Kersey, J.H.; Kruger, J.; Song, C.; Kloster, B.

    1980-05-01

    Current studies were designed to provide long-term survival of allogeneic skin and bone marrow in mice preconditioned with various combinations of cyclophosphamide (CY) and/or total lymphoid irradiation (TLI). Long-term skin graft and bone marrow survival was obtained across the major histocompatibility barrier (BALB/c into C57BL/6) using pregrafting conditioning with either fractionated TLI or the combination of CY with a single dose of TLI. CY alone and a single dose of TLI alone were relatively ineffective as regrafting immunosuppressive combinations. Allogeneic bone marrow was required for long-term skin graft survival with either conditioning regimen. Allogeneic marrow transplantation resulted in somewhat more deaths than syngeneic transplantation with both CY + TLI and fractionated TLI.

  8. Successful semiallogeneic and allogeneic bone marrow reconstitution of lethally irradiated adult mice mediated by neonatal spleen cells

    SciTech Connect

    LaFace, D.M.; Peck, A.B.

    1987-11-01

    Spleens of fetal/newborn mice less than 3-4 days of age contain a naturally occurring cell population capable of suppressing T-dependent and T-independent immune responses of third-party adult cells both in vitro and in vivo. We have utilized newborn spleen cells to prevent acute graft-versus-host (GVH) disease in lethally irradiated adult hosts reconstituted with semiallogeneic or even allogeneic bone marrow cells. Pretreatment of reconstituting cell populations with newborn spleen cells reduced the incidence of GVH disease from 100% to 20% in semiallogeneic and from 100% to 40% in allogeneic combinations. Long-term-surviving reconstituted hosts proved immunologically unresponsive to both donor and host histocompatibility antigens, yet possessed a fully chimeric lymphoid system responsive to T and B cell mitogens, as well as unrelated third-party alloantigens.

  9. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    SciTech Connect

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee; Choi, Hyeong-Jwa; Na, Tae-Young; Nemeno, Judee Grace E.; Lee, Jeong Ik; Yoon, Taek Joon; Choi, In-Soo; Lee, Minyoung; Lee, Jae-Seon; Kang, Young-Sun

    2015-08-07

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.

  10. Evaluation of the radioprotective effect of the leaf extract of Syzygium cumini (Jamun) in mice exposed to a lethal dose of gamma-irradiation.

    PubMed

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2003-06-01

    The effects of various concentrations (5, 10, 20, 30, 40, 50, 60, and 80 mg/kg body weight (b.wt.) of the leaf extracts of Syzygium cumini Linn. and Eugenia cumini (SCE, black plum, Jamun, family Myrtaceae) on the radiation-induced sickness and mortality in mice exposed to 10 Gy gamma-irradiation were studied. The treatment of mice with different doses of SCE, consecutively for five days before irradation, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the nondrug-treated irradiated controls. All doses of SCE provied protection against the gastrointestinal death increasing the survival by 66.66% after treatment with 20, 30, and 40 mg/kg SCE versus a 12% survival in the irradiated control group (oil + irradiation). Similarly, SCE provided protection against the radiation-induced bone marrow death in mice treated with 10-60 mg/kg b.wt. of SCE. However, the best protection was obtained for 30 mg/kg b.wt. SCE, where the number of, survivors after 30 days post-irradiation was highest (41.66%) when compared with the other doses of SCE. PMID:12866620

  11. Multiple Irradiation Capsule Experiment (MICE)-3B Irradiation Test of Space Fuel Specimens in the Advanced Test Reactor (ATR) - Close Out Documentation for Naval Reactors (NR) Information

    SciTech Connect

    M. Chen; CM Regan; D. Noe

    2006-01-09

    Few data exist for UO{sub 2} or UN within the notional design space for the Prometheus-1 reactor (low fission rate, high temperature, long duration). As such, basic testing is required to validate predictions (and in some cases determine) performance aspects of these fuels. Therefore, the MICE-3B test of UO{sub 2} pellets was designed to provide data on gas release, unrestrained swelling, and restrained swelling at the upper range of fission rates expected for a space reactor. These data would be compared with model predictions and used to determine adequacy of a space reactor design basis relative to fission gas release and swelling of UO{sub 2} fuel and to assess potential pellet-clad interactions. A primary goal of an irradiation test for UN fuel was to assess performance issues currently associated with this fuel type such as gas release, swelling and transient performance. Information learned from this effort may have enabled use of UN fuel for future applications.

  12. Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation

    SciTech Connect

    Matsuzaki, G.; Yoshikai, Y.; Kishihara, K.; Nomoto, K.

    1988-01-15

    Sequential appearance of the expression of T cell antigen receptor genes was investigated in the thymus of irradiated mice at the early stage after transplantation of Thy-1 congeneic H-2 compatible allogeneic bone marrow cells. The first cells to repopulate the thymus on day 7 after bone marrow transplantation were intrathymic radioresistant T cell precursors, which expanded mainly to CD4+CD8+ host-type thymocytes by day 14. A high level of gamma gene expression but a much reduced level of alpha and beta gene expression were detected in the host-type thymocytes on day 7. During regeneration of these cells, gamma-chain messages fell to low level and alpha and beta mRNA levels increased. The thymus of the recipients began to be repopulated by donor-derived T cells about 2 wk after bone marrow transplantation and was almost completely replaced by the third week. An ordered expression of gamma then beta and alpha-chain gene transcript was also observed in the donor-type thymocytes at the early stage after bone marrow transplantation. The use of thymocytes at early stage in whole-body irradiated bone marrow chimera provides a pertinent source for investigating the molecular mechanism of T cell differentiation in adult thymus.

  13. Transgenerational inheritance of enhanced susceptibility to radiation-induced medulloblastoma in newborn Ptch1+/− mice after paternal irradiation

    PubMed Central

    Tanno, Barbara; Meschini, Roberta; Cordelli, Eugenia; Benassi, Barbara; Longobardi, Maria Grazia; Izzotti, Alberto; Pulliero, Alessandra; Mancuso, Mariateresa; Pacchierotti, Francesca

    2015-01-01

    The hypothesis of transgenerational induction of increased cancer susceptibility after paternal radiation exposure has long been controversial because of inconsistent results and the lack of a mechanistic interpretation. Here, exploiting Ptch1 heterozygous knockout mice, susceptible to spontaneous and radiation-induced medulloblastoma, we show that exposure of paternal germ cells to 1 Gy X-rays, at the spermatogonial stage, increased by a considerable 1.4-fold the offspring susceptibility to medulloblastoma induced by neonatal irradiation. This effect gained further biological significance thanks to a number of supporting data on the immunohistochemical characterization of the target tissue and preneoplastic lesions (PNLs). These results altogether pointed to increased proliferation of cerebellar granule cell precursors and PNLs cells, which favoured the development of frank tumours. The LOH analysis of tumor DNA showed Ptch1 biallelic loss in all tumor samples, suggesting that mechanisms other than interstitial deletions, typical of radiation-induced medulloblastoma, did not account for the observed increased cancer risk. This data was supported by comet analysis showing no differences in DNA damage induction and repair in cerebellar cells as a function of paternal irradiation. Finally, we provide biological plausibility to our results offering evidence of a possible epigenetic mechanism of inheritance based on radiation-induced changes of the microRNA profile of paternal sperm. PMID:26452034

  14. Passive transfer with serum and IgG antibodies of irradiated cercaria-induced resistance against Schistosoma mansoni in mice

    SciTech Connect

    Mangold, B.L.; Dean, D.A.

    1986-04-01

    The role of humoral immunity to Schistosoma mansoni infection in C57BL/6J mice was examined by employing a passive transfer system. Sera from highly resistant mice that had been exposed to two or three immunizations with 50-kilorad-gamma-irradiated cercariae were tested for their ability to transfer protection against S. mansoni challenge. All five batches of serum tested were observed to have protective activity. Immune serum recipients exhibited statistically significant reductions in challenge worm burdens of 20 to 50% compared with recipients of normal serum or no serum. The most consistent level of resistance was obtained when immune serum was administered several days post-challenge, i.e., at a time coincident with schistosomulum residence in the lungs. Furthermore, it was shown that the protective activity in immune serum was associated with factors that bind to staphylococcal protein A and that are precipitated by 50% ammonium sulfate; thus it appears that the protective factors in immune serum are IgG antibodies.

  15. Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

    PubMed

    Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK.

  16. Interleukin 1 alpha stimulates hemopoiesis but not tumor cell proliferation and protects mice from lethal total body irradiation

    SciTech Connect

    Constine, L.S.; Harwell, S.; Keng, P.; Lee, F.; Rubin, P.; Siemann, D. )

    1991-03-01

    Interleukin 1 alpha (IL-1) is a polypeptide/glycoprotein growth factor with multiple functions including the modulation of hematopoietic cell proliferation and differentiation. In vivo studies were performed with C57BL/6J mice injected with 0, 0.2, or 2.0 micrograms of IL-1 24 hr before or after lethal total body irradiation (TBI) (9.5 Gy). More mice in the groups administered IL-1 before TBI survived (90% of the 2.0 micrograms group) than those treated 2 or 24 hr after TBI, which was still slightly superior to the uninjected group, which all died within 15 days (p = .0001). Proliferation of bone marrow granulocyte/macrophage colonies following split dose TBI was also greatest for mouse groups treated with IL-1 prior to TBI. These experiments support data from other investigators that IL-1 stimulation of BM is related to IL-1 timing with respect to TBI. Stimulation of hemopoiesis was also assessed in terms of changes in peripheral blood and BM cell numbers and cell cycle kinetics using an electronic particle counter and flow cytometric techniques. Mice injected with 2 micrograms of IL-1 showed an initial decline (at 3-6 hr) and then a selective proliferation (24-48 hr) of early and more committed progenitor cells to 125% and 200% of control values, respectively. Peripheral blood counts rose accordingly. Cells in S and G2/M phases increased over 10 hr and then declined in number. It thus appeared that some synchronization of cell cycling occurred, which might place cells in a more radioresistant phase of the cell cycle. The glutathione (GSH) content and synthesis in BM cells were measured by isocratic paired-ion high performance liquid chromatography and 35S-labelled cysteine incorporation into the GSH tripeptide. An increase in cellular GSH content and synthesis was demonstrated following IL-1 which lasted 24 hr.

  17. [The influence of consecutive application of B-190 preparation and interleukin-1beta on survival rate and bone marrow hematopoiesis of irradiated mice].

    PubMed

    Grebeniuk, A N; Zatsepin, V V; Aksenova, N V; Nazarov, V B; Vlasenko, T N

    2010-01-01

    The purpose of research was the experimental estimation of efficiency of consecutive application of a radioprotector B-190 and means of emergency therapy of radiating injury interleukin-1beta at acute irradiation. An estimation of treatment-and-prophylactic action of the given circuit of introduction of preparations carried out by studying 30 day-survival and average life expectancy of the lost animals, research of bone marrow hemopoiesis. It is established, that consecutive application of a radioprotector B-190 in a doze of 50 mg/kg for 15 mines up to an irradiation and interleukin-1beta in a doze of 50 mkg/kg through 15 mines after irradiating increases survival and prevents decrease in quantity of CFU-S9 at the irradiated mice in the greater degree, than their isolated introduction. PMID:20968059

  18. Threshold-like dose of local beta irradiation repeated throughout the life span of mice for induction of skin and bone tumors

    SciTech Connect

    Ootsuyama, A.; Tanooka, H. )

    1991-01-01

    The backs of female ICR mice were irradiated with beta rays from 90Sr-90Y three times a week throughout life. Previously we observed 100% tumor incidence at five different dose levels ranging from 1.5 to 11.8 Gy per exposure, but no tumor on repeated irradiation with 1.35 Gy for 300 days. In the present study, delay of tumor development was again seen at a dose of 1.5 Gy per exposure, with further delay at 1.0 Gy. The final tumor incidence was 100% with these two doses. At 0.75 Gy per exposure, no tumor appeared within 790 days after the start of irradiation, but one osteosarcoma and one squamous cell carcinoma did finally appear. These findings indicate a threshold-like response of tumor induction in this repeated irradiation system and further suggest that the apparent threshold may be somewhat less than 0.75 Gy per exposure.

  19. HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.

    PubMed

    Park, Hae-Ran; Jo, Sung-Kee; Choi, Nam-Hee; Jung, Uhee

    2012-05-01

    Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway. PMID:22439601

  20. HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.

    PubMed

    Park, Hae-Ran; Jo, Sung-Kee; Choi, Nam-Hee; Jung, Uhee

    2012-05-01

    Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.

  1. [Therapeutic effect of rmIL-12 combined with G-CSF on acute radiation sickness produced by γ-ray irradiation in mice].

    PubMed

    Wang, Li; Zhai, Rui-Ren; Pang, Zhao-Xia; Zhang, Chao; Yu, Chang-Lin

    2012-08-01

    The aim of this study is to observe the therapeutic effect of recombinant murine interleukin 12 (rmIL-12) combining with granulocyte colony stimulating factor (G-CSF) on mice irradiated by γ-rays. 56 BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group, rmIL-12 treatment group, G-CSF treatment group and combination therapy (rmIL-12 plus G-CSF) group. rmIL-12 20 µg/kg was administrated intraperitoneally at 1 h following irradiation, and was administrated every 3 days after irradiation for 4 times in rmIL-12 treatment group. G-CSF 100 µg/kg was administrated subcutaneously the 2 h following irradiation for 14 d in G-CSF treatment group. The dose and method of rmIL-12 and G-CSF in combination therapy group were same as in rmIL-12 group and G-CSF group. The general status of mice were observed twice a day, the changes in body weight, peripheral blood cell (WBC and Plt) counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on day 14 and 28 after irradiation. The results showed that WBC count recovery time in combination therapy group was significantly earlier than that of the control group (7 d vs 11 d), WBC count recovery velocity in the combination therapy group was no significant different from that of the G-CSF treatment group. Combined therapy significantly promoted Plt count recovery, resulting in less profound nadirs (16.5% vs 8.1%, P < 0.01) and rapid recovery to normal levels (11 d vs 14 d), Plt count recovery velocity in the combination therapy group was no significant different from that of the rmIL-12 treatment group. Culture of bone marrow cells in semi-solid medium also demonstrated that combination of rmIL-12 and G-CSF could stimulate bone marrow cells to form more CFU-GM and CFU-Mix than those of the irradiation control group in vitro on day 14 and 28 after irradiation (P < 0.05). It is concluded that the combination of rmIL-12 and G

  2. The Lack of Cytotoxic Effect and Radioadaptive Response in Splenocytes of Mice Exposed to Low Level Internal β-Particle Irradiation through Tritiated Drinking Water in Vivo

    PubMed Central

    Flegal, Matthew; Blimkie, Melinda; Roch-Lefevre, Sandrine; Gregoire, Eric; Klokov, Dmitry

    2013-01-01

    Health effects of tritium, a β-emitter and a by-product of the nuclear industry, is a subject of significant controversy. This mouse in vivo study was undertaken to monitor biological effects of low level tritium exposure. Mice were exposed to tritiated drinking water (HTO) at 10 KBq/L, 1 MBq/L and 20 MBq/L concentrations for one month. The treatment did not result in a significant increase of apoptosis in splenocytes. To examine if this low level tritium exposure alters radiosensitivity, the extracted splenocytes were challenged in vitro with 2 Gy γ-radiation, and apoptotic responses at 1 and 24 h were measured. No alterations in the radiosensitivity were detected in cells from mice exposed to tritium compared to sham-treated mice. In contrast, low dose γ-irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive response. Overall, our data suggest that low concentrations of tritium given to mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor do they change cellular sensitivity to additional high dose γ-radiation. The latter may be considered as the lack of a radioadaptive response, typically observed after low dose γ-irradiation. PMID:24317437

  3. The lack of cytotoxic effect and radioadaptive response in splenocytes of mice exposed to low level internal β-particle irradiation through tritiated drinking water in vivo.

    PubMed

    Flegal, Matthew; Blimkie, Melinda; Roch-Lefevre, Sandrine; Gregoire, Eric; Klokov, Dmitry

    2013-12-05

    Health effects of tritium, a β-emitter and a by-product of the nuclear industry, is a subject of significant controversy. This mouse in vivo study was undertaken to monitor biological effects of low level tritium exposure. Mice were exposed to tritiated drinking water (HTO) at 10 KBq/L, 1 MBq/L and 20 MBq/L concentrations for one month. The treatment did not result in a significant increase of apoptosis in splenocytes. To examine if this low level tritium exposure alters radiosensitivity, the extracted splenocytes were challenged in vitro with 2 Gy γ-radiation, and apoptotic responses at 1 and 24 h were measured. No alterations in the radiosensitivity were detected in cells from mice exposed to tritium compared to sham-treated mice. In contrast, low dose γ-irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive response. Overall, our data suggest that low concentrations of tritium given to mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor do they change cellular sensitivity to additional high dose γ-radiation. The latter may be considered as the lack of a radioadaptive response, typically observed after low dose γ-irradiation.

  4. Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after {gamma}-irradiation

    SciTech Connect

    Maruyama, Masaki; Yamamoto, Takashi; Kohara, Yuki; Katsuragi, Yoshinori; Mishima, Yukio; Aoyagi, Yutaka; Kominami, Ryo; E-mail: rykomina@med.niigata-u.ac.jp

    2007-03-02

    Mouse strains exhibit different susceptibilities to {gamma}-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of {gamma}-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas.

  5. [Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice].

    PubMed

    Lomaeva, M G; Fomenko, L A; Vasil'eva, G V; Bezlepkin, V G

    2016-01-01

    Evidence is presented indicating the differences in the polymorphism of microsatellite (MCS) repeats in DNA of somatic tissues in the offspring of BALB/c mice of different sex born from preconceptionally irradiated males or females. Brother-sister groups of the offspring born by non-irradiated parental pairs were compared with the offspring obtained after the irradiation of one parent in the same pairs. The number of MCS repeats in DNA of somatic tissues of the offspring from irradiated males or females was compared by a polymerase chain reaction using an arbitrary primer. It was found that changes in the polymorphism of the number of MCS repeats in the offspring from the males irradiated at a dose of 2 Gy was insignificant as compared with the offspring from control animals. In the offspring born by the females irradiated at a dose of 2 Gy (which does not impair the reproductive capacity), a statistically significant increase in the polymorphism was observed. Changes in the polymorphism were different in the offspring of different sex. A higher level of polymorphism was revealed in the female offspring born from the females of the F0 generation after their irradiation at a dose of 2 Gy. The increase in the polymorphism of the number of MCS repeats in DNA was more pronounced in postmitotic tissues compared with proliferating tissues. PMID:27534065

  6. [Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice].

    PubMed

    Lomaeva, M G; Fomenko, L A; Vasil'eva, G V; Bezlepkin, V G

    2016-01-01

    Evidence is presented indicating the differences in the polymorphism of microsatellite (MCS) repeats in DNA of somatic tissues in the offspring of BALB/c mice of different sex born from preconceptionally irradiated males or females. Brother-sister groups of the offspring born by non-irradiated parental pairs were compared with the offspring obtained after the irradiation of one parent in the same pairs. The number of MCS repeats in DNA of somatic tissues of the offspring from irradiated males or females was compared by a polymerase chain reaction using an arbitrary primer. It was found that changes in the polymorphism of the number of MCS repeats in the offspring from the males irradiated at a dose of 2 Gy was insignificant as compared with the offspring from control animals. In the offspring born by the females irradiated at a dose of 2 Gy (which does not impair the reproductive capacity), a statistically significant increase in the polymorphism was observed. Changes in the polymorphism were different in the offspring of different sex. A higher level of polymorphism was revealed in the female offspring born from the females of the F0 generation after their irradiation at a dose of 2 Gy. The increase in the polymorphism of the number of MCS repeats in DNA was more pronounced in postmitotic tissues compared with proliferating tissues.

  7. Effect of low-level laser therapy on irradiated parotid glands--study in mice.

    PubMed

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028  cm2, 3.57  W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71  J/cm2) or 4 J (40 s, 135  J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results. PMID:26502234

  8. Effect of low-level laser therapy on irradiated parotid glands—study in mice

    NASA Astrophysics Data System (ADS)

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028 cm2, 3.57 W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71 J/cm2) or 4 J (40 s, 135 J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

  9. Early cognitive changes due to whole body γ-irradiation: a behavioral and diffusion tensor imaging study in mice.

    PubMed

    Kumar, Mayank; Haridas, Seenu; Trivedi, Richa; Khushu, Subhash; Manda, Kailash

    2013-10-01

    Radiation-induced aberration in the neuronal integrity and cognitive functions are well known. However, there is a lacuna between sparsely reported immediate effects and the well documented delayed effects of radiation on cognitive functions. The present study was aimed at investigating the radiation-dose dependent incongruities in the early cognitive changes, employing two approaches, behavioral functions and diffusion tensor imaging (DTI). Six-month old female C57BL/6 mice were exposed to whole-body doses of 2, 5 and 8 Gy of γ-radiation and 24 h after exposure, the stress and anxiety levels were examined in the open-field test (OFT). Forty-eight hours after irradiation, the hippocampal dependent recognition memory was observed by the novel object recognition task (NORT), and the cognitive functions related to memory processing and recall were tested using the elevated plus maze (EPM). Magnetic resonance imaging, including diffusion tensor imaging (DTI) was done at 48-hour post-irradiation to visualize microstructural damage in brain parenchyma. Our results indicate a complex dose independent effect on the cognitive functions immediately after exposure to gamma rays. Radiation exposure caused short-term memory dysfunctions at lower doses, which were seen to be abrogated at higher doses, but the long-term memory processing was disrupted at higher doses. The hippocampus emerged as one of the sensitive regions to be affected by whole-body exposure to gamma rays, which led to profound immediate alterations in cognitive functions. Furthermore, the results indicate a cognitive recovery process, which might be dependent on the extent of damage to the hippocampal region. The present study also emphasizes the importance of further research to unravel the complex pattern of neurobehavioral responses immediately following ionizing radiation exposure.

  10. Site requirements and kinetics of immune-dependent elimination of intravascularly administered lung stage schistosomula in mice immunized with highly irradiated cercariae of Schistosoma mansoni

    SciTech Connect

    Mangold, B.L.; Dean, D.A.; Coulson, P.S.; Wilson, R.A.

    1986-03-01

    Experiments were performed to compare the migration and survival of 75Se-labeled schistosomes, introduced by percutaneous cercarial exposure or by intravascular administration of 7-day-old lung stage schistosomula, in control and irradiated cercaria-immunized mice. Schistosomula were intravascularly introduced into the lungs, systemic organs and liver by injection via the femoral vein (FV), left ventricle (LV), and superior mesenteric vein (SMV), respectively. The fate of challenge larvae was examined by autoradiography of host tissues and by recovery of adult worms. It was found that both normal and immune elimination were site-dependent. In control mice 45%-60% of cercarial penetrants and lung schistosomula injected into the FV and LV were recoverable as adult worms, while a significantly greater number (70%-85%) were recoverable when lung schistosomula were injected into the SMV. In immunized mice, parasites introduced as either cercariae or FV-injected schistosomula were both highly sensitive to immune elimination. LV-injected schistosomula were also sensitive but to a slightly lesser degree. In contrast, schistosomula placed directly in the liver by SMV injection were totally insensitive to immune elimination. It was concluded that elimination of schistosomula in irradiated cercaria-immunized mice occurs in the lungs and/or in the systemic organs, but not in the liver. Also, it was concluded that immune elimination is not a rapid process, since more than 7 days were required after intravascular challenge for the development of demonstrable differences between control and immunized mice.

  11. [Features of behavioral reactions of chronically irradiated mice in the raised crosswise labyrinth with various genetically determined radiosensitivity and possibilities of their modification by the fungal biopolymer complex].

    PubMed

    Seniuk, O F; Gorovoĭ, L F; Kovalev, V A; Palamar, L A; Krul', N I; Zhidkov, A V; Chemerskiĭ, G F; Kireev, S I; Khatuntseva, I V

    2013-01-01

    Structural elements of the central nervous system--neurons, along with the higher neuroendocrine structures and the hypothalamus centres, show high sensitivity to a chronic action of low doses of ionizing radiation (IR) in view of their extreme enrichment by phospholipids and intensive supply by oxygen, creating favorable conditions for the development of oxidizing stress. Stressful influences cause negative emotions in the behaviour of animals manifested as fear or uneasiness. The study represents the results of comparative research into the behavioral reactions characterized by uneasiness in the Balb/c and C57bl/6 mice exposed to a chronic irradiation at low doses. The chitin-melanin-glucan complex from fungi Fomes fomentarius (ChMG) was approved as an adaptive agent. It has been shown that under identical conditions, deposition levels of radionuclides 137Cs and 90Sr are raised in mice with IR hypersensitivity--line Balb/c, in comparison with less radio sensitive mice--line C57bl/6. Simultaneously, Balb/c mice were observed to exhibit the signs of a more anxious behaviour in the new environment. Chronic external and internal radiation exposure to rare ionizing radiation at low doses promotes strengthening of anxiety and phobic reactions in mice with IR hypersensitivity. The use of ChMG in animals neutralized the increase in anxiety and phobic reactions after a prolonged irradiation, thus indicating the presence in ChMG of the anxiolitic activity along with the above mentioned powerful radiosorbent, antioxidant, gene protective and immunomodulatory properties.

  12. Neurobehavioral changes in mice exposed to fast neutrons in utero.

    PubMed

    Ishida, Yuka; Ohmachi, Yasushi; Takai, Nobuhiko; Hiraoka, Takeshi; Ogiu, Toshiaki; Nishikawa, Tetsu; Nishimura, Yoshikazu; Shimada, Yoshiya

    2011-01-01

    Epidemiological studies have revealed that radiation causes brain development abnormalities in atomic bomb survivors exposed in utero. Rat and mouse studies have also shown that prenatal exposure to low-linear energy transfer radiation induces developmental brain anomalies. Because the effects of prenatal irradiation on adult behavior patterns remain largely unknown, the present study investigated the effects of neutron exposure in utero on postnatal behavior patterns in mice. [C57BL/6J × C3H/He] hybrid (B6C3F1) mice were exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02-0.2 Gy) or Cs-137 gamma-rays (0.2-1.5 Gy) on embryonic day 13.5. At 5.5-8 months of age, the neurobehavior of male offspring was examined by Rota-rod treadmill and locomotor activity. The accumulation of radio-labeled drug at muscarinic acetylcholine and serotonin receptors in mice from control and neutron-irradiated groups was determined by the tracer method. Locomotor activity during the dark period increased in the 0.02 Gy neutron-irradiated group. Furthermore, at 5.5 months of age, tracer binding in vivo to the muscarinic acetylcholine increased and to the serotonin receptors decreased in the 0.02 Gy neutron-irradiated group. In conclusion, the present study reveals that a certain "low-dose window" may exist for radiation-induced changes in neurobehavior and binding to neurotransmitter receptors, because there was correlation in neurobehavior and binding to neurotransmitter receptors in the 0.02 Gy neutron-irradiated group though there was not correlation in the neutron-irradiated groups more than 0.05 Gy. PMID:21422737

  13. Neurobehavioral changes in mice exposed to fast neutrons in utero.

    PubMed

    Ishida, Yuka; Ohmachi, Yasushi; Takai, Nobuhiko; Hiraoka, Takeshi; Ogiu, Toshiaki; Nishikawa, Tetsu; Nishimura, Yoshikazu; Shimada, Yoshiya

    2011-01-01

    Epidemiological studies have revealed that radiation causes brain development abnormalities in atomic bomb survivors exposed in utero. Rat and mouse studies have also shown that prenatal exposure to low-linear energy transfer radiation induces developmental brain anomalies. Because the effects of prenatal irradiation on adult behavior patterns remain largely unknown, the present study investigated the effects of neutron exposure in utero on postnatal behavior patterns in mice. [C57BL/6J × C3H/He] hybrid (B6C3F1) mice were exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02-0.2 Gy) or Cs-137 gamma-rays (0.2-1.5 Gy) on embryonic day 13.5. At 5.5-8 months of age, the neurobehavior of male offspring was examined by Rota-rod treadmill and locomotor activity. The accumulation of radio-labeled drug at muscarinic acetylcholine and serotonin receptors in mice from control and neutron-irradiated groups was determined by the tracer method. Locomotor activity during the dark period increased in the 0.02 Gy neutron-irradiated group. Furthermore, at 5.5 months of age, tracer binding in vivo to the muscarinic acetylcholine increased and to the serotonin receptors decreased in the 0.02 Gy neutron-irradiated group. In conclusion, the present study reveals that a certain "low-dose window" may exist for radiation-induced changes in neurobehavior and binding to neurotransmitter receptors, because there was correlation in neurobehavior and binding to neurotransmitter receptors in the 0.02 Gy neutron-irradiated group though there was not correlation in the neutron-irradiated groups more than 0.05 Gy.

  14. Adverse Reproductive and Developmental Health Outcomes Following Prenatal Exposure to a Hydraulic Fracturing Chemical Mixture in Female C57Bl/6 Mice.

    PubMed

    Kassotis, Christopher D; Bromfield, John J; Klemp, Kara C; Meng, Chun-Xia; Wolfe, Andrew; Zoeller, R Thomas; Balise, Victoria D; Isiguzo, Chiamaka J; Tillitt, Donald E; Nagel, Susan C

    2016-09-01

    Unconventional oil and gas operations using hydraulic fracturing can contaminate surface and groundwater with endocrine-disrupting chemicals. We have previously shown that 23 of 24 commonly used hydraulic fracturing chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors in a human endometrial cancer cell reporter gene assay and that mixtures can behave synergistically, additively, or antagonistically on these receptors. In the current study, pregnant female C57Bl/6 dams were exposed to a mixture of 23 commonly used unconventional oil and gas chemicals at approximately 3, 30, 300, and 3000 μg/kg·d, flutamide at 50 mg/kg·d, or a 0.2% ethanol control vehicle via their drinking water from gestational day 11 through birth. This prenatal exposure to oil and gas operation chemicals suppressed pituitary hormone concentrations across experimental groups (prolactin, LH, FSH, and others), increased body weights, altered uterine and ovary weights, increased heart weights and collagen deposition, disrupted folliculogenesis, and other adverse health effects. This work suggests potential adverse developmental and reproductive health outcomes in humans and animals exposed to these oil and gas operation chemicals, with adverse outcomes observed even in the lowest dose group tested, equivalent to concentrations reported in drinking water sources. These endpoints suggest potential impacts on fertility, as previously observed in the male siblings, which require careful assessment in future studies. PMID:27560547

  15. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice

    PubMed Central

    Deng, Liufu; Liang, Hua; Burnette, Byron; Beckett, Michael; Darga, Thomas; Weichselbaum, Ralph R.; Fu, Yang-Xin

    2014-01-01

    High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death–ligand 1 (PD-L1, also called B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronically inflamed tissues and tumors. Here, we demonstrate that PD-L1 was upregulated in the tumor microenvironment after IR. Administration of anti–PD-L1 enhanced the efficacy of IR through a cytotoxic T cell–dependent mechanism. Concomitant with IR-mediated tumor regression, we observed that IR and anti–PD-L1 synergistically reduced the local accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs), which suppress T cells and alter the tumor immune microenvironment. Furthermore, activation of cytotoxic T cells with combination therapy mediated the reduction of MDSCs in tumors through the cytotoxic actions of TNF. Our data provide evidence for a close interaction between IR, T cells, and the PD-L1/PD-1 axis and establish a basis for the rational design of combination therapy with immune modulators and radiotherapy. PMID:24382348

  16. Suppression of unprimed T and B cells in antibody responses by irradiation-resistant and plastic-adherent suppressor cells in Toxoplasma gondii-infected mice.

    PubMed Central

    Suzuki, Y; Kobayashi, A

    1983-01-01

    In the acute phase of Toxoplasma infection, the function of both helper T and B cells was suppressed in primary antibody responses to dinitrophenol (DNP)-conjugated protein antigens. During the course of infection, the suppressive effect on T cells seems to continue longer than that on B cells, since suppression in responses to sheep erythrocytes, a T-dependent antigen, persisted longer than those to DNP-Ficoll, a T-independent antigen. Plastic-adherent cells from the spleens of Toxoplasma-infected and X-irradiated (400 rads) mice had strong suppressor activity in primary anti-sheep erythrocyte antibody responses of normal mouse spleen cells in vitro. These data suggest that the activation of irradiation-resistant and plastic-adherent suppressor cells causes the suppression of both T and B cells in Toxoplasma-infected mice. PMID:6219954

  17. Host sex-dependent growth of potential Thy-1+ lymphoma cells that appear in the thymus of X-irradiated NFS mice

    SciTech Connect

    Mori, N.; Takamori, Y. )

    1990-01-01

    During the course of studies designed to detect potentially leukemic cells in radiation lymphomagenesis, using an opposite-sex (male----female) transplantation assay method, we previously found that potential Thy-1- lymphoma cells are generated in the bone marrow of NFS mice exposed to a split-dose irradiation (1.7 Gy X 4), while potential Thy-1+ lymphoma cells are not detectable. In this report, using a (female----male) intrathymic transplantation assay system we show that potential Thy-1+ lymphoma cells were generated in the thymus of female NFS mice exposed to split-dose irradiation, and reconfirm that such cells were not detected in the (male----female) transplantation system. These results demonstrate that the detection of potential Thy-1+ lymphoma cells strictly depends on the transplantation system.

  18. Ultrastructure and light microscope analysis of intact skin after a varying number of low level laser irradiations in mice.

    PubMed

    Iyomasa, Mamie Mizusaki; Leão, Juliane Caroline; Rizzi, Élen Camargo; Issa, João Paulo Mardegan; Dias, Fernando José; Watanabe, Ii-sei; Iyomasa, Daniela Mizusaki

    2014-01-01

    Low level laser therapy (LLLT) has been used to relieve pain, inflammation, and wound healing processes. Thus, the skin is overexposed to laser and this effect is not completely understood. This study analyzed the effects of the number of laser applications (three, six, and 10) on the intact skin of the masseteric region in mice of strain HRS/J. The animals (n = 30) were equally divided into control (0 J/cm(2)) and irradiated (20 J/cm(2)), and each of these groups was further equally divided according to the number of laser applications (three, six, and 10) and underwent LLLT on alternate days. Samples were analyzed by light microscopy and transmission electron microscope (TEM). The animals receiving applications exhibited open channels more dilated between the keratinocytes and photobiomodulation effect on endothelial cells and fibroblasts by TEM. Under the light microscope after 10 laser applications, the type I collagen decreased (P < 0.05) compared to the three and six applications. Under these experimental conditions, all numbers of applications provided photobiomodulatory effect on the epidermis and dermis, without damage. More studies are needed to standardize the energy density and number of applications recommended for laser therapy to have a better cost-benefit ratio associated with treatment.

  19. High-fat diet exacerbates inflammation and cell survival signals in the skin of ultraviolet B-irradiated C57BL/6 mice

    SciTech Connect

    Meeran, Syed M.; Singh, Tripti; Nagy, Tim R.; Katiyar, Santosh K.

    2009-12-15

    Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been implicated in various skin diseases. We formulated the hypothesis that a high-fat diet may influence the UV-induced inflammatory responses in the skin. C57BL/6 mice were fed a high-fat diet or control diet and exposed to UVB radiation (120 mJ/cm{sup 2}) three times/week for 10 weeks. The mice were then sacrificed and skin and plasma samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. We found that the levels of inflammatory biomarkers were increased in the UVB-exposed skin of the mice fed the high-fat diet than the UVB-exposed skin of the mice fed the control diet. The levels of inflammatory biomarkers of early responses to UVB exposure (e.g., myeloperoxidase, cyclooxygenase-2, prostaglandin-E{sub 2}), proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser{sup 473}) were higher in high-fat-diet-fed mouse skin than control-diet-fed mouse skin. The plasma levels of insulin growth factor-1 were greater in the UVB-irradiated mice fed the high-fat diet than the UVB-irradiated mice fed the control diet, whereas the levels of plasma adiponectin were significantly lower. This pronounced exacerbation of the UVB-induced inflammatory responses in the skin of mice fed a high-fat diet suggests that high-fat diet may increase susceptibility to inflammation-associated skin diseases, including the risk of skin cancer.

  20. Single-Dose and Fractionated Irradiation Promote Initiation and Progression of Atherosclerosis and Induce an Inflammatory Plaque Phenotype in ApoE{sup -/-} Mice

    SciTech Connect

    Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.

    2008-07-01

    Purpose: Increased risk of atherosclerosis and stroke has been demonstrated in patients receiving radiotherapy for Hodgkin's lymphoma and head-and-neck cancer. We previously showed that 14 Gy to the carotid arteries of hypercholesterolemic ApoE{sup -/-} mice resulted in accelerated development of macrophage-rich, inflammatory atherosclerotic lesions. Here we investigate whether clinically relevant fractionated irradiation schedules and lower single doses also predispose to an inflammatory plaque phenotype. Methods and Materials: ApoE{sup -/-} mice were given 8 or 14 Gy, or 20 x 2.0 Gy in 4 weeks to the neck, and the carotid arteries were subsequently examinated for presence of atherosclerotic lesions, plaque size, and phenotype. Results: At 4 weeks, early atherosclerotic lesions were found in 44% of the mice after single doses of 14 Gy but not in age-matched controls. At 22 to 30 weeks after irradiation there was a twofold increase in the mean number of carotid lesions (8-14 Gy and 20 x 2.0 Gy) and total plaque burden (single doses only), compared with age-matched controls. The majority of lesions seen at 30 to 34 weeks after fractionated irradiation or 14-Gy single doses were granulocyte rich (100% and 63%, respectively), with thrombotic features (90% and 88%), whereas these phenotypes were much less common in age-matched controls or after a single dose of 8 Gy. Conclusions: We showed that fractionated irradiation accelerated the development of atherosclerosis in ApoE{sup -/-} mice and predisposed to the formation of an inflammatory, thrombotic plaque phenotype.

  1. Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice

    PubMed Central

    Xu, Guoshun; Wu, Hongying; Zhang, Junling; Li, Deguan; Wang, Yueying; Wang, Yingying; Zhang, Heng; Lu, Lu; Li, Chengcheng; Huang, Song; Xing, Yonghua; Zhou, Daohong; Meng, Aimin

    2016-01-01

    Exposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16Ink4a in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury. PMID:26086617

  2. Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice.

    PubMed

    Xu, Guoshun; Wu, Hongying; Zhang, Junling; Li, Deguan; Wang, Yueying; Wang, Yingying; Zhang, Heng; Lu, Lu; Li, Chengcheng; Huang, Song; Xing, Yonghua; Zhou, Daohong; Meng, Aimin

    2015-10-01

    Exposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16(Ink4a) in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury.

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

    SciTech Connect

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

    1986-11-01

    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.

  4. Effects of topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice.

    PubMed

    Burke, K E; Clive, J; Combs, G F; Commisso, J; Keen, C L; Nakamura, R M

    2000-01-01

    This study investigates whether supplementation with topical RRR-alpha-tocopherol (Eol), topical RRR-alpha-tocopheryl succinate, and oral RRR-alpha-tocopheryl acetate can reduce the incidence of acute and chronic damage to the skin (i.e., sunburn and pigmentation and skin cancer, respectively) induced by ultraviolet (UV) irradiation to mice. Groups of twenty Skh:2 female hairless pigmented mice were treated with 1) lotion vehicle, 2) 5% Eol lotion, 3) 5% topical RRR-alpha-tocopheryl succinate lotion, or 4) lotion vehicle and oral RRR-alpha-tocopheryl acetate. Within each group, 15 mice were exposed to 0.24 J/cm2 of UV-B radiation three times per week. The animals' weights and food intakes were monitored, and the vitamin E concentrations of skin, liver, and adipose tissue were measured to determine whether the topical Eol resulted in significant tissue levels. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin concentrations of Eol, as well as levels in the adipose tissue, were increased after topical application. Mice treated with each form of vitamin E showed no signs of toxicity and had significantly less acute and chronic skin damage induced by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

  5. [The influence of consecutive application of radioprotector B-190 and interleukin-1beta on changes of number of peripheral blood leucocytes and functional status of neutrophils of irradiated mice].

    PubMed

    Grebeniuk, A N; Aksenova, N V; Zatsepin, V V; Nazarov, V B; Vlasenko, T N

    2013-01-01

    The estimation of efficiency of consecutive application of radioprotector B-190 and interleukin-1beta administered at early times after acute irradiation by studying the changes of the number of peripheral blood leukocytes, neutrophils and lymphocytes, as well as cytochemical research into the contents of glycogen, myeloperoxidase and alkaline phosphatase in neutrophils of the irradiated mice was carried out. It is established that administration of radioprotector B-190 at a doze of 50 mg/kg for 15 minutes before irradiation and interleukin-1beta at a doze of 50 mkg/kg for 15 minutes after irradiation reduces the expressiveness of post-irradiation leukopenia, accelerates restoration of the number of neutrophils and lymphocytes in peripheral blood, normalizes the functional status of neutrophils of irradiated mice to a greater degree than their isolated introduction. PMID:24450210

  6. Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part I. Experimental observations.

    PubMed

    Peng, Yuanlin; Brown, Natalie; Finnon, Rosemary; Warner, Christy L; Liu, Xianan; Genik, Paula C; Callan, Matthew A; Ray, F Andrew; Borak, Thomas B; Badie, Christophe; Bouffler, Simon D; Ullrich, Robert L; Bedford, Joel S; Weil, Michael M

    2009-04-01

    Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various times postirradiation. Although 56Fe ions were initially some two to three times more effective than X or gamma rays in inducing PU.1 deletions, by 1 month postirradiation, the proportions of cells with PU.1 deletions were similar for the HZE particles and the sparsely ionizing radiations. These results indicate that while 56Fe ions are more effective in inducing PU.1 deletions, they are also more effective in causing collateral damage that removes hit cells from the bone marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate for the incidence of radiation-induced AML measured in large-scale mouse studies. If so, PU.1 loss could be used to systematically assess the potential leukemogenic effects of other ions and energies in the space radiation environment.

  7. Prenatal diagnosis of achondrogenesis.

    PubMed

    Golbus, M S; Hall, B D; Filly, R A; Poskanzer, L B

    1977-09-01

    Severe rhizomelic and mesomelic dwarfism was demonstrated in a 20-week gestation fetus by amniography. A systematic progressive approach to prenatal diagnosis in the absence of a definitive diagnosis and the use of contrast radiography is discussed. PMID:894421

  8. Invasive Prenatal Testing

    PubMed Central

    Hunter, A.

    1988-01-01

    Invasive prenatal diagnosis is a major diagnostic tool which is used in modern obstetrical care. A synopsis of these techniques is provided to assist the family practitioner in providing this information to his patients. PMID:21253097

  9. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training.

    PubMed

    Raber, Jacob; Weber, Sydney J; Kronenberg, Amy; Turker, Mitchell S

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to (28)Si ions (263 MeV/n, LET=78keV/μm; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to (48)Ti ions (1 GeV/n, LET=107keV/μm; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used (40)Ca ion beams (942 MeV/n, LET=90keV/μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. (40)Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to (40)Ca ions had sex-dependent effects on response to shock. (40)Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, (40)Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus (40)Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of (40)Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions. PMID:27345201

  10. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

    PubMed Central

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. PMID:23908553

  11. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

    NASA Astrophysics Data System (ADS)

    Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

  12. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training.

    PubMed

    Raber, Jacob; Weber, Sydney J; Kronenberg, Amy; Turker, Mitchell S

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to (28)Si ions (263 MeV/n, LET=78keV/μm; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to (48)Ti ions (1 GeV/n, LET=107keV/μm; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used (40)Ca ion beams (942 MeV/n, LET=90keV/μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. (40)Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to (40)Ca ions had sex-dependent effects on response to shock. (40)Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, (40)Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus (40)Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of (40)Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

  13. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.

    PubMed

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.

  14. Dose estimation in B16 tumour bearing mice for future irradiation in the thermal column of the TRIGA reactor after B/Gd/LDL adduct infusion.

    PubMed

    Protti, N; Ballarini, F; Bortolussi, S; Bruschi, P; Stella, S; Geninatti, S; Alberti, D; Aime, S; Altieri, S

    2011-12-01

    To test the efficacy of a new (10)B-vector compound, the B/Gd/LDL adduct synthesised at Torino University, in vivo irradiations of murine tumours are in progress at the TRIGA Mark II reactor of the Pavia University. A localised B16 melanoma tumour is generated in C57BL/6 mice and subsequently infused with the adduct. During the irradiation, the mouse will be put in a shield to protect the whole body except the tumour in the back-neck area. To optimise the treatment set-up, MCNP simulations were performed. A very simplified mouse model was built using MCNP geometry capabilities, as well as the geometry of the shield made of 99% (10)B enriched boric acid. A hole in the shield is foreseen in correspondence of the back-neck region. Many configurations of the shield were tested in terms of neutron flux, dose distribution and mean induced activity in the tumour region and in the radiosensitive organs of the mouse. In the final set-up, up to five mice can be treated simultaneously in the reactor thermal column and the neutron fluence in the tumour region for 10 min of irradiation is of about 5×10(12) cm(-2). PMID:21459587

  15. Increased low density lipoprotein degradation in aorta of irradiated mice is inhibited by preenrichment of low density lipoprotein with alpha-tocopherol.

    PubMed

    Tribble, D L; Krauss, R M; Chu, B M; Gong, E L; Kullgren, B R; Nagy, J O; La Belle, M

    2000-10-01

    We previously reported that upper thoracic exposure to ionizing radiation (IR) accelerates fatty streak formation in C57BL/6 mice and that such effects are inhibited by overexpression of the antioxidant enzyme CuZn-superoxide dismutase (SOD). Notably, IR-accelerated lesion formation is strictly dependent on a high fat diet (i.e., atherogenic lipoproteins) but does not involve alterations in circulating lipid or lipoprotein levels. We thus proposed that IR promotes changes in the artery wall that enhance the deposition of lipoprotein lipids. To address this hypothesis, we examined the effects of IR on aortic accumulation and degradation of low density lipoproteins (LDL). Ten-week-old C57BL/6 mice were exposed to a single (8-Gy) dose of (60)Co radiation to the upper thoracic area or were sham irradiated (controls) and were then placed on the high fat diet. Five days postexposure, the mice received either (125)I-labeled LDL ((125)I-LDL) (which was used to measure intact LDL) or (125)I-labeled tyramine cellobiose ((125)I-TC)-LDL (which was used to measure both intact and cell-degraded LDL) via tail vein injection. On the basis of trichloroacetic acid (TCA)-precipitable counts in retroorbital blood samples, > or =95% of donor LDL was cleared within 24 h and there were no differences in time-averaged plasma concentrations of the two forms of LDL among irradiated and control mice. Aortic values increased markedly within the first hour and thereafter exhibited a slow increase up to 24 h. There were no differences between irradiated and control mice at 1 h, when values primarily reflected LDL entry, but a divergence was observed thereafter. At 24 h, (125)I-TC-associated counts were 1.8-fold higher in irradiated mice (P = 0.10). In contrast, (125)I-LDL-associated counts were 30% lower in irradiated mice (P< 0.05), suggesting that most of the retained (125)I-TC was associated with LDL degradation products. Consistent with the proposed involvement of oxidative or redox

  16. Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa

    PubMed Central

    1989-01-01

    Tolerance to Mlsa has been shown to be associated with clonal deletion of cells carrying TCR beta chain variable regions V beta 6 or V beta 8.1 in mice possessing I-E antigens. To evaluate the rules of tolerance induction to Mlsa we prepared irradiation bone marrow chimeras expressing Mlsa or Mlsb and I-E by different cell types. Deletion of V beta 6+, Mlsa-reactive T cells required the presence of Mlsa and I-E products either on bone marrow-derived cells or on irradiated recipient cells. Tolerance was induced when Mlsa and I-E were expressed by distinct cells of the chimera. Also neonatally tolerized mice exhibited depletion of V beta 6+ cells after injection of I-E- Mlsa spleen cells (DBA/1) into newborn I-E+ Mlsb mice (BALB/c x B10.G)F1. These results suggest that the product of the Mlsa locus is soluble and/or may be transferred from cell to cell and bound to I-E antigens. The chimera experiments also showed that tolerance to Mlsa is H-2 allele independent, i.e., is apparently unrestricted. Differentiation of chimeric (H-2d/Mlsa x H-2q/Mlsb)F1 stem cells in either an H-2d or an H- 2q thymus revealed that tolerance assessed by absence of V beta 6+ T cells is not dependent on the thymically determined restriction specificity of T cells. PMID:2526850

  17. EFFECTS OF PRENATAL EXPOSURE TO SODIUM ARSENITE ON MOTOR AND FOOD-MOTIVATED BEHAVIORS FROM BIRTH TO ADULTHOOD IN C57BL6/J MICE

    PubMed Central

    Markowski, Vincent P.; Reeve, Elizabeth A.; Onos, Kristen; Assadollahzadeh, Mina; McKay, Naomi

    2012-01-01

    Consumption of arsenic-contaminated drinking water is associated with numerous cancers and dermal and vascular diseases. Arsenic is also a potent nervous system toxicant and epidemiological studies indicate that intellectual functions in children are compromised following early developmental exposure. This study was designed to examine the effects of arsenic on a broad range of age-specific behaviors including basic sensory-motor responses in neonates, locomotor activity and grip strength in juveniles, and operant measures of learning and attention in adults. Pregnant C57BL6/J mice consumed drinking water containing 0, 8, 25, or 80 ppm sodium arsenite from the fourth day of gestation until birth. Arsenic produced a range of behavioral impairments in male and female offspring at each of the test ages. The most striking effects of arsenic were on the development of gait and other motor responses including acoustic startle, righting reflexes, and forelimb grip. These results suggest that developmental arsenic exposure can produce other behavioral impairments in children in addition to cognitive impairment. PMID:22266078

  18. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation

    PubMed Central

    Kataoka, Takahiro

    2013-01-01

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. PMID:23420683

  19. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation.

    PubMed

    Kataoka, Takahiro

    2013-07-01

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation.

  20. Gamma residual radioactivity measurements on rats and mice irradiated in the thermal column of a TRIGA Mark II reactor for BNCT.

    PubMed

    Protti, Nicoletta; Manera, Sergio; Prata, Michele; Alloni, Daniele; Ballarini, Francesca; di Tigliole, Andrea Borio; Bortolussi, Silva; Bruschi, Piero; Cagnazzo, Marcella; Garioni, Maria; Postuma, Ian; Reversi, Luca; Salvini, Andrea; Altieri, Saverio

    2014-12-01

    The current Boron Neutron Capture Therapy (BNCT) experiments performed at the University of Pavia, Italy, are focusing on the in vivo irradiations of small animals (rats and mice) in order to evaluate the effectiveness of BNCT in the treatment of diffused lung tumors. After the irradiation, the animals are manipulated, which requires an evaluation of the residual radioactivity induced by neutron activation and the relative radiological risk assessment to guarantee the radiation protection of the workers. The induced activity in the irradiated animals was measured by high-resolution open geometry gamma spectroscopy and compared with values obtained by Monte Carlo simulation. After an irradiation time of 15 min in a position where the in-air thermal flux is about 1.2 × 10(10) cm(-2) s(-1), the specific activity induced in the body of the animal is mainly due to 24Na, 38Cl, 42K, 56Mn, 27Mg and 49Ca; it is approximately 540 Bq g(-1) in the rat and around 2,050 Bq g(-1) in the mouse. During the irradiation, the animal body (except the lung region) is housed in a 95% enriched 6Li shield; the primary radioisotopes produced inside the shield by the neutron irradiation are 3H by the 6Li capture reaction and 18F by the reaction sequence 6Li(n,α)3H → 16O(t,n)18F. The specific activities of these products are 3.3 kBq g(-1) and 880 Bq g(-1), respectively. PMID:25353239

  1. Prenatal Influences on the Brain.

    ERIC Educational Resources Information Center

    Eliot, Lise

    2002-01-01

    Gives an overview of embryology and prenatal brain, sensory, and motor development. Includes discussion of maternal nutrition, chemical exposure, prenatal drug and alcohol hazards, cigarette smoking, and some causes of neural tube defects and premature birth. (Author/KB)

  2. Prenatal Genetic Counseling (For Parents)

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Prenatal Genetic Counseling KidsHealth > For Parents > Prenatal Genetic Counseling Print ... how can they help your family? What Is Genetic Counseling? Genetic counseling is the process of: evaluating ...

  3. Your First Prenatal Care Checkup

    MedlinePlus

    ... Prenatal Providers project include HRSA, March of Dimes Foundation, National Coalition for Health Professional Education in Genetics, Genetic ... Prenatal Providers project include HRSA, March of Dimes Foundation, National Coalition for Health Professional Education in Genetics, Genetic ...

  4. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance

    SciTech Connect

    Kelly, E.A.; Colley, D.G.

    1988-04-15

    Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component.

  5. Identification of surface antigens of schistosomula of Schistosoma mansoni recognized by antibodies from mice immunized by chronic infection and by exposure to highly irradiated cercariae

    SciTech Connect

    Simpson, A.J.; James, S.L.; Sher, A.

    1983-08-01

    Surface components of mechanically transformed schistosomula of Schistosoma mansoni were labeled by lactoperoxidase-catalyzed iodination. After solubilization with Triton X-100, antigens were identified by immunoprecipitation. Serum from chronically infected Swiss mice reproducibly precipitated seven major polypeptides with approximate molecular weights (X 10/sup 3/) of 94, 68, 45, 40 to 32, 22, and 16. The antigens of molecular weights (X 10/sup 3/) of 94, 40 to 32, 22, and 16 were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. Sera from several strains of infected inbred mice precipitated the same polypeptides. The antibodies produced during chronic infection were found to be stimulated by adult worms since sera from 6-week-infected animals precipitated none of the surface antigens, and the pattern produced by precipitation with antibodies from a mouse infected with male worms only was indistinguishable from the pattern obtained with sera from mice with bisexual infections. Antibodies from mice immunized with highly irradiated cercariae reproducibly precipitated major polypeptides of approximately (X 10/sup 3/) 94, 68, 45, 32, 22, 19, and 15 daltons. The antigens of (X 10/sup 3/) 94, 43, 32, 22, and 15 daltons were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. The 15 X 10(3)-dalton surface protein was recognized by sera from vaccinated, but not chronically infected, mice, suggesting that it represents a stage-specific immunogen present on schistosomula but not on adult worms. Sera from two inbred strains of mice which develop different degrees of immunity recognized the same antigens.

  6. [Searching Radiation Countermeasures using the Model of Prolonged Irradiation of Mice with Low Dose Rate and Evaluation of Their Influence on Heat Shock Protein Genes Expression].

    PubMed

    Rozhdestvensky, L M; Mikhailov, V F; Schlyakova, T G; Shagirova, J M; Shchegoleva, R A; Raeva, N F; Lisina, N I; Shulenina, L V; Zorin, V V; Pchelka, A V; Trubitsina, K Y

    2015-01-01

    Different radiomodificators (cytokine betaleukine, antioxidant phenoxan, antigipoksant limontar and nucleoside riboxin) were investigated on mice for evaluating their radiation protective capacity against prolonged (21 h) exposure at a dose of 12.6 Gy at a low dose rate of 10 mGy/min. Bone marrow cellularity and endogenic CFUs were used as evaluation criteria 9 days after exposure. Simultaneously, expression of the heat shock proteins of 25, 70 and 90 kDa in unexposed mice bone marrow was studied 2, 24 and 48 h after injections. Betaleukine only had a positive significant effect in both tests in the variants of 50 mcg/kg and 3 mcg/kg when administered 2 h and 22 h before exposure, correspondingly. Effects of betaleukine HSPs on expression were both stimulating and inhibiting, that was in contradiction with a constant positive effect in 5 experiments on exposed mice for each betaleukine variant. It argues against the vital role of HSPs in the betaleukine antiradiation effect. In 2 experiments with high temperatures betaleukine administered at a dose of 50 mcg/kg evoked a very high HSP-70 gene expression after 24 h, and mice exposed to irradiation at that time in a parallel experiment showed an increased radiation effect. It corresponds to the idea that HSPs serve a stress indicator.

  7. Human prenatal diagnosis

    SciTech Connect

    Filkins, K.; Russo, J.F.

    1985-01-01

    Advances in the field of prenatal diagnosis have been rapid during the past decade. Moreover, liberal use of birth control methods and restriction of family size have placed greater emphasis on optimum outcome of each pregnancy. There are many prenatal diagnostic techniques of proven value; the risks, including false negatives and false positives, are known. With the rapid proliferation of new and experimental techniques, many disorders are potential diagnosable or even treatable; however, risk factors are unknown and issues relating to quality control have not been resolved. These problems are readily appreciated in the dramatic new techniques involving recombinant DNA, chorion villus sampling, and fetal surgery. Unfortunately, clinicians may not appreciate the difficulties that may also be encountered in the more mundane prenatal diagnostic tests such as ultrasonography or enzymatic testing. The aim of this volume is to clarify and rationalize certain aspects of diagnosis, genetic counseling, and intervention. New and experimental techniques are presented in the light of current knowledge.

  8. Effect of administration of caffeine or green tea on the mutation profile in the p53 gene in early mutant p53-positive patches of epidermal cells induced by chronic UVB-irradiation of hairless SKH-1 mice.

    PubMed

    Kramata, Pavel; Lu, Yao-Ping; Lou, You-Rong; Cohen, Julie L; Olcha, Meir; Liu, Sandy; Conney, Allan H

    2005-11-01

    Irradiation of SKH-1 mice with UVB light for 20 weeks resulted in a large number of patches of epidermal cells, which was visualized with an antibody that recognizes mutated p53 protein. Oral treatment of mice with caffeine (0.4 mg/ml) or green tea (6 mg tea solids/ml) as the drinking fluid during UVB irradiation decreased the number of patches by approximately 40%. Sequencing analysis of the p53 gene (exons 3 to 9) detected 88, 82 or 39 point mutations in 67, 70 or 29 patches from water, caffeine or tea treated mice, respectively. A major hotspot at codon 270 (Arg-->Cys) accounted for 47.7% (water), 70.7% (caffeine) or 46.2% (tea) of all mutations. Patches from caffeine treated mice had fewer types of mutations than patches from mice treated with water or tea. Administration of caffeine or tea during 20 weeks of UVB irradiation eliminated mutations at codons 149 (Pro-->Ser) and 210 (Arg-->Cys) but increased the frequency of mutations at codon 238 (Ser-->Phe). Topical applications of caffeine (1.2 mg in 100 microl acetone) once a day, five times a week for 6 weeks after stopping UVB decreased the number of patches by 63% when compared with mice treated with acetone. DNA sequencing analysis detected 63 and 68 mutations in 48 and 57 patches from acetone or caffeine treated mice, respectively. Although no differences in the frequency, position or types of mutations were observed, the caffeine group harbored less homozygous mutations (12.3% of the total) than the acetone group (31.3% of the total, P = 0.029). In summary, oral treatment of mice with caffeine or green tea during chronic UVB irradiation changed the mutation profile of the p53 gene in early mutant p53 positive epidermal patches, and topical applications of caffeine after discontinuation of chronic UVB irradiation specifically eliminated patches harboring homozygous p53 mutations.

  9. [THE INFLUENCE OF EXTRACT FROM EMBRYONIC CHICKEN TISSUE ON THE DYNAMIC CHANGES OF MICE BLOOD SERUM C-REACTIVE PROTEIN AND CYTOKINES AFTER γ-IRRADIATION].

    PubMed

    Pogorelaya, M S

    2015-01-01

    The effect of preparations from embryonic chicken tissue on the dynamic changes in the levels of interleukins: 1β (IL-1 β), 6 (IL-6), 4 (IL-4) and C-reactive protein (CRP) were investigated in vivo, in the blood serum of white female laboratory mice exposed to single total γ-irradiation in a dose of 5 Gy. The experiments found that during the first days after the action of γ-radiation the indices of resistance of the organism undergoe significant destabilizing changes. These changes are manifested by an increase in IL-1β proinflammatory cytokine in response to external influences. However, the rapid decline in its level during the first days after irradiation reflects alterations in its production. The content of the serum IL-4 in all time points was higher than in the intact group. Moreover, the dynamics of its level during the first days after the irradiation was observed. An increased level of CRP was detected 6 hours after the exposure, indicating the dynamic changes of the severity of the inflammatory process. Administration of preparations from embryonic chicken tissue causes a considerable increase in the content of IL-1β and IL-6 in 3 and 6 hours after the r-irradiation, with stabilization after 12 hours. When using the preparations before an irradiation, a significantly lower level of CRP was detected in comparison to animals that did not get the preparations. When using the embryonic preparations, the stimulation of synthesis of IL-4 was observed, whose level increased in every time of taking blood samples. Possibility for induction of row of cytokines, in particular, IL-1β and IL-6, plays an important role in stimulation of hematopoiesis and provides a basis to consider this substance as an immunomodulator in pathologic immunosuppressive states. The decrease of serum CRP level can indicate the ability to reduce the severity of radiation injury. In the experimental conditions, an embryonic preparation exhibits inertness relative to the healthy

  10. In vitro quantitation of lethal and physiologic effects of total body irradiation on stromal and hematopoietic stem cells in continuous bone marrow cultures from Rf mice

    SciTech Connect

    Greenberger, J.S.; Eckner, R.J.; Otten, J.A.; Tennant, R.W.

    1982-07-01

    The effects of in vivo total body irradiation (TBI) and interval from TBI to explant of marrow on: stromal cell proliferation in vitro; stromal cell support of hematopoiesis in continuous bone marrow culture; and generation of WEHI-3 growth factor (GF)-dependent lines of hematopoietic progenitor cells were evaluated. Explant of marrow at 2, 4, 5, or 6 months after single fraction TBI (300-800 rad) was associated with decreased longevity of hemopoiesis and a decrease in the proliferative capacity of fibroblastic adherent-stromal colony forming cells (CFUf) as measured by colony size at 14 days and number of colonies per 10/sup 6/ cells plated. In contrast, explant of marrow 8 to 24 months after TBI produced cultures with longevity that was indistinguishable from age-matched control cultures (19-24 weeks). Marrow from irradiated first and second generation recipients of serially transferred marrow demonstrated a similar 7-month in vivo recovery period; however, the plateau maximum duration of hemopoiesis did not return to control levels. Purified stromal cell cultures were prepared by corticosteroid-deprivation of explanted marrow for 28 days and were then engrafted in vitro with marrow from C57BL/6J or RfM/UN mice that had been irradiated 1 month previously. Hemopoiesis in these cultures was restored, and they produced GM-CFUc and granulocytes for 15-24 weeks. Thus, healthy stroma supported growth of recently irradiated hemopoietic cells in vitro. Indirect effects of x-irradiation on hemopoietic stem cells through damage and repair in the stromal cell compartment can be effectively studied with the present bone marrow culture system. (JMT)

  11. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    SciTech Connect

    Vallera, D.A.; Soderling, C.C.B.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed. (JMT)

  12. Prenatal Care Training.

    ERIC Educational Resources Information Center

    Hagen, Michael

    Described is the development and evaluation of a prenatal instructional program designed to prevent birth defects. It is explained that the program, composed of five slide tape units on such topics as nutrition and environmental factors, was field tested and found effective with 97 participants (pregnant high school students, nursing students, and…

  13. Prenatal diagnosis: whose right?

    PubMed

    Heyd, D

    1995-10-01

    The question who is the subject of the right to prenatal diagnosis may be answered in four ways: the parents, the child, society, or no one. This article investigates the philosophical issues involved in each of these answers, which touch upon the conditions of personal identity, the principle of privacy, the scope of social responsibility, and the debate about impersonalism in ethics.

  14. Spleen cells from adult mice given total lymphoid irradiation (TLI) or from newborn mice have similar regulatory effects in the mixed leukocyte reaction (MLR). II. Generation of antigen-specific suppressor cells in the MLR after the addition of spleen cells from newborn mice

    SciTech Connect

    Okada, S.; Strober, S.

    1982-11-01

    Spleen cells from newborn BALB/c mice were added to the mixed leukocyte reaction (MLR) between a variety of responder and stimulator cells. The newborn cells nonspecifically suppressed the uptake of (/sup 3/H)-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. Suppressor cell activity fell rapidly during the first 4 days after birth, and could not be detected by day 20. Newborn spleen cells inhibited the generation of nonspecific suppressor cells during the MLR but did not inhibit the generation of antigen-specific suppressor cells. Thus, newborn spleen cells exhibit a pattern of regulation of the MLR similar to that reported previously for spleen cells from adult mice given total lymphoid irradiation (TLI). These regulatory interactions provide a model that explains the ease of induction of transplantation tolerance in vivo in newborn mice and in TLI-treated adult mice.

  15. Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer

    PubMed Central

    Sato, Y; Shinjyo, N; Sato, M; Osato, K; Zhu, C; Pekna, M; Kuhn, H G; Blomgren, K

    2013-01-01

    Ionizing radiation persistently reduces the pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus (DG) of the hippocampus, which may explain some of the learning deficits observed in patients treated with radiotherapy, particularly pediatric patients. A single dose of 8 Gy irradiation (IR) was administered to the brains of postnatal day 14 (P14) C57BL/6 mice and 1.0 × 105 bromodeoxyuridine-labeled, syngeneic NSPCs were injected into the hippocampus 1 day, 1 week or 6 weeks after IR. Cell survival and phenotype were evaluated 5 weeks after grafting. When grafted 1 day post-IR, survival and neuronal differentiation of the transplanted NSPCs were lower in irradiated brains, whereas the survival and cell fate of grafted cells were not significantly different between irradiated and control brains when transplantation was performed 1 or 6 weeks after IR. A young recipient brain favored neuronal development of grafted cells, whereas the older recipient brains displayed an increasing number of cells developing into astrocytes or unidentified cells. Injection of NSPCs, but not vehicle, induced astrogliosis and reduced thickness of the dorsal blade of the GCL after 5 months. In summary, we demonstrate that age and interval between IR and grafting can affect survival and differentiation of grafted NSPCs. The observed long-term gliosis and degeneration warrant caution in the context of NSPC grafting for therapeutical purposes. PMID:23598403

  16. Effects of a turmeric extract (Curcuma longa) on chronic ultraviolet B irradiation-induced skin damage in melanin-possessing hairless mice.

    PubMed

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2009-12-01

    Turmeric (the rhizomes of Curcuma longa L., Zingiberacease) is widely used as a dietary pigment and spice, and has been traditionally used for the treatment of inflammation, skin wounds and hepatic disorders in Ayurvedic, Unani and Chinese medicine. Although the topical application or oral administration of turmeric is used to improve skin trouble, there is no evidence to support this effect. The aim of this study was to clarify whether turmeric prevents chronic ultraviolet B (UVB)-irradiated skin damage. We examined the effects of a turmeric extract on skin damage including changes in skin thickness and elasticity, pigmentation and wrinkling caused by long-term, low-dose ultraviolet B irradiation in melanin-possessing hairless mice. The extract (at 300 or 1000 mg/kg, twice daily) prevented an increase in skin thickness and a reduction in skin elasticity induced by chronic UVB exposure. It also prevented the formation of wrinkles and melanin (at 1000 mg/kg, twice daily) as well as increases in the diameter and length of skin blood vessels and in the expression of matrix metalloproteinase-2 (MMP-2). Prevention of UVB-induced skin aging by turmeric may be due to the inhibition of increases in MMP-2 expression caused by chronic irradiation.

  17. Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    SciTech Connect

    Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed.

  18. Natural resistance of lethally irradiated F1 hybrid mice to parental marrow grafts is a function of H-2/Hh-restricted effectors

    SciTech Connect

    Daley, J.P.; Nakamura, I.

    1984-04-01

    The natural resistance of F1 hybrid mice against parental bone marrow grafts is thought to be mediated by natural killer (NK)-like effector cells. However, unlike the NK cell activity against a wide range of tumors and normal cells, hybrid resistance is characterized by the immunogenetic specificity controlled by a set of unique noncodominant genes denoted as Hh. Two alternative hypotheses can account for the specificity. Thus, the specificity may reflect either the Hh restriction of effectors or the Hh gene control of mechanisms regulating non-Hh-restricted effector activity. In this study, therefore, we tested the recognition specificity of putative effectors mediating hybrid resistance in lethally irradiated H-2b/d and H-2b/k F1 hybrid mice to the engraftment of parental H-2b bone marrow. As a direct means of defining the effector specificity, rejection of parental bone marrow grafts was subjected to competitive inhibition in situ by irradiated tumor cells. Of the 16 independent lines of lymphoma and other hemopoietic tumor cells tested, the ability to inhibit hybrid resistance was the exclusive property of all tumors derived from mice homozygous for the H-2Db region, regardless of whether the tumor cells were susceptible or resistant to NK cell-mediated cytotoxicity in vitro. Four cell lines heterozygous for the H-2Db were noninhibitory, including one that is susceptible to natural killing. Pretreatment of the F1 hosts with an interferon inducer augmented the resistance with no alteration in the recognition specificity of effector cells. Therefore, natural resistance to parental H-2b bone marrow grafts was mediated by effectors restricted by the H-2Db/Hh-1b gene(s), and not by the nonrestricted NK cells detectable in conventional in vitro assays.

  19. Influence of radiation field and fractionation schedule of total lymphoid irradiation (TLI) on the induction of suppressor cells and stable chimerism after bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-02-01

    When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 x 10/sup 6/ C/sub 57/ B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 x 10/sup 6/) were added to the BM inocolum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.

  20. In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging.

    PubMed

    Kirschner, Stefanie; Felix, Manuela C; Hartmann, Linda; Bierbaum, Miriam; Maros, Máté E; Kerl, Hans U; Wenz, Frederik; Glatting, Gerhard; Kramer, Martin; Giordano, Frank A; Brockmann, Marc A

    2015-04-01

    Small animal imaging is of increasing relevance in biomedical research. Studies systematically assessing the diagnostic accuracy of contrast-enhanced in vivo micro-CT of orthotopic glioma xenografts in mice do not exist. NOD/SCID/γc(-/-) mice (n = 27) underwent intracerebral implantation of 2.5 × 10(6) GFP-Luciferase-transduced U87MG cells. Mice underwent bioluminescence imaging (BLI) to detect tumor growth and afterwards repeated contrast-enhanced (300 µl Iomeprol i.v.) micro-CT imaging (80 kV, 75 µAs, 360° rotation, 1,000 projections, 33 s scan time, resolution 40 × 40 × 53 µm, 0.5 Gy/scan). Presence of tumors, tumor diameter and tumor volume in micro-CT were rated by two independent readers. Results were compared with histological analyses. Six mice with tumors confirmed by micro-CT received fractionated irradiation (3 × 5 Gy every other day) using the micro-CT (5 mm pencil beam geometry). Repeated micro-CT scans were tolerated well. Tumor engraftment rate was 74 % (n = 20). In micro-CT, mean tumor volume was 30 ± 33 mm(3), and the smallest detectable tumor measured 360 × 620 µm. The inter-rater agreement (n = 51 micro-CT scans) for the item tumor yes/no was excellent (Spearman-Rho = 0.862, p < 0.001). Sensitivity and specificity of micro-CT were 0.95 and 0.71, respectively (PPV = 0.91, NPV = 0.83). BLI on day 21 after tumor implantation had a sensitivity and specificity of 0.90 and 1.0, respectively (PPV = 1.0, NPV = 0.5). Maximum tumor diameter and volume in micro-CT and histology correlated excellently (tumor diameter: 0.929, p < 0.001; tumor volume: 0.969, p < 0.001, n = 17). Irradiated animals showed a large central tumor necrosis. Longitudinal contrast enhanced micro-CT imaging of brain tumor growth in live mice is feasible at high sensitivity levels and with excellent inter-rater agreement and allows visualization of radiation effects.

  1. The Prenatal Care at School Program

    ERIC Educational Resources Information Center

    Griswold, Carol H.; Nasso, Jacqueline T.; Swider, Susan; Ellison, Brenda R.; Griswold, Daniel L.; Brooks, Marilyn

    2013-01-01

    School absenteeism and poor compliance with prenatal appointments are concerns for pregnant teens. The Prenatal Care at School (PAS) program is a new model of prenatal care involving local health care providers and school personnel to reduce the need for students to leave school for prenatal care. The program combines prenatal care and education…

  2. [Prenatal care in Latin America].

    PubMed

    Buekens, P; Hernández, P; Infante, C

    1990-01-01

    Available data on the coverage of prenatal care in Latin America were reviewed. In recent years, only Bolivia had a coverage of prenatal care of less than 50 per cent. More than 90 per cent of pregnant women received prenatal care in Chile, Cuba, the Dominican Republic, and Puerto Rico. Prenatal care increased between the 1970 and 1980 in the Dominican Republic, Ecuador, Guatemala, Honduras, Mexico, and Peru. The coverage of prenatal care decreased in Bolivia and Colombia. The mean number of visits increased in Cuba and Puerto Rico. The increase of prenatal care in Guatemala and Honduras is due to increased care by traditional birth attendants, compared to the role of health care institutions. We compared the more recent data on tetanus immunization of pregnant women to the more recent data on prenatal care. The rates of tetanus immunization are always lower than the rates of prenatal care attendance, except in Costa Rica. The rates of tetanus immunization was less than half as compared to the rates of prenatal care in Bolivia, Guatemala, and Peru. To improve the content of prenatal care should be an objective complementary to the increase of the number of attending women.

  3. Kinetics of gamma-H2AX induction and removal in bone marrow and testicular cells of mice after X-ray irradiation.

    PubMed

    Paris, Lorena; Cordelli, Eugenia; Eleuteri, Patrizia; Grollino, Maria Giuseppa; Pasquali, Emanuela; Ranaldi, Roberto; Meschini, Roberta; Pacchierotti, Francesca

    2011-07-01

    Male germ cells have been shown to differ in their DNA damage response (DDR) with respect to somatic cells. In addition, DDR pathways are modulated along spermatogenesis, accompanying profound chromatin modifications. Histone H2AX phosphorylation is a fundamental step of DDR. Few data are available on the long-term kinetics of phosphorylated H2AX (γ-H2AX) after in vivo irradiation. We have investigated, by microscopic and flow cytometric immunochemistry, γ-H2AX induction and removal in testicular cells of irradiated mice, in comparison with bone marrow cells. In unirradiated testicular cells, much higher levels of γ-H2AX were measured by flow cytometry with respect to bone marrow cells. Irradiation induced a redistribution of γ-H2AX into discrete foci detectable by microscopy. In irradiated bone marrow, the percentage of labelled cells peaked at 1 h and rapidly declined, in agreement with data on in vitro cell lines. In contrast, spermatocytes and round spermatids showed persistent labelling until 48 h. During this time, in spermatids, topological changes were observed in γ-H2AX foci from a pattern of many uncountable dots to a pattern of few large spots. Observations of testicular sections confirmed this trend in the reduction of foci number in spite of substantially invariable percentages of labelled cells in the analysed timeframe. To assess whether γ-H2AX persistence in testicular cells was due to unrepaired DNA breaks, we performed comet assay and immunofluorescence analysis of Mdc1, a marker of DDR different from γ-H2AX. Comet assay showed that most breaks were repaired within 2 h. Forty-eight hours after irradiation, contrary to γ-H2AX foci that remained detectable in 80% of initially labelled cells, Mdc1 foci were observed in only 20-30% of cells. These data suggest that, at long times after irradiation, mechanisms additional to impairment of DNA break repair may account for the long persistence of γ-H2AX foci in male germ cells.

  4. Prenatal Surgery: Helping Babies Before Birth

    MedlinePlus

    ... About Zika & Pregnancy Prenatal Surgery: Helping Babies Before Birth KidsHealth > For Parents > Prenatal Surgery: Helping Babies Before ... A Text Size Prenatal Surgery: Helping Babies Before Birth Operating on a baby before birth may seem ...

  5. Human prenatal diagnosis

    SciTech Connect

    Filkins, K.; Russo, R.J.

    1985-01-01

    The multiauthor text is written as a ''guide to rationalize and clarify certain aspects of diagnosis, general counseling and intervention'' for ''health professionals who provide care to pregnant women.'' The text is not aimed at the ultrasonographer but rather at the physicians who are clinically responsible for patient management. Chapters of relevance to radiologists include an overview of prenatal screening and counseling, diagnosis of neural tube defects, ultrasonographic (US) scanning of fetal disorders in the first and second trimesters of pregnancy, US scanning in the third trimester, multiple gestation and selective termination, fetal echo and Doppler studies, and fetal therapy. Also included are overviews of virtually all currently utilized prenatal diagnostic techniques including amniocentesis, fetal blood sampling, fetoscopy, recombinant DNA detection of hemoglobinopathies, chorionic villus sampling, embryoscopy, legal issues, and diagnosis of Mendelian disorders by DNA analysis.

  6. Prenatal diagnosis of colobomatous microphthalmos.

    PubMed

    Dar, Suhail A; Johal, Sheila C; Marino, Meghan J; Singh, Arun D

    2015-04-30

    Optic nerve coloboma and microphthalmos with colobomatous cyst are rare congenital anomalies that are difficult to detect on prenatal ultrasonography and magnetic resonance imaging. Only four cases of optic nerve coloboma and two cases of microphthalmos with colobomatous cyst have been detected on prenatal imaging. The authors report a case of a fetus initially suspected to have retinoblastoma of the right eye on prenatal ultrasonography who was later diagnosed as having microphthalmos on fetal magnetic resonance imaging. Following delivery, she was noted to have microphthalmos with colobomatous cyst of the right eye and optic nerve coloboma of the left eye. The authors also review the prenatal ocular imaging findings of the differential diagnosis.

  7. Administration of an immunomodulatory azaspirane, SK F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice

    SciTech Connect

    King, A.G.; Badger, A.M. )

    1991-08-01

    The immunomodulatory azaspirane SK F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be null cells, that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because the authors hypothesized that the induction of SC was associated with enhanced hematopoiesis, they sought to determine the hematopoietic potential of SK F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in their studies. They demonstrate here that administration of SK F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU-GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In their experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administration of SK F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK F 105685 and rIL-1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation.

  8. Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of 60Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration

    PubMed Central

    Bala, Madhu; Gupta, Manish; Saini, Manu; Abdin, M. Z.; Prasad, Jagdish

    2015-01-01

    A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body 60Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain ‘A' mice demonstrated that SBL-1 treatment before 60Co-gamma-irradiation (10 Gy) significantly (p < 0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration. PMID:26421051

  9. Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of (60)Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration.

    PubMed

    Bala, Madhu; Gupta, Manish; Saini, Manu; Abdin, M Z; Prasad, Jagdish

    2015-01-01

    A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body (60)Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain 'A' mice demonstrated that SBL-1 treatment before (60)Co-gamma-irradiation (10 Gy) significantly (p < 0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration. PMID:26421051

  10. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    PubMed

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  11. Oral Immunization of Mice with Gamma-Irradiated Brucella neotomae Induces Protection against Intraperitoneal and Intranasal Challenge with Virulent B. abortus 2308

    PubMed Central

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4+ and CD8+ T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 109, 1010 and 1011 CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 1011 CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella. PMID:25225910

  12. Transgenerational inheritance of enhanced susceptibility to radiation-induced medulloblastoma in newborn Ptch1⁺/⁻ mice after paternal irradiation.

    PubMed

    Paris, Lorena; Giardullo, Paola; Leonardi, Simona; Tanno, Barbara; Meschini, Roberta; Cordelli, Eugenia; Benassi, Barbara; Longobardi, Maria Grazia; Izzotti, Alberto; Pulliero, Alessandra; Mancuso, Mariateresa; Pacchierotti, Francesca

    2015-11-01

    The hypothesis of transgenerational induction of increased cancer susceptibility after paternal radiation exposure has long been controversial because of inconsistent results and the lack of a mechanistic interpretation. Here, exploiting Ptch1 heterozygous knockout mice, susceptible to spontaneous and radiation-induced medulloblastoma, we show that exposure of paternal germ cells to 1 Gy X-rays, at the spermatogonial stage, increased by a considerable 1.4-fold the offspring susceptibility to medulloblastoma induced by neonatal irradiation. This effect gained further biological significance thanks to a number of supporting data on the immunohistochemical characterization of the target tissue and preneoplastic lesions (PNLs). These results altogether pointed to increased proliferation of cerebellar granule cell precursors and PNLs cells, which favoured the development of frank tumours. The LOH analysis of tumor DNA showed Ptch1 biallelic loss in all tumor samples, suggesting that mechanisms other than interstitial deletions, typical of radiation-induced medulloblastoma, did not account for the observed increased cancer risk. This data was supported by comet analysis showing no differences in DNA damage induction and repair in cerebellar cells as a function of paternal irradiation. Finally, we provide biological plausibility to our results offering evidence of a possible epigenetic mechanism of inheritance based on radiation-induced changes of the microRNA profile of paternal sperm. PMID:26452034

  13. Effects of olive leaf extract and its main component oleuroepin on acute ultraviolet B irradiation-induced skin changes in C57BL/6J mice.

    PubMed

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2010-07-01

    Olive (Olea europaea L.) leaves have long been used in folk medicine and herbal tea in Europe and the Mediterranean area. The Mediterranean climate is characterized by high temperatures, and by strong ultraviolet B (UVB) radiation causing the skin to age, increasing wrinkling, pigmentation and skin thickness. The aim of this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage caused by acute UVB irradiation in C57BL/6J mice. The extract (300 or 1000 mg/kg) and oleuropein (25 or 85 mg/kg) were administered orally twice daily for 14 days. UVB was administered daily at a dose of 120 mJ/cm(2) for the first 5 days and then every other day for 9 days. Both treatments inhibited the increases in skin thickness induced by radiation. They also inhibited increases in the Ki-67- and 8-hydroxy-2'-deoxyguanosine-positive cell numbers, melanin granule area and matrix metalloproteinase-13 (MMP-13) expression. These preventive effects on UVB-induced skin damage might be caused in part by inhibiting the degradation of extracellular matrixes in the corium, and by the proliferation of epidermal cells through the inhibition of increases in MMP-13 levels and reactive oxygen species induced by irradiation. PMID:19957248

  14. Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice

    PubMed Central

    Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae

    2015-01-01

    Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner. PMID:26509812

  15. Effects of internal low-dose irradiation from 131I on gene expression in normal tissues in Balb/c mice

    PubMed Central

    2011-01-01

    Background The aim of this study was to investigate the global gene expression response of normal tissues following internal low absorbed dose irradiation of 131I. Methods Balb/c mice were intravenously injected with 13 to 260 kBq of 131I and euthanized 24 h after injection. Kidneys, liver, lungs, and spleen were surgically removed. The absorbed dose to the tissues was 0.1 to 9.7 mGy. Total RNA was extracted, and Illumina MouseRef-8 Whole-Genome Expression BeadChips (Illumina, Inc., San Diego, California, USA) were used to compare the gene expression of the irradiated tissues to that of non-irradiated controls. The Benjamini-Hochberg method was used to determine differentially expressed transcripts and control for false discovery rate. Only transcripts with a modulation of 1.5-fold or higher, either positively or negatively regulated, were included in the analysis. Results The number of transcripts affected ranged from 260 in the kidney cortex to 857 in the lungs. The majority of the affected transcripts were specific for the different absorbed doses delivered, and few transcripts were shared between the different tissues investigated. The response of the transcripts affected at all dose levels was generally found to be independent of dose, and only a few transcripts showed increasing or decreasing regulation with increasing absorbed dose. Few biological processes were affected at all absorbed dose levels studied or in all tissues studied. The types of biological processes affected were clearly tissue-dependent. Immune response was the only biological process affected in all tissues, and processes affected in more than three tissues were primarily associated with the response to stimuli and metabolism. Conclusion Despite the low absorbed doses delivered to the tissues investigated, a surprisingly strong response was observed. Affected biological processes were primarily associated with the normal function of the tissues, and only small deviations from the normal

  16. Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene

    NASA Technical Reports Server (NTRS)

    Yu, Y.; Okayasu, R.; Weil, M. M.; Silver, A.; McCarthy, M.; Zabriskie, R.; Long, S.; Cox, R.; Ullrich, R. L.

    2001-01-01

    Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

  17. Ethics of prenatal ultrasound.

    PubMed

    Howe, David

    2014-04-01

    Prenatal ultrasound has opened new opportunities to examine, diagnose and treat the fetus, but these advances bring with them ethical dilemmas. In this chapter, I address the ethical principles that need to be considered when treating both mother and fetus as patients, and how these can be applied in practice. In particular, ultrasound practitioners have an ethical duty to maintain their theoretical knowledge and practical skills to ensure they advise parents correctly. I also discuss the ethical issues in carrying out intrauterine therapy, ultrasound-related research, and termination of pregnancy for fetal abnormality.

  18. The Role of DNA Methylation Changes in Radiation-Induced Transgenerational Genomic Instability and Bystander Effects in cranial irradiated Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Gao, Yinglong; Zhang, Baodong

    Heavy-ion radiation could lead to genome instability in the germline, and therefore to transgenerational genome and epigenome instability in offspring of exposed males. The exact mechanisms of radiation-induced genome instability in directly exposed and in bystander organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in genome instability development. The potential of localized body-part exposures to affect the germline and thus induce genome and epigenome changes in the progeny has not been studied. To investigate whether or not the paternal cranial irradiation can exert deleterious changes in the protected germline and the offsprings, we studied the alteration of DNA methylation in the shielded testes tissue. Here we report that the localized paternal cranial irradiation results in a significant altered DNA methylation in sperm cells and leads to a profound epigenetic dysregulation in the unexposed progeny conceived 3 months after paternal exposure. The possible molecular mechanisms and biological consequences of the observed changes are discussed. Keywords: Heavy-ion radiation; Transgenerational effect; Genomic Instability Bystander Effects; DNA methylation.

  19. Protective effect of gelatin and gelatin hydrolysate from salmon skin on UV irradiation-induced photoaging of mice skin

    NASA Astrophysics Data System (ADS)

    Chen, Tiejun; Hou, Hu; Lu, Jiaohan; Zhang, Kai; Li, Bafang

    2016-08-01

    The objective of this study was to investigate the effect of gelatin (SG) isolated from salmon skin and its hydrolysate (SGH) on photoaging skin, and the mechanism responsible for anti-photoaging. The average molecular weights of SG and SGH were 65 kDa and 873 Da, respectively. The amino acid compositions of SG and SGH were similar. Both of them were abundant in hydrophobic amino acids. Twenty-five peptides were identified from SGH. SG and SGH could improve UV irradiation-induced pathological changes of macroscopical tissue texture and skin morphology. Hydroxyproline content is an indicator of matrix collagen content, SG and SGH could inhibit the decrease of hydroxyproline content in photoaging skin in a dose dependent manner. In addition, SG and SGH could alleviate UV irradiation-induced oxidative damages to skin by increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), increasing the content of glutathione (GSH) and decreasing the content of malonaldehyde (MDA). Moreover, SG and SGH could enhance immune regulation system by increasing the thymus index. Thus, the anti-photoaging mechanisms of SG and SGH were by inhibiting the depletion of antioxidant defense components, involving in the synthesis of collagen and enhancing the function of immune system. Besides, SGH showed a better result in protecting skin from photoaging than SG.

  20. Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis.

    PubMed

    Verreet, Tine; Rangarajan, Janaki Raman; Quintens, Roel; Verslegers, Mieke; Lo, Adrian C; Govaerts, Kristof; Neefs, Mieke; Leysen, Liselotte; Baatout, Sarah; Maes, Frederik; Himmelreich, Uwe; D'Hooge, Rudi; Moons, Lieve; Benotmane, Mohammed A

    2016-01-01

    Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8-15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests. PMID:27199692

  1. Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis

    PubMed Central

    Verreet, Tine; Rangarajan, Janaki Raman; Quintens, Roel; Verslegers, Mieke; Lo, Adrian C.; Govaerts, Kristof; Neefs, Mieke; Leysen, Liselotte; Baatout, Sarah; Maes, Frederik; Himmelreich, Uwe; D'Hooge, Rudi; Moons, Lieve; Benotmane, Mohammed A.

    2016-01-01

    Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8–15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests. PMID:27199692

  2. Prenatal vitamins: what is in the bottle?

    PubMed

    Duerbeck, Norman B; Dowling, David D; Duerbeck, Jillinda M

    2014-12-01

    Nearly all obstetricians routinely prescribe prenatal vitamins to their pregnant patients at the time of the first prenatal visit. Many times, patients' understanding of the health benefits of prenatal vitamins differs substantially from that of the prescribing physician. The following is a review of the most common ingredients found in prenatal vitamins and their purported health benefits.

  3. Prenatal nutrition: special considerations.

    PubMed

    Cox, J T; Phelan, S T

    2009-10-01

    Awareness of the importance of nutrition during pregnancy has increased in recent years.Pregnancy outcomes vary by prepregnant weight as well as gestational weight gain. Inappropriate gain may have both short- and long-term consequences for mother and infant. This review article includes the newly released US Institute of Medicine prenatal weight gain guidelines, as well as the Dietary Reference Intakes for the US and selected European societies.Food safety topics are discussed including Listeria, Toxoplasma, peanuts, mercury and other contaminants. Preconceptual nutrition is discussed, as are specific at-risk prenatal nutrients, including folic acid, choline, vitamin B12, omega-3 fatty acids, iodine, calcium, vitamin D, and iron. Current controversies are discussed and practical suggestions are given to safely optimize nutrient intake. As part of the medical team, a local Registered Dietitian or other nutrition professional can give much more detailed guidance and support for a pregnant woman given her particular risk factors, including her pre-existing medical conditions and cultural concerns, and will emphasize nutritional quality rather than just pounds gained. PMID:19749670

  4. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  5. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  6. Eugenics and prenatal testing.

    PubMed

    Hubbard, R

    1986-01-01

    Prejudices against people with disabilities, poor people, and immigrants during the nineteenth century generated a science of "race improvement" called eugenics. In the United States, a number of eugenic measures were enacted early in this century, but it was in Nazi Germany that eugenics flourished under the name of racial hygiene (Rassenhygiene). In the guise of furthering the health of the German people, German scientists and physicians initially designed programs of sterilization. Next came euthanasia and finally mass extermination of "lives not worth living." Remembering this history, many German women oppose the new technical developments in prenatal diagnosis because they see them as yet another way to specify what kinds of people are and are not fit to inhabit the world. This paper tries to place the new technologies in the context of eugenics and to point out some of the ways in which the new, supposedly liberating, choices in fact limit women's control over our lives.

  7. Captopril Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival when Combined with Skin-Burn Trauma in Mice.

    PubMed

    Islam, Aminul; Bolduc, David L; Zhai, Min; Kiang, Juliann G; Swift, Joshua M

    2015-09-01

    Past and recent radiation events have involved a high incidence of radiation combined injury where victims often succumb to serious infections as a consequence of bacterial translocation and subsequent sepsis. The risk of infection is exacerbated in radiation combined skin-burn injury (RCI), which increase vulnerability. Furthermore, no suitable countermeasures for radiation combined skin-burn injury have been established. In this study, we evaluated captopril as a potential countermeasure to radiation combined skin-burn injury. Captopril is an FDA-approved angiotensin-converting enzyme inhibitor that was previously reported to stimulate hematopoietic recovery after exposure to ionizing radiation. Female B6D2F1/J mice were whole-body bilateral (60)Co gamma-photon irradiated (dose rate of 0.4 Gy/min) with 9.5 Gy (LD70/30 for RCI), followed by nonlethal dorsal skin-burn injury under anesthesia (approximately 15% total-body surface-area burn). Mice were provided with acidified drinking water with or without dissolved captopril (0.55 g/l) for 30 days immediately after injury and were administered topical gentamicin (0.1% cream; day 1-10) and oral levofloxacin (90-100 mg/kg; day 3-16). Surviving mice were euthanized on day 30 after analyses of water consumption, body weight and survival. Our data demonstrate that, while treatment with captopril did mitigate mortality induced by radiation injury (RI) alone (55% captopril vs. 80% vehicle; n = 20, P < 0.05), it also resulted in decreased survival after radiation combined skin-burn injury (22% captopril vs. 41% vehicle; n = 22, P < 0.05). Moreover, captopril administration via drinking water produced an uneven dosage pattern among the different injury groups ranging from 74 ± 5.4 to 115 ± 2.2 mg/kg/day. Captopril treatment also did not counteract the negative alterations in hematology, splenocytes or bone marrow cellularity after either radiation injury or radiation combined skin-burn injury. These data suggest that

  8. Prenatal diagnosis of colobomatous microphthalmos.

    PubMed

    Dar, Suhail A; Johal, Sheila C; Marino, Meghan J; Singh, Arun D

    2015-01-01

    Optic nerve coloboma and microphthalmos with colobomatous cyst are rare congenital anomalies that are difficult to detect on prenatal ultrasonography and magnetic resonance imaging. Only four cases of optic nerve coloboma and two cases of microphthalmos with colobomatous cyst have been detected on prenatal imaging. The authors report a case of a fetus initially suspected to have retinoblastoma of the right eye on prenatal ultrasonography who was later diagnosed as having microphthalmos on fetal magnetic resonance imaging. Following delivery, she was noted to have microphthalmos with colobomatous cyst of the right eye and optic nerve coloboma of the left eye. The authors also review the prenatal ocular imaging findings of the differential diagnosis. PMID:25942066

  9. Ethical issues in prenatal testing.

    PubMed

    Burgess, M M

    1994-04-01

    Many ethical concerns raised by prenatal testing are based on the use and effects of genetic information in nonclinical contexts. Correct or incorrect beliefs about social uses of genetic information may limit the voluntariness of informed consent to prenatal testing. A qualitative study of persons predictively tested for Huntington's disease illustrates how the social context, in this case the family history of being at risk, affects the interpretation of the genetic information and alters relationships. This constitutes a risk of genetic testing. Prenatal testing also requires ethical analysis based on careful understanding of how social attitudes and nonclinical uses affect voluntariness and potential harm and benefits of testing. Investigators conducting research on prenatal tests share the responsibility to evaluate social attitudes toward at-risk persons, nonclinical uses of genetic information, and the social benefits and harm of such uses.

  10. Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; Vandeputte, M.; Van der Schueren, E.

    1982-11-01

    Three groups of C/sub 57//BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different perameters involved in the transplantation.

  11. Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; Vandeputte, M.; van der Schueren, E.

    1982-11-01

    Three groups of C/sub 57//BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. In the first group daily fractions of 2 Gy were given during 3 1/2 weeks. In the second group 4 to 5 fractions with 3 1/2 hr interval were given each day, thus delivering 17 fractions in 4 days. In the third group three fractions were given daily for two consecutive days and was repeated two times after 8 or 9 days interval, resulting in a total treatment time of 3 1/2 weeks. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different parameters involved in the transplantation.

  12. Effects of 0.075 Gy x-ray irradiation on the expression of IL-10 and IL-12 in mice

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Dong; Ma, Shu-Mei; Liu, Shu-Zheng

    2003-07-01

    The objective was to observe the effects of 0.075 Gy low dose radiation (LDR) on the synthesis of IL-10 in splenocytes and the secretion of IL-12 by peritoneal macrophages. Kunming mice were selected and randomly grouped. Northern blot and flow cytometry were adopted to detect the changes of IL-10 at mRNA and protein levels, respectively. Northern blot and ELISA were used, respectively, to examine the changes of IL-12 p35/p40 mRNA and IL-12 p70 protein levels. IL-10 mRNA decreased significantly in splenocytes, while both IL-12 p35 and p40 subunit mRNA levels in macrophages increased after whole body irradiation (WBI) with 0.075 Gy x-rays. Meanwhile, IL-10 synthesis in splenocytes decreased beginning from 4 h after exposure and remaining at a lower level up to 48 h, and IL-12 secretion by macrophages was found to take the opposite direction, i.e. increase significantly. In conclusion, WBI with 0.075 Gy x-rays may suppress IL-10 both at the mRNA level and protein level and stimulate IL-12 expression simultaneously, which might contribute to a shift of the immune response in favour of Th1 differentiation.

  13. Prenatal meditation influences infant behaviors.

    PubMed

    Chan, Ka Po

    2014-11-01

    Meditation is important in facilitating health. Pregnancy health has been shown to have significant consequences for infant behaviors. In view of limited studies on meditation and infant temperament, this study aims to explore the effects of prenatal meditation on these aspects. The conceptual framework was based on the postulation of positive relationships between prenatal meditation and infant health. A randomized control quantitative study was carried out at Obstetric Unit, Queen Elizabeth Hospital in Hong Kong. 64 pregnant Chinese women were recruited for intervention and 59 were for control. Outcome measures were cord blood cortisol, infant salivary cortisol, and Carey Infant Temperament Questionnaire. Cord blood cortisol level of babies was higher in the intervention group (p<0.01) indicates positive health status of the newborns verifies that prenatal meditation can influence fetal health. Carey Infant Temperament Questionnaire showed that the infants of intervention group have better temperament (p<0.05) at fifth month reflects the importance of prenatal meditation in relation to child health. Present study concludes the positive effects of prenatal meditation on infant behaviors and recommends that pregnancy care providers should provide prenatal meditation to pregnant women.

  14. Prenatal Depression Restricts Fetal Growth

    PubMed Central

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

    2009-01-01

    Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

  15. Brief change in housing conditions alters the survivability of irradiated C3H/HeN mice. Rept. for Sep 89-Sep 91

    SciTech Connect

    Collins, D.L.; Cohen, S.G.; Mickley, G.A.

    1992-03-04

    The present experiment examined how 24-hours in different housing conditions could effect the longevity of male and female C3H/HeN mice exposed to 8.0, 8.4, and 8.8 Gy Co-60 radiation at a dose rate if 0.40 Gy/minute. Housing conditions had a significant effect on the longevity of mice, as did gender and Gy level. Normal housed male and female mice (i.e., 10 mice per large 15800 cm3 cage) lived longer than did mice housed in isolation (i.e., one mouse per similar cage). Female mice exposed to 8.0 Gy and housed in either a social crowded (i.e., 10 mice per small 1580 cc cage) condition or a social and spatial crowded (i.e., 1 mouse per 158 cc cage - placed side-by-side in a 2x5 matrix) condition lived longer than did either normal or isolated female mice. The housing effect was so pronounced for female mice that 30% of the mice in the social crowded condition and 60% of the mice in the social and spatial crowded condition survived the supra-lethal 8.0 Gy dose. Female mice in the social and spatial condition lived 34% longer than did female mice housed in isolation. Overall, female mice lived 20% (+or- 5%) longer than did male mice. Male mice housed in the social-crowded condition lived on the average 23% (+or- 7%) longer than male mice housed in isolation. Male mice housed in the spatial crowded condition lived on the average 18% (+or- 7%) longer than male mice housed in isolation. Male mice in the 8.0 or 8.4 Gy condition lived an average of 35% (+or- 5%) longer than male mice in the 8.8 Gy condition.

  16. Prenatal exercise research.

    PubMed

    Field, Tiffany

    2012-06-01

    In this review of recent research on prenatal exercise, studies from several different countries suggest that only approximately 40% of pregnant women exercise, even though about 92% are encouraged by their physicians to exercise, albeit with some 69% of the women being advised to limit their exercise. A moderate exercise regime reputedly increases infant birthweight to within the normal range, but only if exercise is decreased in late pregnancy. Lower intensity exercise such as water aerobics has decreased low back pain more than land-based physical exercise. Heart rate and blood pressure have been lower following yoga than walking, and complications like pregnancy-induced hypertension with associated intrauterine growth retardation and prematurity have been less frequent following yoga. No studies could be found on tai chi with pregnant women even though balance and the risk of falling are great concerns during pregnancy, and tai chi is one of the most effective forms of exercise for balance. Potential underlying mechanisms for exercise effects are that stimulating pressure receptors during exercise increases vagal activity which, in turn, decreases cortisol, increases serotonin and decreases substance P, leading to decreased pain. Decreased cortisol is particularly important inasmuch as cortisol negatively affects immune function and is a significant predictor of prematurity. Larger, more controlled trials are needed before recommendations can be made about the type and amount of pregnancy exercise.

  17. Prenatal exercise research.

    PubMed

    Field, Tiffany

    2012-06-01

    In this review of recent research on prenatal exercise, studies from several different countries suggest that only approximately 40% of pregnant women exercise, even though about 92% are encouraged by their physicians to exercise, albeit with some 69% of the women being advised to limit their exercise. A moderate exercise regime reputedly increases infant birthweight to within the normal range, but only if exercise is decreased in late pregnancy. Lower intensity exercise such as water aerobics has decreased low back pain more than land-based physical exercise. Heart rate and blood pressure have been lower following yoga than walking, and complications like pregnancy-induced hypertension with associated intrauterine growth retardation and prematurity have been less frequent following yoga. No studies could be found on tai chi with pregnant women even though balance and the risk of falling are great concerns during pregnancy, and tai chi is one of the most effective forms of exercise for balance. Potential underlying mechanisms for exercise effects are that stimulating pressure receptors during exercise increases vagal activity which, in turn, decreases cortisol, increases serotonin and decreases substance P, leading to decreased pain. Decreased cortisol is particularly important inasmuch as cortisol negatively affects immune function and is a significant predictor of prematurity. Larger, more controlled trials are needed before recommendations can be made about the type and amount of pregnancy exercise. PMID:22721740

  18. Genetic counseling and prenatal diagnosis (image)

    MedlinePlus

    Genetic counseling (and prenatal diagnosis) provides parents with the knowledge to make intelligent, informed decisions regarding possible pregnancy and its outcome. If a pregnancy occurs the couple may want to evaluate the fetus by prenatal diagnosis.

  19. Effects of prenatal exposure to cocaine on brain structure and function.

    PubMed

    McCarthy, Deirdre M; Kabir, Zeeba D; Bhide, Pradeep G; Kosofsky, Barry E

    2014-01-01

    Drug abuse during pregnancy affects the mother and has adverse effects on the unborn child. This chapter highlights our recent findings at the neuroanatomical, molecular, and behavioral levels in a prenatal cocaine exposure mouse model. In the embryonic brains of prenatally cocaine-exposed mice, we observed a delay in the tangential migration of GABA neurons to the cerebral cortex as a result of a significant but transient decrease in the expression of the neurotrophin brain-derived neurotrophic factor (BDNF). These developmental changes lead to lasting deficits in the numerical density of GABA neurons in the mature medial prefrontal cortex (mPFC). In adult prenatally cocaine-exposed mice, we observed a behavioral deficit in the recall of an extinguished cue-conditioned fear, which was rescued by administration of exogenous recombinant BDNF protein directly into the infralimbic cortex of the mPFC, which may result from altered activity-driven transcriptional regulation of BDNF. PMID:24968785

  20. Difficult prenatal diagnosis: fetal coarctation

    PubMed Central

    Buyens, A.; Gyselaers, W.; Coumans, A.; Al Nasiry, S.; Willekes, C.; Boshoff, D.; Frijns, J.-P.; Witters, I.

    2012-01-01

    The prenatal diagnosis of fetal coarctation is still challenging. It is mainly suspected by ventricular disproportion (smaller left ventricle than right ventricle). The sensitivity of ventricular discrepancy is however moderate for the diagnosis of coarctation and there is a high false positive rate. Prenatal diagnosis of coarctation is important because the delivery can be arranged in a centre with a pediatric cardiac intensive careand this reduces postnatal complications and longterm morbidity. For many years the prenatal diagnosis of coarctation has been investigated to improve specificity and sensitivity by several of measurements. This article reviews all relevant articles from 2000 until 2011 searching pubmed and the reference list of interesting articles. An overview of specific measurements and techniques that can improve the diagnosis of coarctation has been made, such as the isthmus diameter, ductal diameter, isthmus/ductal ratio, z-scores derived from measurements of the distal aortic isthmus and arterial duct, the presence of a shelf andisthmal flow disturbance. Also 3-dimensional (3D) and 4-dimensional (4D) imaging with or without STIC has been suggested to be used as newer techniques to improve diagnosis of coarctation in fetal life. Although more methods regarding prenatal diagnosis of coarctationare being investigated, the ultrasound specialist remains challenged to correctly diagnose this cardiac anomaly in prenatal life. PMID:24753914

  1. The nature of tolerance in adult recipient mice made tolerant of alloantigens with supralethal irradiation followed by syngeneic bone marrow cell transplantation plus injection of F1 spleen cells

    SciTech Connect

    Tomita, Y.; Himeno, K.; Mayumi, H.; Tokuda, N.; Nomoto, K. )

    1989-06-01

    The length of time after syngeneic bone marrow reconstitution when tolerance to alloantigens can be induced in adult mice during T cell differentiation from bone marrow cells was studied by exposing those T cells to (recipient x donor)F1 spleen cells. Supralethally irradiated C3H/He Slc(C3H; H-2k) mice were reconstituted with 1 x 10(7) syngeneic T cell-depleted bone marrow cells and then injected intravenously with 5 x 10(7) (C3H x C57BL/6(B6))F1 (B6C3F1; H-2bxk) or (C3H x AKR/J(AKR))F1 (AKC3F1; H-2kxk) spleen cells at various intervals. In the fully allogeneic combination of B6C3F1----C3H, EL-4 tumor originating from B6 was accepted, and survival of grafted B6 skin was significantly prolonged in the tolerant C3H mice treated with irradiation on day -1 followed by injection of syngeneic bone marrow cells on day 0 plus B6C3F1 spleen cells on days 0, 5, or 10, in a tolerogen-specific manner. In the multiminor histocompatibility antigen-disparate combination of AKC3F1----C3H, AKR skin grafts were permanently accepted in the tolerant C3H mice treated with AKC3F1 spleen cells on days 0, 5, 10, or 15. Immunological parameters, including cytotoxic T lymphocyte activity and delayed foot-pad reaction (DFR), were almost completely suppressed in C3H mice made tolerant of B6 or AKR antigens. A chimeric assay using a direct immunofluorescence method revealed that the tolerant C3H mice given B6C3F1 spleen cells on day 0 were mixed-chimeric for at least 8 weeks after syngeneic bone marrow reconstitution, but not definitely chimeric thereafter. The C3H mice given AKC3F1 spleen cells on day 0 were chimeric even 43 weeks after syngeneic bone marrow reconstitution, but the C3H mice given AKC3F1 spleen cells on day 15 showed temporal chimerism that disappeared within 43 weeks. The untolerant mice were never detectably chimeric.

  2. Update on prenatal care.

    PubMed

    Zolotor, Adam J; Carlough, Martha C

    2014-02-01

    Many elements of routine prenatal care are based on tradition and lack a firm evidence base; however, some elements are supported by more rigorous studies. Correct dating of the pregnancy is critical to prevent unnecessary inductions and to allow for accurate treatment of preterm labor. Physicians should recommend folic acid supplementation to all women as early as possible, preferably before conception, to reduce the risk of neural tube defects. Administration of Rho(D) immune globulin markedly decreases the risk of alloimmunization in an RhD-negative woman carrying an RhD-positive fetus. Screening and treatment for iron deficiency anemia can reduce the risks of preterm labor, intrauterine growth retardation, and perinatal depression. Testing for aneuploidy and neural tube defects should be offered to all pregnant women with a discussion of the risks and benefits. Specific genetic testing should be based on the family histories of the patient and her partner. Physicians should recommend that pregnant women receive a vaccination for influenza, be screened for asymptomatic bacteriuria, and be tested for sexually transmitted infections. Testing for group B streptococcus should be performed between 35 and 37 weeks' gestation. If test results are positive or the patient has a history of group B streptococcus bacteriuria during pregnancy, intrapartum antibiotic prophylaxis should be administered to reduce the risk of infection in the infant. Intramuscular or vaginal progesterone should be considered in women with a history of spontaneous preterm labor, preterm premature rupture of membranes, or shortened cervical length (less than 2.5 cm). Screening for diabetes should be offered using a universal or a risk-based approach. Women at risk of preeclampsia should be offered low-dose aspirin prophylaxis, as well as calcium supplementation if dietary calcium intake is low. Induction of labor may be considered between 41 and 42 weeks' gestation. PMID:24506122

  3. Prenatal Nutrition and Later Education

    ERIC Educational Resources Information Center

    Evans, T. N.

    1972-01-01

    Text of an affidavit in the case, Kennedy v. Detroit Board of Education. Reports on a study which established that prenatal nutrition is directly related to brain size and volume determined at 48 hours of infancy and at eight months of age. Pinpoints the relationship between inadequate nutrition in pregnancy, infant brain size, and intellectual…

  4. Prenatal diagnosis of 47,XXX.

    PubMed

    Khoury-Collado, Fady; Wehbeh, Ammar N; Fisher, Allan J; Bombard, Allan T; Weiner, Zeev

    2005-05-01

    We report 2 cases of 47,XXX that were diagnosed prenatally and were screened positive for trisomy 21 by biochemical and ultrasound markers. These cases underline the importance of discussing the sex chromosome abnormalities during the genetic counseling after an abnormal triple screen test or ultrasound examination.

  5. Effect of gamma irradiation on the change of solubility and anti-inflammation activity of chrysin in macrophage cells and LPS-injected endotoxemic mice

    NASA Astrophysics Data System (ADS)

    Byun, Eui-Baek; Jang, Beom-Su; Byun, Eui-Hong; Sung, Nak-Yun

    2016-10-01

    This study evaluated the changes of solubility and anti-inflammatory properties of structurally modified gamma-irradiated chrysin. Chrysin was irradiated at various doses for a physical analysis and determining any structural changes and solubility. As shown through the physical analysis, the main peak of the chrysin was decreased as the irradiation dose increased, and it was concomitant with the appearance of several new peaks, which were highly increased in 50 kGy gamma-irradiated chrysin. The solubility was markedly increased in the gamma-irradiated groups. As shown through a physiological analysis, both gamma-irradiated- (15-50 kGy) and intact-chrysin (0 kGy) did not exert cytotoxicity to bone-marrow derived macrophages. The treatment of LPS-stimulated macrophages with 50 kGy gamma-irradiated chrysin resulted in a dose-dependent decrease in pro-inflammatory mediators, such as iNOS-mediated NO, PGE2, COX-2, and cell surface marker (CD80 and CD86), as well as pro-inflammatory cytokines (TNF-α and IL-6), when compared to the intact-chrysin treated group. Mechanically, we found that the inhibition of these pro-inflammatory mediators induced by gamma-irradiated chrysin occurred through an inhibition of MAPKs (ERK1/2 and p38) and the NF-κB signaling pathways. Furthermore, the anti-inflammatory activity remained in the LPS-injected animal model. In this model, gamma-irradiated chrysin treatment highly increased the mouse survival, and significantly decreased the serum cytokine (TNF-α, IL-6 and IL-1β) levels. From these findings, the anti-inflammatory action by gamma-irradiated chrysin may be closely mediated with structural modification. It seems likely that gamma irradiation can be an effective tool for improvement of the physical and physiological properties of polyphenols.

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

    SciTech Connect

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

    1981-11-15

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

  7. Neuropathological Consequences of Prenatal Cocaine Exposure in the Mouse

    PubMed Central

    Ren, Jia-Qian; Malanga, C.J.; Tabit, Eddy; Kosofsky, Barry E.

    2008-01-01

    We have developed an animal model in Swiss Webster mice to identify mechanisms by which prenatal exposure to cocaine results in persistent alterations in brain structure and function. Clinical data suggests that children who demonstrate the largest impairments in prenatal brain growth, which are positively correlated with the highest level of prenatal cocaine exposure, are more likely to demonstrate selective impairment in postnatal brain growth, as well as postnatal impairments in motor function, attention and language skills. We conducted neuroanatomic studies to identify the postnatal evolution of structural changes in the primary somatosensory (SI) cortex of the developing mouse brain following prenatal exposure to cocaine. Our previous work, and that of others, provides evidence that many of the processes underlying corticogenesis are disrupted by gestational exposure of the developing mouse brain to cocaine, and that from the earliest phases of corticogenesis that there is an imprecision in the development of cortical lamination. We performed morphometric comparisons between the brains of animals prenatally exposed to varying amounts of cocaine with vehicle and malnutrition controls on postnatal (P) days P9 and P50. We found that on P50, but not P9, the relative number of cortical neurons in S1 is significantly less in cocaine exposed animals as compared with controls. The significant decrease in the number of cells in cocaine exposed animals on P50 is evident as a decreased density of cells restricted to the infragranular compartment (layers 5 and 6). Those changes are not seen in malnourished animals. Taken together our findings support the conclusion that cocaine-induced alterations in SI cortical cytoarchitectonics are in part a consequence of altered postnatal survival of infragranular cortical neurons, which are lost during the interval between P9 and P50. Determining whether a similar process is evident in a subset of humans following in utero cocaine

  8. Prenatal exposure to ionizing radiation and subsequent development of seizures

    SciTech Connect

    Dunn, K.; Yoshimaru, H.; Otake, M.; Annegers, J.F.; Schull, W.J. )

    1990-01-01

    Seizures are a frequent sequela of impaired brain development and can be expected to affect more children with radiation-related brain damage than children without such damage. This report deals with the incidence and type of seizures among survivors prenatally exposed to the atomic bombing of Hiroshima and Nagasaki, and their association with specific stages of prenatal development at the time of irradiation. Fetal radiation dose was assumed to be equal to the dose to the maternal uterus. Seizures here include all references in the clinical record to seizure, epilepsy, or convulsion. Histories of seizures were obtained at biennial routine clinical examinations starting at about the age of 2 years. These clinical records were used to classify seizures as febrile or unprovoked (without precipitating cause). No seizures were ascertained among subjects exposed 0-7 weeks after fertilization at doses higher than 0.10 Gy. The incidence of seizures was highest with irradiation at the eighth through the 15th week after fertilization among subjects with doses exceeding 0.10 Gy and was linearly related to the level of fetal exposure. This obtains for all seizures without regard to the presence of fever or precipitating causes, and for unprovoked seizures. When the 22 cases of severe mental retardation were excluded, the increase in seizures was only suggestively significant and only for unprovoked seizures. After exposure at later stages of development, there was no increase in recorded seizures.

  9. Prenatal diagnosis of cloacal malformation.

    PubMed

    Peiro, Jose L; Scorletti, Federico; Sbragia, Lourenco

    2016-04-01

    Persistent cloaca malformation is the most severe type of anorectal and urogenital malformation. Decisions concerning the surgical treatment for this condition are taken during the first hours of life and may determine the quality of life of these patients. Thus, prenatal diagnosis becomes important for a prompt and efficient management of the fetus and newborn, and accurate counseling of the parents regarding its consequences and the future of the baby. Careful evaluation by ultrasonography, and further in-depth analysis with MRI, allow prenatal detection of characteristic findings, which can lead to diagnose or at least suspect this condition. We reviewed our experience and the literature in order to highlight the most important clues that can guide the physician in the differential diagnosis. PMID:26969229

  10. Prenatal exposure to di(2-ethylhexyl) phthalate impairs development of the mouse neocortex.

    PubMed

    Komada, Munekazu; Gendai, Yuuya; Kagawa, Nao; Nagao, Tetsuji

    2016-09-30

    Di(2-ethylhexyl) phthalate (DEHP) is currently the most commonly used phthalate for the production of flexible polyvinyl chloride. Phthalates including DEHP have been labeled as potential endocrine disruptors. The effect on the development of the neocortex, however, is unknown. To evaluate the neurodevelopmental effects of prenatal DEHP exposure at 1 and 100mg/kg/day or 100 and 500mg/kg/day in fetal and newborn mice, we performed a detailed histologic analysis of the developing dorsal telencephalon and neocortex. The observation of fetuses exposed to DEHP revealed reductions of proliferation and neurogenesis (1 and 100mg/kg) and an increase in cell death (500mg/kg). In addition, the newborns prenatally exposed to DEHP showed an abnormal neuronal distribution and a decrease in neurons. These findings suggest that prenatal DEHP exposure induces neurodevelopmental toxicity associated with the neural stem cell niche and corticogenesis. PMID:27472966

  11. The Future of Prenatal Diagnosis and Screening

    PubMed Central

    Pergament, Eugene

    2014-01-01

    The future of prenatal diagnosis and screening lies in developing clinical approaches and laboratory technologies applicable to genetic analyses and therapeutic interventions during embryonic development. PMID:26237604

  12. Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

    PubMed

    Yau, Mabel; Khattab, Ahmed; New, Maria I

    2016-06-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. PMID:27241964

  13. Effects of low-dose heavy ions on embryonic development in mice and on melanocyte differentiation in the epidermis and hair bulb.

    PubMed

    Hirobe, Tomohisa; Eguchi-Kasai, Kiyomi; Sugaya, Kimihiko; Murakami, Masahiro

    2013-05-01

    The effects of prenatal low-dose irradiation with heavy ions on embryonic development in mice and on melanocyte differentiation are not well understood. We performed whole-body irradiation of pregnant C57BL/10J mice at embryonic Day 9 (E9) with a single dose of γ-rays, silicon, argon or iron ions. The number of living embryos and embryonic body weight at E18 decreased after exposure to heavy ions at high doses. Malformations such as small eyes and limb anomalies were observed in heavy-ion-treated embryos, but not in γ-ray-treated embryos. The frequency of abnormally curved tails was increased by exposure to γ-rays and argon and iron ions even at a dose of 0.1 Gy (P < 0.05). In contrast, a dose-dependent decrease in the number of epidermal melanoblasts/melanocytes and hair bulb melanocytes was observed after 0.1 Gy irradiation with γ-rays or heavy ions (P < 0.01). The decrease in the number of dorsal hair bulb melanocytes, dorsal and ventral epidermal melanoblasts/melanocytes and ventral hair bulb melanocytes was not necessarily correlated with the linear energy transfer of the radiation tested. Moreover, the effects of heavy ions were larger on the ventral skin than on the dorsal skin, indicating that the sensitivity of melanocytes to heavy ions differs between the dorsal and ventral skin. Taken together, these results suggest that the effects of the low-dose heavy ions differ between cell types and tissues, and the effects on the prenatal development of mice and melanocyte development are not necessarily greater than those of γ-rays.

  14. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice.

    PubMed

    Uckun, Fatih M; Myers, Dorothea E; Cheng, Jianjun; Qazi, Sanjive

    2015-06-01

    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR-ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.

  15. Humanized Chronic Graft-versus-Host Disease in NOD-SCID il2rγ-/- (NSG) Mice with G-CSF-Mobilized Peripheral Blood Mononuclear Cells following Cyclophosphamide and Total Body Irradiation.

    PubMed

    Fujii, Hisaki; Luo, Zhi-Juan; Kim, Hye Jin; Newbigging, Susan; Gassas, Adam; Keating, Armand; Egeler, R Maarten

    2015-01-01

    Chronic graft-versus-host disease (cGvHD) is the major source of late phase morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Humanized acute GvHD (aGvHD) in vivo models using NOD-SCID il2rγ-/- (NSG) mice are well described and are important tools for investigating pathogenicity of human cells in vivo. However, there have been only few reported humanized cGvHD mouse models. We evaluated if prolonged inflammation driven by low dose G-CSF-mobilized human PBMCs (G-hPBMCs) would lead to cGvHD following cyclophosphamide (CTX) administration and total body irradiation (TBI) in NSG mice. Engraftment was assessed in peripheral blood (PB) and in specific target organs by either flow cytometry or immunohistochemistry (IHC). Tissue samples were harvested 56 days post transplantation and were evaluated by a pathologist. Some mice were kept for up to 84 days to evaluate the degree of fibrosis. Mice that received CTX at 20mg/kg did not show aGvHD with stable expansion of human CD45+ CD3+ T-cells in PB (mean; 5.8 to 23.2%). The pathology and fibrosis scores in the lung and the liver were significantly increased with aggregation of T-cells and hCD68+ macrophages. There was a correlation between liver pathology score and the percentage of hCD68+ cells, suggesting the role of macrophage in fibrogenesis in NSG mice. In order to study long-term survival, 6/9 mice who survived more than 56 days showed increased fibrosis in the lung and liver at the endpoint, which suggests the infiltrating hCD68+ macrophages may be pathogenic. It was shown that the combination of CTX and TBI with a low number of G-hPBMCs (1x106) leads to chronic lung and liver inflammation driven by a high infiltration of human macrophage and mature human T cells from the graft, resulting in fibrosis of lung and liver in NSG mice. In conclusion this model may serve as an important pre-clinical model to further current understanding of the roles of human macrophages in cGvHD.

  16. Combined therapy of septicemia with ofloxacin and/or synthetic trehalose dicorynomycolate (S-TDCM) in irradiated and wounded mice (kombinierte therapie der septikaemie mit ofloxacin und/oder synthetischem trehalose-dicorynomycolat (s-tdcm) bei bestrahlten und verwundeten maeusen)

    SciTech Connect

    Madonna, G.S.; Moore, M.M.; Ledney, G.D.; Elliot, T.B.; Brook, I.

    1989-01-01

    Following lethal irradiation, mice usually succumb to sepsis as a result of translocation of intestinal bacteria and impairment of the host defense system. Additional trauma in these immunocompromised mice further increases susceptibility to bacterial infection from either endogenous or exogenous origin. Treatment with ofloxacin or synthetic trehalose dicorynemycolate (S-TDCM) was evaluated in mice, which were lethally irradiated and wounded, and which died with sepsis within six days. Wounding was performed on C3H/HeN mice anesthetized by inhalation of methoxyfurane. Dorsal skin and muscle equal to 30% total body surface was removed 1 h after 8.0 Gy gamma radiation. S-TDCM, which augments nonspecific resistance to infection in irradiated mice, was given once i.p. immediately after wounding. Oxfloxacin was injected s.c. daily from day 0 to day 10. Staphylococcus aureus, Streptococcus faecium, and Escherichia coli were isolated from both the livers and wound sites of moribund, untreated mice 4 and 5 days postirradiation.

  17. Prenatal diagnosis of inherited metabolic diseases.

    PubMed Central

    Diukman, R; Goldberg, J D

    1993-01-01

    Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus. Images PMID:8236980

  18. Conceptions of Prenatal Development: Behavioral Embryology

    ERIC Educational Resources Information Center

    Gottlieb, Gilbert

    1976-01-01

    Describes recent progress in research on prenatal behavioral development and in a systematic fashion the various ways in which prenatal experience can affect the development of behavior in the neonate as well as in the embryo and fetus. (Author/RK)

  19. Prenatal Maternal Stress Programs Infant Stress Regulation

    ERIC Educational Resources Information Center

    Davis, Elysia Poggi; Glynn, Laura M.; Waffarn, Feizal; Sandman, Curt A.

    2011-01-01

    Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.…

  20. Supernatants from ultraviolet-irradiated keratinocytes decrease the resistance and delayed-type hypersensitivity response to Mycobacterium bovis bacillus Calmette-Guerin in mice and impair the phagocytic ability of macrophages.

    PubMed

    Jeevan, A; Ullrich, S E; Dizon, V V; Kripke, M L

    1991-12-01

    We recently demonstrated that exposure of mice to a single high dose or multiple smaller doses of ultraviolet (UV) radiation decreased the induction of the delayed-type hypersensitivity (DTH) response to bacillus Calmette-Guerin (BCG) from Mycobacterium bovis injected into unexposed sites. In view of the limited ability of UV radiation to penetrate beyond the epidermis and upper layers of the dermis, it is not entirely clear how exposing the dorsal skin of mice to UV radiation causes systemic impairment of the immune response to BCG. In this study we report that mice injected with supernatants from keratinocyte cultures exposed to UV radiation in vitro impaired host resistance to BCG. Both induction and elicitation of the DTH reaction were suppressed after the intravenous injection of supernatants from UV-irradiated keratinocytes. Furthermore, these supernatants interfered with the elimination of viable bacteria from the lymphoid organs. To determine whether macrophages were the target of the UV-induced, keratinocyte-derived, suppressive cytokine, macrophages were isolated from mice injected with the suppressive cytokine or treated in vitro with the supernatants and tested for their ability to ingest and kill BCG in vitro. Injection of the suppressive factor significantly reduced the phagocytosis of BCG by the macrophages but did not alter the rate of intracellular killing. Similarly, phagocytosis was reduced when normal macrophages were treated in vitro with the suppressive factor. These findings suggest that the suppressive cytokine interferes with the elimination of bacteria in vivo by inhibiting the initial step in bacterial clearance, the uptake of the bacteria by host macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1823151

  1. Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

    SciTech Connect

    Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.; James, S. )

    1991-03-01

    Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production, whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.

  2. Prenatal microwave exposure and behavior

    SciTech Connect

    O'Connor, M.E.

    1988-01-01

    The hypotheses for the initial investigation was based on the idea that failure to observe structural teratogenesis following microwave exposure did not preclude the possibility that such exposure would result in behavioral changes. We also proposed that such exposure might specifically alter some aspect of thermoregulatory behavior. The results of these studies support both of these hypotheses. Whether the studies show enhanced thermal sensitivity or enhanced development, they do support the hypothesis that prenatal exposure to microwave radiation is more likely to alter postnatal sensitivity to thermally related stimuli or conditions as compared to stimuli that are thermally neutral.

  3. Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy.

    PubMed

    Blyth, Benjamin J; Kakinuma, Shizuko; Sunaoshi, Masaaki; Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Ogawa, Kanae; Shirakami, Ayana; Shang, Yi; Tsuruoka, Chizuru; Nishimura, Mayumi; Shimada, Yoshiya

    2015-01-01

    Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV x μm(-1)) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to

  4. Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

    PubMed Central

    Blyth, Benjamin J.; Kakinuma, Shizuko; Sunaoshi, Masaaki; Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Ogawa, Kanae; Shirakami, Ayana; Shang, Yi; Tsuruoka, Chizuru; Nishimura, Mayumi; Shimada, Yoshiya

    2015-01-01

    Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV.μm-1) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing

  5. Disposition of Perfluorooctanoic Acid (PFOA) in Pregnant and Lactating CD-1 Mice and Their Pups

    EPA Science Inventory

    Previous studies in mice prenatally-exposed to PFOA demonstrate growth and developmental effects, including impaired body weight gain and mammary gland development, delayed eye opening, and increased mortality. Those dose dependent effects appeared to worsen if offspring exposed ...

  6. Prenatal Stress, Prematurity, and Asthma.

    PubMed

    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C

    2015-12-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health. PMID:26676148

  7. Prenatal Stress, Prematurity, and Asthma.

    PubMed

    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C

    2015-12-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health.

  8. Hemimegalencephaly: prenatal diagnosis and outcome.

    PubMed

    Alvarez, Rosa María; García-Díaz, Lutgardo; Márquez, Javier; Fajardo, Manuel; Rivas, Eloy; García-Lozano, Juan Carlos; Antiñolo, Guillermo

    2011-01-01

    Hemimegalencephaly (HME) is a developmental abnormality of the central nervous system (CNS) which may present as either a syndromic or isolated case. Here, we present two cases of early prenatal diagnosis of HME. Prenatal CNS ultrasound and MRI in the first case revealed ventricular asymmetry, midline shift with displacement of the occipital lobe across the midline, large dilatation mainly at the posterior horn of the left lateral ventricle, and a head circumference in the 90th percentile without involvement of the brain stem and cerebellum, as well as abdominal lymphangioma. Right hemispherectomy was performed at 3 months of age due to intractable seizures. The pathological specimen showed findings characteristic of HME, including a disorganized cytoarchitecture with lack of neuronal lamination, focal areas of polymicrogyria, and neuronal heterotopias with dysplastic cells. In the second case, 2D and 3D neurosonography demonstrated similar findings (asymmetry of cerebral hemispheres, midline shift, and dilation of the posterior horn of the left lateral cerebral ventricle). Posterior fossa structures were unremarkable. HME was diagnosed and the pregnancy was terminated. Autopsy findings confirmed the diagnosis of HME.

  9. Prenatal x-ray exposure and childhood cancer in twins

    SciTech Connect

    Harvey, E.B.; Boice, J.D. Jr.; Honeyman, M.; Flannery, J.T.

    1985-02-28

    A case-control study was conducted to investigate the relation between prenatal exposure to x-rays and childhood cancer, including leukemia, in over 32,000 twins born in Connecticut from 1930 to 1969. Twins as opposed to single births were chosen for study to reduce the likelihood of medical selection bias, since twins were often exposed to x-rays to diagnose the twin pregnancy or to determine fetal positioning before delivery and not because of medical conditions that may conceivably pre-dispose to cancer. Each of 31 incident cases of cancer, identified by linking the Connecticut twin and tumor registries, was matched with four twin controls according to sex, year of birth, and race. Records of hospitals, radiologists, and private physicians were searched for histories of x-ray exposure and other potentially important risk factors. Documented prenatal x-ray exposures were found for 39 per cent of the cases (12 of 31) and for 26 per cent of the controls (28 of 109). No other pregnancy, delivery, or maternal conditions were associated with cancer risk except low birth weight: 38 per cent of the cases as compared with 25 per cent of the controls weighed under 2.27 kg at birth. When birth weight was adjusted for, twins in whom leukemia or other childhood cancer developed were twice as likely to have been exposed to x-rays in utero as twins who were free of disease (relative risk, 2.4; 95 per cent confidence interval, 1.0 to 5.9). The results, though based on small numbers, provide further evidence that low-dose prenatal irradiation may increase the risk of childhood cancer.

  10. The prenatal care at school program.

    PubMed

    Griswold, Carol H; Nasso, Jacqueline T; Swider, Susan; Ellison, Brenda R; Griswold, Daniel L; Brooks, Marilyn

    2013-06-01

    School absenteeism and poor compliance with prenatal appointments are concerns for pregnant teens. The Prenatal Care at School (PAS) program is a new model of prenatal care involving local health care providers and school personnel to reduce the need for students to leave school for prenatal care. The program combines prenatal care and education designed specifically for adolescents. Twenty-eight girls attended PAS in the fall of 2010. Program evaluation results showed a 14.2% increase in school attendance among students enrolled compared to peers enrolled the previous year, a 5.7% increase over a local teen clinic's attendance to their group prenatal care program, and a 42% increase in pregnancy and childbirth knowledge. Satisfaction surveys indicated that participants all believed that PAS helped prepare them for labor and delivery and 92% felt encouraged to stay in school. This pilot program benefited pregnant teens by increasing school educational time, improving preparation for labor and delivery, and increasing participation with prenatal care. PMID:23144051

  11. Prenatal and pre-implantation genetic diagnosis.

    PubMed

    Vermeesch, Joris Robert; Voet, Thierry; Devriendt, Koenraad

    2016-09-15

    The past decade has seen the development of technologies that have revolutionized prenatal genetic testing; that is, genetic testing from conception until birth. Genome-wide single-cell arrays and high-throughput sequencing analyses are dramatically increasing our ability to detect embryonic and fetal genetic lesions, and have substantially improved embryo selection for in vitro fertilization (IVF). Moreover, both invasive and non-invasive mutation scanning of the genome are helping to identify the genetic causes of prenatal developmental disorders. These advances are changing clinical practice and pose novel challenges for genetic counselling and prenatal care. PMID:27629932

  12. Prenatal stress delays inhibitory neuron progenitor migration in the developing neocortex

    PubMed Central

    Stevens, Hanna E.; Su, Tina; Yanagawa, Yuchio; Vaccarino, Flora M.

    2012-01-01

    Summary Prenatal stress has been widely demonstrated to have links with behavioral problems in clinical populations and animal models, however, few investigations have examined the immediate developmental events that are affected by prenatal stress. Here, we utilize GAD67GFP transgenic mice in which GABAergic progenitors express green fluorescent protein (GFP) to examine the impact of prenatal stress on the development of these precursors to inhibitory neurons. Pregnant female mice were exposed to restraint stress three times daily from embryonic day 12 (E12) onwards. Their offspring demonstrated changes in the distribution of GFP-positive (GFP+) GABAergic progenitors in the telencephalon as early as E13 and persisting until postnatal day 0. Changes in distribution reflected alterations in tangential migration and radial integration of GFP+ cells into the developing cortical plate. Fate mapping of GAD67GFP+progenitors with bromodeoxyuridine injected at E13 demonstrated a significant increase of these cells at P0 in anterior white matter. An overall decrease in GAD67GFP+ progenitors at P0 in medial frontal cortex could not be attributed to a reduction in cell proliferation. Significant changes in dlx2, nkx2.1 and their downstream target erbb4, transcription factors which regulate interneuron migration, were found within the prenatally-stressed developing forebrain, while no differences were seen in mash1, a determinant of interneuron fate, bdnf, a maturation factor for GABAergic cells or fgf2, an early growth/differentiation factor. These results demonstrate that early disruption in GABAergic progenitor migration caused by prenatal stress may be responsible for neuronal defects in disorders with GABAergic abnormalities like schizophrenia. PMID:22910687

  13. Prenatal exposure: The effects of prenatal cocaine and methamphetamine exposure on the developing child.

    PubMed

    Smith, Lynne M; Santos, Lucinda S

    2016-06-01

    Prenatal substance use remains a significant issue in the United States. Initial reports regarding prenatal cocaine and methamphetamine exposure suggested profound adverse effects on child development. However, subsequent prospective, longitudinal investigations have found more subtle effects. What follows is a brief review of the health, growth, behavioral, and intellectual outcomes for children exposed to prenatal cocaine and prenatal methamphetamine. Factors that may mitigate or intensify subtle adverse effects manifested in exposed children will also be discussed. Birth Defects Research (Part C) 108:142-146, 2016. © 2016 Wiley Periodicals, Inc. PMID:27345014