Sample records for prenatally irradiated mice

  1. Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

    Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significantmore » changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.« less

  2. Prenatal ethanol weakens the efficacy of reinforcers for adult mice.

    PubMed

    Gentry, G D; Middaugh, L D

    1988-02-01

    Pregnant C57BL/6cr mice were fed a liquid diet containing 20% of the total calories from either ethanol (E) or sucrose (S) for gestation days 5-17. Adult male and female (six of each from both prenatal-treatment groups) offspring were tested under various schedules of food reinforcement. The first phase was a test of fixed-ratio (FR) acquisition in which the required number of responses per unit of reinforcement was increased from 1 to 20 to 100. Prenatal ethanol exposure interacted with other factors to produce an acquisition deficit. The second phase involved responding under extinction (Ext). Under standard Ext procedures there were no prenatal-ethanol effects; however, when a conditioned reinforcer was superimposed on an FR 5, the E males did not increase their rates as much as the S males. Finally, under a multiple FR 5 DRO 15-sec (differential-reinforcement-of-other-behavior) arrangement, prenatal-ethanol effects were found in each component. For the FR 5 component, prenatal ethanol eliminated the sex differences found in the S subjects. For the DRO 15-sec component, prenatal ethanol elevated response rates. The results indicate a general decreased efficacy of positive reinforcement in adult mice following prenatal ethanol exposure.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 resolvingmore » 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.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    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 resolvingmore » 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.« less

  5. 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.

  6. Prenatal Exposure to DEHP Induces Neuronal Degeneration and Neurobehavioral Abnormalities in Adult Male Mice.

    PubMed

    Barakat, Radwa; Lin, Po-Ching; Park, Chan Jin; Best-Popescu, Catherine; Bakery, Hatem H; Abosalum, Mohamed E; Abdelaleem, Nabila M; Flaws, Jodi A; Ko, CheMyong

    2018-04-23

    Phthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies. In this study, we tested the hypothesis that prenatal exposure to DEHP impairs neurobehavior and recognition memory in her male offspring and we investigated one possible mechanism-oxidative damage in the hippocampus. Pregnant CD-1 female mice were orally administered 200μg, 500mg, or 750mg/kg/day DEHP or vehicle from gestational day 11 until birth. The neurobehavioral impact of the prenatal DEHP exposure was assessed at the ages of 16 to 22 months. Elevated plus maze and open field tests were used to measure anxiety levels. Y-maze and novel object recognition tests were employed to measure memory function. The oxidative damage in the hippocampus was measured by the levels of oxidative DNA damage and by SLIM microscopic counting of hippocampal neurons. Adult male mice that were prenatally exposed to DEHP exhibited anxious behaviors and impaired spatial and short-term recognition memory. The number of hippocampal pyramidal neurons was significantly decreased in the DEHP mice. Furthermore, DEHP mice expressed remarkably high levels of cyclooxygenase-2, 8-hydroxyguanine, and thymidine glycol in their hippocampal neurons. DEHP mice also had lower circulating testosterone concentrations and displayed a weaker immunoreactivity than the control mice to androgen receptor expression in the brain. This study found that prenatal exposure to DEHP caused elevated anxiety behavior and impaired recognition memory. These behavioral changes may originate from neurodegeneration caused by oxidative damage and inflammation in the hippocampus. Decreased circulating testosterone concentrations and decreased expression of androgen receptor in the brain also may be factors contributing

  7. Prenatal exposure to psychostimulants increases impulsivity, compulsivity, and motivation for rewards in adult mice.

    PubMed

    Lloyd, S A; Oltean, C; Pass, H; Phillips, B; Staton, K; Robertson, C L; Shanks, R A

    2013-07-02

    Given the widespread use and misuse of methamphetamine (METH) and methylphenidate (MPD), especially in relation to women of childbearing age, it is important to consider the long-lasting effects of these drugs on the brain of the developing fetus. Male and female C57Bl/6J mice were prenatally exposed to METH (5mg/kg), MPD (10mg/kg), or saline. Following a 3-month washout, behavioral analysis using the 5-Choice Serial Reaction Time Task (5CSRTT) was performed on adult mice. After reaching training criteria, performance on a pseudo-random intertrial interval test session revealed decrements in 5CSRTT behavior. Prenatally-treated METH and MPD mice demonstrated significant increases in impulsivity, compulsivity, and motivation for reward compared to their saline controls. There were sex by drug interactions indicating a possible sexually dimorphic response to these prenatal drug exposures. Of particular clinical interest, we find that mice prenatally exposed to METH or MPD express characteristics of both inhibitory control decrements and heightened motivation for rewards, which represent core symptoms of addiction and other impulse control disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2012-07-01

    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). 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, IgG(1) , and IgG(2a) 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. 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. 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. © 2012 John Wiley & Sons A/S.

  9. Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

    PubMed

    Dalterio, S; Steger, R; Mayfield, D; Bartke, A

    1984-01-01

    Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

  10. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    PubMed

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. [Effect of electromagnetic pulse irradiation on mice reproduction].

    PubMed

    Wang, Shui-ming; Wang, De-wen; Peng, Rui-yun; Chen, Hao-yu; Gao, Ya-bing; Cao, Xiao-zhe; Cui, Xue-mei; Zhao, Mei-lan

    2003-10-01

    To evaluate the effect of electromagnetic pulse (EMP) irradiation on mice reproduction. Female/male Kunming mice, 6 - 8 weeks old, prior to mating, or female after pregnancy were treated with whole body irradiation by 6 x 10(4) V/m electromagnetic pulse (EMP) for five times. The pregnant mice were killed on the 18th days, and teratological markers were analysed. EMP irradiation caused no significant changes in most of female organ weight and organ/body weight ratio. But it caused significant shortening in tail length of live foetus in the female mice before conception (prior to mating) or after pregnancy (P < 0.05), and obvious decrease in male offspring ratio (0.85 +/- 0.09 vs 1.09 +/- 0.17, P < 0.05). The male offspring ratio also significantly decreased (0.76 +/- 0.18 vs 1.09 +/- 0.17, P < 0.01) after male mice irradiated by EMP. The tail length of live foetus was shortened and male offspring sex ratio was increased after both male and female mice were irradiated by EMP. EMP irradiation also caused a significantly higher fetal death rate than normal control (P < 0.05). The embryo absorption rate was increased after irradiation except that was decreased in male mice. EMP irradiation has effect on pregnancy and offspring development in both male and female mice before mating and in female mice after pregnancy.

  12. Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Changqing; Gao, Liying; Flaws, Jodi A., E-ma

    Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily frommore » gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.« less

  13. Trehalose Dimycolate Enhances Survival of Fission Neutron-Irradiated Mice and Klebsiella pneumoniae-Challenged Irradiated Mice

    DTIC Science & Technology

    1990-01-01

    SR90-5 Trehalose Dimycolate Enhances Survival of Fission Neutron-Irradiated Mice and Kiebsiella pneumoniae-Challenged Irradiated Mice 1’ 2 D. (. M...doses kines and immunomodulators of nonspecific resistance to of fission neutron radiation is increased when trehalose dimycol- infection might have... trehalose day before exposure to radiation. TDM in an emulsion of squa- dimycolate (TDM) have been shown to be effective in in- lene. Tween 80, and saline

  14. Prenatal stress changes courtship vocalizations and bone mineral density in mice.

    PubMed

    Schmidt, Michaela; Lapert, Florian; Brandwein, Christiane; Deuschle, Michael; Kasperk, Christian; Grimsley, Jasmine M; Gass, Peter

    2017-01-01

    Stress during the prenatal period has various effects on social and sexual behavior in both human and animal offspring. The present study examines the effects of chronic restraint stress in the second vs third trimester in pregnancy and glucocorticoid receptor (GR) heterozygous mutation on C57BL/6N male offspring's vocal courtship behavior in adulthood by applying a novel analyzing method. Finally, corticosterone and testosterone levels as well as bone mineral density were measured. Prenatal stress in the third, but not in the second trimester caused a significant qualitative change in males' courtship vocalizations, independent of their GR genotype. Bone mineral density was decreased also by prenatal stress exclusively in the third trimester in GR mutant and wildtype mice and - in contrast to corticosterone and testosterone - highly correlated with courtship vocalizations. In Gr +/- males corticosterone serum levels were significantly increased in animals that had experienced prenatal stress in the third trimester. Testosterone serum levels were overall increased in Gr +/- males in comparison to wildtypes as a tendency - whereas prenatal stress had no influence. Prenatal stress alters adult males' courtship vocalizations exclusively when applied in the third trimester, with closely related changes in bone mineral density. Bone mineral density seems to reflect best the complex neuroendocrine mechanisms underlying the production of courtship vocalizations. Besides, we demonstrated for the first time elevated basal corticosterone levels in Gr +/- males after prenatal stress which suggests that the Gr +/- mouse model of depression might also serve as a model of prenatal stress in male offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

    Kabir, Zeeba D; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet P; 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 prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor (BDNF) and its downstream signaling molecule, early growth response protein 1 (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 the 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 postnatal day (PD) 25, and increased SI but not USVs at PD35. By PD45 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 PD30 that normalized by PD45. This was concurrent with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (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 neurobiological mechanism mediating the altered social development in juvenile mice. © 2014 S. Karger AG, Basel.

  16. 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

  17. Preservation of chromosomal integrity in murine spermatozoa derived from gonocytes and spermatogonial stem cells surviving prenatal and postnatal exposure to γ-rays in mice.

    PubMed

    Watanabe, Hiroyuki; Kohda, Atsushi; Komura, Jun-Ichiro; Tateno, Hiroyuki

    2017-07-01

    Pre- and postnatal male mice were acutely (659-690 mGy/min) and continuously (0.303 mGy/min) exposed to 2 Gy γ-rays to evaluate spermatogenic potential and chromosome damage in their germ cells as adults. Acute irradiation on Days 15.5, 16.5, and 17.5 post-coitus affected testicular development, as a result of massive quiescent gonocyte loss; the majority of the seminiferous tubules in these testes were devoid of germ cells. Acute irradiation on Days 18.5 and 19.5 post-coitus had less effect on testicular development and spermatogenesis, even though germ cells were quiescent gonocytes on these days. Adverse effects on testicular development and spermatogenesis were observed following continuous irradiation between Days 14.5 and 19.5 post-coitus. Exposure to acute and continuous postnatal irradiation after the differentiation of spermatogonial stem cells and spermatogonia resulted in nearly all of the seminiferous tubules exhibiting spermatogenesis. Neither acute nor continuous irradiation was responsible for the increased number of multivalent chromosomes in primary-spermatocyte descendents of the exposed gonocytes. In contrast, a significant increase in cells with multivalent chromosomes was observed following acute irradiation on Days 4 and 11 post-partum. No significant increases in unstable structural chromosomal aberrations or aneuploidy in spermatozoa were observed, regardless of cell stage at irradiation or the radiation dose-rate. Thus, murine germ cells that survive prenatal and postnatal irradiation can restore spermatogenesis and produce viable spermatozoa without chromosome damage. These findings may provide a better understanding of reproductive potential following accidental, environmental, or therapeutic irradiation during the prenatal and postnatal periods in humans. © 2017 Wiley Periodicals, Inc.

  18. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Prenatal exposure to PCP produces behavioral deficits accompanied by the overexpression of GLAST in the prefrontal cortex of postpubertal mice.

    PubMed

    Lu, Lingling; Mamiya, Takayoshi; Lu, Ping; Toriumi, Kazuya; Mouri, Akihiro; Hiramatsu, Masayuki; Zou, Li-Bo; Nabeshima, Toshitaka

    2011-06-20

    Altered glutamatergic neurotransmission in the prefrontal cortex (PFC) has been implicated in a myriad of neuropsychiatric disorders. We previously reported that prenatal exposure to PCP produced long-lasting behavioral deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors. In addition, these behavioral changes were attenuated by clozapine treatment. However, whether the prenatal exposure adversely affects pre-synaptic glutamatergic neurotransmission in postpubertal mice remains unknown. In the present study, we investigated the involvement of prefrontal glutamatergic neurotransmission in the impairment of cognitive and emotional behavior after prenatal PCP treatment (5mg/kg/day) from E6 to E18 in mice. The PCP-treated mice showed an impairment of recognition memory in a novel object recognition test and enhancement of immobility in a forced swimming test at 8 weeks of age. Moreover, the prenatal treatment reduced the extracellular glutamate level, but increased the expression of a glial glutamate transporter (GLAST) in the PFC. The microinjection of DL-threo-β-benzyloxyaspartate (DL-TBOA, 10 nmol/site/bilaterally), a potent blocker of glutamate transporters, reversed these behavioral deficits by enhancing the prefrontal glutamatergic neurotransmission. Taken together, prenatal exposure to PCP produced impairments of long-term memory and emotional function which are associated with abnormalities of pre-synaptic glutamate transmission in the PFC of postpubertal mice. These findings suggest the prenatal inhibition of NMDA receptor function to contribute partly to the pathophysiology of neurodevelopment-related disorders, such as schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia.

    PubMed

    Avraam, Joanne; Cohen, Gary; Drago, John; Frappell, Peter B

    2015-03-01

    Prenatal nicotine exposure alters breathing and ventilatory responses to stress through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the hypothesis that α4-containing nAChRs are involved in mediating the effects of prenatal nicotine exposure on ventilatory and metabolic responses to intermittent mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation (V̇(E)) and rate of O2 consumption ( V̇(O2)) of wild-type (WT) and α4-knock-out (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed with 2 min of air. Compared to WT, α4 KO mice had increased air V̇(E) and V̇(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the hyperventilatory response (increase in V̇(E)/V̇(O2)) to MA. At P1-2, nicotine suppressed air V̇(E) and V̇(O2) in both genotypes but did not affect the hyperventilatory response to MA. At P7-8 nicotine suppressed air V̇(E) and V̇(O2) of only α4 KO's but also significantly enhanced V̇(E) during MA (nearly double that of WT; p<0.001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. 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

  2. THE PROTECTION ACTION OF HEROIN ON THE EMBRYOS OF WHITE MICE AFTER WHOLE- BODY IRRADIATION OF THE MOTHER (in Russian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shapiro, F.B.

    1959-03-01

    The article presents results of experiments on the use of heroin in the protection of white mice embryos from gamma rays (Co/sup 60/ in whole-body irradiation of the mother. Single total irradiation of females (200 r) was instituted on the 9th and l2th day of pregnancy. Heroin was introduced to gravid females subcutaneously (5 mg) 5 minutes before the irradiation. The protective action of heroin was manifested by: a) reduction of prenatal death of embryos -a decrease of the number of cases of resorption and increase of the quantity of micc in a litter; b) a drop of neonatal mortalitymore » (stillbirth and death immediately after birth); c) a diminution of postnatal mortality; and d) normalization of the growth of animals and a decrease of the number of monstrosities. (auth)« less

  3. 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

    2016-06-03

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Cerebral impact of prenatal irradiation by 131I: an experimental model of clinical neuroradioembryological effects.

    PubMed

    Talko, V V; Loganovsky, K M; Drozd, I P; Tukalenko, Ye V; Loganovska, T K; Nechayev, S Yu; Masiuk, S V; Prokhorova, Ye M

    2017-12-01

    Human brain in prenatal period is a most vulnerable to ionizing radiation body structure. Unlike atomic bombings or radiological interventions in healthcare leading at most to external irradiation the intensive internal exposure may occur upon nuclear reactor accidents followed by substantial release and fallout of radioactive 131I. The latter can lead to specific neuroradioembryological effects. To create an experimental model of prenatal cerebral radiation effects of 131I in human and to determine the experimental and clinical neuroradioembryological effects.Study object. The neuroradioembryological effects in Vistar rats exposed to 131I in prenatal period. Nervous system status and mental status in 104 persons exposed to ionizing radiation in utero due to the ChNPP accident and the same in 78 not exposed subjects. Experimental i.e. behavioral techniques, including the spontaneous locomotive, exploratory activity and learning ability assessment, clinical i.e. neuropsychiatric, neuro and psychometric, neuropsychological, neurophys iological methods, both with dosimetric and statistical methods were applied. Intrauterine irradiation of Wistar rats by 131I was simulated on a model of one time oral 27.5 kBq radionu clide administration in the mid gestation period (0.72±0.14 Gy fetal thyroid dose), which provides extrapolation of neuroradioembryological effects in rats to that in humans exposed to intrauterine radiation as a result of the Chornobyl catastrophe. Abnormalities in behavioral reactions and decreased output of conditioned reflex reactions identified in the 10 month old rats suggest a deterioration of cerebral cognition in exposed animals. Specific cog nitive deficit featuring a disharmonic intellectual development through the relatively decreased verbal intelligence versus relative increase of nonverbal one is remained in prenatally exposed persons. This can indicate to dysfunc tion of cortical limbic system with especial involvement of a dominant

  5. Protective Effect of 940 nm Laser on Gamma-Irradiated Mice

    PubMed Central

    Efremova, Yulia; Navratil, Leos

    2015-01-01

    Abstract Objective: The purpose of this study was to investigate the radioprotective features of 940 nm laser on the life span of mice, and absolute counts of blood cells and their proportions in gamma-irradiated mice. Background data: An important feature of laser light is activation of mitotic division and differentiation of cells, which may be useful in activation of hematopoiesis in gamma-irradiated organisms. Materials and methods: Mice were randomly assigned to 11 groups according to the type(s) of influence. Generally, mice were irradiated in three different ways: with laser at different fluences, with gamma irradiation, or by combination of laser at different fluences and gamma irradiation in a different order. Mice were treated with 940 nm laser at 3, 12, or 18 J/cm2 and/or a lethal dose of gamma irradiation (8.7 Gy). Each group was randomly subdivided into two subgroups, in which the life span of the mice and blood cell counts (on 12th and 45th day after gamma irradiation) were analyzed. Results: Laser (940 nm) at a fluence of 3 J/cm2 significantly prolonged the life span of gamma-irradiated mice (p<0.05). In the same group, counts of white blood cells, lymphocytes, and neutrophils were higher on day 12 than in the gamma group. On day 45 after gamma irradiation, some signs of hematopoiesis repair were found in blood. There were no significant differences in counts of erythrocytes, monocytes, neutrophils, or the proportion of neutrophils between this group and the control group. Conclusions: In summary, 940 nm laser at a fluence of 3 J/cm2 demonstrates radioprotective features in an experiment with lethally irradiated mice. Mechanisms responsible for this effect will be investigated in further studies. PMID:25654740

  6. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

    PubMed Central

    Malloul, Hanaa; Mahdani, Ferdaousse M.; Bennis, Mohammed; Ba-M’hamed, Saadia

    2017-01-01

    Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice (N = 21) were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1), offspring (N = 88) length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were revealed only in the

  7. Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

    PubMed Central

    Zhou, Changqing; Gao, Liying; Flaws, Jodi A.

    2017-01-01

    Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. PMID:28126412

  8. 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

  9. Prenatal Exposure to Urban Air Nanoparticles in Mice Causes Altered Neuronal Differentiation and Depression-Like Responses

    PubMed Central

    Godar, Sean C.; Sander, Thomas K.; Iwata, Nahoko; Pakbin, Payam; Shih, Jean C.; Berhane, Kiros; McConnell, Rob; Sioutas, Constantinos

    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/m3) 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. PMID:23734187

  10. Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice.

    PubMed

    Zhou, Changqing; Gao, Liying; Flaws, Jodi A

    2017-03-01

    Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200μg/kg/day, 200 and 500mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-03-15

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

  12. Prenatal and lactational exposure to low-doses of bisphenol A alters adult mice behavior.

    PubMed

    Nakamura, Keiko; Itoh, Kyoko; Dai, Hongmei; Han, Longzhe; Wang, Xiaohang; Kato, Shingo; Sugimoto, Tohru; Fushiki, Shinji

    2012-01-01

    Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in dentistry and various industries. We previously reported that BPA affected murine neocortical development by accelerating neuronal differentiation/migration, resulting in abnormal neocortical architecture as well as aberrant thalamocortical connections in the brains of adult mice. The aim of this study was to investigate whether prenatal and lactational BPA exposure affected behavior in adult mice. Pregnant mice were injected subcutaneously with 20μg/kg of BPA daily from embryonic day 0 (E0) until postnatal day 21 (P21). Control animals received a vehicle alone. Behavioral tests (n=15-20) were conducted at postnatal 3weeks (P3W) and P10-15W. After an open-field test, an elevated plus maze and Morris water maze tests were performed. The total distance in the elevated plus maze test at P3W and in the open-field test at P10W was significantly decreased in the BPA-exposed group, compared with the control group. Significant sex differences were observed in the time spent in the central area in the open-field test at P3W and in the total distance in the elevated plus maze test at P11W. These results indicated that prenatal and lactational BPA exposure disturbed the murine behavior in the postnatal development period and the adult mice. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    PubMed

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  14. RESISTANCE PRODUCED IN MICE BY EXPOSURE TO IRRADIATED SCHISTOSOMA MANSONI CERCARIAE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Radke, M.G.; Sadun, E.H.

    1963-04-01

    Studies were undertaken to determine whether gamma irradiation of cercariae might provide a means of investigating some of the mechanisms involved in the acquired resistance to schistosomiasis. Control mice received 200 nonirradiated cercariae, and other groups received the same number of cercariae that had been exposed to 6 different doses of Co/sup 60/ gamma irradiation varying from 1000--20000 rep. Eight weeks later the worms recovered were counted. Doses of 4000 rep or higher completely inhibited the development of schistosomes. A few stunted and underdeveloped worms were found in some of the mice receiving cercariae irradiated at 2500 and 3000 rep.more » Some adult schistosomes were observed in the groups receiving 1500 and 2000 rep and eggs were found in the liver but not in the stools of some mice. However, all of the mice exposed to cercariae irradiated with 1000 rep had eggs in liver and stools. The worm burden decreased regularly with increasing dosages up to 3000 rep, beyond which no worms were found at necropsy. The decrease in the number of worms mice acquired was linear only when cercariae were exposed from 1000to 2000 rep, however, even beyond such dosages, it followed a straight line when the logarithm of irradiation dose was plotied. Acquired resistance to S. mansoni was observed in mice following a previous exposure to irradiated cercariae. (TCO)« less

  15. 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.

  16. 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

  17. Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood.

    PubMed

    Salomäki, Henriikka; Vähätalo, Laura H; Laurila, Kirsti; Jäppinen, Norma T; Penttinen, Anna-Maija; Ailanen, Liisa; Ilyasizadeh, Juan; Pesonen, Ullamari; Koulu, Markku

    2013-01-01

    The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. Metformin (300 mg/kg) or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase) and high fat diet (HFD-phase). At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a therapeutic agent during pregnancy.

  18. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring

    PubMed Central

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring. PMID:28553167

  19. alpha-Galactosylceramide (AGL-517) treatment protects mice from lethal irradiation.

    PubMed

    Inoue, H; Koezuka, Y; Nishi, N; Osawa, M; Motoki, K; Kobayashi, E; Kabaya, K; Obuchi, M; Fukushima, H; Mori, K J

    1997-08-01

    AGL-517 (AGL) has an alpha-galactosylceramide structure and is a derivative of agelasphin-9b, which in turn is isolated from Agelas mauritianus and has immunomodulating activity. When administered before irradiation, AGL has been found to increase survival rates in lethally irradiated mice. In this study, we found that a single injection of AGL administered within 2 hours of lethal irradiation resulted in the long-term survival of mice without bone marrow transplantation. Peripheral blood hematology showed that AGL administration accelerated the recovery of hematopoietic parameters, including reticulocytes and red and white blood cells. Recovery of platelets was moderate. In addition, AGL significantly increased the number of endogenous colony forming units-spleen (E-CFU-S). AGL itself displayed no colony-stimulating activity, but AGL-stimulated spleen cell-conditioned medium (AGL-SCM) promoted the proliferation and differentiation of bone marrow mononuclear cells from normal mice and Lin marrow cells from 5-fluorouracil (5-FU)-treated mice. Using suitable assay systems, we analyzed cytokines in AGL-SCM and found significant increases in stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6 levels compared with control SCM. Additionally, using immunoenzymetric assays, we assessed serum levels of these factors in AGL-treated mice after lethal irradiation. The serum concentrations of IL-3, GM-CSF, and IL-6 were substantially elevated, the maximum levels being reached within 2 hours of injection. Despite inducing the in vitro increase in SCF, AGL did not elevate serum SCF levels. However, certain levels of SCF (approximately 5 ng/mL) were detected in mouse serum regardless of irradiation or AGL treatment. When irradiated mice were given a cytokine cocktail composed of recombinant murine (rm) IL-3, rmGM-CSF, and recombinant human (rh) IL-6 three times a day for 6 days (1 microg of each factor per mouse per day

  20. Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice.

    PubMed

    Villasana, Laura E; Rosenthal, Rosalind A; Doctrow, Susan R; Pfankuch, Timothy; Zuloaga, Damian G; Garfinkel, Alexandra Maccoll; Raber, Jacob

    2013-01-01

    Cranial irradiation with (56)Fe, a form of space radiation, causes hippocampus-dependent cognitive changes. (56)Fe irradiation also increases reactive oxygen species (ROS) levels, which may contribute to these changes. Therefore, we investigated the effects of the antioxidant alpha lipoic acid (ALA) on cognition following sham-irradiation and irradiation. Male mice were irradiated (brain only) with (56)Fe (3 Gy) or sham-irradiated at 6-9 months of age. Half of the mice remained fed a regular chow and the other half of the mice were fed a caloric-matched diet containing ALA starting two-weeks prior to irradiation and throughout cognitive testing. Following cognitive testing, levels of 3-nitrotyrosine (3NT), a marker of oxidative protein stress, and levels of microtubule-associated protein (MAP-2), a dendritic protein important for cognition, were assessed using immunohistochemistry and confocal microscopy. ALA prevented radiation-induced impairments in spatial memory retention in the hippocampal and cortical dependent water maze probe trials following reversal learning. However, in sham-irradiated mice, ALA treatment impaired cortical-dependent novel object recognition and amygdala-dependent cued fear conditioning. There was a trend towards lower 3NT levels in irradiated mice receiving a diet containing ALA than irradiated mice receiving a regular diet. In the hippocampal dentate gyrus of mice on regular diet, irradiated mice had higher levels of MAP-2 immunoreactivity than sham-irradiated mice. Thus, ALA might have differential effects on the brain under normal physiological conditions and those involving environmental challenges such as cranial irradiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Enhanced cued fear memory following post-training whole body irradiation of 3-month-old mice.

    PubMed

    Olsen, Reid H J; Weber, Sydney J; Akinyeke, Tunde; Raber, Jacob

    2017-02-15

    Typically, in studies designed to assess effects of irradiation on cognitive performance the animals are trained and tested for cognitive function following irradiation. Little is known about post-training effects of irradiation on cognitive performance. In the current study, 3-month-old male mice were irradiated with X-rays 24h following training in a fear conditioning paradigm and cognitively tested starting two weeks later. Average motion during the extinction trials, measures of anxiety in the elevated zero maze, and body weight changes over the course of the study were assessed as well. Exposure to whole body irradiation 24h following training in a fear conditioning resulted in greater freezing levels 2 weeks after training. In addition, motion during both contextual and cued extinction trials was lower in irradiated than sham-irradiated mice. In mice trained for cued fear conditioning, activity levels in the elevated zero maze 12days after sham-irradiation or irradiation were also lower in irradiated than sham-irradiated mice. Finally, the trajectory of body weight changes was affected by irradiation, with lower body weights in irradiated than sham-irradiated mice, with the most profound effect 7days after training. These effects were associated with reduced c-Myc protein levels in the amygdala of the irradiated mice. These data indicate that whole body X ray irradiation of mice at 3 months of age causes persistent alterations in the fear response and activity levels in a novel environment, while the effects on body weight seem more transient. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. GENETIC EFFECTS OF X IRRADIATION OF 10, 15, AND 20 GENERATIONS OF MALE MICE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spalding, J.F.; Brooks, M.R.; Archuleta, R.F.

    1963-01-01

    Male mice were exposed to 200 rads of x rays (acute whole body exposures) for 20 consecutive generations. Comparative studies were done on breeding characteristics of offspring from 10 and 15 generations of irradinted males. Irradiated line mice were less efficient breeders than were control line mice, and the decrement increased with the number of generations irradiated. Female mice from 10 to 20 generations of irradiated males were studied for resistance to low intensity gamma -rays and were found to be less resistant than control line mice. It was concluded that x irradiation to consecutive generations of male mice producesmore » a genetic decrement affecting both breeding and efficiency and stamina. (auth)« less

  3. Placental glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase-2 recruitment indicates impact of prenatal adversity upon postnatal development in mice.

    PubMed

    Gross, Moshe; Romi, Hava; Gilimovich, Yelena; Drori, Elyashiv; Pinhasov, Albert

    2018-04-12

    Prenatal stress may increase concentrations of maternal glucocorticoids, which restrict fetal growth, with variable impact upon postnatal development. Among key regulators of stress hormone effects are the glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase-2 (11βHSD2), the enzyme that inactivates glucocorticoid. This study utilized mice selectively bred for social dominance (Dom) or submissiveness (Sub), respectively exhibiting resilience or sensitivity to stress, to test whether stress-induced alterations in placental GR and 11βHSD2 protein expression may mediate divergent effects of prenatal adversity upon postnatal development. Pregnant Dom and Sub dams underwent prenatal restraint stress (PRS) for 45 min on gestational days (GD) 15-17. PRS induced a similar spike in serum corticosterone concentrations of dams from each strain on GD15 (p < .001, n = 8), and impaired fetal growth (p < .01, n = 5 litters), although Dom placentae were larger than Sub placentae (p < .01). Among placentae from Dom dams, PRS elevated protein contents of both GR (p < .05, n = 5 litters) and 11βHSD2 (p < .01) on GD19. In contrast, GR contents were reduced among placentae from PRS-exposed Sub mice (p < .01), without changes in 11βHSD2 content. Correspondingly, Dom PRS pup growth recovered by PND14, yet Sub PRS pups remained underweight into adolescence (p < .0001, n = 40 pups). Thus, prenatal stress more strongly increased placental GR and 11βHSD2 levels among Dom mice than in Subs. Increased GR may improve placental function and up-regulate 11βHSD2 expression, protecting fetuses from effects of prenatal stress upon postnatal development. Placental recruitment of GR and 11βHSD2 are potential markers of stress-induced developmental disorders, in accordance with maternal resilience or sensitivity to stress.

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Prenatal Stress and Peripubertal Stimulation of the Endocannabinoid System Differentially Regulate Emotional Responses and Brain Metabolism in Mice

    PubMed Central

    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. PMID:22848620

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Okazaki, Ryuji, E-mail: ryuji-o@med.uoeh-u.ac.j; Ootsuyama, Akira; Kakihara, Hiroyo

    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 situmore » 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.« less

  7. 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

  8. [Protective Effect of S-isopentenyl-L-cysteine against DNA Damage in Irradiated Mice].

    PubMed

    Zheng, Qi-sheng; Yu, Guang-yun; He, Xin; Jiang, Ming; Chu, Xiao-fei; Zhao, Shu-yi; Fan, Sai-jun; Liu, Pei-xun

    2015-10-01

    To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141)‰ to (28.1667±4.1345)‰ (P=0.033) and from (76.5000 ± 4.6242)‰ to (22.8333 ± 3.6553)‰(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S-isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05). S-isopentenyl-L-cysteine has a good protective

  9. 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. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  10. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

    PubMed Central

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Results Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Conclusion Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth. PMID:26372012

  11. Consequences of low or moderate prenatal ethanol exposures during gastrulation or neurulation for open field activity and emotionality in mice.

    PubMed

    Schambra, Uta B; Nunley, Kevin; Harrison, Theresa A; Lewis, C Nicole

    In a previous study we used a mouse model for ethanol exposure during gastrulation or neurulation to investigate the effects of modest and occasional human drinking during the 3rd or 4th week of pregnancy (Schambra et al., 2015). Pregnant C57Bl/6J mice were treated by gavage during gastrulation on gestational day (GD) 7 or neurulation on GD8 with 2 doses 4h apart of either 2.4 or 2.9g ethanol/kg body weight, resulting in peak blood ethanol concentrations (BECs) of 104 and 177mg/dl, respectively. We found that mice exposed to the low dose on either day were significantly delayed in their neonatal sensorimotor development. In the present study, we tested the same cohort of mice in an open field as juveniles on postnatal day (PD) 23-25 and as young adults on PD65-67 for prenatal ethanol effects on exploration and emotionality with measures of activity, rearing, grooming and defecation. We evaluated the effects of dose, sex, day of treatment and day of birth by multiple regression analyses. We found that, compared to the respective gavage controls, juvenile mice that had been prenatally exposed to the low BEC on either GD7 or GD8 were significantly hypoactive on the first 2 test days, reared significantly more on the last 2 test days, and groomed and defecated significantly more on all 3 test days. Only mice that had been treated on GD7 remained hypoactive as adults. Juvenile mice prenatally exposed to the moderate BEC on GD7 groomed significantly more, while those exposed on GD8 reared and defecated significantly more. Sex differences were highly significant in adult control mice, with control males less active and more emotional than females. Similar, but smaller, sex differences were also evident in adults exposed to ethanol prenatally. Persistence into later life of a deleterious effect of premature birth (i.e., birth on GD19 rather than GD20) on weight and behavior was not consistently supported by these data. Importantly, mice shown previously to be delayed in

  12. Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder

    PubMed Central

    Grabrucker, Stefanie; Haderspeck, Jasmin C.; Sauer, Ann Katrin; Kittelberger, Nadine; Asoglu, Harun; Abaei, Alireza; Rasche, Volker; Schön, Michael; Boeckers, Tobias M.; Grabrucker, Andreas M.

    2018-01-01

    A number of studies have reported changes in the hemispheric dominance in autism spectrum disorder (ASD) patients on functional, biochemical, and morphological level. Since asymmetry of the brain is also found in many vertebrates, we analyzed whether prenatal zinc deficient (PZD) mice, a mouse model with ASD like behavior, show alterations regarding brain lateralization on molecular and behavioral level. Our results show that hemisphere-specific expression of marker genes is abolished in PZD mice on mRNA and protein level. Using magnetic resonance imaging, we found an increased striatal volume in PZD mice with no change in total brain volume. Moreover, behavioral patterns associated with striatal lateralization are altered and the lateralized expression of dopamine receptor 1 (DR1) in the striatum of PZD mice was changed. We conclude that zinc signaling during brain development has a critical role in the establishment of brain lateralization in mice. PMID:29379414

  13. 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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Couroucli, Xanthi I., E-mail: xanthic@bcm.edu; Liang Yanhong Wei; Jiang Weiwu

    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 tomore » 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

  14. 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

  15. Effect of pulmonary irradiation from inhaled /sup 90/Y on immunity to Listeria monocytogenes in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    1976-01-01

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

  16. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

    PubMed

    Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

    2016-01-01

    There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

  17. Transgenerational Inheritance of Increased Fat Depot Size, Stem Cell Reprogramming, and Hepatic Steatosis Elicited by Prenatal Exposure to the Obesogen Tributyltin in Mice

    PubMed Central

    Chamorro-García, Raquel; Sahu, Margaret; Abbey, Rachelle J.; Laude, Jhyme; Pham, Nhieu

    2013-01-01

    Background: We have previously shown that exposure to tributyltin (TBT) modulates critical steps of adipogenesis through RXR/PPARγ and that prenatal TBT exposure predisposes multipotent mesenchymal stem cells (MSCs) to become adipocytes by epigenetic imprinting into the memory of the MSC compartment. Objective: We tested whether the effects of prenatal TBT exposure were heritable in F2 and F3 generations. Methods: We exposed C57BL/6J female mice (F0) to DMSO vehicle, the pharmaceutical obesogen rosiglitazone (ROSI), or TBT (5.42, 54.2, or 542 nM) throughout pregnancy via the drinking water. F1 offspring were bred to yield F2, and F2 mice were bred to produce F3. F1 animals were exposed in utero and F2 mice were potentially exposed as germ cells in the F1, but F3 animals were never exposed to the chemicals. We analyzed the effects of these exposures on fat depot weights, adipocyte number, adipocyte size, MSC programming, hepatic lipid accumulation, and hepatic gene expression in all three generations. Discussion: Prenatal TBT exposure increased most white adipose tissue (WAT) depot weights, adipocyte size, and adipocyte number, and reprogrammed MSCs toward the adipocyte lineage at the expense of bone in all three generations. Prenatal TBT exposure led to hepatic lipid accumulation and up-regulated hepatic expression of genes involved in lipid storage/transport, lipogenesis, and lipolysis in all three subsequent generations. Conclusions: Prenatal TBT exposure produced transgenerational effects on fat depots and induced a phenotype resembling nonalcoholic fatty liver disease through at least the F3 generation. These results show that early-life obesogen exposure can have lasting effects. PMID:23322813

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chiang, C.-S.; Liu, W.-C.; Jung, S.-M.

    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 radiationmore » 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

  19. 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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brook, I.; Ledney, G.D.

    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 micemore » (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.« less

  1. Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.

    PubMed

    Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

    2012-03-01

    Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

  2. [Structural and functional status of the hypophyseal-thyroid system in prenatally irradiated children].

    PubMed

    Makiienko, T S; Pavliuk, V P; Pavliuk, I V; Mosiienko, A P

    2001-01-01

    In order to evaluate the morphologic-and-functional state of the hypophysis-thyroid system long after the Chernobyl accident we examined 1491 children from the northern territories of the Zhitomir region. Of these, 261 had not been in utero exposed to radioiodine, 1230 pediatric subjects proved to be postconception-exposed. In utero radioiodine has not been found to affect the thyroid size in any noticeable way. The degree of structural-and-functional indices for the thyreostat system in prenatally irradiated children depends on the stage of the thyroid development just when there happened to be an exposure to radioiodine.

  3. Mice receiving infrared irradiation have a higher survival rate under forced swimming in cold.

    PubMed

    Tsai, Jui-Feng

    2009-10-01

    To explore the effect of infrared (IR) irradiation on the survival rates of mice under forced swimming in cold conditions. IR irradiation has been found to be beneficial for wound healing, tumor reduction, pain relief, and even against depression. However, whether the antidepressant effect of IR irradiation came from heat has remained unanswered. The goals of the study were originally aimed at using an animal model for depression to understand the relationship between the antidepressant effect of IR irradiation and hyperthermia as well as seasonality. Forty-four mice were housed in cages in a room subject to the outdoor temperature, and randomly assigned to the IR-treated group (n = 15), the heat-treated group (n = 14), and the control group (n = 15) during winter. The mice of the IR-treated group received whole-body IR irradiation for 60 min daily, while the heat-treated group received heat diffusion to reach the same temperature level. The control group received neither IR nor heat. All groups of mice underwent a forced swimming test weekly. Incidentally, two episodes of cold current occurred during the study period, and some mice died. The survival rates were compared pairwise against the control. The IR-treated group had a significantly reduced relative risk (p = 0.013) when compared with the control group, while the heat-treated group did not show any significant reduction (p = 0.087). There was no significant difference in body temperatures of the three groups before and after the irradiation. IR irradiation resulted in a significantly higher survival rate for mice that were concurrently subjected to cold and a forced swimming test. This result may be beyond the thermal effect.

  4. Differential expression of thymic DNA repair genes in low-dose-rate irradiated AKR/J mice

    PubMed Central

    Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chul; Choi, Seung Jin

    2013-01-01

    We previously determined that AKR/J mice housed in a low-dose-rate (LDR) (137Cs, 0.7 mGy/h, 2.1 Gy) γ-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) (137Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice. PMID:23820165

  5. Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patchen, M.L.; MacVittie, T.J.

    1985-01-01

    Hemopoietic effects of the reticuloendothelial agent glucan were assayed in normal mice and in mice hemopoietically depleted by exposure to /sup 60/Co radiation. In normal mice, glucan administration increased the content of bone marrow and splenic transplantable pluripotent hemopoietic stem cells (CFU-2), committed granulocyte-macrophage progenitor cells (GM-CFC), and pure macrophage progenitor cells (M-CFC). Erythroid progenitor cells (CFU-e) were increased only in the spleen. In sublethally irradiated mice (650 rads), glucan increased the number of endogeneous pluripotent hemopoietic stem cells (E-CFU) when administered either before or after irradiation. The most pronounced effects were observed when glucan was administered 1 day before,more » 1 h before, or 1 h after irradiation. In addition, the administration of glucan before lethal irradiation (900 rads) enhanced survival. The most significant results were seen when glucan was administered 1 day prior to irradiation. The possibility of using agents such as glucan to enhance hemopoietic reconstitution and prevent septicemia following chemotherapy and/or radiotherapy is discussed.« less

  6. Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice.

    PubMed

    Meyer, Urs; Nyffeler, Myriel; Yee, Benjamin K; Knuesel, Irene; Feldon, Joram

    2008-05-01

    Maternal infection during pregnancy increases the risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. This association appears to be critically dependent on the precise prenatal timing. However, the extent to which distinct adult psychopathological and neuropathological traits may be sensitive to the precise times of prenatal immune activation remains to be further characterized. Here, we evaluated in a mouse model of prenatal immune challenge by the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyIC), whether prenatal immune activation in early/middle and late gestation may influence the susceptibility to some of the critical cognitive, pharmacological, and neuroanatomical dysfunctions implicated in schizophrenia and autism. We revealed that PolyIC-induced prenatal immune challenge on gestation day (GD) 9 but not GD17 significantly impaired sensorimotor gating and reduced prefrontal dopamine D1 receptors in adulthood, whereas prenatal immune activation specifically in late gestation impaired working memory, potentiated the locomotor reaction to the NMDA-receptor antagonist dizocilpine, and reduced hippocampal NMDA-receptor subunit 1 expression. On the other hand, potentiation of the locomotor reaction to the dopamine-receptor agonist amphetamine and reduction in Reelin- and Parvalbumin-expressing prefrontal neurons emerged independently of the precise times of prenatal immune challenge. Our findings thus highlight that prenatal immune challenge during early/middle and late fetal development in mice leads to distinct brain and behavioral pathological symptom clusters in adulthood. Further examination and evaluation of in utero immune challenge at different times of gestation may provide important new insight into the neuroimmunological and neuropathological mechanisms underlying the segregation of different symptom clusters in heterogeneous neuropsychiatric disorders such as schizophrenia and autism.

  7. Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.

    PubMed

    Takeda, Hiroki; Hosoya, Makoto; Fujioka, Masato; Saegusa, Chika; Saeki, Tsubasa; Miwa, Toru; Okano, Hideyuki; Minoda, Ryosei

    2018-01-31

    There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

  8. 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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zou, Yani; Leu, David; Palo Alto Institute of Research and Education, Palo Alto, California

    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, andmore » 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.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Villasana, Laura E.; Benice, Theodore S.; Raber, Jacob, E-mail: raberj@ohsu.ed

    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 memorymore » 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.« less

  11. Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

    PubMed

    Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

    2015-01-01

    Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

  12. Craniofacial divergence by distinct prenatal growth patterns in Fgfr2 mutant mice

    PubMed Central

    2014-01-01

    Background Differences in cranial morphology arise due to changes in fundamental cell processes like migration, proliferation, differentiation and cell death driven by genetic programs. Signaling between fibroblast growth factors (FGFs) and their receptors (FGFRs) affect these processes during head development and mutations in FGFRs result in congenital diseases including FGFR-related craniosynostosis syndromes. Current research in model organisms focuses primarily on how these mutations change cell function local to sutures under the hypothesis that prematurely closing cranial sutures contribute to skull dysmorphogenesis. Though these studies have provided fundamentally important information contributing to the understanding of craniosynostosis conditions, knowledge of changes in cell function local to the sutures leave change in overall three-dimensional cranial morphology largely unexplained. Here we investigate growth of the skull in two inbred mouse models each carrying one of two gain-of-function mutations in FGFR2 on neighboring amino acids (S252W and P253R) that in humans cause Apert syndrome, one of the most severe FGFR-related craniosynostosis syndromes. We examine late embryonic skull development and suture patency in Fgfr2 Apert syndrome mice between embryonic day 17.5 and birth and quantify the effects of these mutations on 3D skull morphology, suture patency and growth. Results We show in mice what studies in humans can only infer: specific cranial growth deviations occur prenatally and worsen with time in organisms carrying these FGFR2 mutations. We demonstrate that: 1) distinct skull morphologies of each mutation group are established by E17.5; 2) cranial suture patency patterns differ between mice carrying these mutations and their unaffected littermates; 3) the prenatal skull grows differently in each mutation group; and 4) unique Fgfr2-related cranial morphologies are exacerbated by late embryonic growth patterns. Conclusions Our analysis of

  13. 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.

  14. SECONDARY TETANUS ANTITOXIN RESPONSES IN MICE ELICITED PRIOR TO IRRADIATION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hale, W.M.; Stoner, R.D.

    1963-02-01

    Secondary tetanus antitoxin responses were abolished in mice when sublethal radiation doses of 650 rads were delivered by short-term exposure 3 hr before the second injection of antigen. Nearly normal secondary responses were observed when the same radiation doses were delivered 4 days after antigenic stimulation, and sera were obtained 8 days later. Radiosensitivity of the seemingly radioresistart secondary antibody responses was demonstrated by ultimate repression of antitoxin titers when radiation was delivered 4 days after antigenic stimulation and sera were obtained 4 weeks after irradiation (32 days after the second injection of toxoid). It was possible to differentiate clearlymore » between the capacity of these irradiated animals to produce nearly normal secondary responses and failure of the same animals to respond to a third antigenic stimulus when radiation was delivered 4 days after the second stimulus, and a third injection of antigen was given 30 min after the single exposure to 650 rads. A marked incorporation of tritium activity appeared in antitoxin produced during secondary responses of irradiated and nonirradiated mice when tritium-labeled /sub L/-histidine was injected on days 4 and 5 and on days 6 and 7 after the second stimulus of tetanus toxoid. The data indicate that the antibody produced during secondary responses in irradiated and nonirradiated mice was not performed during the induction phase and merely released on days 4 or 5, following the second stimulus of antigen. These findings indicate the presence of antibodyproducing cells or their precursors that have proliferated in response to the second antigenic stimulus and survived long enough after irradiation to produce nearly normal secondary tetanus antitoxin responses. (auth)« less

  15. Effect of irradiation on the viability of Toxoplasma gondii cysts in tissues of mice and pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dubey, J.P.; Brake, R.J.; Murrell, K.D.

    1986-03-01

    Muscles from tongue, heart, and limbs of 14 pigs inoculated orally with Toxoplasma gondii oocysts were irradiated with 10, 20, 25, and 30 krad of gamma (cesium-137 and cobalt-60) irradiation. Viability of T gondii cysts was assayed by feeding porcine muscles to T gondii-free cats and/or by inoculation of sediment from acid-pepsin digested porcine muscle into mice. Cats fed 500-g samples of muscles irradiated with up to 20 krad shed T gondii oocysts. Cats fed muscles irradiated with 25 or 30 krad did not shed oocysts. Mice were inoculated with 8 isolates of T gondii, and tissue cysts in theirmore » brains irradiated with up to 40 krad were infective to mice; however, there was a 10,000-fold reduction in the viability of organisms in tissue cysts irradiated with 40 krad, compared with that in nonirradiated cysts. At 50 krad of gamma irradiation, there were no detectable infective organisms in infected mouse brains.« less

  16. Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring.

    PubMed

    Solati, Jalal; Hajikhani, Ramin; Rashidieh, Behnam; Jalilian, Mahshid Fatipour

    2012-04-01

    Maternal infection during pregnancy is a risk factor for some behavioral problems with neurodevelopmental origin. This study aimed to evaluate the effects of exposure of pregnant mice to the bacterial lipopolysaccharide (LPS) on sexual behaviour and serum level of pituitary-gonadal hormones of offspring in adulthood. In this Expremental study, pregnant NMRI mice (n=7/group) were treated with intra-peritoneal administration of LPS (1, 5 and 10 µg/kg) at day 10 of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were measured in maternal serum 2 hours following the maternal LPS challenge. Behavior in the adult male offspring reproductive activity was investigated using receptive female mice. Concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult offspring serum were measured using the enzyme-linked immunosorbent assay (ELISA) method (at postnatal day 60, n=10/group). One-way ANOVA showed that LPS administration induces a significant increase in TNF-α, IL-1β and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexual behavior and serum concentration of LH and testosterone in adult male offspring. The overall results suggest that prenatal exposure to LPS increases pro- inflammatory cytokine levels, affects development of neuroendocrine systems and results in the inhibition of reproductive behaviors and reactivity of hypothalamic-pituitary-gonadal (HPG) axis in adult male offspring.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Madonna, G.S.; Ledney, G.D.; Moore, M.M.

    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 thanmore » 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.« less

  18. Ultraviolet A Eye Irradiation Ameliorates Atopic Dermatitis via p53 and Clock Gene Proteins in NC/Nga Mice.

    PubMed

    Hiramoto, Keiichi; Yamate, Yurika; Yokoyama, Satoshi

    2018-03-01

    Atopic dermatitis (AD) is a widespread chronic skin condition that severely affects quality of life and can lead to more serious complications. Although ultraviolet (UV)A eye irradiation can exert various effects on the skin, it is unknown whether UVA can affect AD. To investigate potential associations, we used an NC/Nga mouse model of AD to study the effects of UVA eye irradiation. The eyes of mice were irradiated with a UVA dose of 100 kJ m -2 using a FL20SBLB-A lamp. Our histological data demonstrated that AD symptoms could be ameliorated by UVA eye irradiation. We also observed an increase in the levels of adrenocorticotropic hormone (ACTH), p53 and retinoid X receptor α (RXRα) in mice with UVA-irradiated eyes. In contrast, the levels of thymic stromal lymphopoietin (TSLP), period 2 (PER2) and differentiated embryo chondrocytes 1 (DEC1) protein were decreased in mice treated with UVA irradiation. Furthermore, UVA eye-irradiated mice exhibited reduced DEC1 and RXRα colocalization compared with nonirradiated mice. These results suggested that p53 and various clock gene proteins played important roles in the amelioration of AD symptoms observed after UVA eye irradiation; this technique may have therapeutic applications in AD. © 2017 The American Society of Photobiology.

  19. Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice.

    PubMed

    Maruoka, Takashi; Kodomari, Ikuko; Yamauchi, Rena; Wada, Etsuko; Wada, Keiji

    2009-04-17

    The maternal environment is thought to be important for fetal brain development. However, the effects of maternal environment are not fully understood. Here, we investigated whether enrichment of the maternal environment can influence prenatal brain development and postnatal behaviors in mice. An enriched environment is a housing condition with several objects such as a running wheel, tube and ladder, which are thought to increase sensory, cognitive and motor stimulation in rodents compared with standard housing conditions. First, we measured the number of BrdU-positive cells in the hippocampal dentate gyrus of fetuses from pregnant dams housed in an enriched environment. Our results revealed that maternal enrichment influences cell proliferation in the hippocampus of female, but not male, fetuses. Second, we used the open-field test to investigate postnatal behaviors in the offspring of dams housed in the enriched environment during pregnancy. We found that maternal enrichment significantly affects the locomotor activity and time spent in the center of the open-field in female, but not male, offspring. These results indicate that maternal enrichment influences prenatal brain development and postnatal behaviors in female offspring.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 bymore » human C. trachomatis serovar A elementary bodies is an ability manifested by live organisms and not by inactivated but antigenic organisms.« less

  1. 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.

  2. 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.

  3. 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

  4. Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays.

    PubMed

    Chi, Cuiping; Hayashi, Daisuke; Nemoto, Masato; Nyui, Minako; Urano, Shiro; Anzai, Kazunori

    2011-01-01

    We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation.

  5. Dose-related cerebellar abnormality in rats with prenatal exposure to X-irradiation by magnetic resonance imaging volumetric analysis.

    PubMed

    Sawada, Kazuhiko; Saito, Shigeyoshi; Horiuchi-Hirose, Miwa; Mori, Yuki; Yoshioka, Yoshichika; Murase, Kenya

    2013-09-01

    Cerebellar abnormalities in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 were examined by magnetic resonance imaging (MRI) volumetry. A 3D T2 W-MRI anatomical sequence with high-spatial resolution at 11.7-tesla was acquired from the fixed rat heads. By MRI volumetry, whole cerebellar volumes decreased dose-dependently. Multiple linear regression analysis revealed that the cortical volume (standardized β=0.901; P<0.001) was a major explanatory variable for the whole cerebellar volume, whereas both volumes of the white matter and deep cerebellar nuclei also decreased depending on the X-irradiation dose. The present MRI volumetric analysis revealed a dose-related cerebellar cortical hypoplasia by prenatal exposure to X-irradiation on E15. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

  6. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    PubMed

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2015-01-01

    Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  7. Reduced adiposity in ob/ob mice following total body irradiation and bone marrow transplantation.

    PubMed

    Ablamunits, Vitaly; Weisberg, Stuart P; Lemieux, Jacob E; Combs, Terry P; Klebanov, Simon

    2007-06-01

    The objective of this study was to assess long-term metabolic consequences of total body irradiation (TBI) and bone marrow transplantation. Severe obesity develops due to both hypertrophy and hyperplasia of adipocytes. We hypothesized that TBI would arrest adipose tissue growth and would affect insulin resistance (IR). We exposed 2-month-old female ob/ob mice to 8 Grays of TBI followed by bone marrow transplantation and tested the animals for body weight (BW) gain, body composition, blood glucose, and insulin sensitivity. Two months after TBI, irradiated mice stopped gaining BW, whereas non-treated mice continued to grow. At the age of 9.5 months, body mass of irradiated mice was 60.6 +/- 1.4 grams, which was only 61% of that in non-treated ob/ob controls (99.4 +/- 1.6 grams). Body composition measurements by DXA showed that decreased BW was primarily due to an impaired fat accumulation. This could not result from the production of leptin by bone marrow-derived adipocyte progenitors because inhibition of the obese phenotype was identical in recipients of both B6 and ob/ob bone marrow. Inability of the irradiated mice to accumulate fat was associated with hepatomegaly, lower levels of monocyte chemoattractant protein-1 expression in adipose tissue, and increased IR. Our data argue in favor of the hypothesis that inability of adipose tissue to expand may increase IR. This mouse model may be valuable for studies of late-onset radiation-induced IR in humans.

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

    PubMed

    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

    2014-10-21

    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

  9. 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

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 radiationmore » 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).« less

  11. [The accumulation of lipid peroxidation products in the eye structures of mice under whole-body x-ray irradiation].

    PubMed

    Sakina, N L; Dontsov, A E; Afanas'ev, G G; Ostrovski, M A; Pelevina, I I

    1990-01-01

    In studying the effect of whole-body X-irradiation on the accumulation of lipid peroxidation products (conjugated dienes, TBA-active products, and Schiff bases) in retina and retinal pigmented epithelium of pigmented and nonpigmented mice it was shown that irradiation of dark-pigmented mice does not cause even a slight accumulation of lipid peroxidation products as compared to that in the controls. Albino mice exhibited a marked increase in the level of lipid peroxidation products which was manifested soon after irradiation and persisted for at least 3 months after irradiation. Melanine is suggested to participate in protecting eye structures against pro-oxidizing action of ionizing radiation.

  12. Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.

    PubMed

    Soffritti, Morando; Belpoggi, Fiorella; Manservigi, Marco; Tibaldi, Eva; Lauriola, Michelina; Falcioni, Laura; Bua, Luciano

    2010-12-01

    Aspartame (APM) is a well-known intense artificial sweetener used in more than 6,000 products. Among the major users of aspartame are children and women of childbearing age. In previous lifespan experiments conducted on Sprague-Dawley rats we have shown that APM is a carcinogenic agent in multiple sites and that its effects are increased when exposure starts from prenatal life. The aim of this study is to evaluate the potential of APM to induce carcinogenic effects in mice. Six groups of 62-122 male and female Swiss mice were treated with APM in feed at doses of 32,000, 16,000, 8,000, 2,000, or 0  ppm from prenatal life (12 days of gestation) until death. At death each animal underwent complete necropsy and all tissues and organs of all animals in the experiment were microscopically examined. APM in our experimental conditions induces in males a significant dose-related increased incidence of hepatocellular carcinomas (P < 0.01), and a significant increase at the dose levels of 32,000  ppm (P < 0.01) and 16,000  ppm (P < 0.05). Moreover, the results show a significant dose-related increased incidence of alveolar/bronchiolar carcinomas in males (P < 0.05), and a significant increase at 32,000  ppm (P < 0.05). The results of the present study confirm that APM is a carcinogenic agent in multiple sites in rodents, and that this effect is induced in two species, rats (males and females) and mice (males). No carcinogenic effects were observed in female mice. Am. J. Ind. Med. 53:1197-1206, 2010. © 2010 Wiley-Liss, Inc.

  13. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice

    PubMed Central

    YANAI, Shogo; HIRANO, Tetsushi; OMOTEHARA, Takuya; TAKADA, Tadashi; YONEDA, Naoki; KUBOTA, Naoto; YAMAMOTO, Anzu; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

    2017-01-01

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life. PMID:28579575

  14. Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice.

    PubMed

    Cherdyntseva, Nadezda; Shishkina, Anna; Butorin, Ivan; Murase, Hironobu; Gervas, Polina; Kagiya, Tsutomu V

    2005-03-01

    A preparation of alpha-tocopherol monoglucoside (TMG) administered i.p. at a dose of 600 mg/kg immediately after whole body gamma irradiation was examined for its radioprotective efficacy towards bone marrow and peripheral blood nucleated cells. When mice received X-rays at a dose of 5,6 Gy, a marked decrease in bone marrow karyocytes and a reduction of peripheral leukocytes within the early post-irradiated period were observed. However these changes were attenuated in TMG-treated mice. Significant protection of blood lymphocytes was found for the TMG group of mice. The return to normal value of the reduced blood leukocyte count starting from the 8th day was more rapid in TMG-treated mice than in untreated irradiated mice. TMG administration was found to enhance hematopoietic recovery, as measured by the exceeded nucleated bone marrow cell count due to elevated amount of both lymphoid and granulocytic elements in the TMG-group, in comparison with that of both control irradiated and non-irradiated animals. These findings indicate that the radioprotective effect of TMG is apparently realized through its influence on hematopoietic system.

  15. [Effect of electromagnetic pulse irradiation on structure and function of Leydig cells in mice].

    PubMed

    Wang, Shui-Ming; Wang, De-Wen; Peng, Rui-Yun; Gao, Ya-Bing; Yang, Yi; Hu, Wen-Hua; Chen, Hao-Yu; Zhang, You-Ren; Gao, Yan

    2003-08-01

    To explore the effect of electromagnetic pulse (EMP) irradiation on structure and function of Leydig cells in mice. One hundred and fourteen male Kunming mice were randomly divided into irradiated and control group, the former radiated generally by 8 x 10(3) V/m, 2 x 10(4) V/m and 6 x 10(4) V/m EMP respectively five times within two minutes. Pathological changes of Leydig cells were observed by light and electron microscope. Serum testosterone (T), luteinizing hormone (LH) and estradiol (E2) were measured dynamically by radioimmunoassay at 6 h, 1 d, 3 d, 7 d, 14 d and 28 d after irradiation. Main pathological changes were edema and vacuolation, swelling of cytoplasmic mitochondria, reduce of lipid droplets, pale staining of most of lipid droplets, and partial or complete cavitation of lipid droplets in Leydig cells within 28 days after EMP radiation. Compared with normal controls, serum T decreased in all in different degrees within 28 days, and dropped significantly at 6 h-14 d, 6 h-7 d and 1 d-28 d after 8 x 10(3) V/m, 2 x 10(4) V/m and 6 x 10(4) V/m EMP irradiation(P < 0.05 or P < 0.01). EMP irradiation caused no significant changes in serum LH and E2. Leydig cells are among those that are the most susceptible to EMP irradiation. EMP irradiation may cause significant injury in structure and function of Leydig cells in mice, whose earlier and continuous effect is bound to affect sexual function and sperm production.

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

    PubMed

    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.

  17. L-carnitine protects against testicular dysfunction caused by gamma irradiation in mice.

    PubMed

    Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Alkafafy, Mohamed; El-Shazly, Samir Ahmed

    2014-07-01

    This study was conducted on mice to evaluate the radioprotective role of L-carnitine against γ-ray irradiation-induced testicular damage. Adult male mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure period either in the absence and/or presence of L-carnitine at an i.p. dose of 10 mg/kg body weight/day. Results revealed that γ-rays irradiation suppressed the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine prior and throughout γ-rays irradiation exposure inhibited this suppression. Treatment with γ-ray irradiation or L-carnitine down-regulated expression of aromatase mRNA. With combined treatment, L-carnitine significantly normalized aromatase expression. γ-Ray irradiation up-regulated expression of FasL and Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also showed that γ-ray-irradiation up-regulated TNF-α, IL1-β and IFN-γ mRNA expressions compared to either controls or the L-carnitine treated group. Moreover, γ-irradiation greatly reduced serum testosterone levels, while L-carnitine, either alone or in combination with irradiation, significantly increased serum testosterone levels compared to controls. In addition, γ-irradiation induced high levels of sperm abnormalities (43%) which were decreased to 12% in the presence of L-carnitine. In parallel with these findings, histological examination showed that γ-irradiation induced severe tubular degenerative changes, which were reduced by L-carnitine pre-treatment. These results clarified the immunostimulatory effects of L-carnitine and its radioprotective role against testicular injury. Copyright © 2014 Elsevier GmbH. All rights reserved.

  18. Rapid Loss of Bone Mass and Strength in Mice after Abdominal Irradiation

    PubMed Central

    Jia, Dan; Gaddy, Dana; Suva, Larry J.; Corry, Peter M.

    2011-01-01

    Localized irradiation is a common treatment modality for malignancies in the pelvic-abdominal cavity. We report here on the changes in bone mass and strength in mice 7–14 days after abdominal irradiation. Male C57BL/6 mice of 10–12 weeks of age were given a single-dose (0, 5, 10, 15 or 20 Gy) or fractionated (3 Gy × 2 per day × 7.5 days) X rays to the abdomen and monitored daily for up to 14 days. A decrease in the serum bone formation marker and ex vivo osteoblast differentiation was detected 7 days after a single dose of radiation, with little change in the serum bone resorption marker and ex vivo osteoclast formation. A single dose of radiation elicited a loss of bone mineral density (BMD) within 14 days of irradiation. The BMD loss was up to 4.1% in the whole skeleton, 7.3% in tibia, and 7.7% in the femur. Fractionated abdominal irradiation induced similar extents of BMD loss 10 days after the last fraction: 6.2% in the whole skeleton, 5.1% in tibia, and 13.8% in the femur. The loss of BMD was dependent on radiation dose and was more profound in the trabecula-rich regions of the long bones. Moreover, BMD loss in the total skeleton and the femurs progressed with time. Peak load and stiffness in the mid-shaft tibia from irradiated mice were 11.2–14.2% and 11.5–25.0% lower, respectively, than sham controls tested 7 days after a single-dose abdominal irradiation. Our data demonstrate that abdominal irradiation induces a rapid loss of BMD in the mouse skeleton. These effects are bone type- and region-specific but are independent of radiation fractionation. The radiation-induced abscopal damage to the skeleton is manifested by the deterioration of biomechanical properties of the affected bone. PMID:21859327

  19. Npas4 deficiency and prenatal stress interact to affect social recognition in mice.

    PubMed

    Heslin, K; Coutellier, L

    2018-06-01

    Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia have an expansive array of reported genetic and environmental contributing factors. However, none of these factors alone can account for a substantial proportion of cases of either disorder. Instead, many gene-by-environment interactions are responsible for neurodevelopmental disturbances that lead to these disorders. The current experiment used heterozygous knock-out mice to examine a potential interaction between 2 factors commonly linked to neurodevelopmental disorders and cognitive deficit: imbalanced excitatory/inhibitory signaling in the cortex and prenatal stress (PNS) exposure. Both of these factors have been linked to disrupt GABAergic signaling in the prefrontal cortex (PFC), a common feature of neurodevelopmental disorders. The neuronal PAS domain protein 4 (Npas4) gene is instrumental in regulation of the excitatory/inhibitory balance in the cortex and hippocampus in response to activation. Npas4 heterozygous and wild-type male and female mice were exposed to either PNS or standard gestation, then evaluated during adulthood in social and anxiety behavioral measures. The combination of PNS and Npas4 deficiency in male mice impaired social recognition. This behavioral deficit was associated with decreased parvalbumin and cFos protein expression in the infralimbic region of the PFC following social stimulation in Npas4 heterozygous males. In contrast, females displayed fewer behavioral effects and molecular changes in PFC in response to PNS and decreased Npas4. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  20. ENHANCED ANTITOXIN RESPONSES IN IRRADIATED MICE ELICITED BY COMPLEXES OF TETANUS TOXOID AND SPECIFIC ANTIBODY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stoner, R.D.; Terres, G.

    1963-12-01

    Enhanced primary antitoxin responses were obtained in mice immunized by intravenous injection with complexes of tetanus toxoid and mouse antitoxin, presumably formed either in vivo, or prepared in vitro in antigen-antibody ratios of antibody excess, equivalence, and antigen excess. The demonstration of the enhancement phenomenon elicited by complexes of toxoid and isologous mouse antitoxin provide conclusive evidence that the antibody portion of the complex does not need to be of heterologous origin in order to elicit enhanced primary antibody responses in mice. Intravenous immunization with the above complexes elicited enhanced primary responses in irradiated animals, whereas minimal responses were obtainedmore » with antigen only. Littie difference was observed in primary responses in nonirradiated mice when antigen only or antigen complexed with specific antibody is given by subcutaneous injection. However, enhanced primary antitoxin responses were obtained in irradiated mice (400 rad) immunized with the various complexes over the responses observed in irradiated animals immunlzed with antigen only. The greatest degree of enhancement occurred when the complexes were prepared in the region of equivalence and antigen excess. Secondary antitoxin responses were repressed when the same complexes of antigen and antibody were injected to elicit secondary responses. A corresponding repression of secondary responses was observed in irradiated mice when radiation doses of 300 rad were delivered 24 hr before the second injection of antigen complexed with specific mouse antitoxin. (BBB)« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 leastmore » 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.« less

  2. 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.

  3. Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.

    PubMed

    Toriumi, Kazuya; Oki, Mika; Muto, Eriko; Tanaka, Junko; Mouri, Akihiro; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

    2016-06-01

    We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.

  4. 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

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

    PubMed

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

    2017-12-01

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

  6. Early effects of whole-body (56)Fe irradiation on hippocampal function in C57BL/6J mice.

    PubMed

    Haley, Gwendolen E; Yeiser, Lauren; Olsen, Reid H J; Davis, Matthew J; Johnson, Lance A; Raber, Jacob

    2013-05-01

    Relatively little is known about early irradiation effects on hippocampal function in wild-type mice. In this study, the effects of (56)Fe irradiation on hippocampal function were assessed starting 2 weeks after whole-body irradiation. Compared to sham irradiation, radiation impaired novel object recognition in female and male C57BL/6J wild-type mice. There were no effects of irradiation on contextual fear conditioning or spatial memory retention in the water maze. It is possible that oxidative damage might contribute to radiation-induced cognitive changes. Therefore, hippocampal and cortical levels of 3-nitrotyrosine (3NT) and lipid peroxidation, measures of oxidative damage were assessed. There were no effects of irradiation on these measures of oxidative damage. As (56)Fe irradiation can increase reactive oxygen species (ROS) levels, which may contribute to the impairments in novel object recognition, the effects of the antioxidant alpha-lipoic acid (ALA) on cognition following sham irradiation and irradiation were also assessed. ALA did not prevent radiation-induced impairments in novel object recognition and impaired spatial memory retention of sham-irradiated and irradiated mice in the probe trial after the first day of hidden platform training in the water maze. Thus, the novel object recognition test is particularly sensitive to detect early cognitive effects of (56)Fe irradiation through a mechanism unlikely involving ROS or oxidative damage.

  7. 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

  8. Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice

    PubMed Central

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

    2017-01-01

    During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body 16O (600 MeV/n) irradiation. The effects of 16O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose 16O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of 16O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of γ-ray irradiation. These adverse effects of 16O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of 16O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs. PMID:29232383

  9. Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tanikawa, S.; Nose, M.; Aoki, Y.

    1990-08-01

    We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony-forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF frommore » day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.« less

  10. DIFFERENTIAL RESPONSE TO ALLOGENIC AND XENOGENIC SKIN GRAFTS BY SUBLETHALLY IRRADIATED (670 RAD) AND NON-IRRADIATED MICE SENSITIZED BY VARIOUS MEANS

    DTIC Science & Technology

    consecutive BALB/c or rat skin tail grafts. One week following the last injection or the rejection of the second, skin graft , the mice either were grafted...resulted in prolonged survival of subsequent allogenic skin grafts in sublethally irradiated mice. The second-set response to a xenogenic skin graft was

  11. Beetroot (Beta vulgaris) rescues mice from γ-ray irradiation by accelerating hematopoiesis and curtailing immunosuppression.

    PubMed

    Cho, Jinhee; Bing, So Jin; Kim, Areum; Lee, Nam Ho; Byeon, Sang-Hee; Kim, Gi-Ok; Jee, Youngheun

    2017-12-01

    Beetroot [Beta vulgaris Linné (Chenopodiaceae)], a vegetable usually consumed as a food or a medicinal plant in Europe, has been reported to have antioxidant and anti-inflammatory properties. Since the lymphohematopoietic system is the most sensitive tissue to ionizing radiation, protecting it from radiation damage is one of the best ways to decrease detrimental effects from radiation exposure. In this study, we evaluated the radio-protective effects of beetroot in hematopoietic stem cells (HSCs) and progenitor cells. Beetroot extract was administered at a dose of 400 mg/mouse per os (p.o.) three times into C57BL/6 mice and, at day 10 after γ-ray irradiation, diverse molecular presentations were measured and compared against non-irradiated and irradiated mice with PBS treatments. Survival of beetroot-fed and unfed irradiated animal was also compared. Beetroot not only stimulated cell proliferation, but also minimized DNA damage of splenocytes. Beetroot also repopulated S-phase cells and increased Ki-67 or c-Kit positive cells in bone marrow. Moreover, beetroot-treated mice showed notable boosting of differentiation of HSCs into burst-forming units-erythroid along with increased production of IL-3. Also, beetroot-treated mice displayed enhancement in the level of hematocrit and hemoglobin as well as the number of red blood cell in peripheral blood. Beetroot diet improved survival rate of lethally exposed mice with a dose reduction factor (DRF) of 1.1. These results suggest that beetroot has the potency to preserve bone marrow integrity and stimulate the differentiation of HSCs against ionizing radiation.

  12. Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

    PubMed

    Hennig, Maria; Fiedler, Saskia; Jux, Christian; Thierfelder, Ludwig; Drenckhahn, Jörg-Detlef

    2017-08-04

    Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  13. 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.

  14. Prenatal treatment prevents learning deficit in Down syndrome model.

    PubMed

    Incerti, Maddalena; Horowitz, Kari; Roberson, Robin; Abebe, Daniel; Toso, Laura; Caballero, Madeline; Spong, Catherine Y

    2012-01-01

    Down syndrome is the most common genetic cause of mental retardation. Active fragments of neurotrophic factors release by astrocyte under the stimulation of vasoactive intestinal peptide, NAPVSIPQ (NAP) and SALLRSIPA (SAL) respectively, have shown therapeutic potential for developmental delay and learning deficits. Previous work demonstrated that NAP+SAL prevent developmental delay and glial deficit in Ts65Dn that is a well-characterized mouse model for Down syndrome. The objective of this study is to evaluate if prenatal treatment with these peptides prevents the learning deficit in the Ts65Dn mice. Pregnant Ts65Dn female and control pregnant females were randomly treated (intraperitoneal injection) on pregnancy days 8 through 12 with saline (placebo) or peptides (NAP 20 µg +SAL 20 µg) daily. Learning was assessed in the offspring (8-10 months) using the Morris Watermaze, which measures the latency to find the hidden platform (decrease in latency denotes learning). The investigators were blinded to the prenatal treatment and genotype. Pups were genotyped as trisomic (Down syndrome) or euploid (control) after completion of all tests. two-way ANOVA followed by Neuman-Keuls test for multiple comparisons, P<0.05 was used to denote statistical significance. Trisomic mice who prenatally received placebo (Down syndrome-placebo; n = 11) did not demonstrate learning over the five day period. DS mice that were prenatally exposed to peptides (Down syndrome-peptides; n = 10) learned significantly better than Down syndrome-placebo (p<0.01), and similar to control-placebo (n = 33) and control-peptide (n = 30). In conclusion prenatal treatment with the neuroprotective peptides (NAP+SAL) prevented learning deficits in a Down syndrome model. These findings highlight a possibility for the prevention of sequelae in Down syndrome and suggest a potential pregnancy intervention that may improve outcome.

  15. 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.

  16. 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.

  17. Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM). (Reannouncement with new availability information)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Madonna, G.S.; Ledney, G.D.; Moore, M.M.

    Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. The authors 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 thrombocytopenicmore » than mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice.« less

  18. The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

    PubMed Central

    Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

    2012-01-01

    The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

  19. Modification of mortality and tumorigenesis by tocopherol-mono-glucoside (TMG) administered after X irradiation in mice and rats.

    PubMed

    Ueno, Megumi; Inano, Hiroshi; Onoda, Makoto; Murase, Hironobu; Ikota, Nobuo; Kagiya, Tsutomu V; Anzai, Kazunori

    2009-10-01

    The effects of TMG [2-(alpha-d-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol], a water-soluble vitamin E derivative, administered after irradiation on the mortality of X-irradiated mice and on the development of tumors in the mammary and pituitary glands in rats were investigated. When TMG (650 mg/kg) was administered intraperitoneally (i.p.) to C3H mice immediately after whole-body exposure to 7 Gy radiation, the 30-day survival was significantly higher than that of the control mice. The i.p. administration of TMG at 4 h after irradiation significantly improved survival compared to that of the controls, but administration 8 h after irradiation did not have a significant effect. Subcutaneous administration of TMG immediately after irradiation also decreased mortality significantly. When dams of lactating Wister rats were exposed to 1.5 Gy of X rays at day 21 after parturition and were then treated with diethylstilbestrol as a tumor promoter, the incidence of mammary tumors and pituitary tumors was increased compared to that in the nonirradiated control group. The administration of TMG (600 mg/kg, i.p.) after irradiation significantly reduced the incidence of mammary tumors and pituitary tumors. The number of rats that were free of both mammary and pituitary gland tumors was enhanced fourfold by TMG. These results suggest that TMG is effective in preventing radiation-induced bone marrow death in mice and in reducing mammary and pituitary tumors in rats even when it is administered after irradiation.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edmondson, Elijah F., E-mail: elijah.edmondson@colostate.edu; Hunter, Nancy R.; Weil, Michael M.

    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. Anmore » 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

  1. [The "light" water effect on lenticular opacity development in mice after repeated low dose gamma-irradiation].

    PubMed

    Abrosimova, A N; Rakov, D V; Siniak, Iu E

    2009-01-01

    Action of "light" water with reduced quantities of heavy stable hydrogen and 18O ions on incidence and progress of lenticular opacity was studied in gamma-irradiated mice (60Co, 1.0 Gy). The animals were subjected to electroophthalmoscopy regularly till end of life time. The observation showed that chronic intake of "light" water safeguarded the irradiated mice against lenticular opacity. The experimental data indicate that "light" water strengthens the general body resistance as well as slows down aging of mammals.

  2. Prenatal Exposure to Unconventional Oil and Gas Operation Chemical Mixtures Altered Mammary Gland Development in Adult Female Mice.

    PubMed

    Sapouckey, Sarah A; Kassotis, Christopher D; Nagel, Susan C; Vandenberg, Laura N

    2018-03-01

    Unconventional oil and gas (UOG) operations, which combine hydraulic fracturing (fracking) and directional drilling, involve the use of hundreds of chemicals, including many with endocrine-disrupting properties. Two previous studies examined mice exposed during early development to a 23-chemical mixture of UOG compounds (UOG-MIX) commonly used or produced in the process. Both male and female offspring exposed prenatally to one or more doses of UOG-MIX displayed alterations to endocrine organ function and serum hormone concentrations. We hypothesized that prenatal UOG-MIX exposure would similarly disrupt development of the mouse mammary gland. Female C57Bl/6 mice were exposed to ~3, ~30, ~ 300, or ~3000 μg/kg/d UOG-MIX from gestational day 11 to birth. Although no effects were observed on the mammary glands of these females before puberty, in early adulthood, females exposed to 300 or 3000 μg/kg/d UOG-MIX developed more dense mammary epithelial ducts; females exposed to 3 μg/kg/d UOG-MIX had an altered ratio of apoptosis to proliferation in the mammary epithelium. Furthermore, adult females from all UOG-MIX-treated groups developed intraductal hyperplasia that resembled terminal end buds (i.e., highly proliferative structures typically seen at puberty). These results suggest that the mammary gland is sensitive to mixtures of chemicals used in UOG production at exposure levels that are environmentally relevant. The effect of these findings on the long-term health of the mammary gland, including its lactational capacity and its risk of cancer, should be evaluated in future studies. Copyright © 2018 Endocrine Society.

  3. THE EFFECT OF X-RAY IRRADIATION ON THE RESISTANCE OF WHITE MICE TO B. TYPHI ABDOMINALIS (in Russian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alexeva, O.G.

    1957-01-01

    White mice were sensitized by intraperitoneal injection of 2.5 million B. typhi abdominalis Felix Ty/sub 2/ or 50 million B. dysenteria Flexner No. 26-w. Four days later they were subjected to total x-ray irradiation with a LD 10/13 dose (300 r). Experiments on 250 mice showed that in irradiated mice the biologic effect of a sensibilizing dose increases from DL 18/13 to DL 48/13 for typhus and from DL 3/13 to DL24/13 for dysentery. Mice sensitized with B. typhus abdominalis and irradiated died after periods typical for radiation sickness, but developed also bacteriemia pointing to a complicated pathologic process. Themore » degree of active antityphus immunization developed after sensibilization by the stated method was determined by intraperitoneal inoculation of 2 DCL (200 million) on the 1, 3, 5, 7, 10, 20, 30 day after irradiation with 300r. Experiments on 600 mice have shown that the earlier developed immunity does not change during the first days of radiation sickness. During the III period of radiation sickness (3-1Oth days) and in the reparation period (20--30th days) the survival of experimental mice is 40--45% less than of the unirradiated controls. The reduced tension of active immunity is also manifested by inhibition of phagocytosis in vivo, accumulation of enormous amounts of bacteria in the place of injection, and, protracted bacteriemia. (tr-auth)« less

  4. Immunity to herpes simplex virus type 2. Suppression of virus-induced immune responses in ultraviolet B-irradiated mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yasumoto, S.; Hayashi, Y.; Aurelian, L.

    1987-10-15

    Ultraviolet B irradiation (280 to 320 nm) of mice at the site of intradermal infection with herpes simplex virus type 2 increased the severity of the herpes simplex virus type 2 disease and decreased delayed-type hypersensitivity (DTH) responses to viral antigen. Decrease in DTH resulted from the induction of suppressor T cells, as evidenced by the ability of spleen cells from UV-irradiated mice to inhibit DTH and proliferative responses after adoptive transfer. Lymph node cells from UV-irradiated animals did not transfer suppression. DTH was suppressed at the induction but not the expression phase. Suppressor T cells were Lyt-1+, L3T4+, andmore » their activity was antigen-specific. However, after in vitro culture of spleen cells from UV-irradiated mice with herpes simplex virus type 2 antigen, suppressor activity was mediated by Lyt-2+ cells. Culture supernatants contained soluble nonantigen-specific suppressive factors.« less

  5. 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.

  6. Effects of low-dose heavy ions on embryonic development in mice and on melanocyte differentiation in the epidermis and hair bulb

    PubMed Central

    Hirobe, Tomohisa; Eguchi-Kasai, Kiyomi; Sugaya, Kimihiko; Murakami, Masahiro

    2013-01-01

    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. PMID:23230241

  7. Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.

    PubMed

    Raber, Jacob; Torres, Eileen Ruth S; Akinyeke, Tunde; Lee, Joanne; Weber Boutros, Sydney J; Turker, Mitchell S; Kronenberg, Amy

    2018-04-20

    The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. ⁴He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued

  8. Paradoxical effects of 137Cs irradiation on pharmacological stimulation of reactive oxygen species in hippocampal slices from apoE2 and apoE4 mice.

    PubMed

    Villasana, Laura E; Akinyeke, Tunde; Weber, Sydney; Raber, Jacob

    2017-09-29

    In humans, apoE, which plays a role in repair, is expressed in three isoforms: E2, E3, and E4. E4 is a risk factor for age-related cognitive decline (ACD) and Alzheimer's disease (AD), particularly in women. In contrast, E2 is a protective factor for ACD and AD. E2 and E4 might also differ in their response to cranial 137 Cs irradiation, a form of radiation typically used in a clinical setting for the treatment of cancer. This might be mediated by reactive oxygen species (ROS) in an-apoE isoform-dependent fashion. E2 and E4 female mice received sham-irradiation or cranial irradiation at 8 weeks of age and a standard mouse chow or a diet supplemented with the antioxidant alpha-lipoic acid (ALA) starting at 6 weeks of age. Behavioral and cognitive performance of the mice were assessed 12 weeks later. Subsequently, the generation of ROS in hippocampal slices was analyzed. Compared to sham-irradiated E4 mice, irradiated E4 mice showed enhanced spatial memory in the water maze. This was associated with increased hippocampal PMA-induction of ROS. Similar effects were not seen in E2 mice. Irradiation increased endogenous hippocampal ROS levels in E2 mice while decreasing those in E4 mice. NADPH activity and MnSOD levels were higher in sham-irradiated E2 than E4 mice. Irradiation increased NADPH activity and MnSOD levels in hemi brains of E4 mice but not in those of E2 mice. ALA did not affect behavioral and cognitive performance or hippocampal formation of ROS in either genotype. Thus, apoE isoforms modulate the radiation response.

  9. 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

  10. Ultraviolet B eye irradiation aggravates atopic dermatitis via adrenocorticotropic hormone and NLRP3 inflammasome in NC/Nga mice.

    PubMed

    Hiramoto, Keiichi; Yamate, Yurika; Yokoyama, Satoshi

    2018-05-01

    Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m 2 using a 20SE sunlamp for the duration of the experimental period. AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice. Treatment with inhibitors of ACTH, caspase-1, interleukin-18, and thymic stromal lymphopoietin (TSLP) partly reversed the effects of irradiation, with the greatest improvement observed upon ACTH inhibition. The NLRP3 inflammasome was implicated in the effects of UVB irradiation. UVB eye irradiation causes AD symptom deterioration, which is likely mediated by ACTH and the activity of the inflammasome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. 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.

  12. 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.

  13. Maternal Stress and Effects of Prenatal Air Pollution on Offspring Mental Health Outcomes in Mice

    PubMed Central

    Huff, Nicole C.; Smith, Susan H.; Mason, S. Nicholas; Foster, W. Michael; Auten, Richard L.; Bilbo, Staci D.

    2013-01-01

    Background: Low socioeconomic status is consistently associated with reduced physical and mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown. Objectives: We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neurocognitive disorders in adulthood. Methods: Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation. Results: Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased proinflammatory interleukin (IL)-1β levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1. Conclusions: These results show that maternal stress during late gestation increases the susceptibility of offspring—particularly males—to the deleterious effects of prenatal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain. Citation: Bolton JL, Huff NC, Smith SH, Mason SN, Foster WM, Auten RL, Bilbo SD. 2013. Maternal stress and effects of prenatal air pollution on

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ratikan, Josephine Anna; Sayre, James William; Schaue, Dörthe, E-mail: dschaue@mednet.ucla.edu

    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 wasmore » 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.« less

  15. PROTECTION OF MICE AGAINST IRRADIATION AND TETANUS BY HOMOLOGOUS BONE MARROW CELLS FROM HYPERIMMUNIZED DONORS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stoloff, I.L.; Weiss, A.J.

    1963-07-01

    Female mice of inbred strains (101 x C3H, BDF, C57B1, Balb/C, C3H, CBA, and LAF) were immunized with 0.2 ml of alum-precipitated tetanus toxoid subcutaneously, followed in 3 weeks by 0.2 ml of fluid toxoid intravenously. Four days after the last injection the marrow was mechanically dispersed and 10- 20 million marrow cells were inoculated intravenously into mice that had received on the previous day a lethal dose of whole-body x irradiation. The LD/sub 96/ for 30 days of each host strain was: BDF, 950 r; LAF, 950 r; 101 x C3H, 900 r; Balb/C, 800 r; C3H, 800 r;more » C57B1, 800 r; and CBA, 700 r. Mice in which isologous bone marrow cells from hyperimmunized donors were transferred to irradiated hosts showed a high degree of protection against irradiation in all strains studied. The percentage of 30-day irradiation survivors follows: C3H, 100%; 101 x C3H, 100%; CBA, 90%; BDF, 90%; Balb/C, 60%; and C57B1, 70%. There were no survivors among groups irradiated but not protected with bone marrow. The percentage of 7- day survivors after toxin challenge for each of 4 different strains receiving isologous cells from hyperimmunized donors ranged between 87 and 100%. Normal mice, similar in weight to the experimental groups (called toxin controls) all died of tetanus within 48 hr of challenge with toxin. Other results showed that homologous disease does not interfere significantly with the in vivo neutralization of tetanus toxin by antitoxin. It was concluded that homologous disease is a clinical entity which, in some donor-host combinations, is associated with a host-vs-graft reaction and, in one strain combination so far tested, is associated with a graft-vshost reaction. The experiments showed that the genetic relation between donor and host is a factor in determining which type of immunologic reaction may occur. (TCO)« less

  16. 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

  17. Contrasting the effects of proton irradiation on dendritic complexity of subiculum neurons in wild type and MCAT mice.

    PubMed

    Chmielewski, Nicole N; Caressi, Chongshan; Giedzinski, Erich; Parihar, Vipan K; Limoli, Charles L

    2016-06-01

    Growing evidence suggests that radiation-induced oxidative stress directly affects a wide range of biological changes with an overall negative impact on CNS function. In the past we have demonstrated that transgenic mice over-expressing human catalase targeted to the mitochondria (MCAT) exhibit a range of neuroprotective phenotypes following irradiation that include improved neurogenesis, dendritic complexity, and cognition. To determine the extent of the neuroprotective phenotype afforded by MCAT expression in different hippocampal regions, we analyzed subiculum neurons for changes in neuronal structure and synaptic integrity after exposure to low dose (0.5 Gy) 150 MeV proton irradiation. One month following irradiation of WT and MCAT mice, a range of morphometric parameters were quantified along Golgi-Cox impregnated neurons. Compared with WT mice, subiculum neurons from MCAT mice exhibited increased trends (albeit not statistically significant) toward increased dendritic complexity in both control and irradiated cohorts. However, Sholl analysis of MCAT mice revealed significantly increased arborization of the distal dendritic tree, indicating a protective effect on secondary and tertiary branching. Interestingly, radiation-induced increases in postsynaptic density protein (PSD-95) puncta were not as pronounced in MCAT compared with WT mice, and were significantly lower after the 0.5 Gy dose. As past data has linked radiation exposure to reduced dendritic complexity, elevated PSD-95 and impaired cognition, reductions in mitochondrial oxidative stress have proven useful in ameliorating many of these radiation-induced sequelae. Data presented here shows similar trends, and again points to the potential benefits of reducing oxidative stress in the brain to attenuate radiation injury. Environ. Mol. Mutagen. 57:364-371, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nomoto, K.; Yokokura, T.; Tsuneoka, K.

    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 radiotherapymore » or radiation accidents.« less

  20. 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.

  1. Dietary lutein/zeaxanthin partially reduces photoaging and photocarcinogenesis in chronically UVB-irradiated Skh-1 hairless mice.

    PubMed

    Astner, S; Wu, A; Chen, J; Philips, N; Rius-Diaz, F; Parrado, C; Mihm, M C; Goukassian, D A; Pathak, M A; González, S

    2007-01-01

    Lutein and zeaxanthin are xanthophyll carotenoids with potent antioxidant properties protecting the skin from acute photodamage. This study extended the investigation to chronic photodamage and photocarcinogenesis. Mice received either a lutein/zeaxanthin-supplemented diet or a standard nonsupplemented diet. Dorsal skin of female Skh-1 hairless mice was exposed to UVB radiation with a cumulative dose of 16,000 mJ/cm(2) for photoaging and 30,200 mJ/cm(2) for photocarcinogenesis. Clinical evaluations were performed weekly, and the animals were sacrificed 24 h after the last UVB exposure. For photoaging experiments, skin fold thickness, suprapapillary plate thickness, mast cell counts and dermal desmosine content were evaluated. For photocarcinogenesis, samples of tumors larger than 2 mm were analyzed for histological characterization, hyperproliferation index, tumor multiplicity, total tumor volume and tumor-free survival time. Results of the photoaging experiment revealed that skin fold thickness and number of infiltrating mast cells following UVB irradiation were significantly less in lutein/zeaxanthin-treated mice when compared to irradiated animals fed the standard diet. The results of the photocarcinogenesis experiment were increased tumor-free survival time, reduced tumor multiplicity and total tumor volume in lutein/zeaxanthin-treated mice in comparison with control irradiated animals fed the standard diet. These data demonstrate that dietary lutein/zeaxanthin supplementation protects the skin against UVB-induced photoaging and photocarcinogenesis. (c) 2007 S. Karger AG, Basel.

  2. 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

    2016-08-03

    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.

  3. 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

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 delivermore » 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.« less

  6. 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.

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

    PubMed

    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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Plum, J.; Huys, J.; De Scheerder, Y.

    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 totalmore » 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.« less

  9. Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites.

    PubMed

    Zorgi, Nahiara Esteves; Galisteo, Andrés Jimenez; Sato, Maria Notomi; do Nascimento, Nanci; de Andrade, Heitor Franco

    2016-08-01

    Toxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90 days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-γ) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an

  10. Survival and Hematopoietic Recovery in Mice after Wound Trauma and Whole-Body Irradiation

    DTIC Science & Technology

    1982-01-01

    approp- riate line transformation of doie to insure an increasing dose meta - meter. Chi square analysis for linearity and paralleliss of the data were made...conceivable that the splenic myeloproliferative response in wounded mice in the post-irradiation period could account for the enhancement of survival. Splenic

  11. Prenatal alcohol exposure affects vasculature development in the neonatal brain.

    PubMed

    Jégou, Sylvie; El Ghazi, Faiza; de Lendeu, Pamela Kwetieu; Marret, Stéphane; Laudenbach, Vincent; Uguen, Arnaud; Marcorelles, Pascale; Roy, Vincent; Laquerrière, Annie; Gonzalez, Bruno José

    2012-12-01

    In humans, antenatal alcohol exposure elicits various developmental disorders, in particular in the brain. Numerous studies focus on the deleterious effects of alcohol on neural cells. Although recent studies suggest that alcohol can affect angiogenesis in adults, the impact of prenatal alcohol exposure on brain microvasculature remains poorly understood. We used a mouse model to investigate effects of prenatal alcohol exposure on the cortical microvascular network in vivo and ex vivo and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF) on activity, plasticity, and survival of microvessels. We used quantitative reverse transcriptase polymerase chain reaction, Western blot, immunohistochemistry, calcimetry, and videomicroscopy. We characterized the effect of prenatal alcohol exposure on the cortical microvascular network in human controls and fetal alcohol syndrome (FAS)/partial FAS (pFAS) patients at different developmental stages. In mice, prenatal alcohol exposure induced a reduction of cortical vascular density, loss of the radial orientation of microvessels, and altered expression of VEGF receptors. Time-lapse experiments performed on brain slices revealed that ethanol inhibited glutamate-induced calcium mobilization in endothelial cells, affected plasticity, and promoted death of microvessels. These effects were prevented by VEGF. In humans, we evidenced a stage-dependent alteration of the vascular network in the cortices of fetuses with pFAS/FAS. Whereas no modification was observed from gestational week 20 (WG20) to WG22, the radial organization of cortical microvessels was clearly altered in pFAS/FAS patients from WG30 to WG38. Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol-induced brain abnormalities. Copyright © 2012 American Neurological Association.

  12. 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

  13. The role of glucocorticoid, interleukin-1β, and antioxidants in prenatal stress effects on embryonic microglia.

    PubMed

    Bittle, Jada; Stevens, Hanna E

    2018-02-16

    Maternal stress during pregnancy is associated with an increased risk of psychopathology in offspring. Resident immune cells of the brain, microglia, may be mediators of prenatal stress and altered neurodevelopment. Here, we demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin-1β (IL-1β), nor the glucocorticoid hormone, corticosterone, recapitulated the full effects of prenatal stress on the morphology of microglial cells in the cortical plate of embryonic mice; IL-1β effects showed greater similarity to prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has antioxidant properties, moderated the effects of prenatal stress on microglia. Microglia changes with prenatal stress were also sensitive to the antioxidant, N-acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.

  14. Specific early fine structural changes in the lung following irradiation. [X rays; mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Penney, D.P.; Rubin, P.

    1977-01-01

    The lungs of mice were irradiated with single and fractionated doses of 1000 R, 2000 R, and 3000 R and recovered 1 hr, 1 day, 1 week, and 1 month following exposure. Electron microscopy revealed early changes in the decrement of lamellar bodies of Type II pneumocytes and increased fibrous content and edema in the septal walls of all animals treated. Those lungs treated with fractionated doses of irradiation displayed more pronounced cellular damage than did singly-dosed lungs. It is proposed that these early changes may predict for subsequent atelectasis.

  15. Cartilaginous metaplasia and overgrowth of neurocranium skull after X-irradiation in utero.

    PubMed

    Schmahl, W; Meyer, I; Kriegel, H; Tempel, K H

    1979-01-01

    Prenatal X-irradiation of mice in the late organogenesis stage either with a fractionated or a single exposure dose (3 X 160 R or 200 R) leads to remarkable, previously undescribed malformations of the skull. These malformations range from mild hyperostotic nodule formation in about 90% of the offspring to excessive formation of desmal bony tissues, which extend deep into the forebrain and are thus only detectable in histological sections. Metaplastic and hyperplastic formation of cartilage in all the neurocranial regions is observed in about 10% of the offspring. The pathogenesis of these overgrowth phenomena is presumably related to a growth disturbance of both the mesenchymal skull primordium and the brain. While malformation of the latter leads to a decrease of intracranial pressure and consequently to altered growth activity of the skull sutures, the reparative and proliferative capacities of the mesenchyme are also stimulated, in a hyperplastic direction, by X-irradiation.

  16. Protection of mice against fission neutron irradiation by WR-2721 or WR-151327

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steel, L.K.; Jacobs, A.J.; Giambarresi, L.I.

    1987-03-01

    Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found tomore » be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.« less

  17. Assessing Cardiac Injury in Mice With Dual Energy-MicroCT, 4D-MicroCT, and MicroSPECT Imaging After Partial Heart Irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Chang-Lung; Min, Hooney; Befera, Nicholas

    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 endothelialmore » 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

  18. NanoTIO(2) (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice.

    PubMed

    Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra; Hougaard, Karin Sørig; Wallin, Håkan; Yauk, Carole L; Vogel, Ulla

    2012-06-01

    Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR) loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development). Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO(2)) produces a long-lasting inflammatory response in mice, it was chosen for the present study. Pregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO(2) UV-Titan L181 (~42.4 mg UV-Titan/m(3)) or filtered clean air on gestation days (GD) 8-18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring) of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls). ESTR mutation rates of 0.029 (maternal allele) and 0.047 (paternal allele) in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele) and 0.061 (paternal allele). We found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.

  19. 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

  20. [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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 inmore » 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.« less

  2. Prenatal NMDA Receptor Antagonism Impaired Proliferation of Neuronal Progenitor, Leading to Fewer Glutamatergic Neurons in the Prefrontal Cortex

    PubMed Central

    Toriumi, Kazuya; Mouri, Akihiro; Narusawa, Shiho; Aoyama, Yuki; Ikawa, Natsumi; Lu, Lingling; Nagai, Taku; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

    2012-01-01

    N-methyl--aspartate (NMDA) receptor is a glutamate receptor which has an important role on mammalian brain development. We have reported that prenatal treatment with phencyclidine (PCP), a NMDA receptor antagonist, induces long-lasting behavioral deficits and neurochemical changes. However, the mechanism by which the prenatal antagonism of NMDA receptor affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that prenatal NMDA receptor antagonism impaired the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and the subventricular zone. Furthermore, using a PCR array focused on neurogenesis and neuronal stem cells, we evaluated changes in gene expression causing the impairment of neuronal progenitor proliferation and found aberrant gene expression, such as Notch2 and Ntn1, in prenatal PCP-treated mice. Consequently, the density of glutamatergic neurons in the prefrontal cortex was decreased, probably resulting in glutamatergic hypofunction. Prenatal PCP-treated mice displayed behavioral deficits in cognitive memory and sensorimotor gating until adulthood. These findings suggest that NMDA receptors regulate the proliferation and maturation of progenitor cells for glutamatergic neuron during neurodevelopment, probably via the regulation of gene expression. PMID:22257896

  3. 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.

  4. 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.

  5. Protection of mice against fission-neutron irradiation by WR-2721 or WR-151327

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steel, L.K.; Jacobs, A.J.; Giambarresi, L.I.

    1987-01-01

    Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission-neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose-modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 were found to be equally radioprotective when comparedmore » using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found to be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.« less

  6. The Preventive Effect of Coffee Compounds on Dermatitis and Epidermal Pigmentation after Ultraviolet Irradiation in Mice.

    PubMed

    Yamate, Yurika; Hiramoto, Keiichi; Sato, Eisuke F

    2017-01-01

    Ultraviolet (UV) irradiation is well known to promote inflammation and pigmentation of skin. UVB mainly affects dermatitis and pigmentation. Coffee contains a number of polyphenols, such as caffeic acid (CA) and chlorogenic acid (CGA) but their in vivo bioactivity for photobiology remains unclear. C57BL/6j male mice were irradiated with UVB (1.0 kJ/m2/day) for 3 days. Five days after the final session of UVB irradiation, the dorsal skin, ear epidermis, and blood samples were analyzed to investigate the inflammatory factors, melanogenesis factors and related hormones. After the oral administration of CA (100 mg/day) or CGA (100 mg/day) for 8 days, only CA was found to inhibit dermatitis and pigmentation. The pathway by which CA inhibits dermatitis is related to the mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK)1/2/cAMP response element binding protein (CREB) pathway. Otherwise, the pathway by which CA inhibits pigmentation is related to the activation of the β-endorphin-μ-opioid receptor and suppresses the cAMP-microphthalmia-associated transcription factor (MITF) pathway. It is suggested that the oral administration of CA prevented dermatitis and pigmentation after UVB irradiation in mice. © 2017 S. Karger AG, Basel.

  7. Transplacental Arsenic Carcinogenesis in Mice

    PubMed Central

    Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from day 8 to 18 of gestation, and the offspring were observed for up to two years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans and

  8. TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schueler, E; Trovati, S; King, G

    Purpose: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. Methods: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance. Mice were irradiated withmore » 20MeV electrons. Following irradiation, the mice were monitored twice daily for morbidity and daily for weight changes. Results: Mice irradiated with FLASH irradiation had lower weight loss compared to the mice receiving conventional irradiation. Following FLASH irradiation, a maximum weight loss of ∼20% was observed at day 6 with subsequent recovery, while following conventional irradiation, higher weight losses was observed with fewer instances of recovery. Concerning survival, all mice in the conventionally irradiated groups had a 100% mortality in the range of 15.5–18 Gy, while the mice irradiated with FLASH irradiation had a 100% survival in the same range. Conclusion: These results have demonstrated proof of principle that FLASH irradiations have a dramatic impact on the overall survival of mice following GI tract irradiations. If the increase in the therapeutic window can be validated and understood, this would revolutionize the field of radiation oncology and lead to increased cure rates with reduced side effects following treatment, resulting in increased quality of life for cancer survivors. Funding: DoD, Award#:W81XWH-14-1-0014, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation; BL and PM

  9. Contrast-enhanced ultrasound evaluation of pancreatic cancer xenografts in nude mice after irradiation with sub-threshold focused ultrasound for tumor ablation

    PubMed Central

    Wang, Rui; Guo, Qian; Chen, Yi Ni; Hu, Bing; Jiang, Li Xin

    2017-01-01

    We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors after irradiation with sub-threshold focused ultrasound (FUS) ablation in pancreatic cancer xenografts in nude mice. Thirty tumor-bearing nude mice were divided into three groups: Group A received sham irradiation, Group B received a moderate-acoustic energy dose (sub-threshold), and Group C received a high-acoustic energy dose. In Group B, B-mode ultrasound (US), color Doppler US, and dynamic contrast-enhanced ultrasound (DCE-US) studies were conducted before and after irradiation. After irradiation, tumor growth was inhibited in Group B, and the tumors shrank in Group C. In Group A, the tumor sizes were unchanged. In Group B, contrast-enhanced ultrasound (CEUS) images showed a rapid rush of contrast agent into and out of tumors before irradiation. After irradiation, CEUS revealed contrast agent perfusion only at the tumor periphery and irregular, un-perfused volumes of contrast agent within the tumors. DCE-US perfusion parameters, including peak intensity (PI) and area under the curve (AUC), had decreased 24 hours after irradiation. PI and AUC were increased 48 hours and 2weeks after irradiation. Time to peak (TP) and sharpness were increased 24 hours after irradiation. TP decreased at 48 hours and 2 weeks after irradiation. CEUS is thus an effective method for early evaluation after irradiation with sub-threshold FUS. PMID:28402267

  10. The regeneration of thermal wound on mice skin (Mus Musculus) after Q-Switch Nd: YAG laser irradiation for cancer therapy candidate

    NASA Astrophysics Data System (ADS)

    Apsari, R.; Nahdliyatun, E.; Winarni, D.

    2017-09-01

    The aims of this study are to investigate the regeneration of mice skin tissue (Mus Musculus) irradiated by Q-Switch Nd: YAG laser and morphological change due to Q-Switch Nd: YAG laser irradiation compared to conventional heating (hairdryer). The 2-3 month of twenty-seven mice were used for experimental animals. Mice were incised in the dorsum by the damage effect of laser energy dose (therapeutic dose) of 29.5 J/cm2 with 10 seconds of exposure time, 10 Hz of repetition rate, and 100 pulses of the given single pulse energy. The mice skin tissue was injuried by hairdryer to get burned effect. Mice were divided into three groups, Group I (control) were not treated by anything, Group II were treated by Q-Switch Nd: YAG laser irradiation and sacrificed on (0, 1, 3, 5) days, and Group III were treated by hairdryer then sacrificed on (0, 1, 3, 5) days. Pathology examination showed that the energy of 29,5 J/cm2 dose produced the hole effect (ablation) through the hypodermic layer caused by optical breakdown and collagen coagulation. Thus, the 60 °C temperature of burn showed coagulation necrosis because piknosis discovered in the injured area. The regeneration process showed that the mice skin tissue's ability to regenerate was irradiated by fast laser because of the focus of Q-Switch Nd: YAG laser. It was showed by the scab releases on third day and completely reepithelialization formation on the fifth day. The collagen fibers distribution was same as normal skin tissue on day 5 and so did angiogenesis. Therefore, Q-Switch Nd: YAG laser can be applied for problems of dermatology medical therapies, especially melasma, nevus of ota and tatto therapy. For skin cancer therapy application, energy dose of unregenerated skin tissue is chosen because the death expected effect is permanent.

  11. EFFECTS OF PERTUSSIS SENSITIZATION AND ROENTGEN IRRADIATION ON THE ADRENAL GLANDS OF RATS AND MICE (in Japanese)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nakamura, M.

    1962-10-01

    Histaminase activity was estimated by the coupled oxidation and deamination method in lung tissue from rats and mice followrng adrenal gland x irradiation, sensitization with B. pertussis, or pertussis sensitization followed by adrenal gland irradiation. Histamine activity was greatly reduced in lung tissue from animals sensitized with pertussis followed by adrenal irradiation, moderately reduced in lung tissue from pertussis sensitized animals, and slightly decreased in lung tissue from the adrenal irradiated group. The activity of succinoxidose and monoamine oxidose in lung tissue was not affected by either adrenal irradiation or pertussis sensitization. The possibility that steroid hormone balance may bemore » affected by disturbance of the adrenal glands in animals sensitized with pertussis is discussed. (C.H.)« less

  12. Prenatal Stress Disrupts Social Behavior, Cortical Neurobiology and Commensal Microbes in Adult Male Offspring.

    PubMed

    Gur, Tamar L; Palkar, Aditi Vadodkar; Rajasekera, Therese; Allen, Jacob; Niraula, Anzela; Godbout, Jonathan; Bailey, Michael T

    2018-06-24

    In utero and early neonatal exposure to maternal stress is linked with psychiatric disorders, and the underlying mechanisms are currently being elucidated. We used a prenatal stressor in pregnant mice to examine novel relationships between prenatal stress exposure, changes in the gut microbiome, and social behavior. Here, we show that males exposed to prenatal stress had a significant reduction in social behavior in adulthood, with increased corticosterone release following social interaction. Male offspring exposed to prenatal stress also had neuroinflammation, decreased oxytocin receptor, and decreased serotonin metabolism in their cortex in adulthood, which are linked to decreased social behavior. Finally, we found a significant difference in commensal microbes, including decreases in Bacteroides and Parabacteroides, in adult male offspring exposed to prenatal stress when compared to non-stressed controls. Our findings indicate that gestation is a critical window where maternal stress contributes to the development of aberrant social behaviors and alterations in cortical neurobiology, and that prenatal stress is sufficient to disrupt the male gut-brain axis into adulthood. Copyright © 2018. Published by Elsevier B.V.

  13. Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice.

    PubMed

    Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Hasebe, Shigeru; Kawase, Haruki; Tanabe, Wataru; Tsukada, Shinji; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-11-01

    Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities. We recently found that prenatal VPA exposure causes hypofunction of the prefrontal dopaminergic system in mice. This suggests that the dopaminergic system may be a potential pharmacological target for treatment of behavioral abnormalities in ASD patients. In the present study, we examined the effects of antipsychotic drugs, which affect the dopaminergic system, on the social interaction deficits, recognition memory impairment, and reduction in dendritic spine density in the VPA mouse model of ASD. Both acute and chronic administrations of the atypical antipsychotic drugs risperidone and aripiprazole increased prefrontal dopamine (DA) release, while the typical antipsychotic drug haloperidol did not. Chronic risperidone and aripiprazole, but not haloperidol, increased the expression of c-Fos in the prefrontal cortex, although they all increased c-Fos expression in the striatum. Chronic, but not acute, administrations of risperidone and aripiprazole improved the VPA-induced social interaction deficits and recognition memory impairment, as well as the reduction in dendritic spine density in the prefrontal cortex and hippocampus. In contrast, chronic administration of haloperidol did not ameliorate VPA-induced abnormalities in behaviors and dendritic spine density. These findings indicate that chronic risperidone and aripiprazole treatments improve VPA-induced abnormalities in behaviors and prefrontal dendritic spine density, which may be mediated by repeated elevation of extracellular DA in the prefrontal cortex. Our results also imply that loss of prefrontal dendritic spines may be involved in the abnormal behaviors in the VPA mouse model of ASD.

  14. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    PubMed

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice

    PubMed Central

    Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2012-01-01

    Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33–35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. PMID:22230260

  16. Technical Note: Partial body irradiation of mice using a customized PMMA apparatus and a clinical 3D planning/LINAC radiotherapy system.

    PubMed

    Karagounis, Ilias V; Abatzoglou, Ioannis M; Koukourakis, Michael I

    2016-05-01

    In vivo radiobiology experiments involving partial body irradiation (PBI) of mice are of major importance because they allow for the evaluation of individual organ tolerance; overcoming current limitations of experiments using lower dose, whole body irradiation. In the current study, the authors characterize and validate an effective and efficient apparatus for multiple animal PBI, directed to the head, thorax, or abdomen of mice. The apparatus is made of polymethylmethacrylate and consists of a rectangular parallelepiped prism (40 cm × 16 cm × 8 cm), in which five holes were drilled to accomodate standard 60 ml syringes, each housing an unanesthetized, fully immobilized mouse. Following CT-scanning and radiotherapy treatment planning, radiation fields were designed to irradiate the head, thorax, or abdomen of the animal. Thermoluminescent dosimeters (TLDs) were used to confirm the treatment planning dosimetry for primary beam and scattered radiation. Mice are efficiently placed into 60 ml syringes and immobilized, without the use of anesthetics. Although partial rotational movement around the longitudinal axis and a minor 2 mm forward/backward movement are permitted, this does not compromise the irradiation of the chosen body area. TLDs confirmed the dose values predicted by the treatment planning dosimetry, both for primary beam and scattered radiation. The customized PMMA apparatus described and validated is cost-effective, convenient to use, and efficient in performing PBI without the use of anesthesia. The developed apparatus permits the isolated irradiation of the mouse head, thorax, and abdomen. Importantly, the apparatus allows the delivery of PBI to five mice, simultaneously, representing an efficient way to effectively expose a large number of animals to PBI through multiple daily fractions, simulating clinical radiotherapy treatment schedules.

  17. [Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice].

    PubMed

    Kabaya, K; Watanabe, M; Kusaka, M; Seki, M; Fushiki, M

    1994-08-25

    The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 micrograms/body/day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also revealed an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation.

  18. Age- and gender-dependent impairments of neurobehaviors in mice whose mothers were exposed to lipopolysaccharide during pregnancy.

    PubMed

    Wang, Hua; Meng, Xiu-Hong; Ning, Huan; Zhao, Xian-Feng; Wang, Qun; Liu, Ping; Zhang, Heng; Zhang, Cheng; Chen, Gui-Hai; Xu, De-Xiang

    2010-02-01

    Lipopolysaccharide (LPS)-induced intrauterine infection has been associated with neurodevelopmental injury in rodents. The purpose of the present study was to analyze the dynamic changes of neurobehaviors in mice whose mothers were exposed to LPS during pregnancy. The pregnant mice were intraperitoneally (i.p.) injected with LPS (8 microg/kg) daily from gestational day (gd) 8 to gd 15. A battery of neurobehavioral tasks was performed in mice at postnatal day (PND) 70, 200, 400 and 600. Results showed that the spatial learning and memory ability, determined by radial six-arm water maze (RAWM), were obviously impaired in two hundred-day-old female mice and four hundred-day-old male mice whose mothers were exposed to LPS during pregnancy. Open field test showed that the number of squares crossed and peripheral time, a marker of anxiety and exploration activity, were markedly increased in two hundred-day-old female mice following prenatal LPS exposure. In addition, prenatal LPS exposure significantly shortened the latency to the first grid crossing in six hundred-day-old female offspring. Moreover, sensorimotor impairment in the beam walking was observed in two hundred-day-old female mice whose mothers were exposed to LPS during pregnancy. Species-typical behavior examination showed that prenatal LPS exposure markedly increased weight burrowed in seventy-day-old male offspring and six hundred-day-old female offspring. Correspondingly, prenatal LPS exposure significantly reduced weight hoarded in two hundred-day-old female offspring. Taken together, these results suggest that prenatal LPS exposure induces neurobehavioral impairments at adulthood in an age- and gender-dependent manner. 2009 Elsevier Ireland Ltd. All rights reserved.

  19. Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.

    PubMed

    Roland, Alison V; Moenter, Suzanne M

    2011-02-01

    Prenatal androgenization (PNA) of female mice with dihydrotestosterone programs reproductive dysfunction in adulthood, characterized by elevated luteinizing hormone levels, irregular estrous cycles, and central abnormalities. Here, we evaluated activity of GnRH neurons from PNA mice and the effects of in vivo treatment with metformin, an activator of AMP-activated protein kinase (AMPK) that is commonly used to treat the fertility disorder polycystic ovary syndrome. Estrous cycles were monitored in PNA and control mice before and after metformin administration. Before metformin, cycles were longer in PNA mice and percent time in estrus lower; metformin normalized cycles in PNA mice. Extracellular recordings were used to monitor GnRH neuron firing activity in brain slices from diestrous mice. Firing rate was higher and quiescence lower in GnRH neurons from PNA mice, demonstrating increased GnRH neuron activity. Metformin treatment of PNA mice restored firing activity and LH to control levels. To assess whether AMPK activation contributed to the metformin-induced reduction in GnRH neuron activity, the AMPK antagonist compound C was acutely applied to cells. Compound C stimulated cells from metformin-treated, but not untreated, mice, suggesting that AMPK was activated in GnRH neurons, or afferent neurons, in the former group. GnRH neurons from metformin-treated mice also showed a reduced inhibitory response to low glucose. These studies indicate that PNA causes enhanced firing activity of GnRH neurons and elevated LH that are reversible by metformin, raising the possibility that central AMPK activation by metformin may play a role in its restoration of reproductive cycles in polycystic ovary syndrome.

  20. X IRRADIATION AND THE SECONDARY RESPONSE TO TETANUS TOXOID IN MICE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crook, J.C.; Ford, C.E.

    1962-04-01

    In 1952 it was recommended that wounded soldiers who had been actively immunized should be given a dose of tetanus toxoid and not tetanus antiserum as had been the practice previously. However, in the event of nuclear warfare, wounded soldiers might be exposed to irradiation, which would be detrimental to toxoid treatment since irradiation inhibits antibody formation. To investigate the problem, male PCT mice were immunized with two doses of tetanus toxoid at a 8- week interval, and their immune response to the second dose was tested by challenge with tetanus toxin 14 days later. Whole-body x irradiation with 35more » days before the second dose of toxoid to 7 days after. The criterion of inhibition of immune response was the percentage of deaths and paralyzed survivals occurring on the eighth day. The secondary response to tetanus toxoid was shown to be radiosensitive and to depend largely on the dose of radiation; a dose of 500 rad produced approximates 50% inhibition. Radiation given from 35 days to 1 day before the second dose of tetanus toxoid prcduced most inhibition; when given 2 days after the second dose it was less effective, and it was ineffective when given 5 or 7 days after. In the 200-rad experiment there was no evidence of inhibition at all. It is concluded that the wounded soldier should receive a booster dose of tetanus toxoid as soon as possible after wounding and probable irradiation from an atomic weapon. If a delay of a day or two occurred, the irradiated soldier might be at a stage of marked inhibition of his secondary response. If it is assumed that these findings are capable of extrapolation to man, he would not be capable of responding fully to any active immunizing procedures for a period of a few weeks at least after irradiation. (BBB)« less

  1. 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

  2. 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.

  3. Effect of whole-body irradiation with x rays on the formation of immunity in tetanus toxoid-immunized mice. Part 2. Secondary immunity to tetanus toxin (in Polish)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galazka, A.; Albrycht, H.; Gajewski, A.K.

    1972-01-01

    White mice were twofold immunized with various doses of adsorbed tetanus toxoid and irradiated with a dose of 500 R at various time intervals before and after the second immunization. The secondary response of the animals was more resistant to irradiation than the primary one. It was found, however, that antibody synthesis was disturbed in mice irradiated 1 to 2 hrs prior to the second immunization. The detrimental effect of irradiation was found to depend to a high extent on antigen dose used for the first, and not the second, immunization. (auth)

  4. CONSIDERATIONS OF THE HISTOLOGIC AND HISTOCHEMICAL INJURY INDUCED BY TOTAL ROENTGEN IRRADIATION IN THE FEMALE GENITAL ORGANS OF PUBERTAL AND PREPUBERTAL MICE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cecio, A.; Cerasuolo, G.

    1961-07-15

    Changes in uterus and ovaries were studied in mice exposed to 700 r whole-body irradiation. Endometrial glands showed an increase in mitotic figures after irradiation and somewhat decreased numbers of cells although histochemical tests for polysaccharides and ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) were intensified. The results were similar in adult and immature mice. In ovary, irradiation caused degeneration of follicles with separation of granulosa cells, which was followed by hyperplasia during the reparative phase. Here also polysaccharides were increased in amounts, especially in the zona pellucida of the oocytes. Epithelium of Fallopiant tube also showed increased histochemical reactionsmore » for polysaccharides, RNA, and DNA. Most of these changes were evident within 24 hr after irradiation; they increased in intensity up to the 2nd day, then tended to decrease. (H.H.D.)« less

  5. [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

  6. Technical Note: Partial body irradiation of mice using a customized PMMA apparatus and a clinical 3D planning/LINAC radiotherapy system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karagounis, Ilias V.; Koukourakis, Michael I., E-mail: targ@her.forthnet.gr, E-mail: mkoukour@med.duth.gr; Abatzoglou, Ioannis M., E-mail: abadzoglou@yahoo.gr

    Purpose: In vivo radiobiology experiments involving partial body irradiation (PBI) of mice are of major importance because they allow for the evaluation of individual organ tolerance; overcoming current limitations of experiments using lower dose, whole body irradiation. In the current study, the authors characterize and validate an effective and efficient apparatus for multiple animal PBI, directed to the head, thorax, or abdomen of mice. Methods: The apparatus is made of polymethylmethacrylate and consists of a rectangular parallelepiped prism (40 cm × 16 cm × 8 cm), in which five holes were drilled to accomodate standard 60 ml syringes, each housingmore » an unanesthetized, fully immobilized mouse. Following CT-scanning and radiotherapy treatment planning, radiation fields were designed to irradiate the head, thorax, or abdomen of the animal. Thermoluminescent dosimeters (TLDs) were used to confirm the treatment planning dosimetry for primary beam and scattered radiation. Results: Mice are efficiently placed into 60 ml syringes and immobilized, without the use of anesthetics. Although partial rotational movement around the longitudinal axis and a minor 2 mm forward/backward movement are permitted, this does not compromise the irradiation of the chosen body area. TLDs confirmed the dose values predicted by the treatment planning dosimetry, both for primary beam and scattered radiation. Conclusions: The customized PMMA apparatus described and validated is cost-effective, convenient to use, and efficient in performing PBI without the use of anesthesia. The developed apparatus permits the isolated irradiation of the mouse head, thorax, and abdomen. Importantly, the apparatus allows the delivery of PBI to five mice, simultaneously, representing an efficient way to effectively expose a large number of animals to PBI through multiple daily fractions, simulating clinical radiotherapy treatment schedules.« less

  7. GROWTH AND DEVELOPMENT OF MICE OFFSPRING AFTER IRRADIATION IN UTERO WITH 2,450-MHZ MICROWAVES

    EPA Science Inventory

    Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm. sq. (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, ...

  8. Prenatal exposure to methanol as a dopamine system sensitization model in C57BL/6J mice

    PubMed Central

    Mackey, Veronica R.; Muthian, Gladson; Smith, Marquitta; King, Jennifer; Charlton, Clivel G.

    2012-01-01

    Aims In this study, the effects of prenatal exposure to methanol (MeOH) on the nigrostriatal dopamine (NSDA) system were examined to determine if the interaction could sensitize this system, and serve as an underpinning for Parkinson's disease (PD) like changes that occur later in life. Methanol was studied because its toxicity resembles the symptoms of PD and the symptoms are relieved by l-dopa meaning that MeOH targets the NSDA system. Since fermentation and wood combustion are major sources for MeOH, the incidence of human encounters with MeOH is high. As a superior solvent and the precursor for formaldehyde, MeOH has a powerful and sometimes, irreversible impact on chemical processes, such as cross-linking proteins and nucleic acids. It may cause subthreshold changes that sensitizes the NSDA system to PD, that occur during aging. Main methods To study the prenatal effects of MeOH, pregnant C57BL/6J mice were administered 40 mg/kg MeOH by oral gavage during gestation days 8–12, twice daily. Twelve weeks after birth, behavior impairments were recorded. The striatum was dissected for the determination of tyrosine hydroxylase (TH), l-aromatic amino acid decarboxylase (LAAD), α-synuclein and levels of dopamine (DA) and its metabolites. Key findings MeOH reduced striatal TH and LAAD protein by 47% and 57% respectively and DA by 32%. Significance The results mean that in utero exposure to toxins similar to MeOH could sensitize the striatal system to changes that cause PD. This study may help identify strategies to block this type of in utero toxicity. PMID:23000099

  9. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee

    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 ofmore » 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.« less

  10. Synthesis of IgM and IgG antibodies in mice irradiated with x rays and immunized with tetanus toxoid (in Polish)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galazka, A.; Albrycht, H.; Aleksandrowicz, J.

    1972-01-01

    White mice were immunized with adsorbed tetanus toxoid 1 to 2 hrs following irradiation with a dose of 300 R. The antibody response was tested in whole sera 7, 14, 28, and 42 days after immunization; it was found to be delayed and repressed compared with controls. In tests for antibody activity of different classes of immunoglobulins, isolated on Sephadex G-200, the IgM- producing mechanisms were found to be highly radiosensitive; peak of the response was greatly delayed (28 days); and peak titers were threefold lower than in controls. IgG antibody production also was delayed and in the initial periodmore » it was repressed. Six weeks after irradiation, IgG antibody levels were equal in the irradiated and control mice. The present results concerning radiosensitivity of IgM-producing mechanisms are discordant with data of other authors, who immunized animals with other antigens or investigated the metabolism of immunoglobulins in irradiated but nonimmunized animals. (auth)« less

  11. 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

  12. Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice

    PubMed Central

    Barber, Ruth; Plumb, Mark A.; Boulton, Emma; Roux, Isabelle; Dubrova, Yuri E.

    2002-01-01

    Mutation rates at two expanded simple tandem repeat loci were studied in the germ line of first- and second-generation offspring of inbred male CBA/H, C57BL/6, and BALB/c mice exposed to either high linear energy transfer fission neutrons or low linear energy transfer x-rays. Paternal CBA/H exposure to either x-rays or fission neutrons resulted in increased mutation rates in the germ line of two subsequent generations. Comparable transgenerational effects were observed also in neutron-irradiated C57BL/6 and x-irradiated BALB/c mice. The levels of spontaneous mutation rates and radiation-induced transgenerational instability varied between strains (BALB/c>CBA/H>C57BL/6). Pre- and postmeiotic paternal exposure resulted in similar increases in mutation rate in the germ line of both generations of CBA/H mice, which together with our previous results suggests that radiation-induced expanded simple tandem repeat instability is manifested in diploid cells after fertilization. The remarkable finding that radiation-induced germ-line instability persists for at least two generations raises important issues of risk evaluation in humans. PMID:11997464

  13. Prenatally administered HMB modifies the enamel surface roughness in spiny mice offspring: An atomic force microscopy study.

    PubMed

    Świetlicka, Izabela; Muszyński, Siemowit; Tomaszewska, Ewa; Dobrowolski, Piotr; Kwaśniewska, Anita; Świetlicki, Michał; Skic, Anna; Gołacki, Krzysztof

    2016-10-01

    The aim of this research was to check the effect of the prenatally administered β-hydroxy β-methylbutyrate (HMB) on the development of enamel surface of the spiny mice offspring. The spiny mice dams were randomly assigned into three groups: control group (not supplemented with HMB) and two experimental groups in which powdered HMB was given at the daily dosage of 0.2g/kg of body weight (group I) and 0.02g/kg of body weight (group II) during the last period of gestation. Newborn pups were euthanized by CO 2 inhalation. The morphology of incisor teeth was analysed using atomic force microscopy (AFM) in semi-contact mode in the height, magnitude and phase domains. Height images became a basis for determination of surface roughness parameters. Conducted study indicated that maternal HMB administration markedly influences enamel development. Enamel of offspring's teeth in both experimental groups was characterized by significantly smaller values of indices describing surface roughness and profile. HMB supplementation influenced the calculated parameters regardless of the diet type and offspring sex, however higher dose of HMB caused stronger changes in enamel surface's physical properties and could be observed in higher intensity in the male group. HMB administration caused reduction in the irregularities of enamel surface, thereby possibly reducing the probability of bacteria adhesion and caries development. These observations may serve to improve nutrition and supplementation of animals and could be a lead for further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Radioprotective effects of Silymarin on the sperm parameters of NMRI mice irradiated with γ-rays.

    PubMed

    Fatehi, Daryoush; Mohammadi, Mohsen; Shekarchi, Babak; Shabani, Arash; Seify, Mohammad; Rostamzadeh, Ayoob

    2018-01-01

    Free radicals and reactive oxygen species (ROS) are generated using various endogenous systems or from external sources such as exposure to different physiochemicals. Ionizing radiation damage to the cell can be caused by the direct or indirect effects of radiotherapy processes. Silymarin (SM), a flavanolignan compound, has been identified as a natural potent antioxidant with cytoprotection activities due to scavenging free radicals. The aim of the present study was to evaluate the radioprotective effect of SM on sperm parameters of mice induced by γ-rays. A total number of 40 adult, male NMRI mice were randomly divided into four equal groups. The control group was neither treated with SM nor irradiated by γ-rays. The second group was only irradiated with 2Gy of γ-rays. The third group was firstly treated with 50mg/kg of SM for 7 consecutive days, and one day later, last injections were irradiated by 2Gy of γ-rays. The fourth groups received only 50mg/kg of SM for 7 consecutive days. All the animals were treated intraperitoneally. Histopathological and morphometrical examinations were performed. The data were analyzed using ANOVA and Tukey post hoc test. A value of p<0.05 was considered significant. The results showed that in the radiation-only group when compared with those treated with SM and irradiated, a significant different was observed in testicular parameters and DNA damage (p<0.05). In conclusion, SM can be considered as a promising herbal radioprotective agent in complementary medicine which may play an important role to protect normal spermatocytes against possible effects of γ-radiation-induced cellular damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 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.

  16. Single-Dose and Fractionated Irradiation Promote Initiation and Progression of Atherosclerosis and Induce an Inflammatory Plaque Phenotype in ApoE{sup -/-} Mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.

    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, plaquemore » 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.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 ofmore » 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.« less

  18. Prenatal Exposure to Tributyltin Decreases GluR2 Expression in the Mouse Brain.

    PubMed

    Ishida, Keishi; Saiki, Takashi; Umeda, Kanae; Miyara, Masatsugu; Sanoh, Seigo; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), a common environmental contaminant, is widely used as an antifouling agent in paint. We previously reported that exposure of primary cortical neurons to TBT in vitro decreased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) expression and subsequently increased neuronal vulnerability to glutamate. Therefore, to identify whether GluR2 expression also decreases after TBT exposure in vivo, we evaluated the changes in GluR2 expression in the mouse brain after prenatal or postnatal exposure to 10 and 25 ppm TBT through pellet diets. Although the mean feed intake and body weight did not decrease in TBT-exposed mice compared with that in control mice, GluR2 expression in the cerebral cortex and hippocampus decreased after TBT exposure during the prenatal period. These results indicate that a decrease in neuronal GluR2 may be involved in TBT-induced neurotoxicity, especially during the fetal period.

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

    PubMed

    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.

  20. 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

  1. Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice.

    PubMed

    Marshall, Christopher J; Desroziers, Elodie; McLennan, Timothy; Campbell, Rebecca E

    2017-01-01

    Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. GABA neurons rarely co-localized with kisspeptin (<2%) or β-endorphin (<1%), and only a small proportion of kisspeptin (∼10%) or β-endorphin (∼3%) neurons co-localized with VGaT in male and female mice. In contrast, one-third of ARN GABA neurons co-localized with NPY, and nearly all NPY neurons (>95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons. © 2016 S. Karger AG, Basel.

  2. Total-body irradiation of postpubertal mice with (137)Cs acutely compromises the microarchitecture of cancellous bone and increases osteoclasts.

    PubMed

    Kondo, Hisataka; Searby, Nancy D; Mojarrab, Rose; Phillips, Jonathan; Alwood, Joshua; Yumoto, Kenji; Almeida, Eduardo A C; Limoli, Charles L; Globus, Ruth K

    2009-03-01

    Ionizing radiation can cause substantial tissue degeneration, which may threaten the long-term health of astronauts and radiotherapy patients. To determine whether a single dose of radiation acutely compromises structural integrity in the postpubertal skeleton, 18-week-old male mice were exposed to (137)Cs gamma radiation (1 or 2 Gy). The structure of high-turnover, cancellous bone was analyzed by microcomputed tomography (microCT) 3 or 10 days after irradiation and in basal controls (tissues harvested at the time of irradiation) and age-matched controls. Irradiation (2 Gy) caused a 20% decline in tibial cancellous bone volume fraction (BV/TV) within 3 days and a 43% decline within 10 days, while 1 Gy caused a 28% reduction 10 days later. The BV/TV decrement was due to increased spacing and decreased thickness of trabeculae. Radiation also increased ( approximately 150%) cancellous surfaces lined with tartrate-resistant, acid phosphatase-positive osteoclasts, an index of increased bone resorption. Radiation decreased lumbar vertebral BV/TV 1 month after irradiation, showing the persistence of cancellous bone loss, although mechanical properties in compression were unaffected. In sum, a single dose of gamma radiation rapidly increased osteoclast surface in cancellous tissue and compromised cancellous microarchitecture in the remodeling appendicular and axial skeleton of postpubertal mice.

  3. Activation of adenosine A(3) receptors supports hematopoiesis-stimulating effects of granulocyte colony-stimulating factor in sublethally irradiated mice.

    PubMed

    Hofer, Michal; Pospísil, Milan; Sefc, Ludek; Dusek, Ladislav; Vacek, Antonín; Holá, Jirina; Hoferová, Zuzana; Streitová, Denisa

    2010-08-01

    Research areas of 'post-exposure treatment' and 'cytokines and growth factors' have top priority among studies aimed at radiological nuclear threat countermeasures. The experiments were aimed at testing the ability of N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), an adenosine A(3) receptor agonist, to modulate hematopoiesis in sublethally irradiated mice, when administered alone or in a combination with granulocyte colony-stimulating factor (G-CSF) in a two-day post-irradiation treatment regimen. A complete analysis of hematopoiesis including determination of numbers of bone marrow hematopoietic progenitor and precursor cells, as well as of numbers of peripheral blood cells, was performed. The outcomes of the treatment were assessed at days 3 to 22 after irradiation. IB-MECA alone has been found to induce a significant elevation of numbers of bone marrow granulocyte-macrophage progenitor cells (GM-CFC) and peripheral blood neutrophils. IB-MECA given concomitantly with G-CSF increased significantly bone marrow GM-CFC and erythroid progenitor cells (BFU-E) in comparison with the controls and with animals administered each of the drugs alone. The findings suggest the ability of IB-MECA to stimulate hematopoiesis and to support the hematopoiesis-stimulating effects of G-CSF in sublethally irradiated mice.

  4. Long-Term Effects of Stem Cells on Total-Body Irradiated Mice

    NASA Astrophysics Data System (ADS)

    Vyalkina, M. V.; Alchinova, I. B.; Yakovenko, E. N.; Medvedeva, Yu S.; Saburina, I. N.; Karganov, M. Yu

    2017-01-01

    C57Bl/6 mice were exposed to γ-radiation in a sublethal dose of 7.5 Gy. In 3 hours injection 106/mouse of bone marrow multipotent mesenchymal stromal cells stem cells intravenously to experimental group was done. Methods used: body weight measurement, open field behavior, subfraction composition of blood serum (laser correlation spectroscopy, LCS), histological examination of the spleen, liver, and pancreas, count of T and B cells, white blood formula. After 1.5 and 3 months the general trend towards intermediate position of the parameters observed in the experimental between those in intact and irradiated controls attests to partial protective/restorative effects of the injected cells.

  5. Changes in antigen-presenting cell function in the spleen and lymph nodes of ultraviolet-irradiated mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gurish, M.F.; Lynch, D.H.; Daynes, R.A.

    1982-03-01

    It has been previously reported that mice exposed to ultraviolet (UV) radiation exhibit a decrease in splenic antigen-presenting cell (APC) function. The results presented here confirm this observation and further demonstrate that animals exposed daily to UV for extended periods of time (5 weeks instead of 6 days) no longer exhibit this depressed capability. In spite of the depression in splenic APC activity found in 6-day UV-irradiated mice, lymph node APC function from these same animals was elevated compared with that found in the lymph nodes from normal animals. Lymph node APC activity in animals that were splenectomized prior tomore » the UV irradiation, however, was not enhanced over controls. Treatment of animals with a chemical irritant (turpentine) also caused a depression in splenic APC function without modifying lymph node activity. Collectively, our findings suggest that the observed decrease in splenic APC activity, found after the first week of UV exposures, may be attributable to the migration of splenic APC to peripheral lymphoid tissue which drain the site of epidermal inflammation.« less

  6. 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. (c) 2009 S. Karger AG, Basel.

  7. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice.

    PubMed

    Ivani, Saeed; Karimi, Isaac; Tabatabaei, Seyed Reza Fatemi; Syedmoradi, Leila

    2016-07-01

    Carbon nanotubes with extraordinary properties may become a novel drug and gene delivery tool in nanomedicine; however, insufficient information is available regarding their biosafety. Therefore, this work was performed to study the effect of prenatal exposure of single-walled carbon nanotubes (SWCNTs) on reproductive and neurobehavioral endpoints in mice. Thirty pregnant female mice were assigned to three groups (n = 10 for each group). The two treated groups were injected intraperitoneally (i.p.) with 1 or 10 mg/kg body weight (b.w.) of SWCNTs suspended in 1 ml of phosphate buffer saline (PBS) on gestational days 0 and 3. The control group was injected i.p. with an equal volume of PBS. The neurobehavioral ontogeny of pups was evaluated using a modified Fox battery. A decrease in litter size on postnatal day 2 was observed in the group treated with 10 mg/kg b.w. of SWCNTs whereas no significant differences between groups were observed in any other parameters. The behavioral development of pups did not show significant differences during growth except for the surface righting reflex, which showed significant delay compared to control in the group treated with 1 mg/kg b.w. SWCNTs. Moreover, exposed offspring (10 mg/kg b.w. SWCNTs) displayed enhanced anxiety in the elevated plus maze; however, other ethological analysis (Morris water maze and open field test) did not show behavioral changes in the experimental groups. In conclusion, the present results demonstrated small changes in offspring sensory and motor development following exposure to SWCNTs and support the idea that SWCNT risk assessment merits further investigation. © The Author(s) 2014.

  9. Strain-dependent effects of prenatal maternal immune activation on anxiety- and depression-like behaviors in offspring.

    PubMed

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-01

    There is converging evidence that prenatal maternal infection can increase the risk of occurrence of neuropsychiatric disorders like schizophrenia, autism, anxiety and depression in later life. Experimental studies have shown conflicting effects of prenatal maternal immune activation on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis development in offspring. We investigated the effects of maternal immune activation during pregnancy on anxiety- and depression-like behaviors in pregnant mice and their offspring to determine whether these effects are dependent on strain. NMRI and C57BL/6 pregnant mice were treated with either saline or lipopolysaccharide on gestational day 17 and then interleukin (IL)-6 and corticosterone (COR) levels; anxiety or depression in the pregnant mice and their offspring were evaluated. The results indicate that maternal inflammation increased the levels of COR and anxiety-like behavior in NMRI pregnant mice, but not in C57BL/6 dams. Our data also demonstrate that maternal inflammation elevated the levels of anxiety-and depression-like behaviors in NMRI offspring on the elevated plus-maze, elevated zero-maze, tail suspension test and forced swimming test respectively, but not in the open field and light-dark box. In addition, we did not find any significant change in anxiety- and depression-like behaviors of adult C57BL/6 offspring. Our findings suggest that prenatal maternal immune activation can alter the HPA axis activity, anxiety- and depression-like behaviors in a strain- and task-dependent manner in offspring and further comprehensive studies are needed to prove the causal relationship between the findings found here and to validate their relevance to neuropsychiatric disorders in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2000-01-01

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

  11. The effects of grape seeds polyphenols on SKH-1 mice skin irradiated with multiple doses of UV-B.

    PubMed

    Filip, Adriana; Daicoviciu, Doina; Clichici, Simona; Bolfa, Pompei; Catoi, Cornel; Baldea, Ioana; Bolojan, Laura; Olteanu, Diana; Muresan, Adriana; Postescu, I D

    2011-11-03

    The study investigated the protective activity of red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on multiple doses of ultraviolet radiation (UV)-B-induced deleterious effects in SKH-1 mice skin. Eighty 8-weeks-old female SKH-1 mice were divided into 8 groups: control, vehicle, UV-B irradiated, vehicle+UV-B irradiated, BM 2.5mg polyphenols (PF)/cm(2)+UV-B irradiated, BM 4 mg PF/cm(2)+UV-B irradiated, UV-B+BM 2.5mg PF/cm(2), UV-B+BM 4 mg PF/cm(2). The extract was applied topically before or after each UV-B exposure (240 mJ/cm(2)), for 10 days consecutively. The antioxidant activity of BM extract is higher than gallic acid (k(BM)=0.017, k(gallic acid)=0.013). Multiple doses of UV-B generated the formation of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, increased glutathione peroxidase (GPx) and catalase (CAT) activities respectively glutathione (GSH) and IL-1β levels in skin. In group treated with 2.5mg PF/cm(2) before UV-B irradiation BM extract inhibited UV-B-induced sunburn cells, restored the superoxide dismutase (MnSOD) activity, increased insignificantly CAT and GPx activities and reduced IL-1β level. The BM 4.0 mg PF/cm(2) treatment decreased GSH level and reduced the percentage of CPDs positive cells in skin. Both doses of BM extract administered after UV-B irradiation increased the MnSOD and GPx activities and reduced the formation of sunburn cells in skin. Our results suggest that BM extract might be a potential chemo-preventive candidate in reducing the oxidative stress and apoptosis induced by multiple doses of UV-B in skin. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Late prenatal immune activation causes hippocampal deficits in the absence of persistent inflammation across aging.

    PubMed

    Giovanoli, Sandra; Notter, Tina; Richetto, Juliet; Labouesse, Marie A; Vuillermot, Stéphanie; Riva, Marco A; Meyer, Urs

    2015-11-25

    Prenatal exposure to infection and/or inflammation is increasingly recognized to play an important role in neurodevelopmental brain disorders. It has recently been postulated that prenatal immune activation, especially when occurring during late gestational stages, may also induce pathological brain aging via sustained effects on systemic and central inflammation. Here, we tested this hypothesis using an established mouse model of exposure to viral-like immune activation in late pregnancy. Pregnant C57BL6/J mice on gestation day 17 were treated with the viral mimetic polyriboinosinic-polyribocytidilic acid (poly(I:C)) or control vehicle solution. The resulting offspring were first tested using cognitive and behavioral paradigms known to be sensitive to hippocampal damage, after which they were assigned to quantitative analyses of inflammatory cytokines, microglia density and morphology, astrocyte density, presynaptic markers, and neurotrophin expression in the hippocampus throughout aging (1, 5, and 22 months of age). Maternal poly(I:C) treatment led to a robust increase in inflammatory cytokine levels in late gestation but did not cause persistent systemic or hippocampal inflammation in the offspring. The late prenatal manipulation also failed to cause long-term changes in microglia density, morphology, or activation, and did not induce signs of astrogliosis in pubescent, adult, or aged offspring. Despite the lack of persistent inflammatory or glial anomalies, offspring of poly(I:C)-exposed mothers showed marked and partly age-dependent deficits in hippocampus-regulated cognitive functions as well as impaired hippocampal synaptophysin and brain-derived neurotrophic factor (BDNF) expression. Late prenatal exposure to viral-like immune activation in mice causes hippocampus-related cognitive and synaptic deficits in the absence of chronic inflammation across aging. These findings do not support the hypothesis that this form of prenatal immune activation may induce

  13. Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

    PubMed Central

    Juliandi, Berry; Tanemura, Kentaro; Igarashi, Katsuhide; Tominaga, Takashi; Furukawa, Yusuke; Otsuka, Maky; Moriyama, Noriko; Ikegami, Daigo; Abematsu, Masahiko; Sanosaka, Tsukasa; Tsujimura, Keita; Narita, Minoru; Kanno, Jun; Nakashima, Kinichi

    2015-01-01

    Summary Prenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running. PMID:26677766

  14. 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

  15. In vivo incorporation of $sup 14$C-labelled amino acids into proteins of placenta and liver of normal and x-irradiated mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tarachand, U.; Eapen, J.

    Effect of x irradiation on in vivo incorporation of /sup 14/C-labeled DL- leucine, DL-phenylalanine, and glycine into placental and hepatic proteins was studied, using 15-day pregnant mice. Pattern of incorporation of leucine and phenylalanine into maternal liver proteins was similar following irradiation. Effect on glycine incorporation was different. Placental incorporation of all the three- amino acids, subsequent to irradiation, was comparable. Starvation per se enhanced incorporation of leucine into hepatic proteins which was further elevated following irradiation. Placental incorporation was reduced by starvation. Subcellular fractions showed disparate changes in leucine incorporation due to irradiation. Acid-soluble pool changed, following irradiation, withoutmore » significantly affecting incorporation of the precursors into proteins. (auth)« less

  16. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

    PubMed

    Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-08-30

    We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

    PubMed

    Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-11-01

    Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. DHA Mitigates Autistic Behaviors Accompanied by Dopaminergic Change in a Gene/Prenatal Stress Mouse Model.

    PubMed

    Matsui, Fumihiro; Hecht, Patrick; Yoshimoto, Kanji; Watanabe, Yoshihisa; Morimoto, Masafumi; Fritsche, Kevin; Will, Matthew; Beversdorf, David

    2018-02-10

    Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction, social communication, and repetitive and stereotyped behaviors. Recent work has begun to explore gene × environmental interactions in the etiology of ASD. We previously reported that prenatal stress exposure in stress-susceptible heterozygous serotonin transporter (SERT) KO pregnant dams in a mouse model resulted in autism-like behavior in the offspring (SERT/S mice). The association between prenatal stress and ASD appears to be affected by maternal SERT genotype in clinical populations as well. Using the mouse model, we examined autistic-like behaviors in greater detail, and additionally explored whether diet supplementation with docosahexaenoic acid (DHA) may mitigate the behavioral changes. Only male SERT/S mice showed social impairment and stereotyped behavior, and DHA supplementation ameliorated some of these behaviors. We also measured monoamine levels in the SERT/S mice after three treatment paradigms: DHA-rich diet continuously from breeding (DHA diet), DHA-rich diet only after weaning (CTL/DHA diet) and control diet only (CTL diet). The dopamine (DA) content in the striatum was significantly increased in the SERT/S mice compared with wild-type (WT) mice, whereas no difference was observed with noradrenaline and serotonin content. Moreover, DA content in the striatum was significantly reduced in the SERT/S mice with the DHA-rich diet provided continuously from breeding. The results indicate that autism-associated behaviors and changes in the dopaminergic system in this setting can be mitigated with DHA supplementation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sakaguchi, N.; Sakaguchi, S.; Miyai, K.

    1992-11-01

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and themore » peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.« less

  20. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. 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 ...

  2. Acidic polysaccharide of Panax ginseng as a defense against small intestinal damage by whole-body gamma irradiation of mice.

    PubMed

    Park, Eunjin; Hwang, Insun; Song, Jie-Young; Jee, Youngheun

    2011-01-01

    An acidic polysaccharide of Panax ginseng (APG), ginsan, has been reported to protect the hematopoietic system by increasing the number of bone marrow cells and spleen cells. Therefore, we evaluated the ability of APG to protect mice from radiation-induced damage of the small intestine. APG treatment caused the lengthening of villi and a numerical increase of crypt cells in the small intestine at 3.5 days after 7Gy irradiation compared to irradiated, non-treated controls. In addition, APG significantly inhibited irradiation-induced apoptosis by decreasing the amount of pro-apoptotic p53 and Bax as well as augmenting that of anti-apoptotic Bcl-2 at 24h after irradiation. These results indicate that APG might be a useful adjunct to therapeutic irradiation as a protective agent for the gastrointestinal tract of cancer patients. Copyright © 2009 Elsevier GmbH. All rights reserved.

  3. The immunogenicity of phagocytosed T4 bacteriophage: cell replacement studies with splenectomized and irradiated mice

    PubMed Central

    Inchley, C. J.; Howard, J. G.

    1969-01-01

    The role of phagocytosed antigen in the production of antibody to bacteriophage T4 has been studied. The ability of mice to give an antibody response to this antigen was first impaired either by splenectomy or by X-irradiation, and then restored by injection of syngeneic lymphoid cells given at various times relative to the injection of T4. In splenectomized animals administration of lymphoid cells had only a marginal effect on the severely depressed response to T4. It was concluded that the presence of an intact spleen is essential to the development of the normal immune response, and that circulating immunocompetent cells are unable to respond to circulating antigen or to antigen sequestered within the liver. On the other hand, in irradiated mice, there was a faster and more complete restoration of the anti-T4 response, confirming the ability of antigen localized within the spleen to stimulate competent cells. It was also found that the immunogenicity of T4 within this organ was not lost at a rate which corresponded to its gross breakdown but persisted without decrease for at least 48 hr. A similar observation was made for sheep red blood cells when this antigen was used in conjunction with T4. PMID:5370054

  4. EFFECTS OF X IRRADIATION ON THE LEVEL OF NUCLEIC ACIDS AND PROTEINS OF THE UTERUS AND VAGINA OF PREPUBERTAL MICE SUBMITTED TO INDUCED HYPERPLASIA (in French)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ledoux, L.; Charles, P.

    1961-12-01

    In 20-day-old mice injected subcutaneously with a single 10 ug. dose of estradiol benzoate the deoxyribonucleic acid (DNA) content rose 100% in uterus and 50% in vagina 72 hr later. Ribonucleic acid (RNA) content rose 250 and 100%, respectively, and protein content rose in parallel with DNA. Similarly treated mice were exposed to x rays (150 to 850 r) 24 hr before, simultaneously with, or 24 to 48 hr after injection of estradiol. Irradiation with 750 r before or with the injection inhibited the rise of DNA and RNA 50 to 80% but did not affect the increase in proteins.more » Irradiation of uninjected control mice diminished DNA and RNA. Irradiation 24 to 38 hr after the injection immediately suppressed the increases of DNA and RNA in uterus and vagina and of protein in uterus. Protein content of vagina was not influenced. (H.H.D.)« less

  5. Prenatal detection of congenital heart disease.

    PubMed

    Friedberg, Mark K; Silverman, Norman H; Moon-Grady, Anita J; Tong, Elizabeth; Nourse, Jennifer; Sorenson, Beatrice; Lee, Jaimie; Hornberger, Lisa K

    2009-07-01

    To define current frequency of prenatal detection of congenital heart disease (CHD), factors affecting prenatal detection, and its influence on postnatal course. We prospectively identified all fetuses and infants < or =6 months of age with major CHD at 3 referral centers in Northern California over 1 year; we obtained prenatal and demographic data, reviewed prenatal ultrasound (US) and postnatal records, and used logistic regression to analyze maternal, fetal, and prenatal-care provider risk factors for prenatal diagnosis. Ninety-eight of 309 infants with major CHD had prenatal diagnosis (36% accounting for 27 pregnancy terminations); 185 infant-families participated in the postnatal survey, and although 99% had prenatal US, only 28% were prenatally diagnosed. Anomalous pulmonary venous return (0%), transposition of the great arteries (19%), and left obstructive lesions (23%) had the lowest prenatal detection. Heterotaxy (82%), single ventricle (64%), and HLHS (61%) had the highest. Prenatal diagnosis was higher at university versus community practices (P = .001). Sociodemographics were not associated with prenatal diagnosis. Infants diagnosed prenatally were less frequently ventilated (P < .01) or treated with prostaglandin (P < .05). Prenatal detection of major CHD significantly alters postnatal course but remains low despite nearly universal US. CHD type and US practice type are important determinants of prenatal detection.

  6. High-fat diet exacerbates inflammation and cell survival signals in the skin of ultraviolet B-irradiated C57BL/6 mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meeran, Syed M.; Singh, Tripti; Nagy, Tim R.

    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 fedmore » 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.« less

  7. Administration of the Antioxidant N-Acetyl-Cysteine in Pregnant Mice Has Long-Term Positive Effects on Metabolic and Behavioral Endpoints of Male and Female Offspring Prenatally Exposed to a High-Fat Diet.

    PubMed

    Berry, Alessandra; Bellisario, Veronica; Panetta, Pamela; Raggi, Carla; Magnifico, Maria C; Arese, Marzia; Cirulli, Francesca

    2018-01-01

    A growing body of evidence suggests the consumption of high-fat diet (HFD) during pregnancy to model maternal obesity and the associated increase in oxidative stress (OS), might act as powerful prenatal stressors, leading to adult stress-related metabolic or behavioral disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy) on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13 weeks (from 5-weeks of age until delivery) and were exposed to the N-acetyl-cysteine (NAC) antioxidant from 10-weeks of age until right before delivery. Body weight of the offspring was assessed following birth, up to weaning and at adulthood. The metabolic, neuroendocrine and emotional profile of the adult offspring was tested at 3-months of age. Prenatal HFD increased mother's body weight and offspring's weight at the time of weaning, when administered in conjunction with NAC. In females, NAC administration reduced high levels of leptin resulting from prenatal HFD. Prenatal NAC administration also resulted in greater glucose tolerance and insulin sensitivity while increasing adiponectin levels, as well as increasing exploratory behavior, an effect accompanied by reduced plasma corticosterone levels in response to restraint stress. Analysis of glutathione levels in the hypothalamus and in brown adipose tissue indicates that, while HFD administration to pregnant dams led to reduced levels of glutathione in the offspring, as in the male hypothalamus, NAC was able to revert this effect and to increase glutathione levels both in the periphery (Brown Adipose Tissue, both males and females) and in the central nervous system (males). Overall, results from this study indicate that the body redox milieu should be tightly regulated during fetal life and that buffering OS during pregnancy can have important long

  8. [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.

  9. Persistent induction of somatic reversions of the pink-eyed unstable mutation in F1 mice born to fathers irradiated at the spermatozoa stage.

    PubMed

    Shiraishi, Kazunori; Shimura, Tsutomu; Taga, Masataka; Uematsu, Norio; Gondo, Yoichi; Ohtaki, Megu; Kominami, Ryo; Niwa, Ohtsura

    2002-06-01

    Untargeted mutation and delayed mutation are features of radiation-induced genomic instability and have been studied extensively in tissue culture cells. The mouse pink-eyed unstable (p(un)) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts back to the wild type in germ cells as well as in somatic cells. The reversion event can be detected in the retinal pigment epithelium as a cluster of pigmented cells (eye spot). We have investigated the reversion p(um) in F1 mice born to irradiated males. Spermatogonia-stage irradiation did not affect the frequency of the reversion in F1 mice. However, 6 Gy irradiation at the spermatozoa stage resulted in an approximately twofold increase in the number of eye spots in the retinal pigment epithelium of F1 mice. Somatic reversion occurred for the paternally derived p(un) alleles. In addition, the reversion also occurred for the maternally derived, unirradiated p(un) alleles at a frequency equal to that for the paternally derived allele. Detailed analyses of the number of pigmented cells per eye spot indicated that the frequency of reversion was persistently elevated during the proliferation cycle of the cells in the retinal pigment epithelium when the male parents were irradiated at the spermatozoa stage. The present study demonstrates the presence of a long-lasting memory of DNA damage and the persistent up-regulation of recombinogenic activity in the retinal pigment epithelium of the developing fetus.

  10. Prenatal Cell-Free DNA Screening

    MedlinePlus

    Prenatal cell-free DNA screening Overview Prenatal cell-free DNA (cfDNA) screening, also known as noninvasive prenatal screening, is a method to screen ... in a developing baby. During prenatal cell-free DNA screening, DNA from the mother and fetus is ...

  11. Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of Down Syndrome

    PubMed Central

    Goodliffe, Joseph W.; Olmos-Serrano, Jose Luis; Aziz, Nadine M.; Pennings, Jeroen L.A.; Guedj, Faycal; Bianchi, Diana W.

    2016-01-01

    Studies in humans with Down syndrome (DS) show that alterations in fetal brain development are followed by postnatal deficits in neuronal numbers, synaptic plasticity, and cognitive and motor function. This same progression is replicated in several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) is a recently developed mouse model of DS in which the entire region of mouse chromosome 16 that is homologous to human chromosome 21 has been triplicated. As such, Dp16 mice may more closely reproduce neurodevelopmental changes occurring in humans with DS. Here, we present the first comprehensive cellular and behavioral study of the Dp16 forebrain from embryonic to adult stages. Unexpectedly, our results demonstrate that Dp16 mice do not have prenatal brain defects previously reported in human fetal neocortex and in the developing forebrains of other mouse models, including microcephaly, reduced neurogenesis, and abnormal cell proliferation. Nevertheless, we found impairments in postnatal developmental milestones, fewer inhibitory forebrain neurons, and deficits in motor and cognitive performance in Dp16 mice. Therefore, although this new model does not express prenatal morphological phenotypes associated with DS, abnormalities in the postnatal period appear sufficient to produce significant cognitive deficits in Dp16. SIGNIFICANCE STATEMENT Down syndrome (DS) leads to intellectual disability. Several mouse models have increased our understanding of the neuropathology of DS and are currently being used to test therapeutic strategies. A new mouse model that contains an expanded number of DS-related genes, known as Dp(16)1Yey/+ (Dp16), has been generated recently. We sought to determine whether the extended triplication creates a better phenocopy of DS-related brain pathologies. We measured embryonic development, forebrain maturation, and perinatal/adult behavior and revealed an absence of prenatal phenotypes in Dp16 fetal brain, but specific cellular and behavioral

  12. The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

    PubMed Central

    Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

    2010-01-01

    In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

  13. Subtle Decreases in DNA Methylation and Gene Expression at the Mouse Igf2 Locus Following Prenatal Alcohol Exposure: Effects of a Methyl-Supplemented Diet

    PubMed Central

    Downing, Chris; Johnson, Thomas E; Larson, Colin; Leakey, Tatiana I; Siegfried, Rachel N; Rafferty, Tonya M; Cooney, Craig A

    2010-01-01

    C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2 (Downing and Gilliam 1999). The best characterized mechanism mediating genomic imprinting is differential DNA methylation. In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure. We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis. In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease. We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5 fold decreases following intrauterine alcohol exposure. Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl-supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations. Thus, while prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis. PMID:20705422

  14. 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.

  15. Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice

    PubMed Central

    Vaid, Mudit; Singh, Tripti; Prasad, Ram; Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.

    2013-01-01

    Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DCs). Co-culture of CD4+ T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of Th-1 type cytokines that was ameliorated when the DCs were obtained from GSPs-fed mice; whereas, DCs obtained from GSPs-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4, dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. PMID:23321928

  16. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. UpStart Parent Survey-Prenatal: A New Tool for Evaluating Prenatal Education Programs.

    PubMed

    Benzies, Karen M; Barker, Leslie; Churchill, Jocelyn; Smith, Jennifer; Horn, Sarah

    2016-09-01

    To evaluate a new prenatal education program evaluation tool, the UpStart Parent Survey - Prenatal, in terms of: (a) reliability and validity; (b) sensitivity to change over time; (c) whether results differed for mothers versus fathers; and (d) whether results differed when using an electronic tablet-computer versus a paper survey. Psychometric study. Participants were 277 expectant mothers (n = 161) and fathers (n = 106) enrolled in Childbirth Essentials, a 6-week prenatal education program. The UpStart Parent Survey - Prenatal is a retrospective pretest/posttest survey with three scales: Parenting Knowledge, Parenting Experience, and Program Satisfaction, and three open-ended questions. The UpStart Parent Survey - Prenatal is sensitive to change and demonstrated significant positive differences in parenting knowledge and parenting experience. There was no difference in results whether the survey was completed by mothers or fathers. Results were similar whether paper or electronic formats were used. The survey was easy to complete. The UpStart Parent Survey - Prenatal holds promise as a reliable and valid evaluation tool to capture outcomes of brief prenatal education programs that target the general population of expectant parents. © 2016 Wiley Periodicals, Inc.

  18. Rodent malaria: BCG-induced protection and immunosuppression. [Mice, gamma radiation, Plasmodium berghei

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smrkovski, L.L.; Strickland, G.T.

    1978-10-01

    One dose of 10/sup 7/ viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10/sup 4/ thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites onlymore » if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge.« less

  19. 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…

  20. Thrombomodulin Contributes to Gamma Tocotrienol-Mediated Lethality Protection and Hematopoietic Cell Recovery in Irradiated Mice

    PubMed Central

    Pathak, Rupak; Shao, Lijian; Ghosh, Sanchita P.; Zhou, Daohong; Boerma, Marjan; Weiler, Hartmut; Hauer-Jensen, Martin

    2015-01-01

    Systemic administration of recombinant thrombomodulin (TM) confers radiation protection partly by accelerating hematopoietic recovery. The uniquely potent radioprotector gamma tocotrienol (GT3), in addition to being a strong antioxidant, inhibits the enzyme hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) and thereby likely modulates the expression of TM. We hypothesized that the mechanism underlying the exceptional radioprotective properties of GT3 partly depends on the presence of endothelial TM. In vitro studies confirmed that ionizing radiation suppresses endothelial TM (about 40% at 4 hr after 5 Gy γ-irradiation) and that GT3 induces TM expression (about 2 fold at the mRNA level after 5 μM GT3 treatment for 4 hr). In vivo survival studies showed that GT3 was significantly more effective as a radioprotector in TM wild type (TM+/+) mice than in mice with low TM function (TMPro/-). After exposure to 9 Gy TBI, GT3 pre-treatment conferred 85% survival in TM+/+ mice compared to only 50% in TMPro/-. Thus, GT3-mediated radiation lethality protection is partly dependent on endothelial TM. Significant post-TBI recovery of hematopoietic cells, particularly leukocytes, was observed in TM+/+ mice (p = 0.003), but not in TMPro/- mice, despite the fact that GT3 induced higher levels of granulocyte colony stimulating factor (G-CSF) in TMPro/- mice (p = 0.0001). These data demonstrate a critical, G-CSF-independent, role for endothelial TM in GT3-mediated lethality protection and hematopoietic recovery after exposure to TBI and may point to new strategies to enhance the efficacy of current medical countermeasures in radiological/nuclear emergencies. PMID:25860286

  1. Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice.

    PubMed

    El-Batal, Ahmed Ibrahim; Ahmed, Salwa Farid

    2018-02-05

    Radiation combined injury, a life-threatening condition, has higher mortality than simple radiation injury. The aim of the present study was to analyze the efficiency of Aloe vera and silver nanoparticles in improving the healing of ulcerated oral mucosa after irradiation. Thirty male Albino mice were divided into five groups: control, radiation, Aloe vera (AV), silver nanoparticles (NS), and AV+NS. The mice were exposed to whole body 6Gy gamma-radiation. After one hour, 20% acetic acid was injected into the submucosal layer of the lower lip for ulcer induction. The animals received topical treatment with the assigned substances for 5 days. Lip specimens were subjected to hematoxylin and eosin and anti alpha-smooth muscle actin immunohistochemical staining. Results demonstrated occurance of ulcer three days post irradiation in all groups except in the AV+NS group where only epithelial detachment was developed. After seven days, data revealed persistent ulcer in radiation group, and almost normal epithelium in the AV+NS group. A significant reduction of epithelial thickness was detected in all groups at the third day as compared to control. At the seventh day, only the AV+NS group restored the epithelial thickness. Area percent of alpha-smooth muscle actin expression was significantly decreased in radiation group at the third day followed by significant increase at the seventh day. However, all treatment groups showed significant increase in alpha-smooth muscle actin at the third day, which decreased to normal level at the seventh day. Our study demonstrated the efficiency of Aloe vera and silver nanoparticles in enhancing ulcer healing after irradiation.

  2. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube X-ray source array

    PubMed Central

    Zhang, Lei; Yuan, Hong; Burk, Laurel M; Inscoe, Christy R; Hadsell, Michael J; Chtcheprov, Pavel; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-01-01

    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. PMID:24556798

  3. 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.

  4. Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice.

    PubMed

    Vaid, Mudit; Singh, Tripti; Prasad, Ram; Elmets, Craig A; Xu, Hui; Katiyar, Santosh K

    2013-03-01

    Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T-cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DC). Co-culture of CD4(+) T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of T-helper (TH) 1-type cytokines that was ameliorated when the DCs were obtained from GSP-fed mice, whereas DCs obtained from GSP-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4,-dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. Cancer Prev Res; 6(3); 242-52. ©2013 AACR. ©2013 AACR.

  5. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology.

    PubMed

    Mullen, Brian R; Ross, Brennan; Chou, Joan Wang; Khankan, Rana; Khialeeva, Elvira; Bui, Kimberly; Carpenter, Ellen M

    2016-06-01

    Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors-reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon-gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology. © The Author(s) 2016.

  6. Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice: dosage and the window of time.

    PubMed

    Kovalenko, Olga A; Azzam, Edouard I; Ende, Norman

    2013-11-01

    The purpose of this study was to evaluate the window of time and dose of human umbilical-cord-blood (HUCB) mononucleated cells necessary for successful treatment of radiation injury in mice. Female A/J mice (27-30 weeks old) were exposed to an absorbed dose of 9-10 Gy of (137)Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 10(8) or 2 × 10(8) HUCB mononucleated cells at 24-52 h after the irradiation. The antibiotic Levaquin was applied 4 h postirradiation. The increased dose of cord-blood cells resulted in enhanced survival. The enhancement of survival in animals that received 2 × 10(8) HUCB mononucleated cells relative to irradiated but untreated animals was highly significant (P < 0.01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24-52 h after exposure.

  7. Studies on acquired resistance to Schistosoma mansoni in mice exposed to X-irradiated cercariae

    PubMed Central

    Perlowagora-Szumlewicz, Alina

    1964-01-01

    In the first part of this paper current information on acquired resistance to schistosomes is reviewed and related to factors which have led to divergent interpretations of experimental results. The author then reports on and discusses experiments performed by her on the development of challenge infections in mice exposed to X-irradiated cercariae of Schistosoma mansoni. While there is some evidence that resistance to S. mansoni may be developed by such exposure, the author considers present findings equivocal and stresses that further research is needed to clarify the situation. ImagesFIG. 2FIG. 3FIG. 4 PMID:14165059

  8. Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis.

    PubMed

    Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi; Ohshima, Yasuhiro; Tago, Fumitoshi; Masada, Ayako; Kojima, Shuji

    2008-07-01

    We previously reported attenuation of autoimmune disease by low-dose gamma-ray irradiation in MRL-lpr/lpr mice. Here, we studied the effect of low-dose gamma-ray irradiation on collagen-induced arthritis (CIA) in DBA/1J mice. Mice were immunized with type II collagen, and exposed to low-dose gamma-rays (0.5 Gy per week for 5 weeks). Paw swelling, redness, and bone degradation were suppressed by irradiation, which also delayed the onset of pathological change and reduced the severity of the arthritis. Production of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6, which play important roles in the onset of CIA, was suppressed by the irradiation. The level of anti-type II collagen antibody, which is essential for the onset of CIA, was also lower in irradiated CIA mice. The population of plasma cells was increased in CIA mice, but irradiation blocked this increase. Since regulatory T cells are known to be involved in suppression of autoimmune disease, the population of CD4(+)CD25(+)Foxp3(+) regulatory T cells was measured. Intriguingly, a significant increase of these regulatory T cells was found in irradiated CIA mice. Overall, our data suggest that low-dose gamma-ray irradiation could attenuate CIA through suppression of pro-inflammatory cytokines and autoantibody production, and induction of regulatory T cells.

  9. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    PubMed

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Suppression of unprimed T and B cells in antibody responses by irradiation-resistant and plastic-adherent suppressor cells in Toxoplasma gondii-infected mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suzuki, Y.; Kobayashi, A.

    1983-04-01

    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 themore » activation of irradiation-resistant and plastic-adherent suppressor cells causes the suppression of both T and B cells in Toxoplasma-infected mice.« less

  11. Molecular mechanisms mediating a deficit in recall of fear extinction in adult mice exposed to cocaine in utero.

    PubMed

    Kabir, Zeeba D; Katzman, Aaron C; Kosofsky, Barry E

    2013-01-01

    Prenatal cocaine exposure has been shown to alter cognitive processes of exposed individuals, presumed to be a result of long-lasting molecular alterations in the brain. In adult prenatal cocaine exposed (PCOC) mice we have identified a deficit in recall of fear extinction, a behavior that is dependent on the medial prefrontal cortex (mPFC) and the hippocampus. While we observed no change in the constitutive expression of brain derived neurotrophic factor (BDNF) protein and mRNA in the mPFC and hippocampus of adult PCOC mice, we observed blunted BDNF signaling in the mPFC of adult PCOC mice after fear extinction compared to the control animals. Specifically, during the consolidation phase of the extinction memory, we observed a decrease in BDNF protein and it's phospho-TrkB receptor expression. Interestingly, at this same time point there was a significant increase in total Bdnf mRNA levels in the mPFC of PCOC mice as compared with controls. In the Bdnf gene, we identified decreased constitutive binding of the transcription factors, MeCP2 and P-CREB at the promoters of Bdnf exons I and IV in the mPFC of PCOC mice, that unlike control mice remained unchanged when measured during the behavior. Finally, bilateral infusion of recombinant BDNF protein into the infralimbic subdivision of the mPFC during the consolidation phase of the extinction memory rescued the behavioral deficit in PCOC mice. In conclusion, these findings extend our knowledge of the neurobiologic impact of prenatal cocaine exposure on the mPFC of mice, which may lead to improved clinical recognition and treatment of exposed individuals.

  12. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice.

    PubMed

    Singh, Vijay K; Wise, Stephen Y; Fatanmi, Oluseyi O; Beattie, Lindsay A; Ducey, Elizabeth J; Seed, Thomas M

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5-12.5 Gy) of (60)Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans.

  13. Germ cell loss induced by 12C6+ ion irradiation in young female mice.

    PubMed

    Zhang, Hong; Zhang, Xu; Yuan, Zhigang; Li, Xiaoda; Li, Wenjian; Zhou, Qingming; Min, Fengling; Xie, Yi; Liu, Bing; Duan, Xin

    2006-06-01

    The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of 12C6+ ion in the Bragg peak or the plateau region. At 10th day after irradiation, ovarian and uterine weights were measured; normal and atretic (identified with the oocyte to be degenerating or absent) primordial, primary and preantral follicles were identified in the largest cross-section of each ovary. Percentage (%) of normal follicles of each developmental stage of oogenesis was calculated. The data showed that compared to controls, there was a dose-related decrease in percentage of normal follicles in each developmental stage. And the weights of ovary and uterus were also reduced with doses of irradiation. Moreover, these effects were much more significant in the Bragg peak region and the region close to the Bragg peak than in the beam's entrance (the plateau region). Radiosensitivity varied in different follicle maturation stages. Primordial follicles, which are thought to be extremely sensitive to ionizing irradiation, were reduced by 86.6%, while primary and preantral follicles reduced only by 72.5% and 61.8% respectively, by exposure with 6 Gy of 12C6+ ion in the Bragg peak region and the region close to the Bragg peak. The data suggested that due to their optimal depth-dose distribution in the Bragg peak region, heavy ions are ones of the best particles for radiotherapy of tumors located next of vital organs or/and surrounded by normal tissues, especially radiosensitive tissues such as gonads.

  14. 16,16-Dimethyl prostaglandin E2 increases survival in mice following irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Walden, T.L. Jr.; Patchen, M.; Snyder, S.L.

    1987-03-01

    16,16-Dimethyl prostaglandin E2 (DiPGE2), a stable analog of PGE2, increases the LD50/30 survival in CD2F1 male mice when given prior to ionizing radiation. Subcutaneous administration of 40 micrograms of DiPGE2 30 min prior to /sup 60/Co gamma irradiation extends the LD50/30 from 9.39 Gy in the control animals to 16.14 Gy in DiPGE2 treated, with a dose reduction factor of 1.72 (95% confidence limits: 1.62, 1.82). The degree of protection is dependent on both the time of administration and the dose of the prostaglandin. Ten micrograms administered 5 min prior to receiving a lethal dose of 10 Gy provides 90%more » survival but only 10% survival if administered 30 min prior to irradiation. Experiments to determine the in vivo concentration of DiPGE2 in organs postinjection show increased levels over time, but these are not correlated with protection. At 30 min after injection, as much as 80% of the DiPGE2 present in the spleen and plasma is unmetabolized. These results suggest that the protection results from the physiologic action of DiPGE2 rather than direct in vivo detoxification of radicals.« less

  15. HZE Radiation Leukemogenesis in Mice

    NASA Astrophysics Data System (ADS)

    Peng, Yuanlin

    Radiation exposure is a risk factor for acute myeloid leukemia (AML). The Leukemogenesis NSCOR was developed to compare this risk for low LET vs HZE radiations as a means to better assess the leukemia risk to astronauts posed by space radiation. Individual projects within the NSCOR explore HZE radiation leukemogenesis in murine model systems and extend the findings to AML in humans. AML sensitive CBA/CaJ mice have been irradiated with 1 GeV 56 Fe particles at NSRL and with 137 Cs gamma-rays at Colorado State University and followed to 800 days of age for the development of AML. Molecular and cytogenetic analyses of HZE- and gamma-induced AML, including assays for chromosomal aberrations, PU.1 deletion, gene expression, array CGH and microsatellite instability are ongoing. Preliminary data indicate that 56 Fe particles are no more effective in inducing AML or shortening lifespan than gamma-rays. Studies designed to address the individual molecular steps in leukemogenesis and determine the effects of radiation and genetic background on each step have been initiated using knockout mice. Deletion of the PU.1 gene on mouse chromosome 2 is a critical step in this murine model of radiation leukemogenesis. Two of the three HZE-induced AMLs that could be assayed and thirteen of fourteen γ-induced AMLs had PU.1 loss as determined by Fluorescence in Situ Hybridization (FISH). We have found that AML sensitive CBA/CaJ mice have a higher incidence of Chr. 2 deletion in bone marrow cells following 56 Fe irradiation than AML resistant C57BL/6 mice. This study is being extended to proton irradiated mice. Our preliminary results indicate that microsatellite instability may be common in HZE irradiated progenitor cells. To determine if these cytogenetic changes can be induced in human myeloid progenitor cells by gamma, proton or HZE irradiation we are generating NOD/SCID mice that have been "humanized" by being transplanted with human hematopoietic stem cells. We are currently

  16. X-rays and photocarcinogenesis in hairless mice.

    PubMed

    Lerche, Catharina M; Philipsen, Peter A; Wulf, Hans Christian

    2013-08-01

    It is well known that excessive X-ray radiation can cause non-melanoma skin cancers. With the increased incidence of sun-related skin cancer there is a need to investigate the combination of sunlight and X-rays. Immunocompetent C3.Cg/TifBomTac mice (n = 298) were divided into 12 groups. Mice were irradiated with 12, 29 or 50 kV X-rays. The mice received a total dose of 45 Gy. They were irradiated with 3 SED simulated solar radiation (SSR) either before or after irradiation with X-rays. The groups irradiated with X-rays alone, 0, 3, 9 and 10 mice (0, 12, 29 and 50 kV, respectively) developed squamous cell carcinoma. In the groups irradiated with SSR after X-rays the development of tumours was significantly faster in the 50 kV group than in the corresponding control group (175 vs. 194 days, p < 0.001). In the groups irradiated with SSR prior to the X-ray radiation the development of tumours was significantly faster in the 29 and the 50 kV groups than in the corresponding control group (175 vs. 202 days, p < 0.001 and 158 vs. 202 days, p < 0.001, respectively). In conclusion, X-ray radiation alone is a weak carcinogen in hairless mice. There is an added carcinogenic effect if X-ray radiation is given on prior sun-exposed skin or if the skin is sun-exposed after X-rays. We still believe that X-ray radiation is a safe and effective therapy for various dermatological diseases but caution should be observed if a patient has severely sun-damaged skin or has a high-risk sun behaviour.

  17. Repeated irradiation from micro-computed tomography scanning at 2, 4 and 6 months of age does not induce damage to tibial bone microstructure in male and female CD-1 mice.

    PubMed

    Sacco, Sandra M; Saint, Caitlin; Longo, Amanda B; Wakefield, Charles B; Salmon, Phil L; LeBlanc, Paul J; Ward, Wendy E

    2017-01-01

    Long-term effects of repeated i n vivo micro-computed tomography (μCT) scanning at key stages of growth and bone development (ages 2, 4 and 6 months) on trabecular and cortical bone structure, as well as developmental patterns, have not been studied. We determined the effect of repetitive μCT scanning at age 2, 4 and 6 months on tibia bone structure of male and female CD-1 mice and characterized developmental changes. At 2, 4 and 6 months of age, right tibias were scanned using in vivo μCT (Skyscan 1176) at one of three doses of radiation per scan: 222, 261 or 460 mGy. Left tibias of the same mice were scanned only at 6 months to serve as non-irradiated controls to determine whether recurrent radiation exposure alters trabecular and cortical bone structure at the proximal tibia. In males, eccentricity was lower ( P <0.05) in irradiated compared with non-irradiated tibias (222 mGy group). Within each sex, all other structural outcomes were similar between irradiated and non-irradiated tibias regardless of dose. Trabecular bone loss occurred in all mice due to age while cortical development continued to age 6 months. In conclusion, repetitive μCT scans at various radiation doses did not damage trabecular or cortical bone structure of proximal tibia in male and female CD-1 mice. Moreover, scanning at 2, 4 and 6 months of age highlight the different developmental time course between trabecular and cortical bone. These scanning protocols can be used to investigate longitudinal responses of bone structures to an intervention.

  18. Neurobehavioral effects of combined prenatal exposure to low-level mercury vapor and methylmercury.

    PubMed

    Yoshida, Minoru; Suzuki, Megumi; Satoh, Masahiko; Yasutake, Akira; Watanabe, Chiho

    2011-01-01

    We evaluated the effects of prenatal exposure to low-level mercury (Hg(0)) or methylmercury (MeHg) as well as combined exposure (Hg(0) + MeHg exposure) on the neurobehavioral function of mice. The Hg(0) exposure group was exposed to Hg(0) at a mean concentration of 0.030 mg/m(3) for 6 hr/day during gestation period. The MeHg exposure was supplied with food containing 5 ppm of MeHg from gestational day 1 to postnatal day 10. The combined exposure group was exposed to both Hg(0) vapor and MeHg according to above described procedure. After delivery, when their offspring reached the age of 8 weeks, behavioral analysis was performed. Open field (OPF) tests of the offspring showed an increase and decrease in voluntary activity in male and female mice, respectively, in the MeHg exposure group. In addition, the rate of central entries was significantly higher in this group than in the control group. The results of OPF tests in the Hg(0) + MeHg exposure group were similar to those in the MeHg exposure group in both males and females. The results in the Hg(0) exposure group did not significantly differ from those in the control group in males or females. Passive avoidance response (PA) tests revealed no significant differences in avoidance latency in the retention trial between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in males or females. Morris water maze tests showed a delay in the latency to reach the platform in the MeHg and Hg(0) + MeHg exposure groups compared with the control group in males but no significant differences between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in females. The results of OPF tests revealed only slight effects of prenatal low-level Hg(0) exposure (0.03 mg/m(3)), close to the no-observable-effect level (NOEL) stated by the WHO (0.025 mg/m(3)), on the subsequent neurobehavioral function. However, prenatal exposure to 5 ppm of MeHg affected exploratory activity in the OPF test, and, in

  19. 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

  20. Long-term effects of prenatal exposure to low levels of gamma rays on open-field activity in male mice.

    PubMed

    Minamisawa, T; Hirokaga, K

    1995-11-01

    The open-field activity of first-generation (F1) hybrid male C57BL/6 x C3H mice irradiated with gamma rays on day 14 of gestation was studied at the following ages: 6-7 months (young), 12-13 months (adult) and 19-20 months (old). Doses were 0.5 Gy or 1.0 Gy. Open-field activity was recorded with a camera. The camera output signal was recorded every second through an A/D converter to a personal computer. The field was divided into 25 8-cm2 units. All recordings were continuous for 60 min. The walking speed of the 1.0-Gy group recorded at 19-20 months was higher than that for the comparably aged control group. The time which the irradiated group, recorded at 19-20 months, spent in the corner fields was high in comparison with the control group at the same age. Conversely, the time spent by the irradiated group in the middle fields when recorded at 19-20 months was shorter than in the comparably aged control group. No effect of radiation was shown for any of the behaviors observed and recorded at 6-7 and 12-13 months. The results demonstrate that such exposure to gamma rays on day 14 of gestation results in behavioral changes which occur at 19-20 months but not at 6-7 or 12-13 months.

  1. Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram

    PubMed Central

    Neigh, Gretchen N.; Nemeth, Christina L; Kelly, Sean D.; Hardy, Emily E.; Bourke, Chase; Stowe, Zachary N.; Owens, Michael J.

    2016-01-01

    Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function. PMID:27422674

  2. Protective effects of HemoHIM on immune and hematopoietic systems against γ-irradiation.

    PubMed

    Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee; Yee, Sung-Tae; Kim, Sung-Ho

    2014-02-01

    We examined the effect of HemoHIM on the protective efficacy of hematopoietic stem cells and on the recovery of immune cells against sublethal doses of ionizing radiation. Two-month-old mice were exposed to γ-rays at a dose of 8, 6.5, or 5 Gy for a30-day survival study, endogenous spleen colony formation, or other experiments, respectively. HemoHIM was injected intraperitoneally before and after irradiation. Our results showed that HemoHIM significantly decreased the mortality of sublethally irradiated mice. The HemoHIM administration decreased the apoptosis of bone marrow cells in irradiated mice. On the other hand, HemoHIM increased the formation of endogenous spleen colony in irradiated mice. In irradiated mice, the recovery of total leukocytes in the peripheral blood and lymphocytes in the spleen were enhanced significantly by HemoHIM. Moreover, the function of B cells, T cells, and NK cells regenerated in irradiated mice were significantly improved by the administration of HemoHIM. HemoHIM showed an ideal radioprotector for protecting hematopoietic stem cells and for accelerating the recovery of immune cells. We propose HemoHIM as a beneficial supplement drug during radiotherapy to alleviate adverse radiation-induced effects for cancer patients. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Tumor induction in mice after local irradiation with single doses of either carbon-ion beams or gamma rays.

    PubMed

    Ando, Koichi; Koike, Sachiko; Ohmachi, Yasushi; Ando, Yutaka; Kobashi, Gen

    2014-12-01

    To determine the dose-dependent relative biological effectiveness (RBE) for tumor prevalence in mice receiving single localized doses to their right leg of either carbon ions (15, 45 or 75 keV/μm) or 137Cs gamma rays. A total of 1647 female C3H mice were irradiated to their hind legs with a localized dose of either reference gamma rays or 15, 45 or 75 keV/μm carbon-ion beams. Irradiated mice were evaluated for tumors twice a month during their three-year life span, and the dimensions of any tumors found were measured with a caliper. The tumor induction frequency was calculated by Kaplan-Meier analysis. The incidence of tumors from 50 Gy of 45 keV/μm carbon ions was marginally higher than those from 50 Gy of gamma rays. However, 60 Gy of 15 keV/μm carbon ions induced significantly fewer tumors than did gamma rays. RBE values of 0.87 + 0.12, 1.29 + 0.08 or 2.06 + 0.39 for lifetime tumorigenesis were calculated for 15, 45 or 75 keV/μm carbon-ion beams, respectively. Fibrosarcoma predominated, with no Linear Energy Transfer (LET)-dependent differences in the tumor histology. Experiments measuring the late effect of leg skin shrinkage suggested that the carcinogenic damage of 15 keV/μm carbon ions would be less than that of gamma rays. We conclude that patients receiving radiation doses to their normal tissues would face less risk of secondary tumor induction by carbon ions of intermediate LET values compared to equivalent doses of photons.

  4. Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome.

    PubMed

    Jaques, Alice M; Collins, Veronica R; Muggli, Evelyne E; Amor, David J; Francis, Ivan; Sheffield, Leslie J; Halliday, Jane L

    2010-06-01

    To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening. State-wide data collections of prenatal screening and diagnostic tests were linked to all Victorian births and pregnancy terminations for birth defects. Overall, 52% of women had a prenatal test (65 692/126 305); screening (44.9%), diagnostic testing (3.9%), or both (3.2%). Uptake of diagnostic testing was 71.4% (2390/3349) after an increased risk screen result, and 2.5% (1381/54 286) after a low risk result. Variation in uptake of diagnostic testing reduced the effectiveness of the screening program by 11.2%: from 87.4% (sensitivity - 125/143) to 76.2% (prenatal diagnoses of Down syndrome - 109/143). In both the increased and low risk groups, uptake was influenced by absolute numerical risk, as well as by the change in numerical risk from a priori risk. This comprehensive follow-up demonstrates clearly that numerical risk is being used to aid in decision making about confirmatory diagnostic testing. Collectively, these fundamental individual decisions will impact on the overall effectiveness of screening programmes for Down syndrome.

  5. Survival of Mice with Gastrointestinal Acute Radiation Syndrome through Control of Bacterial Translocation.

    PubMed

    Suzuki, Fujio; Loucas, Bradford D; Ito, Ichiaki; Asai, Akira; Suzuki, Sumihiro; Kobayashi, Makiko

    2018-07-01

    Macrophages (Mϕ) with the M2b phenotype (Pheno2b-Mϕ) in bacterial translocation sites have been described as cells responsible for the increased susceptibility of mice with gastrointestinal acute radiation syndrome to sepsis caused by gut bacteria. In this study, we tried to reduce the mortality of mice exposed to 7-10 Gy of gamma rays by controlling Pheno2b-Mϕ polarization in bacterial translocation sites. MicroRNA-222 was induced in association with gamma irradiation. Pheno2b-Mϕ polarization was promoted and maintained in gamma-irradiated mice through the reduction of a long noncoding RNA growth arrest-specific transcript 5 (a CCL1 gene silencer) influenced by this microRNA. Therefore, the host resistance of 7-9-Gy gamma-irradiated mice to sepsis caused by bacterial translocation was improved after treatment with CCL1 antisense oligodeoxynucleotide. However, the mortality of 10-Gy gamma-irradiated mice was not alleviated by this treatment. The crypts and villi in the ileum of 10-Gy gamma-irradiated mice were severely damaged, but these were markedly improved after transplantation of intestinal lineage cells differentiated from murine embryonic stem cells. All 10-Gy gamma-irradiated mice given both of the oligodeoxynucleotide and intestinal lineage cells survived, whereas all of the same mice given either of them died. These results indicate that high mortality rates of mice irradiated with 7-10 Gy of gamma rays are reducible by depleting CCL1 in combination with the intestinal lineage cell transplantation. These findings support the novel therapeutic possibility of victims who have gastrointestinal acute radiation syndrome for the reduction of their high mortality rates. Copyright © 2018 by The American Association of Immunologists, Inc.

  6. Relative biological effectiveness of fast neutrons compared with X-rays: Prenatal mortality in the mouse

    NASA Technical Reports Server (NTRS)

    Friedberg, W.; Hanneman, G. D.; Faulkner, D. N.; Darden, E. B., Jr.

    1972-01-01

    The effects of fission neutrons and of X-rays on the mouse zygote are discussed. Seven-week-old virgin mice were allowed a 12-hour mating opportunity beginning at 7:00 P.M. Between 1:30 and 4:00 P.M., except where indicated otherwise, the females which had mated (vaginal plug) during the night were either irradiated or sham-irradiated. At the time of irradiation the zygotes were in a pronuclear stage. Sixteen days later the mice were killed and the uteri dissected. The number of dead embryos, live embryos, and gross anomalies were determined. Dead embryos were classified as to stage of development.

  7. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.

    PubMed

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne; Bianchi, Diana W; Bergmann, Carsten; Borry, Pascal; Chitty, Lyn S; Fellmann, Florence; Forzano, Francesca; Hall, Alison; Henneman, Lidewij; Howard, Heidi C; Lucassen, Anneke; Ormond, Kelly; Peterlin, Borut; Radojkovic, Dragica; Rogowski, Wolf; Soller, Maria; Tibben, Aad; Tranebjærg, Lisbeth; van El, Carla G; Cornel, Martina C

    2015-11-01

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non

  8. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

    PubMed Central

    Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne; Bianchi, Diana W; Bergmann, Carsten; Borry, Pascal; Chitty, Lyn S; Fellmann, Florence; Forzano, Francesca; Hall, Alison; Henneman, Lidewij; Howard, Heidi C; Lucassen, Anneke; Ormond, Kelly; Peterlin, Borut; Radojkovic, Dragica; Rogowski, Wolf; Soller, Maria; Tibben, Aad; Tranebjærg, Lisbeth; van El, Carla G; Cornel, Martina C

    2015-01-01

    This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non

  9. Prenatal care: associations with prenatal depressive symptoms and social support in low-income urban women.

    PubMed

    Sidebottom, Abbey C; Hellerstedt, Wendy L; Harrison, Patricia A; Jones-Webb, Rhonda J

    2017-10-01

    We examined associations of depressive symptoms and social support with late and inadequate prenatal care in a low-income urban population. The sample was prenatal care patients at five community health centers. Measures of depressive symptoms, social support, and covariates were collected at prenatal care entry. Prenatal care entry and adequacy came from birth certificates. We examined outcomes of late prenatal care and less than adequate care in multivariable models. Among 2341 study participants, 16% had elevated depressive symptoms, 70% had moderate/poor social support, 21% had no/low partner support, 37% had late prenatal care, and 29% had less than adequate prenatal care. Women with both no/low partner support and elevated depressive symptoms were at highest risk of late care (AOR 1.85, CI 1.31, 2.60, p < 0.001) compared to women with both good partner support and low depressive symptoms. Those with good partner support and elevated depressive symptoms were less likely to have late care (AOR 0.74, CI 0.54, 1.10, p = 0.051). Women with moderate/high depressive symptoms were less likely to experience less than adequate care compared to women with low symptoms (AOR 0.73, CI 0.56, 0.96, p = 0.022). Social support and partner support were negatively associated with indices of prenatal care use. Partner support was identified as protective for women with depressive symptoms with regard to late care. Study findings support public health initiatives focused on promoting models of care that address preconception and reproductive life planning. Practice-based implications include possible screening for social support and depression in preconception contexts.

  10. Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ribes, Diana; Fuentes, Silvia; Torrente, Margarita

    2010-02-15

    Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided inmore » two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.« less

  11. Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice

    PubMed Central

    Duan, Yabin; Chen, Fan; Yao, Xingchen; Zhu, Junbo; Wang, Cai; Zhang, Juanling; Li, Xiangyang

    2015-01-01

    The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg), L. ruthenicum middle dose (4 g/kg), L. ruthenicum low dose (2 g/kg) treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721) at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05). The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05). L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice. PMID:26193298

  12. Prenatal anxiety effects: A review.

    PubMed

    Field, Tiffany

    2017-11-01

    This review is based on literature on prenatal anxiety effects that was found on Pubmed and PsycINFO for the years 2010-2016. Prenatal anxiety is thought to have distinct features, although it has been measured both by specific prenatal anxiety symptoms as well as by standardized anxiety scales. Its prevalence has ranged from 21 to 25% and it has been predicted by a number of pregnancy - related variables such as unintended pregnancy, demographic variables such as low acculturation and income and psychosocial factors including pessimism and partner tension. Prenatal anxiety effects on pregnancy include increased cortisol levels, pro-inflammatory cytokines, obstetric problems and cesarean section. Effects on the neonate include lower gestational age, prematurity, less insulin-like growth factor in cord blood, less exclusive breast-feeding and less self-regulation during the heelstick procedure. Prenatal anxiety effects continue into infancy and childhood both on physiological development and emotional/mental development. Among the physiological effects are lower vagal activity across the first two years, and lower immunity, more illnesses and reduced gray matter in childhood. Prenatal anxiety effects on emotional/mental development include greater negative emotionality and in infants, lower mental development scores and internalizing problems. Anxiety disorders occur during childhood and elevated cortisol and internalizing behaviors occur during adolescence. Interventions for prenatal anxiety are virtually nonexistent, although stroking (massaging) the infant has moderated the pregnancy - specific anxiety effects on internalizing behaviors in the offspring. The limitations of this literature include the homogeneity of samples, the frequent use of anxiety measures that are not specific to pregnancy, and the reliance on self-report. Nonetheless, the literature highlights the negative, long-term effects of prenatal anxiety and the need for screening and early

  13. Prenatal exposure to bisphenol A and risk of allergic diseases in early life.

    PubMed

    Zhou, Aifen; Chang, Huailong; Huo, Wenqian; Zhang, Bin; Hu, Jie; Xia, Wei; Chen, Zhong; Xiong, Chao; Zhang, Yaqi; Wang, Youjie; Xu, Shunqing; Li, Yuanyuan

    2017-06-01

    Prenatal exposure to bisphenol A (BPA) affects immune system and promotes allergy and asthma in mice, but findings in human studies are limited. We investigated whether prenatal exposure to BPA is associated with increased risk of allergic diseases in infants. We measured BPA concentrations in maternal urine samples collected at delivery from 412 women in Wuhan, China. The occurrence of allergic diseases including eczema and wheeze were assessed at age 6 mo through questionnaires. We used logistic regression to evaluate the association between urinary BPA levels and the risk of allergic diseases. Mothers of infants with allergic diseases had significantly higher urinary BPA levels than those of infants without allergic diseases (median: 2.35 vs. 4.55 µg/l, P = 0.03). Increased risk of infant allergic diseases was associated with creatinine-adjusted maternal urinary BPA concentrations. And this association was limited to females (odds ratio (OR) = 1.36; 95% confidence interval (CI): 1.10-1.79) rather than males. After stratification by maternal age, the association was only significant in infants of mothers who were younger than 25 y old (OR = 1.90; 95% CI: 1.09-3.29). Prenatal exposure to BPA may potentially increase the risk of allergic diseases at very early life in female infants.

  14. 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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Prenatal Genetic Screening Tests

    MedlinePlus

    ... information about the rates of false-positive and false-negative results for each test. What should I consider when deciding whether to have prenatal genetic testing? It is your choice whether to have prenatal testing. Your personal beliefs and values are important factors in the decision ...

  16. UV Irradiation of Skin Enhances Glycolytic Flux and Reduces Migration Capabilities in Bone Marrow-Differentiated Dendritic Cells.

    PubMed

    McGonigle, Terence A; Keane, Kevin N; Ghaly, Simon; Carter, Kim W; Anderson, Denise; Scott, Naomi M; Goodridge, Helen S; Dwyer, Amy; Greenland, Eloise; Pixley, Fiona J; Newsholme, Philip; Hart, Prue H

    2017-09-01

    A systemic immunosuppression follows UV irradiation of the skin of humans and mice. In this study, dendritic cells (DCs) differentiating from the bone marrow (BM) of UV-irradiated mice had a reduced ability to migrate toward the chemokine (C-C motif) ligand 21. Fewer DCs also accumulated in the peritoneal cavity of UV-chimeric mice (ie, mice transplanted with BM from UV-irradiated mice) after injection of an inflammatory stimulus into that site. We hypothesized that different metabolic states underpin altered DC motility. Compared with DCs from the BM of nonirradiated mice, those from UV-irradiated mice produced more lactate, consumed more glucose, and had greater glycolytic flux in a bioenergetics stress test. Greater expression of 3-hydroxyanthranilate 3,4-dioxygenase was identified as a potential contributor to increased glycolysis. Inhibition of 3-hydroxyanthranilate 3,4-dioxygenase by 6-chloro-dl-tryptophan prevented both increased lactate production and reduced migration toward chemokine (C-C motif) ligand 21 by DCs differentiated from BM of UV-irradiated mice. UV-induced prostaglandin E 2 has been implicated as an intermediary in the effects of UV radiation on BM cells. DCs differentiating from BM cells pulsed in vitro for 2 hours with dimethyl prostaglandin E 2 were functionally similar to those from the BM of UV-irradiated mice. Reduced migration of DCs to lymph nodes associated with increased glycolytic flux may contribute to their reduced ability to initiate new immune responses in UV-irradiated mice. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Comparison of the effects of bisphenol A alone and in a combination with X-irradiation on sperm count and quality in male adult and pubescent mice.

    PubMed

    Dobrzyńska, Małgorzata M; Jankowska-Steifer, Ewa A; Tyrkiel, Ewa J; Gajowik, Aneta; Radzikowska, Joanna; Pachocki, Krzysztof A

    2014-11-01

    Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester-styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8-week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X-irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X-rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X-rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X-ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low-dose irradiation showed sometimes protective or additive effects in pubescent mice. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  18. 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. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. A Technique for Murine Irradiation in a Controlled Gas Environment

    PubMed Central

    Walb, M. C.; Moore, J. E.; Attia, A.; Wheeler, K. T.; Miller, M. S.; Munley, M. T.

    2013-01-01

    NASA’s extra-vehicular activities (EVAs) involve exposure to high energy photons while breathing 100% oxygen. Using previously verified mouse models, our laboratory is studying whether low dose irradiation under these hyperoxic conditions could lead to an increase in carcinogenic potential. To simulate the environment astronauts encounter during an EVA, enclosed chambers were constructed that allowed for mouse movement, controlled gas conditions, and uniform radiation dose delivery. Custom-built gas chambers with input/output gas valves and dividers that allowed for uniform gas flow were used to keep 6 unanesthetized mice separated while they were irradiated. The chambers were supplied with 100% oxygen or air using ball valves linked together with T-splitters. A calibrated ion chamber was used to verify the radiation dose distribution across an entire chamber. Mice were placed in the gas environments for 0.5 h, irradiated with a 10 or 18 MV photon beam from a medical linear accelerator, and left in their gas environment for 2 h post-irradiation. We irradiated 200 mice (5 different doses between 0–1000 mGy) under normoxic or 100% oxygen conditions. For the next step of this research, these mice will be euthanized 9 months post-irradiation, and lung tumors will be counted and sized to determine if hyperoxia increases the carcinogenic effect for this model. PMID:22846321

  20. Diet-Induced Obesity Modulates Epigenetic Responses to Ionizing Radiation in Mice

    PubMed Central

    Vares, Guillaume; Wang, Bing; Ishii-Ohba, Hiroko; Nenoi, Mitsuru; Nakajima, Tetsuo

    2014-01-01

    Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6J mice fed a control normal fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (0.75 Gy ×4). Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Using MSP, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6J mice fed a HF diet (irradiated and non-irradiated); Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice) as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6J mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. miR-466e was upregulated in non-irradiated obese mice. In vitro free fatty acid (palmitic acid, oleic acid) administration sensitized AML12 mouse liver cells to ionizing radiation, but the inhibition of miR-466e counteracted this radio-sensitization, suggesting that the modulation of radiation responses by diet-induced obesity might involve miR-466e expression. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations) in mice, possibly in relationship with obesity-induced chronic oxidative stress. PMID:25171162

  1. 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.

  2. Prenatal exposure to LPS leads to long-lasting physiological consequences in male offspring.

    PubMed

    Asiaei, Masoud; Solati, Jalal; Salari, Ali-Akbar

    2011-12-01

    Growing evidence suggests that early life events are critical determinants for disorders later in life. According to a comprehensive number of epidemiological/animal studies, exposure to lipopolysaccharide, causes alteration in pro-inflammatory cytokine levels, hypothalamic-pituitary-adrenal functioning and the hormonal system which may contribute to behavioral and neurological injuries. In this study we investigated the effects of lipopolysaccharide administration on physiological parameters in pregnant dams and their male offspring aged 9 weeks. In gestational Day 10, pregnant mice were injected intrapritoneally with Salmonella enterica lipopolysaccharide to model prenatal exposure to infection. The following results were obtained for offspring from dams stressed during pregnancy: (a) reduced anxiety-related behavior in the elevated plus maze; (b) reduced food and water intake; (c) reduced body weight from birth up to postnatal Day 40. The observed data provide experimental evidence showing that prenatal stress can have complex and long-lasting physiological/behavioral consequences in offspring. Copyright © 2011 Wiley Periodicals, Inc.

  3. 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

  4. Prenatal care services in the public and private arena.

    PubMed

    Blackwell, Deborah A

    2002-12-01

    This exploratory study described the prenatal care experience in the public and private arena from the perceptions of childbearing women using interpretive interactionism. A face-to-face interview comprised of eight open-ended questions was used to obtain pregnant women's perceptions of their prenatal care experience and prenatal care needs. The purposive sample consisted of six women who received private prenatal care and 14 women who received public prenatal care. Five essential elements of the prenatal care experience were identified. Prenatal care was viewed as a cooperative effort between informal self-care and formal care by health professionals. Issues related to individuality and normality were important considerations in the delivery of prenatal care. Controversy exists over the effectiveness of prenatal care in preventing poor outcomes, as the definition of what constitutes adequate prenatal care remains unclear. Advanced practice nurses (APNs) continue to play a pivotal role in the provision of prenatal care services. The expanded knowledge and skills possessed by APNs place them in a pivotal position to develop and implement individualized, developmentally appropriate prenatal care that the women in this study so desperately wanted. In addition, they can assist women in continuing the health promoting behaviors initiated prenatally through out their lifespan.

  5. Prenatal Antidepressants and Autism Spectrum Disorder

    DTIC Science & Technology

    2014-09-01

    citalopram, fluoxetine, bupropion, valproic acid, autism spectrum disorder, developmental disorders, prenatal effects, neurodevelopment , rat, behavior...1 AWARD NUMBER: W81XWH-13-1-0306 TITLE: Prenatal Antidepressants and Autism Spectrum Disorder PRINCIPAL INVESTIGATOR...TYPE Annual 3. DATES COVERED 1Sept 2013-31Aug2014 4. TITLE AND SUBTITLE Prenatal Antidepressants and Autism Spectrum Disorder 5a

  6. Relationship between prenatal care and maternal complications in women with preeclampsia: implications for continuity and discontinuity of prenatal care.

    PubMed

    Liu, Ching-Ming; Chang, Shuenn-Dyh; Cheng, Po-Jen

    2012-12-01

    Prenatal care is associated with better pregnancy outcome and may be a patient safety issue. However, no studies have investigated the types and quality of prenatal care provided in northern Taiwan. This retrospective study assessed whether the hospital-based continuous prenatal care model at tertiary hospitals reduced the risk of perinatal morbidity and maternal complications in pre-eclampsia patients. Of 385 pre-eclampsia patients recruited from among 23,665 deliveries, 198 were classified as patients with little or no prenatal care who received traditional, individualized, and physician-based discontinuous prenatal care (community-based model), and 187 were classified as control patients who received tertiary hospital-based continuous prenatal care. The effects on perinatal outcome were significantly different between the two groups. The cases in the hospital-based care group were less likely to be associated with preterm delivery, low birth weight, very low birth weight, and intrauterine growth restriction. After adjustment of confounding factors, the factors associated with pregnant women who received little or no prenatal care by individualized physician groups were diastolic blood pressure ≥ 105 mmHg, serum aspartate transaminase level ≥ 150 IU/L, and low-birth-weight deliveries. This study also demonstrated the dose-response effect of inadequate, intermediate, adequate, and intensive prenatal care status on fetal birth weight and gestational periods (weeks to delivery). The types of prenatal care may be associated with different pregnancy outcomes and neonatal morbidity. Factors associated with inadequate prenatal care may be predictors of pregnancy outcome in pregnant women with pre-eclampsia. Copyright © 2012. Published by Elsevier B.V.

  7. A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

    PubMed

    Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

    2017-01-01

    Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

  8. Respiratory and intraperitoneal infection of mice with encephalomyocarditis virus: effect of sublethal x-irradiation on host resistance and survival

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bogaerts, W.J.C.; Durville-vanderoord, B.J.

    1975-01-01

    The relationships governing host resistance to viral infection were evaluated in mice following respiratory or peritoneal infection with three strains of encephalomyocarditis (EMC) virus, which were antigenically similar but differed in virulence. Host resistance to each strain was evaluated by determining the mean lethal dose LD50, and the mean infectious dose ID50. The contribution of non-specific resistance to the overall defense of the host was assessed in mice that had received 450 R of x irradiation prior to viral infection. Experimental results indicate that host capacity to resist respiratory infection exceeds that for peritoneal infection for the three EMC strains.more » It is concluded that respiratory inoculation of virus affords better immunization against EMC virus infection than does peritoneal infection. (Author) (GRA)« less

  9. Developmental Implications for Prenatal Exposure to Environmental Toxins: Consumption Habits of Pregnant Women and Prenatal Nicotine Exposure in a Mouse Model

    NASA Astrophysics Data System (ADS)

    Santiago, Sarah Emily

    This dissertation provides a discussion of the effects of maternal consumption of environmental toxins, and will hopefully contribute to the prevention and understanding of developmental disorders and physiological deficits. Developing systems are particularly susceptible to toxic insults, and small changes in utero can result in long-term deficits. Chapter one of this dissertation reviews the potential teratogenicity of nicotine, alcohol, caffeine, MeHg, PCBs, BPA, and tap water contaminants, so as to characterize the current body of literature detailing the effects and implications of prenatal exposure to toxins. In chapter two, research on maternal consumption habits is presented, with an emphasis on commonly-consumed, potentially-teratogenic substances. Occurrences and frequencies of maternal intake of healthy and unhealthy foods, beverages, and medications in a population of predominantly Hispanic women in Southern California were assessed using the Food, Beverage, and Medication Intake Questionnaire (FBMIQ). The described study reveals that a proportion of pregnant women consumed BPA, MeHg, caffeine, and alcohol at varied levels during pregnancy. The following chapters provide an in-depth analysis of the postnatal effects of a particular neuroteratogen, nicotine, which has been shown to impart various detrimental postnatal effects on exposed offspring. A CD-1 mouse model of prenatal nicotine exposure (PNE) was used to analyze aspects of the brain and neocortex that may underly some of the cognitive and behavioral phenotypes seen with PNE. Analyses included postnatal measurements of brain weight, brain widths and lengths, development of neocortical circuitry, and cortical thickness measures. Exposed mice were found to exhibit reduced brain and body weights at birth, a phenotype that recovered by postnatal day 10. No changes in neocortical circuity or thickness in sensory and motor areas were found. PNE also resulted in persistent behavioral effects, including

  10. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rowe, Alexander M.; Brundage, Kathleen M.; Schafer, Rosana

    2006-07-01

    Atrazine is a widely used herbicide applied to corn, sugar and other crops as a broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that prenatal/lactational exposure to atrazine alters adult immune function. Pregnant Balb/c dams were exposed subcutaneously for 21 days via time release pellets to 700 {mu}g per day of atrazine beginning between days 10 and 12 of pregnancy. Prenatal/Lactational exposure caused no overt physical malformations in the offspring and had no effect on the number of litters carried to term or the litter size. Upon reaching early adulthood (approximately 3 months of age), themore » state of their immune system was evaluated. There were no changes in body weight or in the organ to body weight ratio of the spleen. Additionally, no changes were observed in the number of CD8{sup +} T cell, CD4{sup +} T cell, or B220{sup +} B cell subpopulations in the spleen. T cell function was assessed by measuring proliferation and cytolytic activity after in vitro allogeneic stimulation. Male mice which had been prenatally/lactationally exposed to atrazine had an increase in both T cell proliferation and cytolytic activity. The humoral immune response was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP). There was a significant increase in the number of HKSP-specific IgM secreting B cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as atrazine is a widespread environmental contaminant, this immunopotentiation raises concerns that it may potentiate clinical diseases, such as autoimmune disease and hypersensitivity, and needs to be carefully monitored and studied.« less

  11. The effect of ultraviolet radiation on the pathogenesis of Candida albicans in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Denkins, Y.M.

    1991-01-01

    This dissertation addresses questions concerning the effects of UV radiation on the pathogenesis of opportunistic fungal pathogens such as Candida albicans. UV radiation decreased the survival of Candida-infected mice; however, no correlation was found between suppression of the delayed type hypersensitivity (DTH) response and the course of lethal infection. This suggested that DTH was not protective against lethal disease with this organism. UV radiation also changed the persistence of the organism in the internal organs. UV-irradiated, infected animals had increased numbers of Candida in their kidneys compared to non-irradiated mice. Sensitization prior to UV irradiation aided clearance of the organismmore » from the kidneys of UV-irradiated mice. These data show that UV radiation suppresses cell-mediated immunity to Candida albicans in mice and increases mortality of Candida-infected mice. Moreover, the data suggest that an increase in environmental UV radiation could increase the severity of pathogenic infections.« less

  12. Prenatal diagnosis of intra-abdominal cystic lesions by fetal ultrasonography: diagnostic agreement between prenatal and postnatal diagnosis.

    PubMed

    Marchitelli, Giulia; Stirnemann, Julien; Acanfora, Marta Maddalena; Rousseau, Veronique; Salomon, Laurent J; Ville, Yves

    2015-09-01

    The aim of this study was to assess the diagnostic agreement between the prenatal diagnosis of intra-abdominal cystic lesions made by ultrasound examination and the postnatal diagnosis. We reviewed all consecutive cases referred for an anechoic abdominal cyst from 2009 to 2013. Prenatal ultrasound diagnosis was compared with postnatal diagnosis. Prenatal diagnosis was defined as 'correct' if a specific prenatal diagnosis or one of the possible diagnoses was confirmed postnatally, as 'not confirmed' if the postnatal examination revealed no abnormalities and as 'incorrect' if the postnatal diagnosis was different from those suggested prenatally. Seventy-three cases were included, and prenatal diagnoses were made at a median gestational age of 27 weeks (range: 13-36). Correct diagnoses were made in 66 cases (90.4%), including four in which the lesion resolved spontaneously in utero; two diagnoses were 'not confirmed' postnatally, and one was incorrect (a prenatal diagnosis of intestinal duplication was in fact an anorectal malformation). Postnatal diagnosis was not achieved in four cases: None of them required surgery, and clinical follow-up was favorable. The abdominal cysts were isolated in 52 cases (71%) and associated with other anomalies in 21 cases (29%). Aneuploidies were diagnosed in three cases (all trisomy 21). Eight cases underwent termination of pregnancy; there were no fetal deaths and one neonatal death. Postnatal surgery was performed in 30 out of 65 liveborn infants (46.1%). Overall diagnostic agreement between prenatal and postnatal diagnosis of fetal intra-abdominal cystic lesions is high. © 2015 John Wiley & Sons, Ltd.

  13. THE EFFECT OF IRRADIATION OF THE BODY ON THE VIRULENCE OF TYPHOID FEVER BACILLI (in Russian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chekatilo, G.A.

    1958-03-01

    The study was carried out on the pathogenic properties of typhoid fever bacilli from the organism of irradiated (by 100, 200, and 300 r) and non- irradiated (control) guinea pigs. The animals were infected intracutaneously, after irradiation. The pathogenic properties of the microbes, isolated from the cutaneous foci, were examined by intraperitoneal inoculation of white mice with the dose of 15 and 30 million microbes. The total of 156 strains were examined and 762 mice were infected. lt was established that the mortality of mice infected with the bacterial cultures isolated from irradiated guinea pigs was higher than in micemore » infected with cultures isolated from non-irradiated mice (54.5% in the experimental group, as against 38% in the control group). Besides, it was revealed that the longer the microbes remained in the tissues of the macroorganism the greater became their virulence. This property was more pronounced in irradiated animals. Therefore, increase of the microbe virulence in the irradiated orgaaism is connected with the effect of irradiation which acts upon the microbes through the organism. (tr-auth)« less

  14. Restoration of Cognitive Performance in Mice Carrying a Deficient Allele of 8-Oxoguanine DNA Glycosylase by X-ray Irradiation.

    PubMed

    Hofer, Tim; Duale, Nur; Muusse, Martine; Eide, Dag Marcus; Dahl, Hildegunn; Boix, Fernando; Andersen, Jannike M; Olsen, Ann Karin; Myhre, Oddvar

    2018-05-01

    Environmental stressors inducing oxidative stress such as ionizing radiation may influence cognitive function and neuronal plasticity. Recent studies have shown that transgenic mice deficient of DNA glycosylases display unexpected cognitive deficiencies related to changes in gene expression in the hippocampus. The main objectives of the present study were to determine learning and memory performance in C57BL/6NTac 8-oxoguanine DNA glycosylase 1 (Ogg1) +/- (heterozygote) and Ogg1 +/+ (wild type, WT) mice, to study whether a single acute X-ray challenge (0.5 Gy, dose rate 0.457 Gy/min) influenced the cognitive performance in the Barnes maze, and if such differences were related to changes in gene expression levels in the hippocampus. We found that the Ogg1 +/- mice exhibited poorer early-phase learning performance compared to the WT mice. Surprisingly, X-ray exposure of the Ogg1 +/- animals improved their early-phase learning performance. No persistent effects on memory in the late-phase (6 weeks after irradiation) were observed. Our results further suggest that expression of 3 (Adrb1, Il1b, Prdx6) out of in total 35 genes investigated in the Ogg1 +/- hippocampus is correlated to spatial learning in the Barnes maze.

  15. Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex.

    PubMed

    Bose, Sonali; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Di, Qian; Rosa, Maria José; Lee, Alison; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Wright, Robert O; Cohen, Sheldon; Coull, Brent A; Wright, Rosalind J

    2017-12-01

    Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. We implemented Bayesian-distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO 3 - ) on child asthma, accounting for effect modification by sex and stress. Analyses included 752 mother-child dyads. Daily ambient NO 3 - exposure during pregnancy was derived using a hybrid chemical transport (Geos-Chem)/land-use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician-diagnosed asthma by age 6 years. Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7-19 and 33-40 wk gestation), during which increased NO 3 - was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO 3 - across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27-5.39; per interquartile range increase in ln NO 3 - ). Prenatal NO 3 - exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

  17. Protective Effect of Chitosan Oligosaccharides Against Cyclophosphamide-Induced Immunosuppression and Irradiation Injury in Mice.

    PubMed

    Zhai, Xingchen; Yang, Xin; Zou, Pan; Shao, Yong; Yuan, Shoujun; Abd El-Aty, A M; Wang, Jing

    2018-02-01

    Chitosan oligosaccharides (COS), hydrolyzed products of chitosan, was found to display various biological activities. Herein, we assessed the immunostimulatory activity of COS both in in vitro and in vivo studies. In vitro cytotoxicity studies to murine macrophage RAW264.7 revealed that COS is safe even at the maximum tested concentration of 1000 μg/mL. It also stimulates the production of nitric oxide (NO) and tumor necrosis factor (TNF-α) and enhances the phagocytosis in COS-stimulated RAW264.7. We have shown that the COS could significantly (P < 0.05) restore the reduced immune organs indices, phagocytic index, lymphocyte proliferation, natural killer cell activity, and antioxidant enzyme activities in a cyclophosphamide-induced immunosuppressed mice model. COS can also improve the survival rate in irradiation injury mice and significantly (P < 0.05) increased the spleen indices and up-regulates the CD4+/CD8+ ratio in splenocytes. In sum, the aforementioned results suggest that COS might has the potential to be used as an immunostimulatory agent in patients with immune dysfunctions or be a model for functional food development. COS might has the potential to be used as an immunostimulatory agent in patients with immune dysfunctions or be a model for functional food development. © 2018 Institute of Food Technologists®.

  18. Dopamine and serotonin levels following prenatal viral infection in mouse--implications for psychiatric disorders such as schizophrenia and autism.

    PubMed

    Winter, Christine; Reutiman, Teri J; Folsom, Timothy D; Sohr, Reinhard; Wolf, Rainer J; Juckel, Georg; Fatemi, S Hossein

    2008-10-01

    Prenatal viral infection has been associated with neurodevelopmental disorders such as schizophrenia and autism. It has previously been demonstrated that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and middle-late second trimester (E18) administration of influenza virus. Neurochemical analysis following infection on E18 using this model has revealed significantly altered levels of serotonin, 5-hydroxyindoleacetic acid, and taurine, but not dopamine. In order to monitor these different patterns of monoamine expression in exposed offspring in more detail and to see if there are changes in the dopamine system at another time point, pregnant C57BL6J mice were infected with a sublethal dose of human influenza virus or sham-infected using vehicle solution on E16. Male offspring of the infected mice were collected at P0, P14, and P56, their brains removed and cerebellum dissected and flash frozen. Dopamine and serotonin levels were then measured using HPLC-ED technique. When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14. No differences in levels of dopamine were observed in exposed and control mice, although there was a significant decrease in dopamine at P14 and P56 when compared to P0. The present study shows that the serotonergic system is disrupted following prenatal viral infection, potentially modelling disruptions that occur in patients with schizophrenia and autism.

  19. 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)

  20. Prolonged prenatal hypoxia selectively disrupts collecting duct patterning and postnatal function in male mouse offspring.

    PubMed

    Walton, Sarah L; Singh, Reetu R; Little, Melissa H; Bowles, Josephine; Li, Joan; Moritz, Karen M

    2018-04-20

    In this study we investigated whether hypoxia during late pregnancy impairs kidney development in mouse offspring, and also whether this has long-lasting consequences affecting kidney function in adulthood. Hypoxia disrupted growth of the kidney, particularly the collecting duct network, in juvenile male offspring. By mid-late adulthood, these mice developed early signs of kidney disease, notably a compromised response to water deprivation. Female offspring showed no obvious signs of impaired kidney development and did not develop kidney disease, suggesting a underlying protection mechanism from the hypoxia insult. These results help us better understand the long-lasting impact of gestational hypoxia on kidney development and the increased risk of chronic kidney disease. Prenatal hypoxia is a common perturbation to arise during pregnancy, and can lead to adverse health outcomes in later life. The long-lasting impact of prenatal hypoxia on postnatal kidney development and maturation of the renal tubules, particularly the collecting duct system, is relatively unknown. Here, we used a model of moderate chronic maternal hypoxia throughout late gestation (12% O 2 exposure from E14.5 until birth). Histological analyses revealed marked changes in the tubular architecture of male hypoxia-exposed neonates as early as postnatal day 7, with disrupted medullary development and altered expression of Ctnnb1, and Crabp2 (encoding a retinoic acid binding protein). Kidneys of RARElacZ line offspring exposed to hypoxia showed reduced β-galactosidase activity indicating reduced retinoic acid-directed transcriptional activation. Wildtype male mice exposed to hypoxia had an early decline in urine concentrating capacity, evident at 4 months of age. At 12 months of age, hypoxia-exposed male mice displayed a compromised response to a water deprivation challenge which was was correlated with altered cellular composition of the collecting duct and diminished expression of AQP2. There

  1. 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 ...

  2. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: Comparison of pefloxacin, ciprofloxacin, and ofloxacin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brook, I.; Elliott, T.B.; Ledney, G.D.

    Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolatedmore » from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts.« less

  4. Evaluation of the testicular toxicity of prenatal exposure to bisphenol A based on microarray analysis combined with MeSH annotation.

    PubMed

    Tainaka, Hitoshi; Takahashi, Hikari; Umezawa, Masakazu; Tanaka, Hiromitsu; Nishimune, Yoshitake; Oshio, Shigeru; Takeda, Ken

    2012-01-01

    Bisphenol A (BPA) is known to be an endocrine disruptor that affects the development of reproductive system. The aim of the present study was to investigate a group of testicular genes dysregulated by prenatal exposure to BPA. Pregnant ICR mice were treated with BPA by subcutaneous administration on days 7 and 14 of pregnancy. Tissue and blood samples were collected from 6-week-old male offspring. Testes were subjected to gene expression analysis using a testis-specific microarray (Testis2), consisting of 2,482 mouse cDNA clones annotated with Medical Subject Headings (MeSH) terms indicative of testicular components and functions. To interpret the microarray data, we used the MeSH terms significantly associated with the altered genes. As a result, MeSH terms related to androgens and Sertoli cells were extracted in BPA-treated groups. Among the genes related to Sertoli cells, downregulation of Msi1h, Ncoa1, Nid1, Hspb2, and Gata6 were detected in the testis of mice treated with BPA (twice administered 50 mg/kg). The MeSH terms associated with this group of genes may provide useful means to interpret the testicular toxicity of BPA. This article concludes that prenatal BPA exposure downregulates expression of genes associated with Sertoli cell function and affects the reproductive function of male offspring. Additionally, a method using MeSH to extract a group of genes was useful for predicting the testicular and reproductive toxicity of prenatal BPA exposure.

  5. 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis

    PubMed Central

    Grace, Marcy B.; Singh, Vijay K.; Rhee, Juong G.; Jackson, William E.; Kao, Tzu-Cheg; Whitnall, Mark H.

    2012-01-01

    The steroid androst-5-ene-3ß,17ß-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-κB (NFκB)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not well understood. The aim of this study was to investigate the mechanisms of action of 5-AED administered subcutaneously (s.c.) to mice 24 h before total body γ- or X-irradiation (TBI). We used neutralizing antibodies, flow cytometric functional assays of circulating innate immune cells, analysis of expression of genes related to cell cycle progression, DNA repair and apoptosis, and assessment of DNA strand breaks with halo-comet assays. Neutralization experiments indicated endogenous G-CSF but not IL-6 was involved in survival enhancement by 5-AED. In keeping with known effects of G-CSF on the innate immune system, s.c. 5-AED stimulated phagocytosis in circulating granulocytes and oxidative burst in monocytes. 5-AED induced expression of both bax and bcl-2 in irradiated animals. Cdkn1a and ddb1, but not gadd45a expression, were upregulated by 5-AED in irradiated mice. S.c. 5-AED administration caused decreased DNA strand breaks in splenocytes from irradiated mice. Our results suggest 5-AED survival enhancement is G-CSF-dependent, and that it stimulates innate immune cell function and reduces radiation-induced DNA damage via induction of genes that modulate cell cycle progression and apoptosis. PMID:22843381

  6. 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis.

    PubMed

    Grace, Marcy B; Singh, Vijay K; Rhee, Juong G; Jackson, William E; Kao, Tzu-Cheg; Whitnall, Mark H

    2012-11-01

    The steroid androst-5-ene-3ß,17ß-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-κB (NFκB)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not well understood. The aim of this study was to investigate the mechanisms of action of 5-AED administered subcutaneously (s.c.) to mice 24 h before total body γ- or X-irradiation (TBI). We used neutralizing antibodies, flow cytometric functional assays of circulating innate immune cells, analysis of expression of genes related to cell cycle progression, DNA repair and apoptosis, and assessment of DNA strand breaks with halo-comet assays. Neutralization experiments indicated endogenous G-CSF but not IL-6 was involved in survival enhancement by 5-AED. In keeping with known effects of G-CSF on the innate immune system, s.c. 5-AED stimulated phagocytosis in circulating granulocytes and oxidative burst in monocytes. 5-AED induced expression of both bax and bcl-2 in irradiated animals. Cdkn1a and ddb1, but not gadd45a expression, were upregulated by 5-AED in irradiated mice. S.c. 5-AED administration caused decreased DNA strand breaks in splenocytes from irradiated mice. Our results suggest 5-AED survival enhancement is G-CSF-dependent, and that it stimulates innate immune cell function and reduces radiation-induced DNA damage via induction of genes that modulate cell cycle progression and apoptosis.

  7. Human prenatal diagnosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Filkins, K.; Russo, J.F.

    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,more » 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.« less

  8. Neurocognitive and neurodevelopmental impact of prenatal methamphetamine exposure: A comparison study of prenatally exposed children with nonexposed ADHD peers.

    PubMed

    Brinker, Michael J; Cohen, Jodie G; Sharrette, Johnathan A; Hall, Trevor A

    2017-11-29

    Prenatal methamphetamine exposure has become an increasingly pervasive concern, especially in rural-based populations and populations of lower socioeconomic status. While research has begun to highlight the effects of prenatal methamphetamine exposure, the long-term impact of this exposure remains an under-investigated topic. This study attempts to investigate the neurocognitive and neurodevelopmental effects of prenatal methamphetamine exposure by comparing the index and full-scale IQ scores on the WISC-IV between a sample of clinically referred children prenatally exposed to methamphetamine (N = 80) and a sample of clinically referred nonexposed children diagnosed with ADHD (N = 44). Children prenatally exposed to methamphetamine showed significantly lower scores on all WISC-IV domains when compared to peers with ADHD. When taking into account polysubstance exposure to alcohol, these differences remained statistically significant, with the exception of the Processing Speed Index (PSI); children reported to have been prenatally exposed to methamphetamine and to alcohol (PME) remained below ADHD peers on all other WISC-IV index scores. Within the prenatally exposed sample, regression analyses indicated that age was a significant negative predictor of PSI scores. Overall findings suggest that prenatal methamphetamine exposure is associated with a notable cognitive impact independent of polysubstance exposure to alcohol, and that the impact of this exposure on processing speed skills may become more pronounced with age.

  9. Genome-Wide Alteration of Histone H3K9 Acetylation Pattern in Mouse Offspring Prenatally Exposed to Arsenic

    PubMed Central

    Cronican, Andrea A.; Fitz, Nicholas F.; Carter, Alexis; Saleem, Muzamil; Shiva, Sruti; Barchowsky, Aaron; Koldamova, Radosveta; Schug, Jonathan; Lefterov, Iliya

    2013-01-01

    Chronic exposure to arsenic in drinking water, especially in utero or perinatal exposure, can initiate neurological and cognitive dysfunction, as well as memory impairment. Several epidemiological studies have demonstrated cognitive and learning deficits in children with early exposure to low to moderate levels of arsenic, but pathogenic mechanisms or etiology for these deficits are poorly understood. Since in vivo studies show a role for histone acetylation in cognitive performance and memory formation, we examined if prenatal exposure to arsenic causes changes in the epigenomic landscape. We exposed C57Bl6/J mice to 100 μg/L arsenic in the drinking water starting 1 week before conception till birth and applied chromatin immunoprecipitation followed by high-throughput massive parallel sequencing (ChIP-seq) to evaluate H3K9 acetylation pattern in the offspring of exposed and control mice. Arsenic exposure during embryonic life caused global hypo-acetylation at H3K9 and changes in functional annotation with highly significant representation of Krüppel associated box (KRAB) transcription factors in brain samples from exposed pups. We also found that arsenic exposure of adult mice impaired spatial and episodic memory, as well as fear conditioning performance. This is the first study to demonstrate: a) genome wide changes in H3K9 acetylation pattern in an offspring prenatally exposed to arsenic, and b) a connection between moderate arsenic exposure and cognitive impairment in adult mice. The results also emphasize the applicability of Next Generation Sequencing methodology in studies aiming to reveal the role of environmental factors, other than dietary restriction, in developmental reprogramming through histone modifications during embryonic development. PMID:23405071

  10. The transplantation of neural stem cells and predictive factors in hematopoietic recovery in irradiated mice.

    PubMed

    Filip, S; Mokrý, J; Karbanová, J; Vávrová, J; Vokurková, J; Bláha, M; English, D

    2005-04-01

    A number of surprising observations have shown that stem cells, in suitable conditions, have the ability to produce a whole spectrum of cell types, regardless, whether these tissues are derived from the same germ layer or not. This phenomenon is called stem cell plasticity, which means that tissue-specific stem cells are mutually interchangeable. In our experiments, as a model, we used neural stem cells (NSCs) harvested from fetal (E14-15) neocortex and beta-galactosidase positive. In the first experiment we found that on days 12 and 30 after sub-lethal irradiation (LD 8.5 Gy) and (beta-galactosidase(+)) NSCs transplantation all mice survived, just as the group with bone marrow transplantation. Moreover, the bone marrow of mice transplanted NSCs contained the number of CFU-GM colonies with beta-galactosidase(+) cells which was as much as 50% higher. These differences were statistically significant, p<0.001. In the second experiment, we studied kinetics of (beta-galactosidase(+)) NSCs after their transplantation to sub-lethally irradiated mice. Histochemistry of tissues was performed on days 12 and 30 post-transplantation, and beta-galactosidase(+) cells were detected with the help of histochemical examination of removed tissues (lung, liver, spleen, thymus, and skeletal muscle). In tissues removed on day 12 post-transplantation, we found a significantly higher number of beta-galactosidase(+) cells in the spleen and thymus on day 30. While we presumed the presence beta-galactosidase(+) cells in the spleen, as spleen and reticuloendothelial system represent an important retaining system for different cell types, the presence of beta-galactosidase(+) cells in the thymus was rather surprising but very interesting. This indicates a certain mutual and close interconnection of transplanted stem cells and immune system in an adult organism. In the third experiment, we verified the mutual interchange of Sca-1 surface antigen in the bone marrow cells and NSCs before

  11. 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

  12. 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.

  13. An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome.

    PubMed

    Guedj, Faycal; Pennings, Jeroen LA; Massingham, Lauren J; Wick, Heather C; Siegel, Ashley E; Tantravahi, Umadevi; Bianchi, Diana W

    2016-09-02

    Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls, and embryonic day 15.5 forebrains from Ts1Cje, Ts65Dn, and Dp16 mice. The new datasets were compared to other publicly available datasets from humans with DS. We used the human Connectivity Map (CMap) database and created a murine adaptation to identify FDA-approved drugs that can rescue affected pathways. USP16 and TTC3 were dysregulated in all affected human cells and two mouse models. DS-associated pathway abnormalities were either the result of gene dosage specific effects or the consequence of a global cell stress response with activation of compensatory mechanisms. CMap analyses identified 56 molecules with high predictive scores to rescue abnormal gene expression in both species. Our novel integrated human/murine systems biology approach identified commonly dysregulated genes and pathways. This can help to prioritize therapeutic molecules on which to further test safety and efficacy. Additional studies in human cells are ongoing prior to pre-clinical prenatal treatment in mice.

  14. The effect of prenatal education curriculum on mother's prenatal examination utilization, delivery mode and recovery status: a cross-sectional survey in China.

    PubMed

    Shi, Yuhui; Wang, Dongxu; Yuan, Yanfei; Jiang, Ying; Zeng, Qingqi; Chang, Chun

    2015-11-01

    To examine the participation, implementation, and effect of the prenatal education curriculum provided by hospitals in China, and to provide evidence for the improvement of prenatal education. A cross-sectional survey was conducted in the hospitals in Hunan Province, China. Mothers aged 20-45 years who had given birth between 1 May 2011 and 1 May 2012 and not diagnosed with pregnancy-related complications were invited to participate in the study. A self-administered, structured questionnaire was used to examine the effect of prenatal education curriculum on prenatal examination utilization, delivery mode, and recovery status from delivery. Among the total 604 respondents, only 175 (29.1 %) surveyed mothers participated in prenatal education curriculum provided by hospitals during their latest delivery. These mothers had a higher rate of attending all the required prenatal examinations (57.9 vs. 48.3 %), and a higher rate of recovering very well and well (80 vs. 73.7 %) from the latest delivery, than those who did not participate in prenatal education curriculum (P < 0.05). However, there was no statistical difference in the delivery mode between mothers who participated and those who did not participate in the prenatal education curriculum provided by hospitals. Prenatal education is indispensable for the improvement of maternal and child health, and thus should be advocated. In China, a standard and convenient specification prenatal education curriculum provided by hospitals and their doctors is appropriated for providing prenatal education to pregnant women.

  15. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    PubMed

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

  16. Prenatal Testing: MedlinePlus Health Topic

    MedlinePlus

    ... Dept. of Health and Human Services Office on Women's Health Start Here Prenatal Tests (Nemours Foundation) Also in Spanish Prenatal Tests (March of Dimes Birth Defects Foundation) Also in Spanish ...

  17. Cactus cladodes (Opuntia humifusa) extract minimizes the effects of UV irradiation on keratinocytes and hairless mice.

    PubMed

    Park, Kyungmi; Choi, Hyeon-Son; Hong, Yang Hee; Jung, Eun Young; Suh, Hyung Joo

    2017-12-01

    Cactus cladodes [Opuntia humifusa (Raf.) Raf. (Cactaceae)] is one of the cactus genera, which has long been used as a folk medicine for skin disorders. This study investigated the skincare potential of cactus cladodes extract (OHE), including its ability to regulate ultraviolet B (UVB)-induced hyaluronic acid (HA) production. Gene expression levels of hyaluronic acid synthases (HASs) and hyaluronidase (HYAL) were measured in UVB-irradiated HaCaT cells with OHE treatment (10, 25, 50, 100 μg/mL) by real-time polymerase chain reaction (PCR). The HA content was analyzed in hairless mice (SKH-1, male, 6 weeks old) treated with OHE for 10 weeks by using enzyme-linked immunosorbent assay (ELISA). Haematoxylin and eosin (H&E) and immunohistological staining were performed to examine epidermal thickness and levels of CD44 and hyaluronic acid-binding protein (HABP). HA synthases (HAS,1 HAS2, HAS3) mRNA levels were increased by 1.9-, 2.2- and 1.6-fold, respectively, with OHE treatment (100 μg/mL), while UVB-induced increase of hyaluronidase mRNA significantly decreased by 35%. HA content in animal was decreased from 42.9 to 27.1 ng/mL by OHE treatment. HAS mRNA levels were decreased by 39%, but HYAL mRNA was increased by 50% in OHE group. CD44 and HABP levels, which were greatly increased by UVB-irradiation, were reduced by 64 and 60%, respectively. Epidermal thickness, transepidermal water loss (TEWL), and erythema formation was also decreased by 45 (45.7 to 24.2 μm), 48 (48.8 to 25 g/h/m 2 ) and 33%, respectively. OHE protects skin from UVB-induced skin degeneration in HaCaT cells and hairless mice.

  18. Prenatal and Postnatal Management of Hydronephrosis

    PubMed Central

    Rao, Pravin K.; Palmer, Jeffrey S.

    2009-01-01

    The majority of pregnant women in the U.S. undergo prenatal ultrasonography and approximately 0.5% of these examinations will detect fetal malformations. Up to one-half of these abnormalities include the genitourinary system and the most common urological finding is hydronephrosis. Some conditions associated with prenatal hydronephrosis portend a poor prognosis, while others can follow a fairly benign course. This review focuses on the definition and prenatal assessment of hydronephrosis, fetal intervention, and postnatal management. PMID:19618087

  19. Effects of Galla chinensis extracts on UVB-irradiated MMP-1 production in hairless mice.

    PubMed

    Sun, Zheng-wang; Hwang, Eunson; Lee, Hyun Ji; Lee, Tae Youp; Song, Hyun Geun; Park, Sang-Yong; Shin, Heon-Sub; Lee, Don-Gil; Yi, Tae Hoo

    2015-01-01

    Galla chinensis (GAC) is a natural traditional Chinese medicine that has been widely used in folk medicine. Although GAC compounds (mainly gallic acid and methyl gallate) possess strong antiviral, antibacterial, anticancer, and antioxidant activities, there is no report regarding topical or oral administration of GAC compounds on UVB irradiation-induced photoaging in hairless mice (SKH: HR-1). In the present study, we examined cell viability, intracellular reactive oxygen species (ROS), matrix metalloproteinase-1 (MMP-1), and interleukin-6 (IL-6) in skin fibroblasts and keratinocytes induced by UVB in vitro. We also studied skin damage by measuring skin thickness, elasticity, wrinkling and levels of protein MMP-1, elastin, procollagen type I, and transforming growth factor-β1 (TGF-β1) in hairless mouse skin chronically irradiated by UVB in vivo. GAC treatment significantly prevented skin photoaging by reducing the levels of ROS, MMP-1, and IL-6 and promoting production of elastin, procollagen type I, and TGF-β1. According to the results of H&E staining and Masson's trichrome staining, GAC reduced skin thickness and wrinkle formation while it increased skin elasticity. The effects of GAC on UVB-induced skin photoaging may be due to suppressed MMP-1 expression. These findings could be referenced for the development of new agents that target UVB-induced photoaging.

  20. Invasive prenatal diagnosis of fetal thalassemia.

    PubMed

    Li, Dong-Zhi; Yang, Yan-Dong

    2017-02-01

    Thalassemia is the most common monogenic inherited disease worldwide, affecting individuals originating from many countries to various extents. As the disease requires long-term care, prevention of the homozygous state presents a substantial global disease burden. The comprehensively preventive programs involve carrier detections, molecular diagnostics, genetic counseling, and prenatal diagnosis. Invasive prenatal diagnosis refers to obtaining fetal material by chorionic villus sampling (CVS) at the first trimester, and by amniocentesis or cordocentesis at the second trimester. Molecular diagnosis, which includes multiple techniques that are aimed at the detection of mutations in the α- or β-globin genes, facilitates prenatal diagnosis and definitive diagnosis of the fetus. These are valuable procedures for couples at risk, so that they can be offered options to have healthy offspring. According to local practices and legislation, genetic counseling should accompany the invasive diagnostic procedures, DNA testing, and disclosure of the results. The most critical issue in any type of prenatal molecular testing is maternal cell contamination (MCC), especially when a fetus is found to inherit a particular mutation from the mother. The best practice is to perform MCC studies on all prenatal samples. The recent successful studies of fetal DNA in maternal plasma may allow future prenatal testing that is non-invasive for the fetus and result in significant reduction of invasive diagnostic procedures. Copyright © 2016. Published by Elsevier Ltd.

  1. Differences in irradiation susceptibility and turnover between mucosal and connective tissue-type mast cells of mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fukuzumi, T.; Waki, N.; Kanakura, Y.

    Although precursors of mast cells are derived from the bone marrow, phenotypes of mast cells are influenced by the tissues in which final differentiation occurs. Connective tissue-type mast cells (CTMC) and mucosal mast cells (MMC) are different in morphological, biochemical, immunological, and functional criteria. The purpose of the present study was to obtain information about the differentiation process of MMC. First, we compared changes in irradiation susceptibility in mice during the differentiation process of CTMC and MMC. The decrease in irradiation susceptibility was remarkable in the CTMC differentiation process, but it was moderate in that of MMC. Some morphologically identifiablemore » CTMC in the peritoneal cavity had proliferative potential and were highly radioresistant, whereas such a radioresistant population of MMC was not detectable in the gastric mucosa. Second, we estimated the turnover of CTMC and MMC by determining the proportion of mast cells that were labeled with continuously administered bromodeoxyuridine. The turnover of MMC was significantly faster than that of CTMC. The absence of the radioresistant mast cell population in the gastric mucosa appeared to be related to the short life span of MMC.« less

  2. Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure.

    PubMed

    Kirsten, Thiago B; Queiroz-Hazarbassanov, Nicolle; Bernardi, Maria M; Felicio, Luciano F

    2015-06-01

    Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS),which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism.We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia.Materials and methods:We evaluated the effects of LPS and zinc on female reproductive performance. Communication,which is impaired in autism,was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker.Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction.Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls.Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments.The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway.

  3. Regulation of cellular marker modulated upon irradiation of low power laser light in burn injured mice

    NASA Astrophysics Data System (ADS)

    Rathnakar, Bharath; Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Chandra, Subhash; Rai, Sharada; Mahato, Krishna Kishore

    2016-12-01

    The present study intends to understand the importance of cellular marker in tissue regeneration regulated upon irradiation of low power laser light in burn inflicted mice. Under anesthetic conditions, the thermal injury was induced on Swiss albino mice of either sex. Following injury, the animals were randomly divided into three groups; i. e., un-illuminated control, the group treated with 5% Povidone iodine (reference standard) and single exposure of 3 J/cm2 (830 nm). Burn tissue samples from each group were excised at day 6 post burn injury upon euthanization and used for histological and immunohistochemical analysis. Haematoxylin and Eosin (H and E) staining was performed on the selected sections to asses proliferation and angiogenesis at day 6 post-injury. For immunohistochemical analysis, tissue sections from all the three treatment groups on day 6 were stained using specific antibody against Proliferating cell nuclear antigen (PCNA). The results of the histological and immunohistochemical analysis showed improved tissue restoration in animals treated with optimal laser influence as compared to un-illuminated controls. The findings of present study clearly demonstrated the beneficial effects of 830 nm laser in burn wound healing and its influence in regulating the cellular marker.

  4. Should prenatal hydronephrosis that resolves before birth be followed postnatally? Analysis and comparison to persistent prenatal hydronephrosis.

    PubMed

    Scarborough, Patrick L; Ferrara, Elizabeth; Storm, Douglas W

    2015-09-01

    Prenatal ultrasonography has greatly enhanced detection of congenital genitourinary abnormalities. However, although persistent prenatal hydronephrosis (PPH) is typically imaged and followed postnatally, it remains unclear if prenatal hydronephrosis that resolves in utero (RPH) should be similarly managed. We determined postnatal abnormalities associated with RPH and compared these to those associated with PPH. We performed a retrospective review of all consecutive patients evaluated for prenatal hydronephrosis over 24 months. Patients were followed prenatally with serial ultrasounds and postnatally with ultrasonography and a voiding cystourethrogram. Of the consecutive 165 patients enrolled in the study, 72 had RPH. The average prenatal anterior-posterior renal pelvis length was significantly longer in patients with PPH (5.5 mm) than in those with RPH (4.9 mm) (p = 0.01). Recurrent postnatal hydronephrosis occurred in 44% of patients with RPH, with eventual resolution in 34% of those affected. In comparison, 29% of PPH cases resolved postnatally. Mean time to resolution was statistically shorter for PPH (116 days) than for RPH (175 days) (p = 0.01). Seven PPH patients required surgery, while no RPH patients needed intervention (difference was statistically significant). A significant number of RPH children had postnatal hydronephrosis. Despite a slower resolution time, no children with RPH required intervention. Although RPH may recur postnatally, the significantly lower chance of intervention being required suggests that these children may not require postnatal imaging.

  5. DELETERIOUS EFFECTS OF HIGH FAT DIETS ON SURVIVAL TIME OF X-IRRADIATED MICE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ershoff, B.H.

    1961-02-01

    The effects of multiple sublethal doses of total body x-irradiation were determined on survival time of male mice fed either a purified fat-free ration or a similar diet supplemented with 2, 10, 20, or 30% cottonseed oil, marganine fat, or butter fat. The effects obtnined were dependent on the amount and source of dietary fat. At levels of 2 or 10% of the diet, cottonseed oil and margarine fat increased survival time over that on the fat-free ration. When these fats were fed at higher levels (i.e., 20 or 30% of the diet), however, survival time was decreased below thatmore » obtained at the lower levels of supplementation. In contrast to the results obtained with the cottonseed oil or margarine fat supplements, butter fat at levels of 2 or 10% of the diet did not prolong survival over that on the fat-free ration; nor did it decrease survival time when fed at higher levels in the diet. (auth)« less

  6. Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep

    PubMed Central

    Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit

    2015-01-01

    Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insulin sensitizer, rosiglitazone; 5) prenatal T and postnatal flutamide; 6) prenatal T and postnatal rosiglitazone; and 7) prenatal T and postnatal metformin. Prenatal treatments spanned 30–90 days of gestation and postnatal treatments began at approximately 8 weeks of age and continued throughout. Blood samples were taken twice weekly, beginning at approximately 12 weeks of age to time puberty. Two-hour samples after the synchronization with prostaglandin F2α were taken for 120 hours to characterize LH surge dynamics at 7 and 19 months of age. Prenatal T females entered puberty earlier than controls, and all interventions prevented this advancement. Prenatal T reduced the percentage of animals having LH surge, and females that presented LH surge exhibited delayed timing and dampened amplitude of the LH surge. Prenatal androgen antagonist, but not other interventions, restored LH surges without normalizing the timing of the surge. Normalization of pubertal timing with prenatal/postnatal androgen antagonist and insulin sensitizer interventions suggests that pubertal advancement is programmed by androgenic actions of T involving insulin as a mediary. Restoration of LH surges by cotreatment with androgen antagonist supports androgenic programming at the organizational level. PMID:25919188

  7. Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep.

    PubMed

    Padmanabhan, Vasantha; Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit

    2015-07-01

    Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insulin sensitizer, rosiglitazone; 5) prenatal T and postnatal flutamide; 6) prenatal T and postnatal rosiglitazone; and 7) prenatal T and postnatal metformin. Prenatal treatments spanned 30-90 days of gestation and postnatal treatments began at approximately 8 weeks of age and continued throughout. Blood samples were taken twice weekly, beginning at approximately 12 weeks of age to time puberty. Two-hour samples after the synchronization with prostaglandin F2α were taken for 120 hours to characterize LH surge dynamics at 7 and 19 months of age. Prenatal T females entered puberty earlier than controls, and all interventions prevented this advancement. Prenatal T reduced the percentage of animals having LH surge, and females that presented LH surge exhibited delayed timing and dampened amplitude of the LH surge. Prenatal androgen antagonist, but not other interventions, restored LH surges without normalizing the timing of the surge. Normalization of pubertal timing with prenatal/postnatal androgen antagonist and insulin sensitizer interventions suggests that pubertal advancement is programmed by androgenic actions of T involving insulin as a mediary. Restoration of LH surges by cotreatment with androgen antagonist supports androgenic programming at the organizational level.

  8. Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species.

    PubMed

    Villasana, Laura E; Weber, Sydney; Akinyeke, Tunde; Raber, Jacob

    2016-09-01

    Apolipoprotein E (apoE), involved in cholesterol and lipid metabolism, also influences cognitive function and injury repair. In humans, apoE is expressed in three isoforms. E4 is a risk factor for age-related cognitive decline and Alzheimer's disease, particularly in women. E4 might also be a risk factor for developing behavioral and cognitive changes following (56) Fe irradiation, a component of the space environment astronauts are exposed to during missions. These changes might be related to enhanced generation of reactive oxygen species (ROS). In this study, we compared the behavioral and cognitive performance of sham-irradiated and irradiated wild-type (WT) mice and mice expressing the human E3 or E4 isoforms, and assessed the generation of ROS in hippocampal slices from these mice. E4 mice had greater anxiety-like and conditioned fear behaviors than WT mice, and these genotype differences were associated with greater levels of ROS in E4 than WT mice. The greater generation of ROS in the hippocampus of E4 than WT mice might contribute to their higher anxiety levels and enhanced fear conditioning. In E4, but not WT, mice, phorbol-12-myristate-13-acetate-treated hippocampal slices showed more dihydroxy ethidium oxidation in sham-irradiated than irradiated mice and hippocampal heme oxygenase-1 levels were higher in irradiated than sham-irradiated E4 mice. Mice with apolipoprotein E4 (E4), a risk factor for Alzheimer's disease, have greater anxiety-like and conditioned fear behaviors than wild-type (WT) mice. Generation of reactive oxygen species (ROS, in red) 3 months following (56) Fe irradiation, a component of the space environment astronauts are exposed to, is more pronounced in the hippocampus of E4 than WT mice. In E4, but not WT, mice, hippocampal levels of the oxidative stress-relevant marker heme oxygenase-1 are higher in irradiated than sham-irradiated E4 mice. © 2016 International Society for Neurochemistry.

  9. Prenatal Stress as a Risk-and an Opportunity-Factor.

    PubMed

    Hartman, Sarah; Freeman, Sara M; Bales, Karen L; Belsky, Jay

    2018-04-01

    Two separate lines of research indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences. Therefore, prenatal stress may increase sensitivity to the rearing environment. We tested this hypothesis by manipulating prenatal stress and rearing-environment quality, using a cross-fostering paradigm, in prairie voles. Results showed that prenatally stressed voles, as adults, displayed the highest behavioral and physiological reactivity when cross-fostered to low-contact (i.e., low-quality) rearing but the lowest behavioral and physiological reactivity when cross-fostered to high-contact (i.e., high-quality) rearing; non-prenatally stressed voles showed no effect of rearing condition. Additionally, while neither prenatal stress nor rearing condition affected oxytocin receptor binding, prenatally stressed voles cross-fostered to high-contact rearing showed the highest vasopressin-1a receptor binding in the amygdala. Results indicate that prenatal stress induces greater environmental sensitivity, making it both a risk and an opportunity factor.

  10. Prenatal counselling for congenital anomalies: a systematic review.

    PubMed

    Marokakis, Sarah; Kasparian, Nadine A; Kennedy, Sean E

    2016-07-01

    Prenatal diagnosis of fetal anomalies may arouse fear, anxiety and distress in parents, and counselling may assist parents to cope with the diagnosis. This systematic review aimed to (1) synthesise the evidence on the impact of non-genetic, prenatal counselling after fetal diagnosis of a congenital anomaly on parental knowledge and psychological adjustment and (2) identify parents' preferences for the timing and format of counselling. Five electronic databases were systematically searched to identify studies assessing prenatal counselling provided to parents after prenatal diagnosis of one or more structural congenital anomalies. Data were extracted using predefined data forms, according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and synthesised. Twenty four articles were included for review; most articles reported results of retrospective surveys and the quality of included studies was variable. Only three studies assessed parental anxiety, and each reported a significant decrease in anxiety following prenatal counselling. Parents expressed a preference for counselling on all aspects of their baby's anomaly as soon as possible after prenatal diagnosis, and desired written, visual and web-based information resources, and support group contacts. Although prenatal counselling reduced parental anxiety, further research is needed to adequately assess the impact of prenatal counselling on other psychological outcomes. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  11. Functional modifications of macrophage activity after sublethal irradiation. [Toxoplasma gondii

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytesmore » exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin.« less

  12. GESTATIONAL PFOA EXPOSURE OF MICE IS ASSOCIATED WITH ALTERED MAMMARY GLAND DEVELOPMENT IN DAMS AND FEMALE OFFSPRING

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA), a ubiquitous and persistent synthetic compound, has been detected in human serum. Previous studies in mice linked prenatal PFOA exposure to increased neonatal mortality and decreased pup weights, in a dose responsive manner. To determine whether dev...

  13. [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.

  14. 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)

  15. Medicaid reimbursement, prenatal care and infant health.

    PubMed

    Sonchak, Lyudmyla

    2015-12-01

    This paper evaluates the impact of state-level Medicaid reimbursement rates for obstetric care on prenatal care utilization across demographic groups. It also uses these rates as an instrumental variable to assess the importance of prenatal care on birth weight. The analysis is conducted using a unique dataset of Medicaid reimbursement rates and 2001-2010 Vital Statistics Natality data. Conditional on county fixed effects, the study finds a modest, but statistically significant positive relationship between Medicaid reimbursement rates and the number of prenatal visits obtained by pregnant women. Additionally, higher rates are associated with an increase in the probability of obtaining adequate care, as well as a reduction in the incidence of going without any prenatal care. However, the effect of an additional prenatal visit on birth weight is virtually zero for black disadvantaged mothers, while an additional visit yields a substantial increase in birth weight of over 20 g for white disadvantaged mothers. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life.

    PubMed

    Newbold, Retha R; Jefferson, Wendy N; Padilla-Banks, Elizabeth

    2009-06-01

    Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a "high-volume production" chemical with widespread human exposure. In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Ovarian cysts were significantly increased in the 1-mug/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

  17. Prenatal vitamin intake during pregnancy and offspring obesity

    PubMed Central

    Dougan, Marcelle M.; Willett, Walter C.; Michels, Karin B.

    2014-01-01

    Background/Objectives In animal studies, exposure to multi-vitamins may be associated with obesity in the offspring; however, data in humans is sparse. We therefore examined the association between prenatal vitamin intake during pregnancy and offspring obesity. Subjects/Methods We investigated the association between prenatal vitamin intake and obesity among 29 160 mother-daughter dyads in the Nurses’ Health Study II. Mothers of participants provided information on prenatal vitamin use during pregnancy with the nurse daughter. Information on body fatness at ages 5 and 10, body mass index (BMI) at age 18, weight in 1989 and 2009, waist circumference, and height was obtained from the daughter. Polytomous logistic regression was used to predict BMI in early adulthood and adulthood, and body fatness in childhood. Linear regression was used to predict waist circumference in adulthood. Results In utero exposure to prenatal vitamins was not associated with body fatness, either in childhood or adulthood. Women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted odds ratio of being obese in adulthood of 0.99 (95% CI 0.92 – 1.05, P-value = 0.68) compared to women whose mothers did not take prenatal vitamins. Women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted odds ratio of having the largest body shape at age 5 of 1.02 (95% CI 0.90 – 1.15, P-value = 0.78). In additional analyses, in utero exposure to prenatal vitamins was also unrelated to adult abdominal adiposity. Conclusions Exposure to prenatal vitamins was not associated with body fatness either in childhood or in adulthood. PMID:24942869

  18. Ambiguous genitalia: what prenatal genetic testing is practical?

    PubMed

    Adam, Margaret P; Fechner, Patricia Y; Ramsdell, Linda A; Badaru, Angela; Grady, Richard E; Pagon, Roberta A; McCauley, Elizabeth; Cheng, Edith Y; Parisi, Melissa A; Shnorhavorian, Margarett

    2012-06-01

    Concern for ambiguous genitalia or chromosome-phenotype discordance detected in a prenatal setting has increased over the last two decades. Practitioners faced with this prenatal finding have a variety of genetic tests available to them; however, it is unclear to what extent prenatal testing for disorders of sex development (DSD) is useful or practical. We undertook a retrospective review of the medical records of 140 individuals evaluated through the DSD clinic at Seattle Children's Hospital with birthdates from 01/01/1994 through 08/16/2011 to determine the rate of prenatal detection of ambiguous genitalia in individuals with DSD, what prenatal diagnostic workup was undertaken, and the postnatal outcome, including whether a postnatal genetic diagnosis was confirmed. Of all 140 subjects, 34 (24%) were identified prenatally. The most common postnatal diagnoses were penoscrotal hypospadias with transposition of the scrotum with no known genetic cause (24/140; 17%) and 21-hydroxylase deficiency (20/140; 14%). Apart from these, no single diagnosis comprised more than a few cases. Prenatal diagnostic testing varied widely, from no tests to multiple molecular tests with amniotic fluid hormone concentrations. In the absence of other fetal anomalies or growth retardation on ultrasound, prenatal karyotype with fluorescence in situ hybridization for the SRY gene is the most useful test when ambiguous genitalia is suspected. Further prenatal testing for Smith-Lemli-Opitz syndrome in 46,XY individuals and congenital adrenal hyperplasia in 46,XX individuals may be considered. However, targeted molecular testing for rare DSD conditions in the absence of a family history of DSD has a low yield. Copyright © 2012 Wiley Periodicals, Inc.

  19. Cardiac allograft prolongation in mice treated with combined posttransplantation total-lymphoid irradiation and anti-L3T4 antibody therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trager, D.K.; Banks, B.A.; Rosenbaum, G.E.

    1989-04-01

    Neonatal cardiac allograft survival was examined in mice treated with anti-L3T4 antibody, posttransplantation total lymphoid irradiation (TLI) or a combination of both therapies. Independently, both posttransplantation TLI and short-course antibody treatment allowed minimal prolongation. However, synergistic prolongation in graft survival was observed with the combination (synergistic) therapy. Fluorescence-activated cell sorter analysis of peripheral blood lymphocytes from animals treated with combined anti-L3T4 and posttransplantation TLI additionally revealed ''synergy'' with respect to the degree of peripheral lymphocyte depletion.

  20. Prenatal coke: what's behind the smoke? Prenatal cocaine/alcohol exposure and school-age outcomes: the SCHOO-BE experience.

    PubMed

    Delaney-Black, V; Covington, C; Templin, T; Ager, J; Martier, S; Compton, S; Sokol, R

    1998-06-21

    Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgement of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be

  1. Development of Protective Immunity against Inactivated Iranian Isolate of Foot-and-Mouth Disease Virus Type O/IRN/2007 Using Gamma Ray-Irradiated Vaccine on BALB/c Mice and Guinea Pigs.

    PubMed

    Motamedi-Sedeh, Farahnaz; Soleimanjahi, Hoorieh; Jalilian, Amir Reza; Mahravani, Homayoon; Shafaee, Kamalodin; Sotoodeh, Masood; Taherkarami, Hamdolah; Jairani, Faramarz

    2015-01-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease in cloven-hoofed animals and is the most damaging disease of livestock worldwide, leading to great economic losses. The aim of this research was the inactivation of FMDV type O/IRN/1/2007 to produce a gamma ray-irradiated (GRI) vaccine in order to immunize mice and guinea pigs. In this research, the Iranian isolated FMDV type O/IRN/1/2007 was irradiated by gamma ray to prepare an inactivated whole virus antigen and formulated as a GRI vaccine with unaltered antigenic characteristics. Immune responses against this vaccine were evaluated on mice and guinea pigs. The comparison of the immune responses between the GRI vaccine and conventional vaccine did not show any significant difference in neutralizing antibody titer, memory spleen T lymphocytes or IFN-γ, IL-4, IL-2 and IL-10 concentrations (p > 0.05). In contrast, there were significant differences in all of the evaluated immune factors between the two vaccinated groups of mice and negative control mice (p < 0.05). The protective dose 50 for the conventional and GRI vaccines obtained were 6.28 and 7.07, respectively, which indicated the high potency of both vaccines. GRI vaccine is suitable for both routine vaccination and control of FMDV in emergency outbreaks.

  2. Prenatal education for congenital toxoplasmosis.

    PubMed

    Di Mario, Simona; Basevi, Vittorio; Gagliotti, Carlo; Spettoli, Daniela; Gori, Gianfranco; D'Amico, Roberto; Magrini, Nicola

    2013-02-28

    Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. To assess the effects of prenatal education for preventing congenital toxoplasmosis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 January 2012), PubMed (1966 to 15 January 2012), EMBASE (1980 to 15 January 2012), CINAHL (1982 to 15 January 2012), LILACS (1982 to 15 January 2012), IMEMR (1984 to 15 January 2012), and reference lists of relevant papers, reviews and websites. Randomized and quasi-randomized controlled trials (RCTs) of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were included. Two review authors independently assessed trials for inclusion and study quality. Two review authors extracted data. Data were checked for accuracy. Two cluster-randomized controlled trials (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways which meant that meta-analysis of the results was not possible One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. The authors did not report measure of association but only provided P values (P less than 0.05) for all outcomes. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect

  3. Long-term behavioral consequences of prenatal MDMA exposure.

    PubMed

    Thompson, Valerie B; Heiman, Justin; Chambers, James B; Benoit, Stephen C; Buesing, William R; Norman, Mantana K; Norman, Andrew B; Lipton, Jack W

    2009-03-23

    The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning.

  4. Susceptible cytotoxicity to ultraviolet B light in fibroblasts and keratinocytes cultured from autoimmune-prone MRL/Mp-lpr/lpr mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Furukawa, F.; Lyon, M.B.; Norris, D.A.

    1989-09-01

    The MRL/Mp-lpr/lpr (MRL/l) mouse is an autoimmune model of spontaneous lupus erythematosus (LE), in addition to lupus nephritis. In order to better understand the mechanisms of photosensitivity in LE, in vitro photocytotoxicity was examined by using fibroblasts and keratinocytes cultured from MRL/l mice, control MRL/Mp- +/+ (MRL/n) mice, and normal BALB/c mice. A colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and the acridine orange/ethidium bromide assay were used for determination of cytotoxicity. Fibroblasts cultured from newborn MRL/l mice showed higher susceptibility to single ultraviolet light B (UVB) light irradiation at a dose of 100-500 mJ than those from MRL/n, F1 hybrid ofmore » (MRL/l x MRL/n mice), and BALB/c mice. However, the susceptibility to UVB was not observed in young (1-month-old) and adult (4-month-old) MRL/l mice. UVA light irradiation was not cytotoxic. Keratinocytes cultured from MRL mice showed lower cytotoxicity to UVB irradiation than fibroblasts cultured. However, keratinocytes from newborn MRL/l mice showed higher cytotoxicity to 50 mJ UVB irradiation than cells from MRL/n mice. Syngeneic or allogeneic sera augmented UVB-induced cytotoxicity of fibroblasts cultured. UVB irradiation of spleen cells induced no significant difference of cytotoxicity between MRL/l and MRL/n mice. Based on the results of F1 hybrid of (MRL/l x MRL/n) mice, the susceptibility seemed to be associated with autoimmune traits and to be regulated by genetical background.« less

  5. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

  6. Prenatal Tests

    MedlinePlus

    ... disease (STD) or cervical cancer In a developing child, prenatal tests can: identify treatable health problems that can affect the baby show characteristics of the baby, including size, sex, age, and position in the uterus help determine ...

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki

    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 ofmore » 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

  8. Effective adoptive transfer of haploidentical tumor-specific T cells in B16-melanoma bearing mice.

    PubMed

    Cui, Nai-peng; Xie, Shao-jian; Han, Jin-sheng; Ma, Zhen-feng; Chen, Bao-ping; Cai, Jian-hui

    2012-03-01

    Adoptive transfer of allogeneic tumor-specific T cells often results in severe graft-versus-host disease (GVHD). Here, we sought to maximize graft-versus-tumor and minimize GVHD by using haploidentical T cells in pre-irradiated B16-melanoma bearing mice. C57BL/6 mice bearing B16-melanoma tumors were irradiated with 0, 5, or 7 Gy total body irradiation (TBI), or 7 Gy TBI plus bone marrow transplantation. Tumor areas were measured every 3 days to assess the influence of irradiation treatment on tumor regression. B16-melanoma bearing mice were irradiated with 7 Gy TBI; sera and spleens were harvested at days 1, 3, 5, 7, 9, 11, and 13 after irradiation. White blood cell levels were measured and transforming growth factor β1 (TGF-b1) and interleukin 10 (IL-10) levels in serum were detected using enzyme-linked immunosorbent assay (ELISA) kits. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed to test TGF-b1, IL-10 and Foxp3 mRNA levels and the proportion of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) in spleens. B16-melanoma bearing C57BL/6 mice were irradiated with 7 Gy TBI followed by syngeneic (Syn1/Syn2) or haploidentical (Hap1/Hap2), dendritic cell-induced cytotoxic T lymphocytes (DC-CTLs) treatment, tumor areas and system GVHD were observed every 3 days. Mice were killed 21 days after the DC-CTLs adoptive transfer; histologic analyses of eyes, skin, liver, lungs, and intestine were then performed. Irradiation with 7 Gy TBI on the B16-melanoma-bearing mice did not influence tumor regression compared to the control group; however, it down-regulated the proportion of Tregs in spleens and the TGF-b1 and IL-10 levels in sera and spleens, suggesting inhibition of autoimmunity and intervention of tumor microenvironment. Adoptive transfer of haploidentical DC-CTLs significantly inhibited B16-melanoma growth. GVHD assessment and histology analysis showed no significant difference among the groups. Adoptive transfer of

  9. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    PubMed

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these

  10. Acemannan-containing wound dressing gel reduces radiation-induced skin reactions in C3H mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roberts, D.B.; Travis, E.L.

    To determine (a) whether a wound dressing gel that contains acemannan extracted from aloe leaves affects the severity of radiation-induced acute skin reactions in C3H mice; (b) if so, whether other commercially available gels such as a personal lubricating jelly and a healing ointment have similar effects; and (c) when the wound dressing gel should be applied for maximum effect. Male C3H mice received graded single doses of gamma radiation ranging from 30 to 47.5 Gy to the right leg. In most experiments, the gel was applied daily beginning immediately after irradiation. Dose-response curves were obtained by plotting the percentagemore » of mice that reached or exceeded a given peak skin reaction as a function of dose. Curves were fitted by logit analysis and ED{sub 50} values, and 95% confidence limits were obtained. The average peak skin reactions of the wound dressing gel-treated mice were lower than those of the untreated mice at all radiation doses tested. The ED{sub 50} values for skin reactions of 2.0-2.75 were approximately 7 Gy higher in the wound dressing gel-treated mice. The average peak skin reactions and the ED{sub 50} values for mice treated with personal lubricating jelly or healing ointment were similar to irradiated control values. Reduction in the percentage of mice with skin reactions of 2.5 or more was greatest in the groups that received wound dressing gel for at least 2 weeks beginning immediately after irradiation. There was no effect if gel was applied only before irradiation or beginning 1 week after irradiation. Wound dressing gel, but not personal lubricating jelly or healing ointment, reduces acute radiation-induced skin reactions in C3H mice if applied daily for at least 2 weeks beginning immediately after irradiation. 31 refs., 4 figs., 1 tab.« less

  11. Effects of prenatal care on maternal postpartum behaviors

    PubMed Central

    Reichman, Nancy E.; Corman, Hope; Schwartz-Soicher, Ofira

    2010-01-01

    Most research on the effectiveness of prenatal care has focused on birth outcomes and has found small or no effects. It is possible, however, that prenatal care is “too little too late” to improve pregnancy outcomes in the aggregate, but that it increases the use of pediatric health care or improves maternal health-related parenting practices and, ultimately, child health. We use data from the Fragile Families and Child Wellbeing birth cohort study that have been augmented with hospital medical record data to estimate effects of prenatal care timing on pediatric health care utilization and health-related parenting behaviors during the first year of the child’s life. We focus on maternal postpartum smoking, preventive health care visits for the child, and breastfeeding. We use a multi-pronged approach to address the potential endogeneity of the timing of prenatal care. We find that first trimester prenatal care appears to decrease maternal postpartum smoking by about 5 percentage points and increase the likelihood of 4 or more well-baby visits by about 1 percentage point, and that it may also have a positive effect on breastfeeding. These findings suggest that there are benefits to standard prenatal care that are generally not considered in evaluations of prenatal care programs and interventions. PMID:20582158

  12. Prenatal diagnosis of holoprosencephaly.

    PubMed

    Kousa, Youssef A; du Plessis, Adré J; Vezina, Gilbert

    2018-05-17

    Holoprosencephaly is a spectrum of congenital defects of forebrain development characterized by incomplete separation of the cerebral hemispheres. In vivo diagnosis can be established with prenatal brain imaging and disease severity correlates with extent of abnormally developed brain tissue. Advances in magnetic resonance imaging (MRI) over the past 25 years and their application to the fetus have enabled diagnosis of holoprosencephaly in utero. Here, we report on the prenatal diagnosis of holoprosencephaly using MRI as part of a diagnostic and management evaluation at a tertiary and quaternary referral center. Using an advanced MRI protocol and a 1.5-Tesla magnet, we show radiographic data diagnostic for the holoprosencephaly spectrum, including alobar, semilobar, lobar, middle interhemispheric, and septopreoptic variant. Accurate prenatal evaluation is important because the severity of imaging findings correlates with postnatal morbidity and mortality in holoprosencephaly. Therefore, this work has implications for the evaluation, diagnosis, management, and genetic counseling that families can receive during a pregnancy. © 2018 Wiley Periodicals, Inc.

  13. Prenatal programming of childhood overweight and obesity.

    PubMed

    Huang, Jennifer S; Lee, Tiffany A; Lu, Michael C

    2007-09-01

    To review the scientific evidence for prenatal programming of childhood overweight and obesity, and discuss its implications for MCH research, practice, and policy. A systematic review of observational studies examining the relationship between prenatal exposures and childhood overweight and obesity was conducted using MOOSE guidelines. The review included literature posted on PubMed and MDConsult and published between January 1975 and December 2005. Prenatal exposures to maternal diabetes, malnutrition, and cigarette smoking were examined, and primary study outcome was childhood overweight or obesity as measured by body mass index (BMI) for children ages 5 to 21. Four of six included studies of prenatal exposure to maternal diabetes found higher prevalence of childhood overweight or obesity among offspring of diabetic mothers, with the highest quality study reporting an odds ratio of adolescent overweight of 1.4 (95% CI 1.0-1.9). The Dutch famine study found that exposure to maternal malnutrition in early, but not late, gestation was associated with increased odds of childhood obesity (OR 1.9, 95% CI 1.5-2.4). All eight included studies of prenatal exposure to maternal smoking showed significantly increased odds of childhood overweight and obesity, with most odds ratios clustering around 1.5 to 2.0. The biological mechanisms mediating these relationships are unknown but may be partially related to programming of insulin, leptin, and glucocorticoid resistance in utero. Our review supports prenatal programming of childhood overweight and obesity. MCH research, practice, and policy need to consider the prenatal period a window of opportunity for obesity prevention.

  14. Policy analysis for prenatal genetic diagnosis.

    PubMed

    Thompson, M; Milunsky, A

    1979-01-01

    Consideration of the analytic difficulties faced in estimating the benefits and costs of prenatal genetic diagnosis, coupled with a brief review of existing benefit-cost studies, leads to the conclusion that public subsidy of prenatal testing can yield benefits substantially in excess of costs. The practical obstacles to such programs include the attitudes of prospective parents, a lack of knowledge, monetary barriers, inadequately organized medical resources, and the political issue of abortion. Policy analysis can now nevertheless formulate principles and guide immediate actions to improve present utilization of prenatal testing and to facilitate possible future expansion of these diagnostic techniques.

  15. Near-infrared laser irradiation improves the development of mouse pre-implantation embryos.

    PubMed

    Yokoo, Masaki; Mori, Miho

    2017-05-27

    The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing of blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. Copyright © 2017 Elsevier Inc. All rights

  16. SU-E-T-664: Radiobiological Modeling of Prophylactic Cranial Irradiation in Mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, D; Debeb, B; Woodward, W

    Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with ALL and SCLC, and we have shown the potential of PCI in select breast cancer patients through a mouse model (manuscript in preparation). We developed a computational model using our experimental results to demonstrate the advantage of treating brain micro-metastases early. Methods: MATLAB was used to develop the computational model of brain metastasis and PCI in mice. The number of metastases per mouse and the volume of metastases from four- and eight-week endpoints were fitmore » to normal and log-normal distributions, respectively. Model input parameters were optimized so that model output would match the experimental number of metastases per mouse. A limiting dilution assay was performed to validate the model. The effect of radiation at different time points was computationally evaluated through the endpoints of incidence, number of metastases, and tumor burden. Results: The correlation between experimental number of metastases per mouse and the Gaussian fit was 87% and 66% at the two endpoints. The experimental volumes and the log-normal fit had correlations of 99% and 97%. In the optimized model, the correlation between number of metastases per mouse and the Gaussian fit was 96% and 98%. The log-normal volume fit and the model agree 100%. The model was validated by a limiting dilution assay, where the correlation was 100%. The model demonstrates that cells are very sensitive to radiation at early time points, and delaying treatment introduces a threshold dose at which point the incidence and number of metastases decline. Conclusion: We have developed a computational model of brain metastasis and PCI in mice that is highly correlated to our experimental data. The model shows that early treatment of subclinical disease is highly advantageous.« less

  17. Neurobehavioral Disorder Associated With Prenatal Alcohol Exposure

    PubMed Central

    Hagan, Joseph F.; Balachova, Tatiana; Bertrand, Jacquelyn; Chasnoff, Ira; Dang, Elizabeth; Fernandez-Baca, Daniel; Kable, Julie; Kosofsky, Barry; Senturias, Yasmin N.; Singh, Natasha; Sloane, Mark; Weitzman, Carol; Zubler, Jennifer

    2017-01-01

    Children and adolescents affected by prenatal exposure to alcohol who have brain damage that is manifested in functional impairments of neurocognition, self-regulation, and adaptive functioning may most appropriately be diagnosed with neurobehavioral disorder associated with prenatal exposure. This Special Article outlines clinical implications and guidelines for pediatric medical home clinicians to identify, diagnose, and refer children regarding neurobehavioral disorder associated with prenatal exposure. Emphasis is given to reported or observable behaviors that can be identified as part of care in pediatric medical homes, differential diagnosis, and potential comorbidities. In addition, brief guidance is provided on the management of affected children in the pediatric medical home. Finally, suggestions are given for obtaining prenatal history of in utero exposure to alcohol for the pediatric patient. PMID:27677572

  18. Neurocognitive sparing of desktop microbeam irradiation.

    PubMed

    Bazyar, Soha; Inscoe, Christina R; Benefield, Thad; Zhang, Lei; Lu, Jianping; Zhou, Otto; Lee, Yueh Z

    2017-08-11

    Normal tissue toxicity is the dose-limiting side effect of radiotherapy. Spatial fractionation irradiation techniques, like microbeam radiotherapy (MRT), have shown promising results in sparing the normal brain tissue. Most MRT studies have been conducted at synchrotron facilities. With the aim to make this promising treatment more available, we have built the first desktop image-guided MRT device based on carbon nanotube x-ray technology. In the current study, our purpose was to evaluate the effects of MRT on the rodent normal brain tissue using our device and compare it with the effect of the integrated equivalent homogenous dose. Twenty-four, 8-week-old male C57BL/6 J mice were randomly assigned to three groups: MRT, broad-beam (BB) and sham. The hippocampal region was irradiated with two parallel microbeams in the MRT group (beam width = 300 μm, center-to-center = 900 μm, 160 kVp). The BB group received the equivalent integral dose in the same area of their brain. Rotarod, marble burying and open-field activity tests were done pre- and every month post-irradiation up until 8 months to evaluate the cognitive changes and potential irradiation side effects on normal brain tissue. The open-field activity test was substituted by Barnes maze test at 8th month. A multilevel model, random coefficients approach was used to evaluate the longitudinal and temporal differences among treatment groups. We found significant differences between BB group as compared to the microbeam-treated and sham mice in the number of buried marble and duration of the locomotion around the open-field arena than shams. Barnes maze revealed that BB mice had a lower capacity for spatial learning than MRT and shams. Mice in the BB group tend to gain weight at the slower pace than shams. No meaningful differences were found between MRT and sham up until 8-month follow-up using our measurements. Applying MRT with our newly developed prototype compact CNT-based image-guided MRT system

  19. PRENATAL STRESS AND RISK FOR AUTISM

    PubMed Central

    Kinney, Dennis K.; Munir, Kerim M.; Crowley, David J.; Miller, Andrea M.

    2008-01-01

    This paper reviews several converging lines of research that suggest that prenatal exposure to environmental stress may increase risk for Autistic Disorder (AD). We first discuss studies finding that prenatal exposure to stressful life events is associated with significantly increased risk of AD, as well as other disorders, such as schizophrenia and depression. We then review evidence from animal and human studies that prenatal stress can produce both (a) abnormal postnatal behaviors that resemble the defining symptoms of AD, and (b) other abnormalities that have elevated rates in AD, such as learning deficits, seizure disorders, perinatal complications, immunologic and neuroinflammatory anomalies, and low postnatal tolerance for stress. We explain why an etiologic role for prenatal stress is compatible with genetic factors in AD, and describe how stress can disrupt fetal brain development. Finally, we discuss implications for understanding underlying processes in AD, including potential gene-environment interactions, and developing new therapies and early prevention programs. PMID:18598714

  20. Consumerism in prenatal diagnosis: a challenge for ethical guidelines

    PubMed Central

    Henn, W.

    2000-01-01

    The ethical guidelines for prenatal diagnosis proposed by the World Health Organisation (WHO), as well as by national regulations, only refer to paternity and gender of the fetus as unacceptable, disease-unrelated criteria for prenatal selection, as no other such parameters are at hand so far. This perspective is too narrow because research on complex genetic systems such as cognition and ageing is about to provide clinically applicable tests for genetic constituents of potentially desirable properties such as intelligence or longevity which could be misused as parameters for prenatal diagnosis. Moreover, there is an increasing number of prenatally testable genetic traits, such as heritable deafness, which are generally regarded as pathological but desired by some prospective parents and taken into account as parameters for pro-disability selection. To protect prenatal diagnosis from ethically unacceptable genetic consumerism, guidelines must be clarified as soon as possible and updated towards a worldwide restriction of prenatal genetic testing to immediately disease-determining traits. Key Words: Genetics • prenatal diagnosis • ethics • consumerism PMID:11129845

  1. Applying the chronic care model to prenatal care: Patient activation, productive interactions, and prenatal outcomes.

    PubMed

    Ledford, Christy J W; Sadler, Kerry P; Jackson, Jeremy T; Womack, Jasmyne J; Rider, Heather A; Seehusen, Angela B

    2018-04-30

    To demonstrate how the chronic care model can be applied in prenatal care. This study was conducted through analysis of data generated in the women's health and family medicine departments of one community hospital and two medical centers across three states (Georgia, Nevada, and Virginia). 159 low-risk obstetric patients were monitored throughout their pregnancy for patient activation and biometric measures including: blood pressure at each appointment, baby's gestational age at birth, and mode of delivery. Patient activation was assessed with the validated, licensed patient activation measure. Patient activation was strongly associated with the Prenatal Interpersonal Processes of Care metric (F (2, 155) = 3.41, p < .05). Also, increased age, decreased Prenatal Interpersonal Processes of Care, fewer pregnancies, and increased diastolic blood pressure were associated with an increased likelihood of cesarean delivery and the model correctly predicted 81% of cases. Women who identified as feeling more activated reported more positive pregnancy experiences, and women who reported more positive pregnancy experiences were more likely to experience a vaginal delivery. Activated patients, more positive prenatal experience, and improved delivery outcomes can be achieved through applying the chronic care model. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation.

    PubMed

    Hirouchi, Tokuhisa; Ito, Koichi; Nakano, Manabu; Monzen, Satoru; Yoshino, Hironori; Chiba, Mitsuru; Hazawa, Masaharu; Nakano, Akira; Ishikawa, Junya; Yamaguchi, Masaru; Tanaka, Kimio; Kashiwakura, Ikuo

    2015-01-01

    It is important to establish an easy-to-use therapeutic protocol for the emergency medical care of patients involved in radiation accidents to reduce the radiation-related casualties. The present study aimed to establish an optimum therapeutic protocol using currently approved pharmaceutical drugs to increase the survival of victims exposed to lethal radiation. Different combinations of four drugs-recombinant human erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), c-mpl receptor agonist romiplostim (RP) and nandrolone decanoate (ND)-were administered to mice within 2 h after exposure to a lethal 7 Gy dose of γ-irradiation. On day 30 after irradiation, the condition of the mice was analyzed using various hematological parameters, such as the number of peripheral blood cells, bone marrow cells, hematopoietic progenitor cells and the expression of cell surface antigens. Approximately 10% of the untreated irradiated control mice survived for 21 days, but all of the control mice died by day 30. The combined administration of G-CSF, EPO and RP for five days immediately after irradiation led to a complete survival of the irradiated mice until day 30. However, the treatment with G-CSF, EPO and RP with ND led to only 75% survival at day 30. The hematological analyses showed that the numbers of almost all of hematopoietic cells in the surviving mice treated with effective medications recovered to the levels of non-irradiated mice. The present findings show that the combination of G-CSF, EPO and RP may be a useful countermeasure for victims exposed to accidental lethal irradiation.

  3. The changing pattern of prenatal care utilization in the United States, 1981-1995, using different prenatal care indices.

    PubMed

    Kogan, M D; Martin, J A; Alexander, G R; Kotelchuck, M; Ventura, S J; Frigoletto, F D

    1998-05-27

    Two measures traditionally used to examine adequacy of prenatal care indicate that prenatal care utilization remained unchanged through the 1980s and only began to rise slightly in the 1990s. In recent years, new measures have been developed that include a category for women who receive more than the recommended amount of care (intensive utilization). To compare the older and newer indices in the monitoring of prenatal care trends in the United States from 1981 to 1995, for the overall population and for selected subpopulations. Second, to examine factors associated with receiving intensive utilization. Cross-sectional and trend analysis of national birth records. The United States. All live births between 1981 and 1995 (N=54 million). Trends in prenatal care utilization, according to 4 indices (the older indices: the Institute of Medicine Index and the trimester that care began, and the newer indices: the R-GINDEX and the Adequacy of Prenatal Care Utilization Index). Multiple logistic regression was used to assess the risk of intensive prenatal care use in 1981 and 1995. The newer indices showed a steadily increasing trend toward more prenatal care use throughout the study period (R-GINDEX, intensive or adequate use, 32.7% in 1981 to 47.1 % in 1995; the Adequacy of Prenatal Care Utilization Index, intensive use, 18.4% in 1981 to 28.8% in 1995), especially for intensive utilization. Women having a multiple birth were much more likely to have had intensive utilization in 1995 compared with 1981 (R-GINDEX, 22.8% vs 8.5%). Teenagers were more likely to begin care later than adults, but similar proportions of teens and adults had intensive utilization. Intensive use among low-risk women also increased steadily each year. Factors associated with a greater likelihood of receiving intensive use in 1981 and 1995 were having a multiple birth, primiparity, being married, and maternal age of 35 years or older. The proportion of women who began care early and received at least

  4. [Protective effects of WR2721 on early bone marrow hematopoietic function in mice exposed to 6.5 Gy of (60)Co γ-rays].

    PubMed

    Deng, Zi-Liang; Zhang, Liu-Zhen; Cong, Yue; Liu, Xiao-Lan; Yu, Zu-Ying; Shan, Ya-Jun; Cui, Yu; Wang, Li-Mei; Xing, Shuang; Cong, Yu-Wen; Luo, Qing-Liang

    2014-06-01

    The aim of this study was to investigate the effect of WR2721(amifostine) against bone marrow hematopoietic damage of mice exposed to 6.5 Gy of (60)Co-γ ray. A total of 60 C57/BL6J mice was divided into 3 groups:normal group (mice were injected with physiological salt solution), irradiation group (mice were injected with physiologic salt solution before irradiation) and WR2721 group (mice were injected with WR2721 before irradiation). The WBC, neutrophil (Neut), Plt and RBC levels in peripheral blood of 3 group mice were counted within 60 days after irradiation; the bone marrow nuclear cells (BMNC) were counted at 2 and 24 hours after irradiation; the hematopoietic stem/progenitor cell (LK/LSK) level and colony formation capability were detected by flow cytometry at 2 and 24 hours after irradiation. The results indicated that the counts of WBC and neut at 4 and 18 days, Plt at 7-18 days and RBC at 10-30 day after irradiation in WR2721 group were higher than those in irradiation group (P < 0.05); the BMNC, LSK and LK levels obviously increased at 24 hours after irradiation (P < 0.05), the CFU-GEMM, CFU-GM, CFU-MK BFU-E and CFU-E all significantly increased at 2 and 24 hours after irradiation (P < 0.01), as compared with irradiation group. It is concluded that WR2721 can effectively alleviate early hematopoietic damage and promote the fast recovery of peripheral blood cells in mice exposed to γ-ray, suggesting that the WR2721 has significant radioprotective effect on hematopoietic system.

  5. Sociodemographic factors and the quality of prenatal care.

    PubMed Central

    Hansell, M J

    1991-01-01

    BACKGROUND: In this study, maternal sociodemographic factors are examined in relationship to the quality of prenatal health services US women receive. METHODS: Data from the 1980 National Natality Survey and 1980 Fetal Mortality Survey were used for the analysis. Indicator variables for prenatal care quality are the percentages of prenatal visits at which blood pressure and urine were tested, the performance of hemoglobin or hematocrit tests, and the presence or absence of advice regarding salt restriction and diuretics usage during pregnancy. RESULTS: Distribution of the basic examinations in prenatal care vary according to marital status, parity, education, and residence in a metropolitan or nonmetropolitan county. The advice received concerning salt and diuretics usage was also influenced by sociodemographic variables. CONCLUSIONS: The analyses reveal that prenatal care is not of even minimally acceptable quality for many women. PMID:1953875

  6. Prenatal education for congenital toxoplasmosis.

    PubMed

    Di Mario, Simona; Basevi, Vittorio; Gagliotti, Carlo; Spettoli, Daniela; Gori, Gianfranco; D'Amico, Roberto; Magrini, Nicola

    2015-10-23

    Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. To assess the effects of prenatal education for preventing congenital toxoplasmosis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials.One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a

  7. The renal effects of prenatal testosterone in rats.

    PubMed

    Bábíčková, Janka; Borbélyová, Veronika; Tóthová, L'ubomíra; Kubišová, Katarína; Janega, Pavol; Hodosy, Július; Celec, Peter

    2015-05-01

    Previous studies have shown that prenatal testosterone affects the development of not only reproductive organs but also the brain and even glucose metabolism. Whether prenatal testosterone influences the kidney development is largely unknown. We analyzed whether testosterone modulation during prenatal development would affect renal function and the number of nephrons in adult offspring. Pregnant rats were treated with olive oil, testosterone (2 mg/kg), the androgen receptor blocker flutamide (5 mg/kg) or testosterone plus flutamide via daily intramuscular injections from gestation day 14 until delivery. Renal histology and functional parameters were assessed in male and female adult offspring. Macerated kidneys were used for nephron counting. Prenatal testosterone administration increased proteinuria in male rats by 256%. A similar 134% effect in female rats was not statistically significant. This effect was prevented when flutamide was co-administered. In male rats prenatal testosterone increased blood urea nitrogen. In female rats flutamide increased creatinine clearance. In male rats prenatal testosterone and flutamide led to higher and lower, respectively, interstitial collagen deposition in adulthood. Prenatal testosterone induces proteinuria in adulthood. This effect is mediated via androgen receptor. Additional effects seem to be sex specific. Further studies should focus on the timing and dosing of testosterone as well as the applicability to human development. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Prenatal and pubertal testosterone affect brain lateralization.

    PubMed

    Beking, T; Geuze, R H; van Faassen, M; Kema, I P; Kreukels, B P C; Groothuis, T G G

    2018-02-01

    After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in puberty. We performed a longitudinal study, investigating the relationship between prenatal testosterone concentrations in amniotic fluid, pubertal testosterone concentrations in saliva, and brain lateralization (measured with functional Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric Faces and Word Generation tasks. Thirty boys and 30 girls participated in this study at the age of 15 years. For boys, we found a significant interaction effect between prenatal and pubertal testosterone on lateralization of Mental Rotation and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal testosterone was positively related to the strength of lateralization in the right hemisphere, while in the boys with high prenatal testosterone levels, pubertal testosterone was negatively related to the strength of lateralization. For Word Generation, pubertal testosterone was negatively related to the strength of lateralization in the left hemisphere in boys. For girls, we did not find any significant effects, possibly because their pubertal testosterone levels were in many cases below quantification limit. To conclude, prenatal and pubertal testosterone affect lateralization in a task-specific way. Our findings cannot be explained by simple models of prenatal testosterone affecting brain lateralization in a similar way for all tasks. We discuss alternative models involving age dependent effects of testosterone, with a role for androgen receptor distribution and efficiency. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. [Ultrahigh dose-rate, "flash" irradiation minimizes the side-effects of radiotherapy].

    PubMed

    Favaudon, V; Fouillade, C; Vozenin, M-C

    2015-10-01

    Pencil beam scanning and filter free techniques may involve dose-rates considerably higher than those used in conventional external-beam radiotherapy. Our purpose was to investigate normal tissue and tumour responses in vivo to short pulses of radiation. C57BL/6J mice were exposed to bilateral thorax irradiation using pulsed (at least 40 Gy/s, flash) or conventional dose-rate irradiation (0.03 Gy/s or less) in single dose. Immunohistochemical and histological methods were used to compare early radio-induced apoptosis and the development of lung fibrosis in the two situations. The response of two human (HBCx-12A, HEp-2) tumour xenografts in nude mice and one syngeneic, orthotopic lung carcinoma in C57BL/6J mice (TC-1 Luc+), was monitored in both radiation modes. A 17 Gy conventional irradiation induced pulmonary fibrosis and activation of the TGF-beta cascade in 100% of the animals 24-36 weeks post-treatment, as expected, whereas no animal developed complications below 23 Gy flash irradiation, and a 30 Gy flash irradiation was required to induce the same extent of fibrosis as 17 Gy conventional irradiation. Cutaneous lesions were also reduced in severity. Flash irradiation protected vascular and bronchial smooth muscle cells as well as epithelial cells of bronchi against acute apoptosis as shown by analysis of caspase-3 activation and TUNEL staining. In contrast, the antitumour effectiveness of flash irradiation was maintained and not different from that of conventional irradiation. Flash irradiation shifted by a large factor the threshold dose required to initiate lung fibrosis without loss of the antitumour efficiency, suggesting that the method might be used to advantage to minimize the complications of radiotherapy. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  10. Near-infrared laser irradiation improves the development of mouse pre-implantation embryos

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yokoo, Masaki; Mori, Miho

    The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing ofmore » blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. - Highlights: • Irradiation of

  11. Toxicological and radiological safety of chicken meat irradiated with 7.5 MeV X-rays

    NASA Astrophysics Data System (ADS)

    Song, Beom-Seok; Lee, Yunjong; Park, Jong-Heum; Kim, Jae-Kyung; Park, Ha-Young; Kim, Dong-Ho; Kim, Chang-Jong; Kang, Il-Jun

    2018-03-01

    This study was conducted to evaluate the toxicological and radiological safety of chicken meat that had been irradiated at 30 kGy with 7.5 MeV X-rays. In a sub-chronic toxicity study, ICR mice were fed X-ray-irradiated chicken meat at 2500 mg/kg body weight daily for 90 days, and no mortality or abnormal clinical signs were observed throughout the study period. However, several hematological and serum biochemical parameters of the ICR mice differed significantly from those in the control group; nevertheless, the observed values were all within the normal range for the respective parameters. In addition, no toxicological effects were determined in male or female mice. Furthermore, no differences in gamma-ray spectrometric patterns were detected between the non-irradiated and irradiated samples, indicating that the radioactivity induced by 7.5 MeV X-ray irradiation was below the detection limit. These results tentatively suggest that chicken meat irradiated with 7.5 MeV X-rays would be safe for human consumption in terms of toxicology and radiology.

  12. An atlas of the prenatal mouse brain: gestational day 14.

    PubMed

    Schambra, U B; Silver, J; Lauder, J M

    1991-11-01

    A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer.

  13. Playfulness and prenatal alcohol exposure: a comparative study.

    PubMed

    Pearton, Jordan Louise; Ramugondo, Elelwani; Cloete, Lizahn; Cordier, Reinie

    2014-08-01

    South Africa carries a high burden of alcohol abuse. The effects of maternal alcohol consumption during pregnancy are most pronounced in poor, rural communities. Earlier research suggests that children with prenatal alcohol exposure have poor social behaviour; however, to date, no research has investigated their playfulness. This study investigated the differences in playfulness of children with and without prenatal alcohol exposure. Grade one learners with a positive history of prenatal alcohol exposure (n = 15) and a reference group without a positive history of prenatal alcohol exposure (n = 15) were filmed engaging in free play at their schools. The Test of Playfulness was used to measure playfulness from recordings. Data were subjected to Rasch analysis to calculate interval level measure scores for each participant. The overall measure scores and individual Test of Playfulness social items were subjected to paired samples t-tests to calculate if significant differences existed between the groups. Children with prenatal alcohol exposure had a significantly lower mean overall playfulness score than the reference group (t = -2.51; d.f. = 28; P = 0.02). Children with prenatal alcohol exposure also scored significantly lower than the reference group on 5 of the 12 Test of Playfulness items related to social play. This research suggests that children with prenatal alcohol exposure are more likely to experience poorer overall quality of play, with particular deficits in social play. Considering play is a child's primary occupation, this finding becomes pertinent for occupational therapy practice, particularly in post-apartheid South Africa, where high prenatal alcohol exposure prevalence rates are couched within persistent socio-economic inequalities. © 2014 Occupational Therapy Australia.

  14. The caspase-3/p120 RasGAP stress-sensing module reduces liver cancer incidence but does not affect overall survival in gamma-irradiated and carcinogen-treated mice.

    PubMed

    Vanli, Güliz; Sempoux, Christine; Widmann, Christian

    2017-06-01

    Activation of oncogenes is the initial step in cellular transformation. Oncogenes favor aberrant proliferation, which, at least initially, induces cellular stress. This oncogenic stress can act as a safeguard mechanism against further transformation by inducing senescence or apoptosis. Yet, the few premalignant cells that tolerate and escape these senescent or apoptotic responses are those that will ultimately generate tumors. The caspase-3/p120 RasGAP module is a stress-sensing device that promotes survival under mild stress conditions. A point mutation in RasGAP that prevents its cleavage by caspase-3 inactivates the pro-survival capacity of the device. When the mice homozygous for this mutation (D455A knock-in mice) are patho-physiologically challenged, they experience much stronger cellular damage than their wild-type counterparts and the affected organs rapidly lose their functionality. We reasoned that the caspase-3/p120 RasGAP module could help premalignant cells to cope with oncogenic stress and hence favor the development of tumors. Using gamma-irradiation and N-ethyl-N-nitrosourea (ENU) as tumor initiators, we assessed the survival advantage that the caspase-3/p120 RasGAP module could provide to premalignant cells. No difference in overall mortality between wild-type and D455A knock-in mice were observed. However, the number of ENU-induced liver tumors in the knock-in mice was higher than in control mice. These results indicate that the caspase-3/p120 RasGAP stress-sensing module impacts on carcinogen-induced liver cancer incidence but not sufficiently so as to affect overall survival. Hence, gamma irradiation and ENU-induced tumorigenesis processes do not critically rely on a survival mechanism that contributes to the maintenance of organ homeostasis in stressed healthy tissues. © 2017 Wiley Periodicals, Inc.

  15. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

    PubMed

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-11-03

    The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

  16. 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.

  17. 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. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  18. Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

    PubMed Central

    Basil, P; Li, Q; Dempster, E L; Mill, J; Sham, P-C; Wong, C C Y; McAlonan, G M

    2014-01-01

    Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment. PMID:25180573

  19. Thinking outside the box: prenatal care and the call for a prenatal advance directive.

    PubMed

    Catlin, Anita

    2005-01-01

    The concept of advance directives is well-known in the care of adults as a mechanism for choosing in advance the extent of medical interventions desired in clinical situations, particularly life-extending interventions such as ventilation support and drugs to maintain cardiopulmonary status. Infants born extremely prematurely often require life-supporting measures for which their parents or guardians report feeling unprepared to make decisions about. Current prenatal care does not include an educational component that teaches women about the length of gestation needed for a healthy viability, survivorship, and outcome without major impairment. Women who go into preterm labor are asked to make immediate decisions during times of crisis without any formal education base for this decision making. Feminist ethics (the philosophical stance that articulates that women's moral experience is worthy of respect and disallows women's subordination) (Becker LB, Becker CB, eds. Feminist ethics. In: Encyclopedia of Ethics. New York: Routledge Press; 2001) requires that healthcare decisions be based on education, context, and particular situations. The purpose of this article is to examine the current content of typical prenatal care and education and to suggest an additional educational component to prenatal care-education of women about infant viability and the planning of future decisions if a nonviable or critically ill newborn is delivered. A prenatal discussion and parental/family directive is suggested.

  20. Prenatal Famine and Adult Health

    PubMed Central

    Lumey, L.H.; Stein, Aryeh D.; Susser, Ezra

    2013-01-01

    We review human studies on the relation between acute exposures to prenatal famine and adult physical and mental health. These studies are observational and include exposures to a famine environment by natural or man-made causes or, more commonly, from the interplay between natural and human factors. These natural experiments provide an opportunity to examine long-term outcomes after famine exposures by comparing exposed and nonexposed individuals. The studies show consistent associations between prenatal famine and adult body size, diabetes, and schizophrenia. For other measures of adult health, findings are less robust. A relation between prenatal famine and some reported epigenetic changes may provide a potential mechanism to explain specific associations. Much progress can be made if current separate studies are further analyzed with comparable definitions of exposures and outcomes and using common analytic strategies. PMID:21219171

  1. Prenatal Exposure to Bisphenol A at Environmentally Relevant Doses Adversely Affects the Murine Female Reproductive Tract Later in Life

    PubMed Central

    Newbold, Retha R.; Jefferson, Wendy N.; Padilla-Banks, Elizabeth

    2009-01-01

    Background Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure. Objectives In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Methods Timed pregnant CD-1 mice were treated on days 9–16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 μg/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Results Ovarian cysts were significantly increased in the 1-μg/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. Conclusions These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation. PMID:19590677

  2. Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice

    PubMed Central

    Jiang, Shuqi; Shen, Xianrong; Liu, Yuming; He, Ying; Jiang, Dingwen; Chen, Wei

    2015-01-01

    This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy 60Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body. PMID:25852150

  3. Prenatal nutrition services: a cost analysis.

    PubMed

    Splett, P L; Caldwell, H M; Holey, E S; Alton, I R

    1987-02-01

    The scarcity of information about program costs in relation to quality care prompted a cost analysis of prenatal nutrition services in two urban settings. This study examined prenatal nutrition services in terms of total costs, per client costs, per visit costs, and cost per successful outcome. Standard cost-accounting principles were used. Outcome measures, based on written quality assurance criteria, were audited using standard procedures. In the studied programs, nutrition services were delivered for a per client cost of $72 in a health department setting and $121 in a hospital-based prenatal care program. Further analysis illustrates that total and per client costs can be misleading and that costs related to successful outcomes are much higher. The three levels of cost analysis reported provide baseline data for quantifying the costs of providing prenatal nutrition services to healthy pregnant women. Cost information from these cost analysis procedures can be used to guide adjustments in service delivery to assure successful outcomes of nutrition care. Accurate cost and outcome data are necessary prerequisites to cost-effectiveness and cost-benefit studies.

  4. Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice.

    PubMed

    Bolton, Jessica L; Huff, Nicole C; Smith, Susan H; Mason, S Nicholas; Foster, W Michael; Auten, Richard L; Bilbo, Staci D

    2013-09-01

    Low socioeconomic status is consistently associated with reduced physical and mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown. We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neurocognitive disorders in adulthood. Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation. Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased proinflammatory interleukin (IL)-1β levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1. These results show that maternal stress during late gestation increases the susceptibility of offspring-particularly males-to the deleterious effects of prenatal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain.

  5. 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.

  6. Cytokine-dependent bidirectional connection between impaired social behavior and susceptibility to seizures associated with maternal immune activation in mice

    PubMed Central

    Washington, James; Kumar, Udaya; Medel-Matus, Jesus-Servando; Shin, Don; Sankar, Raman; Mazarati, Andrey

    2015-01-01

    Maternal immune activation (MIA) results in the development of autism in the offspring via hyperactivation of IL-6 signaling. Furthermore, experimental studies showed that the MIA-associated activation of interleukin-1β (IL-1β) concurrently with IL-6 increases the rate and the severity of hippocampal kindling in mice, thus offering an explanation for autism-epilepsy comorbidity. We examined whether epileptic phenotype triggered by prenatal exposure to IL-6 and IL-1β combination is restricted to kindling or whether it is reproducible in another model of epilepsy, whereby spontaneous seizures develop following kainic acid (KA)- induced status epilepticus. We also examined whether in mice prenatally exposed to IL-6 and IL-6+IL-1β, the presence of spontaneous seizures would exacerbate autism-like features. Between days 12 and 16 of pregnancy, C57bl/6j mice received daily injections of IL-6, IL-1β or IL-6+IL-1β combination. At postnatal day 40, male offspring was examined for the presence of social behavioral deficit and status epilepticus was induced by intrahippocampal KA injection. After six weeks of monitoring for spontaneous seizures, sociability was tested again. Both IL-6 and IL-6+IL-1β offspring presented with social behavioral deficit. Prenatal exposure to IL-6 alleviated, while such exposure to IL-6+IL-1β exacerbated the severity of KA-induced epilepsy. Increased severity of epilepsy in the IL-6+IL-1β mice correlated with the improvement of autism-like behavior. We conclude that complex and not necessarily agonistic relationships exist between epileptic and autism-like phenotypes in an animal model of MIA coupled with KA-induced epilepsy, and that the nature of these relationships depends on components of MIA involved. PMID:26103532

  7. The Motivation-Facilitation Theory of Prenatal Care Access.

    PubMed

    Phillippi, Julia C; Roman, Marian W

    2013-01-01

    Despite the availability of services, accessing health care remains a problem in the United States and other developed countries. Prenatal care has the potential to improve perinatal outcomes and decrease health disparities, yet many women struggle with access to care. Current theories addressing access to prenatal care focus on barriers, although such knowledge is minimally useful for clinicians. We propose a middle-range theory, the motivation-facilitation theory of prenatal care access, which condenses the prenatal care access process into 2 interacting components: motivation and facilitation. Maternal motivation is the mother's desire to begin and maintain care. Facilitation represents the goal of the clinic to create easy, open access to person-centered beneficial care. This simple model directs the focus of research and change to the interface of the woman and the clinic and encourages practice-level interventions that facilitate women entering and maintaining prenatal care. © 2013 by the American College of Nurse‐Midwives.

  8. 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.

  9. Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of 60Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration

    PubMed Central

    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

  10. Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour.

    PubMed

    Hay-Schmidt, Anders; Finkielman, Olivia T Ejlstrup; Jensen, Benjamin A H; Høgsbro, Christine F; Bak Holm, Jacob; Johansen, Kristoffer Haurum; Jensen, Tina Kold; Andrade, Anderson Martino; Swan, Shanna H; Bornehag, Carl-Gustaf; Brunak, Søren; Jegou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

    2017-08-01

    Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women. © 2017 Society for Reproduction and Fertility.

  11. Prenatal cigarette smoke exposure causes hyperactivity and aggressive behavior: role of altered catecholamines and BDNF.

    PubMed

    Yochum, Carrie; Doherty-Lyon, Shannon; Hoffman, Carol; Hossain, Muhammad M; Zelikoff, Judith T; Richardson, Jason R

    2014-04-01

    Smoking during pregnancy is associated with a variety of untoward effects on the offspring. However, recent epidemiological studies have brought into question whether the association between neurobehavioral deficits and maternal smoking is causal. We utilized an animal model of maternal smoking to determine the effects of prenatal cigarette smoke (CS) exposure on neurobehavioral development. Pregnant mice were exposed to either filtered air or mainstream CS from gestation day (GD) 4 to parturition for 4h/d and 5d/wk, with each exposure producing maternal plasma concentration of cotinine equivalent to smoking <1 pack of cigarettes per day (25ng/ml plasma cotinine level). Pups were weaned at postnatal day (PND) 21 and behavior was assessed at 4weeks of age and again at 4-6months of age. Male, but not female, offspring of CS-exposed dams demonstrated a significant increase in locomotor activity during adolescence and adulthood that was ameliorated by methylphenidate treatment. Additionally, male offspring exhibited increased aggression, as evidenced by decreased latency to attack and number of attacks in a resident-intruder task. These behavioral abnormalities were accompanied by a significant decrease in striatal and cortical dopamine and serotonin and a significant reduction in brain-derived neurotrophic factor (BDNF) mRNA and protein. Taken in concert, these data demonstrate that prenatal exposure to CS produces behavioral alterations in mice that are similar to those observed in epidemiological studies linking maternal smoking to neurodevelopmental disorders. Further, these data also suggest a role for monaminergic and BDNF alterations in these effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Slatkin, D.N.; Stoner, R.D.; Rosander, K.M.

    1988-06-01

    Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose formore » CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo.« less

  13. Congenitally athymic nude (nu/nu) mice have Thy-1-bearing immunocompetent helper T cells in their peritoneal cavity

    PubMed Central

    1980-01-01

    Heavily irradiated peritoneal cells (PC) from congenitally athymic nude (nu/nu) mice markedly restored the impaired in vitro antibody response of nu/nu spleen cells to sheep erythrocyte antigens (T-dependent antigen), whereas irradiated spleen or lymph node cells from nu/nu mice had no effect on the response. This activity of the irradiated PC of nu/nu mice was completely abolished by treatment with anti-Thy-1.2 antiserum plus normal guinea pig serum (C') and is, therefore, attributable to a function of matured T cells. PMID:6966314

  14. Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

    PubMed

    Dulka, Eden A; Moenter, Suzanne M

    2017-11-01

    Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

  15. Prenatal and postnatal cocaine exposure predict teen cocaine use

    PubMed Central

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2015-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

  16. Prenatal maternal stress in relation to the effects of prenatal lead exposure on toddler cognitive development.

    PubMed

    Zhou, Leilei; Xu, Jian; Zhang, Jinsong; Yan, Chonghuai; Lin, Yanfen; Jia, Yinan; Hu, Wenjing

    2017-03-01

    To evaluate the effects of maternal lead exposure during pregnancy on toddler cognitive development and the potential effect modification by maternal stress. We conducted a prospective birth-cohort study in Shanghai from 2010 to 2012 and investigated 225 mother-infant pairs. The mothers were recruited in mid-to-late pregnancy and children were followed up until 24-36 months old. A self-administered Symptom Checklist-90-Revised Scale (SCL-90-R) was used to assess maternal emotional stress during pregnancy. Maternal whole blood lead levels were measured during gestational weeks 28-36. The toddlers' cognitive levels were assessed using the Gesell Development Scale. Multiple linear regression models were established to explore the main effects of prenatal lead exposure on toddlers' cognitive abilities and the modifying effects of maternal stress. Covariate information was collected through interviews, questionnaires and medical records. The mean maternal blood lead concentration was 3.30 (95%CI: 3.05, 3.57) μg/dL. After adjusting for relevant confounders, no significant associations of maternal blood lead concentrations with toddlers' cognitive levels were observed in all five domains of the Gesell scale (P>0.05). However, the interaction between prenatal maternal blood lead and stress was significant in the domains of adaptive behavior, language and social behavior. When stratified by maternal stress levels, compared with non-significant associations (P>0.05) among low (P1-P75) prenatal stress group, adverse associations between maternal blood lead concentrations (log10-transformed) and toddlers' cognitive levels were observed among high (P75-P100) prenatal stress group in the domains of language (β=-33.82, 95%CI: -60.04, -7.59), social behavior (β=-41.00, 95%CI: -63.11, -18.89) and adaptive behavior (β=-17.93, 95%CI: -35.83, -0.03). Prenatal maternal stress may exacerbate the deleterious effects of prenatal exposure to lead on toddler cognitive development

  17. Fetuses with Down's Syndrome detected by prenatal screening are more likely to abort spontaneously than fetuses with Down's Syndrome not detected by prenatal screening.

    PubMed

    Leporrier, Nathalie; Herrou, Michel; Morello, Rémy; Leymarie, Pierre

    2003-01-01

    Pregnancy with Down's Syndrome is often terminated by miscarriage. We have investigated whether prenatal screening would lead preferentially to the identification of fetuses with Down's Syndrome prone to abort spontaneously. A comparison between the observed and the expected decrease in the prevalence of Down's Syndrome at term following extensive prenatal screening. A study from 1990 to 1998 in a limited and well controlled area of western France (Basse Normandie), with a birth rate close to 20,000 a year. Women under 38 years of age among whom prenatal screening for Down's Syndrome using biochemical tests and ultrasound findings became progressively extensive in this era. Our study was based on the registration of Down's Syndrome cases detected prenatally from screening, and live births with Down's Syndrome. Fetal loss rate in the population of prenatally detectable Down's Syndrome was evaluated by comparing the increase in detection of cases of Down's Syndrome following prenatal screening with the expected decrease in the number of cases of Down's Syndrome at birth. The results obtained were compared with published data on the rates of fetal losses postulated to occur among fetuses with Down's Syndrome. Comparison of the potential fetal loss rate in a population in whom Down's Syndrome was detected prenatally with the expected fetal loss rate of unselected ones. Prenatal screening resulted in a significant (42%) decrease (P < 0.001) in the prevalence at term of the disorder. Among the 53 fetuses with Down's Syndrome detected prenatally during the last three years of the study, about 50% would have aborted spontaneously if the pregnancy had been allowed to continue. This figure was significantly higher (P < 0.002) than expected on the basis of results from the literature, indicating that current estimates of miscarriage rates among fetuses with Down's Syndrome do not apply to the selected group of cases detectable from prenatal screening. Our results suggest that

  18. ANTIBODY FORMATION BY TRANSPLANTED BONE MARROW, SPLEEN, LYMPH NODE AND THYMUS CELLS IN IRRADIATED RECIPIENTS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stoner, R.D.; Bond, V.P.

    1963-01-14

    Immunological competence of immunized mouse bone marrow, spleen, lymph node, and thymus cells was demonstrated when specific recall tetanus antitoxin responses were elicited after transfer of these cells to isologous irradiated mice or rats. Lesser amounts of antibody were obtained as the genetic strain distance was increased between the relation of donor and host in the parental to F/sub 1/ and in the homologous combination within the same species. It was not possible in the heterologous situation to elicit significant amounts of antibody from rat bone marrow and other lymphoid cells following their transplantation into irradiated mice. Minimal but notmore » significant antibody responses were elicited from cells obtained from immunized rat spleen and thymus tissue. In a few experiments, it was possible to elicit antibody formation from a buffy coat suspension of circulating white cells following their transfer to irradiated recipients. Isologous nonimmunized bone marrow did not stimulate or hasten recovery of the ability to eiicit secondary antibody responses in previously immunized irradiated mice. The capacity to elicit primary antibody responses to tetanus toxoid was depressed in parental-bone-marrow-protected F/sub 1/ mice when these chimeras exhibited varying degrees of secondary disease. The depression of primary antibody responses in irradiated F/sub 1/ mice given parental bone marrow provides evidence for a donor mediated immunological depression of antibody synthesis by host-lymphoid tissues. (auth)« less

  19. The protective effect of 18β-Glycyrrhetinic acid against UV irradiation induced photoaging in mice.

    PubMed

    Kong, Song-Zhi; Chen, Hai-Ming; Yu, Xiu-Ting; Zhang, Xie; Feng, Xue-Xuan; Kang, Xin-Huang; Li, Wen-Jie; Huang, Na; Luo, Hui; Su, Zi-Ren

    2015-01-01

    It has been confirmed that repeated exposure of skin to ultraviolet (UV) radiation results in cutaneous oxidative stress and inflammation, which act in concert to cause premature skin aging, well known as photoaging. 18β-Glycyrrhetinic acid (GA), widely used to treat various tissue inflammations, is the main active component of licorice root, and has also been shown to possess favorable anti-oxidative property and modulating immunity function. In the present study, we investigated the potential protective effect of GA on UV-induced skin photoaging in a mouse model. During the experimental period of ten consecutive weeks, the dorsal depilated skin of mice was treated with topical GA for 2 hours prior to UV irradiation. The results showed that GA pretreatment significantly alleviated the macroscopic and histopathological damages in mice skin caused by UV. Meanwhile, the data also indicated that GA markedly up-regulated the activities of the antioxidant enzymes (SOD, GSH-Px), and increased the content of skin collagen, while obviously decreased malonaldehyde level and inhibited high expressions of matrix metalloproteinase-1 (MMP-1) and -3 (MMP-3), as well as down-regulated the expression of inflammatory cytokines such as IL-6, TNF-α and IL-10. Taken together, these findings amply demonstrate that GA observably attenuates UV-induced skin photoaging mainly by virtue of its antioxidative and anti-inflammatory properties, as well as regulating the abnormal expression of MMP-1 and MMP-3. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Prenatal Influences on Human Sexual Orientation: Expectations versus Data.

    PubMed

    Breedlove, S Marc

    2017-08-01

    In non-human vertebrate species, sexual differentiation of the brain is primarily driven by androgens such as testosterone organizing the brains of males in a masculine fashion early in life, while the lower levels of androgen in developing females organize their brains in a feminine fashion. These principles may be relevant to the development of sexual orientation in humans, because retrospective markers of prenatal androgen exposure, namely digit ratios and otoacoustic emissions, indicate that lesbians, on average, were exposed to greater prenatal androgen than were straight women. Thus, the even greater levels of prenatal androgen exposure experienced by fetal males may explain why the vast majority of them grow up to be attracted to women. However, the same markers indicate no significant differences between gay and straight men in terms of average prenatal androgen exposure, so the variance in orientation in men cannot be accounted for by variance in prenatal androgen exposure, but may be due to variance in response to prenatal androgens. These data contradict several popular notions about human sexual orientation. Sexual orientation in women is said to be fluid, sometimes implying that only social influences in adulthood are at work, yet the data indicate prenatal influences matter as well. Gay men are widely perceived as under-masculinized, yet the data indicate they are exposed to as much prenatal androgen as straight men. There is growing sentiment to reject "binary" conceptions of human sexual orientations, to emphasize instead a spectrum of orientations. Yet the data indicate that human sexual orientation is sufficiently polarized that groups of lesbians, on average, show evidence of greater prenatal androgen exposure than groups of straight women, while groups of gay men have, on average, a greater proportion of brothers among their older siblings than do straight men.

  1. Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin.

    PubMed

    Hiramoto, Keiichi; Yokoyama, Satoshi; Yamate, Yurika

    2017-03-01

    We previously reported that ultraviolet (UV) A eye irradiation reduces the ulcerative colitis induced by dextran sodium sulfate (DSS). This study examined the effects of UVA on colon carcinoma induced by azoxymethane (AOM) and DSS. We irradiated the eyes of ICR mice with UVA at a dose of 110 kJ/m 2 using an FL20SBLB-A lamp for the experimental period. In mice treated with these drugs, the symptom of colon carcinoma was reduced by UVA eye irradiation. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the blood were increased in AOM + DSS-treated mice; however, those levels were reduced by UVA eye irradiation. The expression of β-endorphin, methionine-enkephalin (OGF), μ-opioid receptor, and opioid growth factor receptor (OGFR) of the colon was increased in the AOM + DSS-treated mice, and these levels were increased further following UVA eye irradiation. When β-endorphin inhibitor was administered, the ameliorative effect of UVA eye irradiation was reduced, and the effect of eye irradiation disappeared entirely following the administration of naltrexone (inhibitor of both opioid receptor and OGFR). These results suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Women's experiences receiving abnormal prenatal chromosomal microarray testing results.

    PubMed

    Bernhardt, Barbara A; Soucier, Danielle; Hanson, Karen; Savage, Melissa S; Jackson, Laird; Wapner, Ronald J

    2013-02-01

    Genomic microarrays can detect copy-number variants not detectable by conventional cytogenetics. This technology is diffusing rapidly into prenatal settings even though the clinical implications of many copy-number variants are currently unknown. We conducted a qualitative pilot study to explore the experiences of women receiving abnormal results from prenatal microarray testing performed in a research setting. Participants were a subset of women participating in a multicenter prospective study "Prenatal Cytogenetic Diagnosis by Array-based Copy Number Analysis." Telephone interviews were conducted with 23 women receiving abnormal prenatal microarray results. We found that five key elements dominated the experiences of women who had received abnormal prenatal microarray results: an offer too good to pass up, blindsided by the results, uncertainty and unquantifiable risks, need for support, and toxic knowledge. As prenatal microarray testing is increasingly used, uncertain findings will be common, resulting in greater need for careful pre- and posttest counseling, and more education of and resources for providers so they can adequately support the women who are undergoing testing.

  3. [Social factors associated with use of prenatal care in Ecuador].

    PubMed

    Sánchez-Gómez, Amaya; Cevallos, William; Grijalva, Mario J; Silva-Ayçaguer, Luis C; Tamayo, Susana; Jacobson, Jerry O; Costales, Jaime A; Jiménez-Garcia, Rodrigo; Hernández-Barrera, Valentín; Serruya, Suzanne; Riera, Celia

    2016-11-01

    Prenatal care is a pillar of public health, enabling access to interventions including prevention of mother-to-child transmission of HIV and congenital syphilis. This paper describes social factors related to use of prenatal care in Ecuador. In 2011 and 2012, participant clinical history and interview information was analyzed from a national probability sample of 5 998 women presenting for delivery or miscarriage services in 15 healthcare facilities in Ecuador, to estimate prevalence of HIV, syphilis, and Chagas disease, and prenatal care coverage. The study found that 94.1% of women had attended at least one prenatal visit, but that attendance at no less than four visits was 73.1%. Furthermore, lower educational level, greater number of pregnancies, occupation in the agriculture or livestock sector, and membership in ethnic indigenous, Afro-Ecuadorian, or other minority groups were factors associated with lack of use (no prenatal visits) or insufficient use of prenatal care (fewer than four visits or first visit at >20 weeks gestation) in Ecuador. These results point to persistence of marked inequalities in access to and use of prenatal health services attributable to socioeconomic factors and to the need to strengthen strategies to address them, to reach the goal of universal prenatal care coverage.

  4. Prenatal cadmium exposure alters postnatal immune cell development and function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal

    2012-06-01

    Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspringmore » were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during

  5. Social Behavior of Offspring Following Prenatal Cocaine Exposure in Rodents: A Comparison with Prenatal Alcohol

    PubMed Central

    Sobrian, Sonya K.; Holson, R. R.

    2011-01-01

    Clinical and experimental reports suggest that prenatal cocaine exposure (PCE) alters the offsprings’ social interactions with caregivers and conspecifics. Children exposed to prenatal cocaine show deficits in caregiver attachment and play behavior. In animal models, a developmental pattern of effects that range from deficits in play and social interaction during adolescence, to aggressive reactions during competition in adulthood is seen. This review will focus primarily on the effects of PCE on social behaviors involving conspecifics in animal models. Social relationships are critical to the developing organism; maternally directed interactions are necessary for initial survival. Juvenile rats deprived of play behavior, one of the earliest forms of non-mother directed social behaviors in rodents, show deficits in learning tasks and sexual competence. Social behavior is inherently complex. Because the emergence of appropriate social skills involves the interplay between various conceptual and biological facets of behavior and social information, it may be a particularly sensitive measure of prenatal insult. The social behavior surveyed include social interactions, play behavior/fighting, scent marking, and aggressive behavior in the offspring, as well as aspects of maternal behavior. The goal is to determine if there is a consensus of results in the literature with respect to PCE and social behaviors, and to discuss discrepant findings in terms of exposure models, the paradigms, and dependent variables, as well as housing conditions, and the sex and age of the offspring at testing. As there is increasing evidence that deficits in social behavior may be sequelae of developmental exposure alcohol, we compare changes in social behaviors reported for prenatal alcohol with those reported for prenatal cocaine. Shortcomings in the both literatures are identified and addressed in an effort to improve the translational value of future experimentation. PMID:22144967

  6. Long-term bioavailability of redox nanoparticles effectively reduces organ dysfunctions and death in whole-body irradiated mice.

    PubMed

    Feliciano, Chitho P; Tsuboi, Koji; Suzuki, Kenshi; Kimura, Hiroyuki; Nagasaki, Yukio

    2017-06-01

    Radioprotective agents have been developed to protect patients against the damaging and lethal effects of ionizing radiation. However, in addition to the intrinsic ability to target reactive oxygen species (ROS), the ability to retain a significant level of bioavailability is desirable in radioprotective agents because that would increase and prolong their radioprotective efficacy and improve its safety. Here, we report the development of a novel nanoparticle-based radioprotective agent with improved bioavailability, which suppressed the adverse effects typically associated with low-molecular-weight (LMW) antioxidants. We developed biocompatible and colloidally stable nanoparticles in which nitroxide radicals that were covalently conjugated (redox nanoparticles, RNP N ) effectively scavenged radiation-induced ROS with a characteristically prolonged bioavailability and tissue-residence time compared with that of conventional LMW antioxidants. The confinement of the nitroxide radicals in the RNP N core prevented its rapid metabolism and excretion out of the body. The nano-sized formulation prevented internalization of RNP N in healthy cells, thereby preserving the normal function of the redox reactions in the cell. This improved pharmacological performance dramatically reduced the radiation-induced organ dysfunctions and increased the survival time of the lethally irradiated mice when the nanoparticles were administered 3-24 h before whole-body irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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…

  8. [Adaptation of the process of prenatal care in accordance with criteria established by the Humanization of Prenatal and Birth Program and the World Health Organization].

    PubMed

    Polgliane, Rúbia Bastos Soares; Leal, Maria do Carmo; Amorim, Maria Helena Costa; Zandonade, Eliana; dos Santos Neto, Edson Theodoro

    2014-07-01

    The scope of this article is to assess the adequacy of the process of prenatal care provided to users of the Unified Health System in the city of Vitória, in accordance with criteria established by the Humanization of Prenatal and Birth Program (PHPN) and the World Health Organization (WHO). The information on the prenatal care records of 360 pregnant women interned in public hospitals in the city at the time of delivery were assessed. The information was collected, processed and submitted to descriptive statistical analysis for calculations of absolute and relative frequencies and confidence intervals. None of the pregnant women were given entirely appropriate prenatal care in accordance with WHO criteria, and only 5% of pregnant women received prenatal care in line with PHPN. 44.7% of the women did not begin prenatal care until the 4th month. With respect to conducting technical procedures in the appointments, the main emphasis was on checking maternal weight (95.0%) and blood pressure (95.6%). The results indicate the need for a review of the number of prenatal appointments in the municipality and the adoption of strategies to meet the minimum criteria that need to be performed during prenatal care in public health services.

  9. Prenatal testosterone and stuttering.

    PubMed

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Pathogenetic mechanisms in immune polioencephalomyelitis: induction of disease in immunosuppressed mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duffey, P.S.; Martinez, D.; Abrams, G.D.

    1976-02-01

    Immune polioencephalomyelitis (IPE) was induced by the i. p. injection of x-irradiated (10,000 R) syngeneic line I/sub b/ malignant lymphocytes into C58 mice that were 7 or more months old and in young mice immunosuppressed by x-ray or drugs. The occurrence of IPE in young immunosuppressed C58 mice was systematically analyzed. When mice less than 2 weeks old were x-irradiated with 600 R, IPE could not be induced. The incidence in 1-month-old mice was approximately 50 percent and increased progressively with the age except for a drop in incidence at 3 months. An analysis of the dose effects of x-irradiationmore » on the occurrence of IPE in mice of different ages revealed a marked increase in the incidence in 3- and 5-month-old mice beginning at dose levels of 450 R and 300 R, respectively. Considered together, these data indicated that two sub- populations of immunocytes differing in x-ray sensitivity interacted to protect mice from IPE. It appears that under natural conditions an x-ray sensitive cell population, possibly having suppressor function, decreased with age and made mice susceptible to induction of IPE. Five-month-old mice were immunosuppressed with an LD$sub 10$ of cyclophosphamide, prednisolone, or methotrexate to determine whether mice immunosuppressed with drugs also were susceptible to the induction of IPE. (auth)« less

  11. Associations between Prenatal Exposure to Black Carbon and Memory Domains in Urban Children: Modification by Sex and Prenatal Stress.

    PubMed

    Cowell, Whitney J; Bellinger, David C; Coull, Brent A; Gennings, Chris; Wright, Robert O; Wright, Rosalind J

    2015-01-01

    Whether fetal neurodevelopment is disrupted by traffic-related air pollution is uncertain. Animal studies suggest that chemical and non-chemical stressors interact to impact neurodevelopment, and that this association is further modified by sex. To examine associations between prenatal traffic-related black carbon exposure, prenatal stress, and sex with children's memory and learning. Analyses included N = 258 mother-child dyads enrolled in a Boston, Massachusetts pregnancy cohort. Black carbon exposure was estimated using a validated spatiotemporal land-use regression model. Prenatal stress was measured using the Crisis in Family Systems-Revised survey of negative life events. The Wide Range Assessment of Memory and Learning (WRAML2) was administered at age 6 years; outcomes included the General Memory Index and its component indices [Verbal, Visual, and Attention Concentration]. Relationships between black carbon and WRAML2 index scores were examined using multivariable-adjusted linear regression including effect modification by stress and sex. Mothers were primarily minorities (60% Hispanic, 26% Black); 67% had ≤12 years of education. The main effect for black carbon was not significant for any WRAML2 index; however, in stratified analyses, among boys with high exposure to prenatal stress, Attention Concentration Index scores were on average 9.5 points lower for those with high compared to low prenatal black carbon exposure (P3-way interaction = 0.04). The associations between prenatal exposure to black carbon and stress with children's memory scores were stronger in boys than in girls. Studies assessing complex interactions may more fully characterize health risks and, in particular, identify vulnerable subgroups.

  12. Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner.

    PubMed

    Bolton, Jessica L; Smith, Susan H; Huff, Nicole C; Gilmour, M Ian; Foster, W Michael; Auten, Richard L; Bilbo, Staci D

    2012-11-01

    Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pregnant mice were exposed to filtered air (FA) or diesel exhaust (DE) on embryonic days (E) 9-17. Prenatal DE induced a significant fetal brain cytokine response at E18 (46-390% over FA). As adults, offspring were fed either a low-fat diet (LFD) or high-fat diet (HFD) for 6 wk. Adult DE male offspring weighed 12% more and were 35% less active than FA male offspring at baseline, whereas there were no differences in females. Following HFD, DE males gained weight at the same rate as FA males, whereas DE females gained 340% more weight than FA females. DE-HFD males had 450% higher endpoint insulin levels than FA-HFD males, and all males on HFD showed decreased activity and increased anxiety, whereas females showed no differences. Finally, both DE males and females fed HFD showed increased microglial activation (30-66%) within several brain regions. Thus, prenatal air pollution exposure can "program" offspring for increased susceptibility to diet-induced weight gain and neuroinflammation in adulthood in a sex-specific manner.

  13. Hematological and TGF-beta variations after whole-body proton irradiation

    NASA Technical Reports Server (NTRS)

    Kajioka, E. H.; Andres, M. L.; Mao, X. W.; Moyers, M. F.; Nelson, G. A.; Gridley, D. S.

    2000-01-01

    The acute effects of proton whole-body irradiation on five bone-marrow-derived cell types and transforming growth factor-beta 1 (TGF-beta 1) were examined and compared to the effects of photons (60Co). C57BL/6 mice were exposed to 3 Gy (0.4 Gy/min) protons at spread-out Bragg peak (SOBP), protons at entry (E), or 60Co and euthanized on days 0.5-17 thereafter. 60Co-irradiated animals had decreased erythrocytes, hemoglobin and hematocrit at 12 hours post-exposure; depression was not noted in proton (SOBP or E)-irradiated groups until day 4. Significantly decreased leukocyte counts were observed at this same time in all irradiated groups, with lymphocyte loss being greater than that of monocytes, and the depression was generally maintained. In contrast, the levels of neutrophils and thrombocytes fluctuated, especially during the first week; significant differences were noted among irradiated groups in neutrophil levels. Plasma TGF-beta 1 was elevated on day 7 in the 60Co, but not proton, irradiated mice. Collectively, the data show that dramatic and persistent changes occurred in all irradiated groups. However, few differences in assay results were seen between animals exposed to protons (SOBP or E) or photons, as well as between the groups irradiated with either of the two regions of the proton Bragg curve.

  14. 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.…

  15. Promises, pitfalls and practicalities of prenatal whole exome sequencing.

    PubMed

    Best, Sunayna; Wou, Karen; Vora, Neeta; Van der Veyver, Ignatia B; Wapner, Ronald; Chitty, Lyn S

    2018-01-01

    Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

  16. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    PubMed

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse model.

    PubMed

    Guidi, Sandra; Stagni, Fiorenza; Bianchi, Patrizia; Ciani, Elisabetta; Giacomini, Andrea; De Franceschi, Marianna; Moldrich, Randal; Kurniawan, Nyoman; Mardon, Karine; Giuliani, Alessandro; Calzà, Laura; Bartesaghi, Renata

    2014-02-01

    Intellectual impairment is a strongly disabling feature of Down's syndrome, a genetic disorder of high prevalence (1 in 700-1000 live births) caused by trisomy of chromosome 21. Accumulating evidence shows that widespread neurogenesis impairment is a major determinant of abnormal brain development and, hence, of intellectual disability in Down's syndrome. This defect is worsened by dendritic hypotrophy and connectivity alterations. Most of the pharmacotherapies designed to improve cognitive performance in Down's syndrome have been attempted in Down's syndrome mouse models during adult life stages. Yet, as neurogenesis is mainly a prenatal event, treatments aimed at correcting neurogenesis failure in Down's syndrome should be administered during pregnancy. Correction of neurogenesis during the very first stages of brain formation may, in turn, rescue improper brain wiring. The aim of our study was to establish whether it is possible to rescue the neurodevelopmental alterations that characterize the trisomic brain with a prenatal pharmacotherapy with fluoxetine, a drug that is able to restore post-natal hippocampal neurogenesis in the Ts65Dn mouse model of Down's syndrome. Pregnant Ts65Dn females were treated with fluoxetine from embryonic Day 10 until delivery. On post-natal Day 2 the pups received an injection of 5-bromo-2-deoxyuridine and were sacrificed after either 2 h or after 43 days (at the age of 45 days). Untreated 2-day-old Ts65Dn mice exhibited a severe neurogenesis reduction and hypocellularity throughout the forebrain (subventricular zone, subgranular zone, neocortex, striatum, thalamus and hypothalamus), midbrain (mesencephalon) and hindbrain (cerebellum and pons). In embryonically treated 2-day-old Ts65Dn mice, precursor proliferation and cellularity were fully restored throughout all brain regions. The recovery of proliferation potency and cellularity was still present in treated Ts65Dn 45-day-old mice. Moreover, embryonic treatment restored

  18. 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"…

  19. Prenatal and adult androgen activities in alcohol dependence.

    PubMed

    Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

    2017-07-01

    Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Sensory Processing Disorder in a Primate Model: Evidence from a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

    ERIC Educational Resources Information Center

    Schneider, Mary L.; Moore, Colleen F.; Gajewski, Lisa L.; Larson, Julie A.; Roberts, Andrew D.; Converse, Alexander K.; DeJesus, Onofre T.

    2008-01-01

    Disrupted sensory processing, characterized by over- or underresponsiveness to environmental stimuli, has been reported in children with a variety of developmental disabilities. This study examined the effects of prenatal stress and moderate-level prenatal alcohol exposure on tactile sensitivity and its relationship to striatal dopamine system…

  1. Adequacy of Prenatal Care and Gestational Weight Gain

    PubMed Central

    Crandell, Jamie L.; Jones-Vessey, Kathleen

    2016-01-01

    Abstract Background: The goal of prenatal care is to maximize health outcomes for a woman and her fetus. We examined how prenatal care is associated with meeting the 2009 Institute of Medicine (IOM) guidelines for gestational weight gain. Sample: The study used deidentified birth certificate data supplied by the North Carolina State Center for Health Statistics. The sample included 197,354 women (≥18 years) who delivered singleton full-term infants in 2011 and 2012. Methods: A generalized multinomial model was used to identify how adequate prenatal care was associated with the odds of gaining excessive or insufficient weight during pregnancy according to the 2009 IOM guidelines. The model adjusted for prepregnancy body size, sociodemographic factors, and birth weight. Results: A total of 197,354 women (≥18 years) delivered singleton full-term infants. The odds ratio (OR) for excessive weight gain was 2.44 (95% CI 2.37–2.50) in overweight and 2.33 (95% CI 2.27–2.40) in obese women compared with normal weight women. The OR for insufficient weight gain was 1.15 (95% CI 1.09–1.22) for underweight and 1.34 (95% CI 1.30–1.39) for obese women compared with normal weight women. Prenatal care at the inadequate or intermediate levels was associated with insufficient weight gain (OR: 1.32, 95% CI 1.27–1.38; OR: 1.15, 95% CI 1.09–1.21, respectively) compared with adequate prenatal care. Women with inadequate care were less likely to gain excessive weight (OR: 0.88, 95% CI 0.86–0.91). Conclusions: Whereas prenatal care was effective for preventing insufficient weight gain regardless of prepregnancy body size, educational background, and racial/ethnic group, there were no indications that adequate prenatal care was associated with reduced risk for excessive gestational weight gain. Further research is needed to improve prenatal care programs for preventing excess weight gain. PMID:26741198

  2. Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.

    PubMed

    McFarland, Hugh I; Berkson, Julia D; Lee, Jay P; Elkahloun, Abdel G; Mason, Karen P; Rosenberg, Amy S

    2015-07-31

    Sublethal γ irradiation eliminates CD8+ T cell mediated memory responses. In this work, we explored how these memory responses could be rescued in the aftermath of such exposure. We utilized two models of CD8+ T cell mediated immunity: a mouse model of Listeria monocytogenes (LM) infection in which CD8+ T cells specific for LM expressed antigens (Listeriolysin O, LLO) can be tracked, and a murine skin graft model in which CD8+ T cells mediate rejection across a MHC class I (D(d)) disparity. In the LM immunized mice, LL0 specific CD8+ T memory cells were lost on irradiation, preserved with rapid revaccination with an attenuated strain 1-3 days post-irradiation (PI), and these mice survived a subsequent wild type LM challenge. A genetic "signature of rescue" identified a group of immune-associated mRNA maintained or upregulated following irradiation and rescue. A number of these factors, including IL-36γ, dectin-2 (Clec4n), and mir101c are upregulated rapidly after exposure of mice to sublethal γ radiation alone and are sustained by early, but not later rescue. Such factors will be evaluated as potential therapeutics to replace individual vaccines for global rescue of CD8+ T memory cell responses following sublethal γ irradiation. The skin allograft model mirrored that of the LM model in that the accelerated D(d) skin allograft rejection response was lost in mice exposed to sublethal γ radiation, but infusion of allogeneic D(d) expressing bone marrow cells 1-4 days PI preserved the CD8+ T memory mediated accelerated rejection response, further suggesting that innate immune responses may not always be essential to rescue of CD8+ memory T cells following γ irradiation. Published by Elsevier Ltd.

  3. Best practices for online Canadian prenatal health promotion: A public health approach.

    PubMed

    Chedid, Rebecca A; Terrell, Rowan M; Phillips, Karen P

    2017-11-04

    Prenatal health promotion provides information regarding pregnancy risks, protective behaviours and clinical and community resources. Typically, women obtain prenatal health information from health care providers, prenatal classes, peers/family, media and increasingly, Internet sites and mobile apps. Barriers to prenatal health promotion and related services include language, rural/remote location, citizenship and disability. Online public health platforms represent the capacity to reach underserved women and can be customised to address the needs of a heterogeneous population of pregnant women. Canadian government-hosted websites and online prenatal e-classes were evaluated to determine if accessible, inclusive, comprehensive and evidence-based prenatal health promotion was provided. Using a multijurisdictional approach, federal, provincial/territorial, municipal and public health region-hosted websites, along with affiliated prenatal e-classes, were evaluated based on four criteria: comprehensiveness, evidence-based information, accessibility and inclusivity. Online prenatal e-classes, federal, provincial/territorial and public health-hosted websites generally provided comprehensive and evidence-based promotion of essential prenatal topics, in contrast to municipal-hosted websites which provided very limited prenatal health information. Gaps in online prenatal health promotion were identified as lack of French and multilingual content, targeted information and representations of Indigenous peoples, immigrants and women with disabilities. Canadian online prenatal health promotion is broadly comprehensive and evidence-based, but fails to address the needs of non-Anglophones and represent the diverse population of Canadian pregnant women. It is recommended that agencies enhance the organisation of website pregnancy portals/pages and collaborate with other jurisdictions and community groups to ensure linguistically accessible, culturally-competent and inclusive

  4. Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure

    PubMed Central

    Blossom, Sarah J.; Melnyk, Stepan B.; Li, Ming; Wessinger, William D.; Cooney, Craig A.

    2016-01-01

    Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4+ T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1 mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4+ T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE. PMID:26812193

  5. Disorganized Cortical Patches Suggest Prenatal Origin of Autism

    MedlinePlus

    ... 2014 Disorganized cortical patches suggest prenatal origin of autism NIH-funded study shows disrupted cell layering process ... study suggests that brain irregularities in children with autism can be traced back to prenatal development. “While ...

  6. Primary Pupils' Preconceptions about Child Prenatal Development

    ERIC Educational Resources Information Center

    Zoldosova, Kristina; Prokop, Pavol

    2007-01-01

    The research deals a problem of primary pupils' preconceptions about a child prenatal development. Even the pupils cannot experience the phenomenon and can get only mediate information; their idea about the prenatal development is quite well constructed. The quality of the preconceptions depends mainly upon variety of informational sources kept at…

  7. Sexual orientation of male mouse offspring prenatally exposed to ethanol.

    PubMed

    Watabe, T; Endo, A

    1994-01-01

    Pregnant mice were intubated with either low (2 g/kg) or high (4 g/kg) dose of ethanol twice daily throughout the last third of the gestational period (from dg14 to dg18: gestational day; plug positive = dg 0). Ninety days after birth, the sexual orientation test was conducted on male offspring. This test was designed to observe a two-choice preference for either male or female partners in a setting in which the test animal could move freely between the two incentive compartments within which a stud male and an estrous female had been placed. We found that young adult males that had been exposed to ethanol prenatally have a decreased preference for the opposite sex and an increased preference for the same sex as a partner, although their physical development was apparently unaffected.

  8. Associations between Prenatal Exposure to Black Carbon and Memory Domains in Urban Children: Modification by Sex and Prenatal Stress

    PubMed Central

    Cowell, Whitney J.; Bellinger, David C.; Coull, Brent A.; Gennings, Chris; Wright, Robert O.; Wright, Rosalind J.

    2015-01-01

    Background Whether fetal neurodevelopment is disrupted by traffic-related air pollution is uncertain. Animal studies suggest that chemical and non-chemical stressors interact to impact neurodevelopment, and that this association is further modified by sex. Objectives To examine associations between prenatal traffic-related black carbon exposure, prenatal stress, and sex with children’s memory and learning. Methods Analyses included N = 258 mother-child dyads enrolled in a Boston, Massachusetts pregnancy cohort. Black carbon exposure was estimated using a validated spatiotemporal land-use regression model. Prenatal stress was measured using the Crisis in Family Systems-Revised survey of negative life events. The Wide Range Assessment of Memory and Learning (WRAML2) was administered at age 6 years; outcomes included the General Memory Index and its component indices [Verbal, Visual, and Attention Concentration]. Relationships between black carbon and WRAML2 index scores were examined using multivariable-adjusted linear regression including effect modification by stress and sex. Results Mothers were primarily minorities (60% Hispanic, 26% Black); 67% had ≤12 years of education. The main effect for black carbon was not significant for any WRAML2 index; however, in stratified analyses, among boys with high exposure to prenatal stress, Attention Concentration Index scores were on average 9.5 points lower for those with high compared to low prenatal black carbon exposure (P 3-way interaction = 0.04). Conclusion The associations between prenatal exposure to black carbon and stress with children’s memory scores were stronger in boys than in girls. Studies assessing complex interactions may more fully characterize health risks and, in particular, identify vulnerable subgroups. PMID:26544967

  9. Human prenatal diagnosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Filkins, K.; Russo, R.J.

    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.more » 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.« less

  10. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haley, Gwendolen E.; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR; Villasana, Laura

    2012-11-01

    Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 56}Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, wemore » assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.« less

  11. Psychopathology and Special Education Enrollment in Children with Prenatal Cocaine Exposure

    PubMed Central

    Levine, Todd P.; Lester, Barry; Lagasse, Linda; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Whitaker, Toni M.; Higgins, Rosemary; Hammond, Jane; Roberts, Mary B.

    2012-01-01

    Objective This study evaluated how enrollment in special education services in 11 year old children relates to prenatal cocaine exposure, psychopathology, and other risk factors. Method Participants were 498 children enrolled in The Maternal Lifestyle Study, a prospective, longitudinal, multisite study examining outcomes of children with prenatal cocaine exposure. Logistic regression was used to examine the effect of prenatal cocaine exposure and psychopathology on enrollment in an individualized education plan (a designation specific to children with special education needs), with environmental, maternal, and infant medical variables as covariates. Results Prenatal cocaine exposure, an interaction of prenatal cocaine exposure and Oppositional Defiant Disorder, child Attention Deficit Hyperactivity Disorder, parent-reported internalizing behaviors, and teacher-reported externalizing behaviors, predicted enrollment in an individualized education plan. Other statistically significant variables in the model were male gender, low birth weight, being small for gestational age, white race, caregiver change, low socio-economic status, low child intelligence quotient, caregiver depression, and prenatal marijuana exposure. Conclusions Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan with adjustment for covariates. Psychopathology also predicted this special education outcome, in combination with and independent of prenatal cocaine exposure. PMID:22487696

  12. Pathology of Serially Sacrificed Female B6C3F1 Mice Continuously Exposed to Very Low-Dose-Rate Gamma Rays.

    PubMed

    Tanaka, I B; Komura, J; Tanaka, S

    2017-03-01

    We have previously reported on life span shortening as well as increased incidence rates in several neoplasms in B6C3F1 mice that were continuously exposed to 21 mGy/day of gamma rays for 400 days. To clarify whether the life shortening was due to early appearance of neoplasms (shortened latency) or increased promotion/progression, 8-week-old female specific-pathogen-free B6C3F1 mice were gamma-ray irradiated at a low dose rate of 20 mGy/day for 400 days. At 100 days postirradiation, 60-90 mice were sacrificed, and thereafter every 100 days alongside the age-matched nonirradiated controls, for 700 days. Additional groups were allowed to live out their natural life span. Pathological examination was performed on all mice to identify lesions, non-neoplastic and neoplastic, as well as to determine the cause of death. Body weights were significantly increased in irradiated mice from sacrifice days 200-500. Incidence rates for spontaneously occurring non-neoplastic lesions, such as adrenal subcapsular cell hyperplasia, fatty degeneration of the liver, atrophy and tubulostromal hyperplasia of the ovaries, were significantly increased in irradiated mice. Significantly increased incidence rates with no shortening of latency periods were observed in irradiated mice for malignant lymphomas, hepatocellular adenomas/carcinomas, bronchioloalveolar adenomas, harderian gland adenoma/adenocarcinoma. Shortened latencies with significantly increased incidence rates were observed for adrenal subcapsular cell adenomas and ovarian neoplasms (tubulostromal adenoma, granulosa cell tumors) in irradiated mice. Life span shortening in mice exposed to 20 mGy/day was mostly due to malignant lymphomas. Multiple primary neoplasms were significantly increased in mice exposed to 20 mGy/day from sacrifice days 400-700 and in the life span group. Our results confirm that continuous low-dose-rate gamma-ray irradiation of female B6C3F1 mice causes both cancer induction (shortened latency) and

  13. Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

    PubMed

    McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

    2016-11-15

    Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

  14. Prenatal stress and hemodynamics in pregnancy: a systematic review.

    PubMed

    Levine, Terri A; Alderdice, Fiona A; Grunau, Ruth E; McAuliffe, Fionnuala M

    2016-10-01

    Maternal prenatal stress is associated with preterm birth, intrauterine growth restriction, and developmental delay. However, the impact of prenatal stress on hemodynamics during pregnancy remains unclear. This systematic review was conducted in order to assess the quality of the evidence available to date regarding the relationship between prenatal stress and maternal-fetal hemodynamics. The PubMed/Medline, EMBASE, PsycINFO, Maternity and Infant Care, Trip, Cochrane Library, and CINAHL databases were searched using the search terms pregnancy; stress; fetus; blood; Doppler; ultrasound. Studies were eligible for inclusion if prenatal stress was assessed with standardized measures, hemodynamics was measured with Doppler ultrasound, and methods were adequately described. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-accepted quality appraisal guidelines. Of 2532 studies reviewed, 12 met the criteria for inclusion. Six reported that prenatal stress significantly affects maternal or fetal hemodynamics; six found no significant association between maternal stress and circulation. Significant relationships between prenatal stress and uterine artery resistance (RI) and pulsatility (PI) indices, umbilical artery RI, PI, and systolic/diastolic ratio, fetal middle cerebral artery PI, cerebroplacental ratio, and umbilical vein volume blood flow were found. To date, there is limited evidence that prenatal stress is associated with changes in circulation. More carefully designed studies with larger sample sizes, repeated assessments across gestation, tighter control for confounding factors, and measures of pregnancy-specific stress will clarify this relationship.

  15. Prenatal corticosteroid exposure alters early developmental seizures and behavior

    PubMed Central

    Velíšek, Libor

    2011-01-01

    In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

  16. Group prenatal care attendance: determinants and relationship with care satisfaction

    PubMed Central

    Cunningham, Shayna D.; Grilo, Stephanie; Lewis, Jessica B.; Novick, Gina; Rising, Sharon Schindler; Tobin, Jonathan N; Ickovics, Jeannette R.

    2016-01-01

    Introduction Group prenatal care results in improved birth outcomes in randomized controlled trials, and better attendance at group prenatal care visits is associated with stronger clinical effects. This paper’s objectives are to identify determinants of group prenatal care attendance, and to examine the association between proportion of prenatal care received in a group context and satisfaction with care. Methods We conducted a secondary data analysis of pregnant adolescents (n=547) receiving group prenatal care in New York City (2008–2012). Multivariable linear regression models were used to test associations between patient characteristics and percent of group care sessions attended, and between the proportion of prenatal care visits that occurred in a group context and care satisfaction. Results Sixty-seven groups were established. Group sizes ranged from 3 to 15 women (mean=8.16, SD=3.08); 87% of groups enrolled at least five women. Women enrolled in group prenatal care supplemented group sessions with individual care visits. However, the percent of women who attended each group session was relatively consistent, ranging from 56% to 63%. Being born outside of the United States was significantly associated with higher group session attendance rates (B[SE]=11.46 [3.46], p=0.001), and women who received a higher proportion of care in groups reported higher levels of care satisfaction (B[SE]=0.11 [0.02], p<0.001). Discussion Future research should explore alternative implementation structures to improve pregnant women’s ability to receive as much prenatal care as possible in a group setting, as well as value-based reimbursement models and other incentives to encourage more widespread adoption of group prenatal care. PMID:27485493

  17. Oregon's Coordinated Care Organizations Increased Timely Prenatal Care Initiation And Decreased Disparities.

    PubMed

    Muoto, Ifeoma; Luck, Jeff; Yoon, Jangho; Bernell, Stephanie; Snowden, Jonathan M

    2016-09-01

    Policies at the state and federal levels affect access to health services, including prenatal care. In 2012 the State of Oregon implemented a major reform of its Medicaid program. The new model, called a coordinated care organization (CCO), is designed to improve the coordination of care for Medicaid beneficiaries. This reform effort provides an ideal opportunity to evaluate the impact of broad financing and delivery reforms on prenatal care use. Using birth certificate data from Oregon and Washington State, we evaluated the effect of CCO implementation on the probability of early prenatal care initiation, prenatal care adequacy, and disparities in prenatal care use by type of insurance. Following CCO implementation, we found significant increases in early prenatal care initiation and a reduction in disparities across insurance types but no difference in overall prenatal care adequacy. Oregon's reforms could serve as a model for other Medicaid and commercial health plans seeking to improve prenatal care quality and reduce disparities. Project HOPE—The People-to-People Health Foundation, Inc.

  18. Maternal age–based prenatal screening for chromosomal disorders

    PubMed Central

    Carroll, June C.; Rideout, Andrea; Wilson, Brenda J.; Allanson, Judith; Blaine, Sean; Esplen, Mary Jane; Farrell, Sandra; Graham, Gail E.; MacKenzie, Jennifer; Meschino, Wendy S.; Prakash, Preeti; Shuman, Cheryl; Taylor, Sherry; Tobin, Stasey

    2013-01-01

    Objective To explore views of women and health care providers (HCPs) about the changing recommendations regarding maternal age–based prenatal screening. Design Mixed-methods design. Setting Ontario. Participants A sample of women who had given birth within the previous 2 years and who had attended a family medicine centre, midwifery practice, or baby and mother wellness program (n = 42); and a random sample of family physicians (n = 1600), and all Ontario obstetricians (n = 694) and midwives (n = 334) who provided prenatal care. Methods We used focus groups (FGs) to explore women's views. Content analysis was used to uncover themes and delineate meaning. To explore HCPs' views, we conducted a cross-sectional self-completion survey. Main findings All FG participants (42 women in 6 FGs) expressed the importance of individual choice of prenatal screening modality, regardless of age. They described their perception that society considers women older than 35 to be at high obstetric risk and raised concerns that change in the maternal age–related screening policy would require education. The HCP survey response rate was 40%. Results showed 24% of HCPs agreed that women of any age should be eligible for invasive diagnostic testing regardless of prenatal screening results; 15% agreed that the age for diagnostic testing should be increased to 40 years, 14% agreed that diagnostic testing should be reserved for women with positive prenatal screening results, and 45% agreed that prenatal screening should remain unchanged. Conclusion Maternity care organizations have recommended that maternal age–based prenatal screening is no longer appropriate. Informed choice is of paramount importance to women and should be part of any change. Health care providers need to be engaged in and educated about any change to screening guidelines to offer women informed choices. PMID:23341678

  19. Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops.

    PubMed

    Lennikov, Anton; Kitaichi, Nobuyoshi; Fukase, Risa; Murata, Miyuki; Noda, Kousuke; Ando, Ryo; Ohguchi, Takeshi; Kawakita, Tetsuya; Ohno, Shigeaki; Ishida, Susumu

    2012-01-01

    Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice. C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 μl) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm². Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity. UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective effect increased with the dose of AST. Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.

  20. Photoprotection against UV-induced damage by skin-derived precursors in hairless mice.

    PubMed

    Xian, Dehai; Gao, Xiaoqing; Xiong, Xia; Xu, Jixiang; Yang, Lingyu; Pan, Lun; Zhong, Jianqiao

    2017-10-01

    Skin photodamage is associated with UV-induced overproduction of reactive oxygen species (ROS) and the inactivation of NF-E2-related factor 2 (Nrf2). Skin-derived precursor cells (SKPs), a population of dermal stem cells, are considered to be involved in wound repair and skin regeneration through the activation of Nrf2. However, no reports concentrate on the treatment of skin photodamage with SKPs. To investigate the photoprotective role of SKPs against UV-induced damage in mice. Fifty Balb/c hairless mice were divided into five groups (n=10), namely, normal (no intervention), model, prevention, treatment, and control groups. The latter four groups were dorsally exposed to UVA+UVB irradiation over a 2-week period. Mice in the prevention group received weekly SKP injections for 2weeks the day before irradiation. Mice in the treatment and Hanks groups received a two-time injection of SKPs and Hanks, respectively, after irradiation. One week after final intervention, skin appearance, pathological alterations, and oxidative indicators were evaluated by enzyme-linked immunosorbent assay, immunohistochemical analysis, and western blotting. After irradiation, lesions were observed on the dorsal skin of mice, including erythema, edema, scales, and wrinkles; however, these were significantly ameliorated by subcutaneous SKP injection. Hyperkeratosis, acanthosis, and spongiosis in the epidermis, as well as dermal papillae edema and inflammatory cell infiltration, were observed in both model and control groups; however, these conditions resolved with either pretreatment or posttreatment with SKPs. In addition, SKPs increased Nrf2, heme oxygenase-1, glutathione peroxidase, superoxide dismutase, catalase, and gluthathione expression, while decreasing levels of ROS, MDA, and H 2 O 2 . These findings suggest that SKPs have a photoprotective role against UV-induced damage in mice, which may be associated with their ability to scavenge photo-oxidative insults and activate Nrf2

  1. Prenatal Care: A Content-Based ESL Curriculum.

    ERIC Educational Resources Information Center

    Hassel, Elissa Anne

    A content-based curriculum in English as a Second Language (ESL) focusing on prenatal self-care is presented. The course was designed as a solution to the problem of inadequate prenatal care for limited-English-proficient Mexican immigrant women. The first three sections offer background information on and discussion of (1) content-based ESL…

  2. Ethnicity, education attainment, media exposure, and prenatal care in Vietnam.

    PubMed

    Trinh, Ha Ngoc; Korinek, Kim

    2017-02-01

    Prenatal care coverage in Vietnam has been improving, but ethnic minority women still lag behind in receiving adequate level and type of care. This paper examines ethnic disparities in prenatal care utilization by comparing two groups of ethnic minority and majority women. We examine the roots of ethnic disparity in prenatal care utilization, focusing on how education and media exposure change health behaviours and lessen disparities. We rely on the 2002 Vietnam Demographic and Health Survey to draw our sample, predictors and the three dimensions of prenatal care, including timing of onset, frequency of visits, and type of provider. Results from multinomial-, and binary-logistic regression provide evidence that ethnic minority women are less likely to obtain frequent prenatal care and seek care from professional providers than their majority counterparts. However, we find that ethnic minority women are more likely to obtain early care compared to ethnic majority women. Results for predicted probabilities suggest that education and media exposure positively influenced prenatal care behaviours with higher level of education and media exposure associating with accelerated probability of meeting prenatal care requirements. Our results imply the needs for expansion of media access and schools as well as positive health messages being broadcasted in culturally competent ways.

  3. Prenatal and early-life diesel exhaust exposure causes autism-like behavioral changes in mice.

    PubMed

    Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G

    2018-04-20

    Escalating prevalence of autism spectrum disorders (ASD) in recent decades has triggered increasing efforts in understanding roles played by environmental risk factors as a way to address this widespread public health concern. Several epidemiological studies show associations between developmental exposure to traffic-related air pollution and increased ASD risk. In rodent models, a limited number of studies have shown that developmental exposure to ambient ultrafine particulates or diesel exhaust (DE) can result in behavioral phenotypes consistent with mild ASD. We performed a series of experiments to determine whether developmental DE exposure induces ASD-related behaviors in mice. C57Bl/6J mice were exposed from embryonic day 0 to postnatal day 21 to 250-300 μg/m 3 DE or filtered air (FA) as control. Mice exposed developmentally to DE exhibited deficits in all three of the hallmark categories of ASD behavior: reduced social interaction in the reciprocal interaction and social preference tests, increased repetitive behavior in the T-maze and marble-burying test, and reduced or altered communication as assessed by measuring isolation-induced ultrasonic vocalizations and responses to social odors. These findings demonstrate that exposure to traffic-related air pollution, in particular that associated with diesel-fuel combustion, can cause ASD-related behavioral changes in mice, and raise concern about air pollution as a contributor to the onset of ASD in humans.

  4. HYDRONEPHROSIS IN MICE EXPOSED TO TCDD-CONTAMINATED BREAST MILK: IDENTIFICATION OF THE PEAK PERIOD OF SENSITIVITY AND ASSESSMENT OF POTENTIAL RECOVERY

    EPA Science Inventory

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of hydronephrosis in mice both pre- and post-natally. ritical period of sensitivity to TCDD could not be identified for the hydronephrotic response induced prenatally since the urinary tract appeared equally sensitive...

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guo, Yixian; Zhang, Lanfang; Wan, Suigui

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

  6. [Recent advances in prenatal diagnostics].

    PubMed

    Lapaire, O; Holzgreve, W; Miny, P; Hösli, I; Hahn, S; Tercanli, S

    2006-11-01

    During the last years, technical improvements have increased the possibilities in prenatal ultrasound. During the eighties and nineties, fetal malformations were increasingly detected and specified. Since a few years, the measurement of the fetal nuchal translucency between 11 and 14 weeks of gestation has been implemented to calculate the individual risk, in combination with most recent biochemical markers. Today, the sonographic measurement of the nuchal translucency is regarded as a valuable screening tool for chromosomal anomalies in prenatal medicine. Beside standardized examinations, a profound information and counseling of the pregnant women should be emphasized. With the improvement of the specific maternal risk calculation, using the sonographic measurement of the nuchal translucency, the biochemical markers and the maternal age, unnecessary invasive examinations may be prevented and their overall number can significantly be reduced. The same trend is seen in the whole field of prenatal medicine, illustrated by the detection of the fetal rhesus D status from the maternal blood and the use of Doppler ultrasound in the management of fetal anemia.

  7. Disentangling prenatal and inherited influences in humans with an experimental design.

    PubMed

    Rice, Frances; Harold, Gordon T; Boivin, Jacky; Hay, Dale F; van den Bree, Marianne; Thapar, Anita

    2009-02-17

    Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

  8. Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice: protective effect of alpha-lipoic acid.

    PubMed

    Manda, Kailash; Ueno, Megumi; Moritake, Takashi; Anzai, Kazunori

    2007-02-12

    Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role alpha-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such cognitive dysfunction. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Moreover, alpha-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that alpha-lipoic acid is potent neuroprotective antioxidant.

  9. Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.

    PubMed

    Aryankalayil, Molykutty J; Chopra, Sunita; Makinde, Adeola; Eke, Iris; Levin, Joel; Shankavaram, Uma; MacMillan, Laurel; Vanpouille-Box, Claire; Demaria, Sandra; Coleman, C Norman

    2018-06-19

    Accidental exposure to life-threatening radiation in a nuclear event is a major concern; there is an enormous need for identifying biomarkers for radiation biodosimetry to triage populations and treat critically exposed individuals. To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice. Mice were whole body irradiated with X-rays (2 Gy-15 Gy); blood was collected at various time-points post-exposure; total RNA was isolated; miRNA microarrays were performed; miRNAs differentially expressed in irradiated vs. unirradiated controls were identified; feature extraction and classification models were applied to predict dose-differentiating miRNA signature. We observed a time and dose responsive alteration in the expression levels of miRNAs. Maximum number of miRNAs were altered at 24-h and 48-h time-points post-irradiation. A 23-miRNA signature was identified using feature selection algorithms and classifier models. An inverse correlation in the expression level changes of miR-17 members, and their targets were observed in whole body irradiated mice and non-human primates. Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.

  10. Radiation Exposure Decreases the Quantity and Quality of Cardiac Stem Cells in Mice

    PubMed Central

    Luo, Lan; Urata, Yoshishige; Yan, Chen; Hasan, Al Shaimaa; Goto, Shinji; Guo, Chang-Ying; Tou, Fang-Fang; Xie, Yucai; Li, Tao-Sheng

    2016-01-01

    Radiation exposure may increase cardiovascular disease risks; however, the precise molecular/cellular mechanisms remain unclear. In the present study, we examined the hypothesis that radiation impairs cardiac stem cells (CSCs), thereby contributing to future cardiovascular disease risks. Adult C57BL/6 mice were exposed to 3 Gy γ-rays, and heart tissues were collected 24 hours later for further experiments. Although c-kit-positive cells were rarely found, radiation exposure significantly induced apoptosis and DNA damage in the cells of the heart. The ex vivo expansion of CSCs from freshly harvested atrial tissues showed a significantly lower production of CSCs in irradiated mice compared with healthy mice. The proliferative activity of CSCs evaluated by Ki-67 expression was not significantly different between the groups. However, compared to the healthy control, CSCs expanded from irradiated mice showed significantly lower telomerase activity, more 53BP1 foci in the nuclei, lower expression of c-kit and higher expression of CD90. Furthermore, CSCs expanded from irradiated mice had significantly poorer potency in the production of insulin-like growth factor-1. Our data suggest that radiation exposure significantly decreases the quantity and quality of CSCs, which may serve as sensitive bio-parameters for predicting future cardiovascular disease risks. PMID:27195709

  11. Leukopenia, Neutropenia and Bacteremia in Mouse Following Two Successive Irradiations by X-Rays; LEUCOPENIE, NEUTROPENIE ET BACTERIEMIE CHEZ LA SOURIS, APRES DEUX IRRADIATIONS SUCCESSIVES PAR RAYONS X

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mewissen, D.J.; Betz, E.H.; Betz-Bareau, M.

    A study was made of the course of leukopenia, neutropenia, and bacteremia in mice subjected to whole body x radiation to determine a possible correlation between their variations and the bimodal nature of the lethal response. The mice, five days apart, were subjected to two whole-body x irradiations of 220 r each. The mice were sacrificed at intervals of 9, 12, 14, 19, 29, and 40 days after the first exposure. Spleen and cardiac blood examinations were made on each mouse. The results showed that the percentage of animals in which the leukopenia was marked passed through maxima near themore » 12th day and the 22nd day. The maxima coincide in time with the highest mortality rates observed in irradiated mice. The neutropenia goes through two critical minima which are essentially contemporaneous with these rates. A bacteremia was observed only in the vicinity of the first maximum in the mortality rate. (J.S.R.)« less

  12. Expectations and satisfaction of pregnant women: unveiling prenatal care in primary care.

    PubMed

    Aparecida Maciel Cardelli, Alexandrina; Li Marrero, Tai; Aparecida Pimenta Ferrari, Rosângela; Trevisan Martins, Júlia; Serafim, Deise

    2016-06-01

    To analyze the perception of primiparous women about prenatal care in Basic Health Units in a municipality in southern Brazil. This is a qualitative research from the perspective of Social Representation Theory, from the following question: How has been the pre-natal care for you? Eighteen pregnant women were interviewed. The analysis resulted in three categories: Expectation representation about prenatal care; Rescuing the care offered in prenatal consultation; Unveiling the (dis) satisfaction with prenatal consultation. The prenatal care was apprehended as an essential moment for safe pregnancy, although centered on the doctor's figure and guarantee access to early laboratory and imaging tests. On the other hand, dissatisfaction was revealed from the reception at the entrance to the health unit to the consultations access, although some statements suggest timely satisfaction. Prenatal care did not meet the specific expectations of the study group and unveiled that the nurse did not supply it, as a member of the multidisciplinary team. The organization of the nursing work process in primary care, related to prenatal care, needs to be revisited to promote the effectiveness of its actions.

  13. Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice.

    PubMed

    Duan, Yabin; Yao, Xingchen; Zhu, Junbo; Li, Yongping; Zhang, Juanling; Zhou, Xuejiao; Qiao, Yijie; Yang, Meng; Li, Xiangyang

    2017-12-01

    The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation. Yak-activated protein was administered orally to mice in the treatment groups and an equal volume of saline was administered orally to mice in the normal control and radiation model groups for 14 days. The positive control group received amifostine (150 mg/kg) via intraperitoneal injection. With the exception of the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body once. Changes in the peripheral hemogram, thymus and spleen indices, DNA content in the bone marrow, interleukin (IL)-2 and IL-6 levels, and the expression levels of B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) following irradiation were assessed. The low dose of yak-activated protein significantly increased Spleen indices in mice 14 days after irradiation and the high and middle dose of yak-activated protein significantly increased Thymus indices in mice 14 days after irradiation (P<0.05) compared with the control group. In addition, hemogram results increased gradually in the low-yak-activated protein dose group and were significantly higher 7 days after irradiation compared with the radiation model group (P<0.05). The DNA content in the bone marrow was markedly increased in the yak-activated protein groups, and increased significantly in the low dose group at 7 days post-irradiation compared with the radiation model group (P<0.05). The IL-2 content was significantly

  14. Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice

    PubMed Central

    Duan, Yabin; Yao, Xingchen; Zhu, Junbo; Li, Yongping; Zhang, Juanling; Zhou, Xuejiao; Qiao, Yijie; Yang, Meng; Li, Xiangyang

    2017-01-01

    The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation. Yak-activated protein was administered orally to mice in the treatment groups and an equal volume of saline was administered orally to mice in the normal control and radiation model groups for 14 days. The positive control group received amifostine (150 mg/kg) via intraperitoneal injection. With the exception of the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body once. Changes in the peripheral hemogram, thymus and spleen indices, DNA content in the bone marrow, interleukin (IL)-2 and IL-6 levels, and the expression levels of B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) following irradiation were assessed. The low dose of yak-activated protein significantly increased Spleen indices in mice 14 days after irradiation and the high and middle dose of yak-activated protein significantly increased Thymus indices in mice 14 days after irradiation (P<0.05) compared with the control group. In addition, hemogram results increased gradually in the low-yak-activated protein dose group and were significantly higher 7 days after irradiation compared with the radiation model group (P<0.05). The DNA content in the bone marrow was markedly increased in the yak-activated protein groups, and increased significantly in the low dose group at 7 days post-irradiation compared with the radiation model group (P<0.05). The IL-2 content was significantly

  15. Prenatal screening: current practice, new developments, ethical challenges.

    PubMed

    de Jong, Antina; Maya, Idit; van Lith, Jan M M

    2015-01-01

    Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing (NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent 'reproductive autonomy' is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue. © 2014 John Wiley & Sons Ltd.

  16. Prenatal Nutritional Deficiency and Risk of Adult Schizophrenia

    PubMed Central

    Brown, Alan S.; Susser, Ezra S.

    2008-01-01

    Converging evidence suggests that a neurodevelopmental disruption plays a role in the vulnerability to schizophrenia. The authors review evidence supporting in utero exposure to nutritional deficiency as a determinant of schizophrenia. We first describe studies demonstrating that early gestational exposure to the Dutch Hunger Winter of 1944–1945 and to a severe famine in China are each associated with an increased risk of schizophrenia in offspring. The plausibility of several candidate micronutrients as potential risk factors for schizophrenia and the biological mechanisms that may underlie these associations are then reviewed. These nutrients include folate, essential fatty acids, retinoids, vitamin D, and iron. Following this discussion, we describe the methodology and results of an epidemiologic study based on a large birth cohort that has tested the association between prenatal homocysteine, an indicator of serum folate, and schizophrenia risk. The study capitalized on the use of archived prenatal serum specimens that make it possible to obtain direct, prospective biomarkers of prenatal insults, including levels of various nutrients during pregnancy. Finally, we discuss several strategies for subjecting the prenatal nutritional hypothesis of schizophrenia to further testing. These approaches include direct assessment of additional prenatal nutritional biomarkers in relation to schizophrenia in large birth cohorts, studies of epigenetic effects of prenatal starvation, association studies of genes relevant to folate and other micronutrient deficiencies, and animal models. Given the relatively high prevalence of nutritional deficiencies during pregnancy, this work has the potential to offer substantial benefits for the prevention of schizophrenia in the population. PMID:18682377

  17. Neonatal Neurobehavioral and Neuroanatomic Correlates of Prenatal Cocaine Exposure

    PubMed Central

    FRANK, DEBORAH A.; AUGUSTYN, MARILYN; ZUCKERMAN, BARRY S.

    2008-01-01

    Complex methodologic challenges face researchers studying the effects of prenatal cocaine exposure on infant outcome. These include unavoidable imprecision in ascertaining the gestational timing and dose of cocaine to which the fetus was exposed and difficulties in identifying and quantifying the confounding, mediating, and moderating variables. Review of research on neonatal behavioral and cranial ultrasound findings following in utero cocaine exposure is used to illustrate these issues. We conclude that there are measurable but not dramatic dose-related effects of prenatal cocaine exposure on infant central nervous system structure and function. The effects of dose of prenatal cocaine exposure on later child development remain to be determined. Such research would be facilitated by a scientific consensus delineating relative doses of prenatal cocaine exposure. PMID:9668396

  18. Psychosexual development: an examination of the role of prenatal hormones.

    PubMed

    Ehrhardt, A A; Meyer-Bahlburg, H F

    Naturally occurring endocrine syndromes and the offspring from steroid-treated pregnancies are the major sources of evidence for a role of prenatal hormones in psychosexual development in man. Effects of prenatal androgens have been established for the sex-dimorphic behaviour clusters of energy expenditure (increased), parenting rehearsal (decreased), peer associations (shifted to male), and grooming-related behaviour (decreased); most of the information was obtained on the syndrome of congenital adrenal hyperplasia and in progestin-induced female hermaphroditism. Studies of children and adults exposed prenatally to exogenous oestrogens and/or progestagens suggest slight demasculinizing effects but cannot yet be considered conclusive. Gender identity is largely dependent on the sex of rearing; a direct role of prenatal hormones in its formation has not been shown. The evidence for the role of prenatal hormones in the development of sexual orientation is inconclusive.

  19. Korean women's attitudes toward pregnancy and prenatal care.

    PubMed

    Pritham, U A; Sammons, L N

    1993-01-01

    A convenience sample of 40 native-born pregnant Korean women receiving prenatal care at a U.S. military facility in a major metropolitan area in Korea completed a questionnaire about attitudes toward pregnancy and prenatal care. Responses revealed a family life characterized by positive maternal and paternal perceptions of the pregnancy and less preference for a male child than we had anticipated. Traditional beliefs in Tae Mong, a conception dream, and Tae Kyo, rituals for safe childbirth, were followed. Food taboos, including protein sources, were reported. Attitudes toward prenatal care services, care providers, and maternal health habits are described.

  20. Moral maturity and delinquency after prenatal alcohol exposure.

    PubMed

    Schonfeld, Amy M; Mattson, Sarah N; Riley, Edward P

    2005-07-01

    Prenatal exposure to alcohol is associated with cognitive, behavioral and social deficits, including delinquency. Although delinquent populations and those with intellectual and behavioral deficits exhibit impaired moral judgment and reasoning, this area remains unexplored in alcohol-exposed individuals. Moral maturity and delinquency were evaluated in 27 participants with prenatal alcohol exposure (ALC group) and 29 nonexposed controls (CON group) matched on age (range: 10-18), gender, handedness, socioeconomic status and ethnicity. Moral maturity was evaluated using the Sociomoral Reflection Measure-Short Form, and delinquency was evaluated with the Conduct Disorder (CD) Questionnaire. Additional measures included social desirability and inhibition. The ALC group performed at a lower level of moral maturity than the CON group. Whereas Verbal IQ primarily predicted this difference, a deficit on the moral value judgment having to do with relationships with others was specific to prenatal alcohol exposure. Furthermore, delinquency was higher in the ALC group, and specific sociomoral values were predictive of delinquent behavior. Finally, half of the children and adolescents with a history of prenatal alcohol exposure but without fetal alcohol syndrome had probable CD. The results of this study indicate that interventions aimed at reducing delinquency in those with prenatal alcohol exposure are necessary, and targeting moral judgment for this purpose may be beneficial.

  1. Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hanson, Miranda L.; Brundage, Kathleen M.; Schafer, Rosana

    2010-01-15

    Cadmium (Cd) is both an environmental pollutant and a component of cigarette smoke. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports in the literature of immunomodulatory effects of prenatal exposure to Cd. The sonic hedgehog (Shh) and Wnt/beta-catenin pathways are required for thymocyte maturation. Several studies have demonstrated that Cd exposure affects these pathways in different organ systems. This study was designed to investigate the effect of prenatal Cd exposure on thymocyte development, and to determine if these effects were linked to dysregulation of Shh and Wnt/beta-catenin pathways. Pregnant C57Bl/6more » mice were exposed to an environmentally relevant dose (10 ppm) of Cd throughout pregnancy and effects on the thymus were assessed on the day of birth. Thymocyte phenotype was determined by flow cytometry. A Gli:luciferase reporter cell line was used to measure Shh signaling. Transcription of target genes and translation of key components of both signaling pathways were assessed using real-time RT-PCR and western blot, respectively. Prenatal Cd exposure increased the number of CD4{sup +} cells and a subpopulation of double-negative cells (DN; CD4{sup -}CD8{sup -}), DN4 (CD44{sup -}CD25{sup -}). Shh and Wnt/beta-catenin signaling were both decreased in the thymus. Target genes of Shh (Patched1 and Gli1) and Wnt/beta-catenin (c-fos, and c-myc) were affected differentially among thymocyte subpopulations. These findings suggest that prenatal exposure to Cd dysregulates two signaling pathways in the thymus, resulting in altered thymocyte development.« less

  2. Effects of low-level chronic irradiation on radiosensitivity of mammals: modeling and experimental studies

    NASA Astrophysics Data System (ADS)

    Smirnova, O. A.; Yonezawa, M.

    Effects of low dose rate chronic irradiation on radiosensitivity of mammals mice are studied by experimental and modeling methods Own and reference experiments show that priming chronic low-level short-term and long-term exposures to radiation induce respectively elevated radiosensitivity and lowered radiosensitivity radioresistance in mice The manifestation of these radiosensitization and radioprotection effects are respectively increased and decreased mortality of preirradiated specimens after challenge acute irradiation in comparison with those for previously unexposed ones Taking into account that the reason of the animal death in the experiments was the hematopoietic syndrome the biophysical models of the critical body system hematopoiesis are used to simulate the dynamics of the major hematopoietic lines in mice exposed to challenge acute irradiation following the chronic one Juxtaposition of the modeling results obtained and the relevant experimental data shows that the radiosensitization effect of chronic low-level short-term less than 1 month preirradiation on mice is due to increased radiosensitivity of lymphopoietic granulocytopoietic and erythropoietic systems accompanied by increased or close to the normal level radiosensitivity of thrombocytopoietic system which are induced by the above-indicated exposure In turn the radioprotection effect of chronic low-level long-term more than 1 month preirradiation on mice is caused by decreased radiosensitivity radioresistance of the granulocytopoietic system which

  3. Postnatal outcomes of prenatally diagnosed 45,X/46,XX.

    PubMed

    Tokita, Mari J; Sybert, Virginia P

    2016-05-01

    High quality information is critical for informed decision-making in pregnancy following a prenatal diagnosis of sex chromosome aneuploidy. The goal of this study was to define the spectrum of outcomes in patients with prenatally diagnosed 45,X/46,XX mosaic Turner syndrome in order to provide a better basis for genetic counseling at the time of intrauterine diagnosis. Phenotype data for twenty-five patients with prenatally diagnosed 45,X/46,XX mosaicism were collected by retrospective chart review and, when possible, semi-structured telephone interview. Existing data from a cohort of 58 patients with postnatally diagnosed 45,X/46,XX mosaicism were used for comparison. Relative to those diagnosed postnatally, prenatal patients were more likely to have normal growth and normal secondary sexual development, less likely to manifest distinctive Turner syndrome features such as nuchal webbing and edema, and had significantly fewer renal defects. These differences underscore the need for a nuanced approach to prenatal counseling in cases of 45,X/46,XX mosaicism. © 2016 Wiley Periodicals, Inc.

  4. Breaking bad news in prenatal medicine: a literature review.

    PubMed

    Luz, Rita; George, Astrid; Spitz, Elisabeth; Vieux, Rachel

    2017-02-01

    The diagnosis of a fetal anomaly in perinatal medicine forces expectant parents and healthcare providers to face the difficult process of breaking bad news. This exploratory literature review was aimed at providing a medical and psychological view of the psychological experience in expectant parents and physicians in the context of prenatal diagnosis of a fetal anomaly. An exploratory search of PubMed and PsycINFO/PsycARTICLES databases performed by an interdisciplinary team composed of a physician and psychologists. Search terms were: prenatal diagnosis AND bad news; prenatal diagnosis AND psychological consequences; prenatal diagnosis AND psychological sequelae; prenatal diagnosis AND fetal abnormality. The processing of selected articles followed a standardised five-step procedure. A total of 860 articles were screened of which 32 were retained for analysis. Four main themes emerged from the explanatory content analysis: (1) parents' subjective experience; (2) physicians' subjective experience; (3) encounters between expectant parents and professionals; and (4) ethical challenges in breaking bad news in prenatal medicine. Expectant parents go through a complex and multidimensional experience when the diagnosis of a fetal anomaly is disclosed. Simultaneously, physicians consider breaking bad news as a very stressful event and are poorly prepared in this regard. A better knowledge of factors underlying psychological adjustment of the parental dyad and on the subjective experience of physicians delivering these diagnoses could enable better adaptation for both patients and professionals.

  5. MicroCT and microMRI imaging of a prenatal mouse model of increased brain size

    NASA Astrophysics Data System (ADS)

    López, Elisabeth K. N.; Stock, Stuart R.; Taketo, Makoto M.; Chenn, Anjen; Ravosa, Matthew J.

    2008-08-01

    There are surprisingly few experimental models of neural growth and cranial integration. This and the dearth of information regarding fetal brain development detract from a mechanistic understanding of cranial integration and its relevance to the patterning of skull form, specifically the role of encephalization on basicranial flexion. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of β-catenin to isolate the effects of relative brain size on craniofacial development. These mice develop highly enlarged brains due to an increase in neural precursors, and differences between transgenic and wild-type mice are predicted to result solely from variation in brain size. Comparisons of wild-type and transgenic mice at several prenatal ages were performed using microCT (Scanco Medical MicroCT 40) and microMRI (Avance 600 WB MR spectrometer). Statistical analyses show that the larger brain of the transgenic mice is associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification using microCT also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life history factors are held constant, the ontogeny of a metabolically costly structure such as a brain may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.

  6. Prenatal Maternal Depressive Symptoms Predict Early Infant Health Concerns.

    PubMed

    Coburn, S S; Luecken, L J; Rystad, I A; Lin, B; Crnic, K A; Gonzales, N A

    2018-06-01

    Recent research suggests that health disparities among low-SES and ethnic minority populations may originate from prenatal and early life exposures. Postpartum maternal depressive symptoms have been linked to poorer infant physical health, yet prenatal depressive symptoms not been thoroughly examined in relation to infant health. In a prospective study of low-income Mexican American mothers and their infants, women (N = 322, median age 27.23, IQR = 22.01-32.54) completed surveys during pregnancy (median gestation 39.50, IQR = 38.71-40.14 weeks) and 12 weeks after birth. We investigated (1) if prenatal depressive symptoms predicted infant physical health concerns at 12 weeks of age, (2) whether these associations occurred above and beyond concurrent depressive symptoms, and (3) if birth weight, gestational age, and breastfeeding were mediators of prenatal depression predicting subsequent infant health. Higher prenatal depressive symptoms were associated with more infant physical health concerns at 12 weeks (p < .001), after accounting for 12-week maternal depressive symptoms, breastfeeding, gestational age, and birth weight. Twelve-week maternal depressive symptoms were concurrently associated with more infant health concerns (p < .01). Birth weight, gestational age, and breastfeeding were not associated with maternal depression or infant health concerns. Results establish a link between prenatal depressive symptoms and an elevated risk of poor health evident shortly after birth. These findings underscore the importance of the prenatal period as a possible sensitive period for infants' health, and the need for effective interventions for depression during pregnancy to mitigate potentially teratogenic effects on the developing fetus and reduce risks for later health concerns.

  7. Investigation of the effects of head irradiation with gamma rays and protons on startle and pre-pulse inhibition behavior in mice.

    PubMed

    Haerich, Paul; Eggers, Cara; Pecaut, Michael J

    2012-05-01

    With the increased international emphasis on manned space exploration, there is a growing need to understand the impact of the spaceflight environment on health and behavior. One particularly important aspect of this environment is low-dose radiation. In the present studies, we first characterized the γ- and proton-irradiation dose effect on acoustic startle and pre-pulse inhibition behaviors in mice exposed to 0-5 Gy brain-localized irradiation, and assessed these effects 2 days later. Subsequently, we used 2 Gy to assess the time course of γ- and proton-radiation effects on startle reactivity 0-8 days after exposure. Exposures targeted the brain to minimize the impact of peripheral inflammation-induced sickness behavior. The effects of radiation on startle were subtle and acute. Radiation reduced the startle response at 2 and 5 Gy. Following a 2-Gy exposure, the response reached a minimum at the 2-day point. Proton and γ-ray exposures did not differ in their impact on startle. We found there were no effects of radiation on pre-pulse inhibition of the startle response.

  8. Nurses' Unique Opportunity to Promote Patient Engagement in Prenatal Care.

    PubMed

    Dyess-Nugent, Phyllis

    2018-01-01

    To report an analysis of the concept of patient engagement in prenatal care. Engagement in health care has been widely discussed but vaguely defined. Patients benefit more from their health care when they are fully engaged in their care. Patient engagement in prenatal care is an important element of prenatal care utilization that has not been analyzed, standardized as a concept, or measured. Concept analysis. CINAHL, MEDLINE, PsycINFO databases, and the internet were searched for literature published in English with a focus on peer-reviewed journals from disciplines of business, allied health sciences, health administration, psychology, and nursing, focusing on the period of 2010-2015. Hybrid version of the Walker and Avant concept analysis method (2011). This concept analysis provides 4 defining attributes of patient engagement in prenatal care and a table of related empirical referents of engagement. These elements offer a foundation for further nursing scholarship toward measurement and evaluation of patient engagement in prenatal care. Patient engagement in prenatal care represents a human response to a health condition. Efforts to increase patient engagement in health care are best addressed by the nursing profession through continued research and intervention development. © 2017 Wiley Periodicals, Inc.

  9. [Normative prenatal evaluation at a philanthropic maternity hospital in São Paulo].

    PubMed

    Corrêa, Claudia Regina Hostim; Bonadio, Isabel Cristina; Tsunechiro, Maria Alice

    2011-12-01

    This cross-sectional study counted with the participation of 301 pregnant women seen in 2009 at a philanthropic maternity hospital in the city of São Paulo (a prenatal support program named Pré-Natal do Amparo Maternal - PN-AM). The objectives of this study were to evaluate the prenatal care according to the initial gestational age, the number of appointments that were held, the continuity of the assistance, and relate the appropriateness with the socio-demographic, obstetric and local variables of the initial prenatal care. The analysis criteria used was initiating prenatal care before 120 days of gestation and attending at least six appointments. The relationship between the variables was analyzed using the Chi-Square Test. Results showed that 41.5% of the pregnant women initiated prenatal care at another health care service and transferred spontaneously to the PN-AM; 74.1% initiated the prenatal care early and 80.4% attended at least six appointments; 63.1% met both criteria simultaneously. Appropriate prenatal care showed a statistically significant difference for mother's age, steady partner, employment, place of residence, having a companion during the appointment and place where prenatal care was initiated.

  10. [Preliminary establishment of transplanted human chronic myeloid leukemia model in nude mice].

    PubMed

    Li, Xian-Min; Ding, Xin; Zhang, Long-Zhen; Cen, Jian-Nong; Chen, Zi-Xing

    2011-12-01

    Chronic myeloid leukemia (CML) is a malignant clonal disease derived from hematopoietic stem cells. CML stem cells were thought to be the root which could lead disease development and ultimately rapid change. However, a stable animal model for studying the characteristics of CML stem cells is currently lacking. This study was aimed to establish a transplanted human CML nude-mice model to further explore the biological behavior of CML stem cells in vivo, and to enrich CML stem cells in nude mice by series transplantation. The 4 - 6 weeks old BALB/c nude mice pretreated by splenectomy (S), cytoxan intraperitoneal injection (C) and sublethal irradiation (I) were transplanted intravenously with (5 - 7) × 10(7) of bone marrow mononuclear cells from CML patients in chronic phase. Alternatively, 4 - 6 weeks old BALB/c nude mice pretreated by lethal irradiation were transplanted intravenously with 5 × 10(6) homologous bone marrow cells of BALB/c nude mice together with (5 - 7) × 10(7) of bone marrow mononuclear cells from CML patients in chronic phase simultaneously. The leukemic cells engrafted and infiltrated in organs and bone marrow of the mice were tracked by reverse transcription-polymerase chain reaction (RT-PCR), plastic-embedded biopsy and flow cytometry. The results of these two methods were compared. The results showed that human CML cells engrafted and infiltrating into the bone marrow of two nude mice pretreated with SCI could be detected. In spite of the low successful rate, results suggested the feasibility of this method by using BALB/c nude mice as a human CML animal model. In contrast, in nude mice pretreated by the lethal dose irradiation, CML cells in the bone marrow could not be found. It is concluded that human bone marrow CML cells can results in leukemia in nude mice pretreated by SCI. Thus this study provides a new strategy for establishment of CML animal models which deserves further elaboration.

  11. Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure.

    PubMed

    Blossom, Sarah J; Melnyk, Stepan B; Li, Ming; Wessinger, William D; Cooney, Craig A

    2017-03-01

    Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4 + T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4 + T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. THE RELATION OF RADIATION INJURY TO NUTRITION IN MICE SUBMITTED TO WHOLE- BODY LD$sub 50$ X-RAY IRRADIATION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hata, T.

    1960-01-01

    The relation of radiation injury to the qualitative and quantitative changes of nutrition was studied in mice. From the qualitative standpoint of nutrition, the high protein, high casein, and butter diet showed a degree of radiation protection in the changes of the peripheral blood, changes of body weight, and survival rate. The carbohydrate diet showed some effect in radiation protection and recovery. Quantitatively a low caloric diet was conducive to radiation injury and the high caloric diet showed protection and recovery effects in changes of the peripheral blood and body weight which is proportional to the number of calories. Themore » decrease of caloric intake after irradiation showed an undesirable effect on recovery. (Absts. Japan. Med., 1: No. 7, 1960.)« less

  13. Identity, difference and the ethical politics of prenatal testing.

    PubMed

    Stainton, T

    2003-10-01

    This paper explores the role of identity in relation to the ethics of prenatal testing for conditions that cause intellectual disabilities. Specifically, it considers the question of identity and the moral status of the fetus. It argues that both the arguments in favour and opposed to prenatal testing mistakenly presuppose that there is no moral status attached to the fetus. That status is grounded in an identity-constituting characteristic, such as 'intellectual disability', which is brought about by the purpose of genetic testing, and the meaning of which is culturally constructed. This paper examines the implications this has for the debate around both prenatal testing and termination in general and considers the nature of the ethical politics which follows from this position with regard to prenatal testing related to intellectual disability.

  14. The Chinese Herbal Mixture Tien-Hsien Liquid Augments the Anticancer Immunity in Tumor Cell–Vaccinated Mice

    PubMed Central

    Yang, Pei-Ming; Du, Jia-Ling; Wang, George Nian-Kae; Chia, Jean-San; Hsu, Wei-Bin; Pu, Pin-Ching; Sun, Andy; Chiang, Chun-Pin; Wang, Won-Bo

    2016-01-01

    Background. The Chinese herbal mixture, Tien-Hsien liquid (THL), has been used as an anticancer dietary supplement for more than 20 years. Our previous studies have shown that THL can modulate immune responseand inhibit tumor growth. In this study, we further evaluated the effect of THL on anticancer immune response in mice vaccinated with γ-ray-irradiated tumor cells. Methods. The antitumor effect of THL was determined in mice vaccinated with low-tumorigenic CT-26-low colon cancer cells or γ-ray-irradiated high-tumorigenic CT-26-high colon cancer cells. The number of natural killer (NK) cells and T lymphocytes in the spleen was analyzed by flow cytometry. The tumor-killing activities of NK cells and cytotoxic T lymphocytes (CTLs) were analyzed by flow cytometry using YAC-1 and CT-26-high cells, respectively, as target cells. The levels of IFN-γ, IL-2, and TNF-α were determined by ELISA. Results. THL suppressed the growth of CT-26-high tumor in mice previously vaccinated with low-tumorigenic CT-26-low cells or γ-irradiated CT-26-high cells. THL increased the populations of NK cells and CD4+ T lymphocytes in the spleen and enhanced the tumor-killing activities of NK cells and CTL in mice vaccinated with γ-irradiated CT-26-high cells. THL increased the production of IFN-γ, IL-2, and TNF-α in mice vaccinated with γ-irradiated CT-26-high cells. Conclusion. THL can enhance the antitumor immune responses in mice vaccinated with killed tumor cells. These results suggest that THL may be used as a complementary medicine for cancer patients previously treated with killed tumor cell vaccines, radiotherapy, or chemotherapy. PMID:27252074

  15. Toddler temperament and prenatal exposure to lead and maternal depression.

    PubMed

    Stroustrup, Annemarie; Hsu, Hsiao-Hsien; Svensson, Katherine; Schnaas, Lourdes; Cantoral, Alejandra; Solano González, Maritsa; Torres-Calapiz, Mariana; Amarasiriwardena, Chitra; Bellinger, David C; Coull, Brent A; Téllez-Rojo, Martha M; Wright, Robert O; Wright, Rosalind J

    2016-06-16

    Temperament is a psychological construct that reflects both personality and an infant's reaction to social stimuli. It can be assessed early in life and is stable over time Temperament predicts many later life behaviors and illnesses, including impulsivity, emotional regulation and obesity. Early life exposure to neurotoxicants often results in developmental deficits in attention, social function, and IQ, but environmental predictors of infant temperament are largely unknown. We propose that prenatal exposure to both chemical and non-chemical environmental toxicants impacts the development of temperament, which can itself be used as a marker of risk for maladaptive neurobehavior in later life. In this study, we assessed associations among prenatal and early life exposure to lead, mercury, poverty, maternal depression and toddler temperament. A prospective cohort of women living in the Mexico City area were followed longitudinally beginning in the second trimester of pregnancy. Prenatal exposure to lead (blood, bone), mercury, and maternal depression were assessed repeatedly and the Toddler Temperament Scale (TTS) was completed when the child was 24 months old. The association between each measure of prenatal exposure and performance on individual TTS subscales was evaluated by multivariable linear regression. Latent profile analysis was used to classify subjects by TTS performance. Multinomial regression models were used to estimate the prospective association between prenatal exposures and TTS performance. 500 mother-child pairs completed the TTS and had complete data on exposures and covariates. Three latent profiles were identified and categorized as predominantly difficult, intermediate, or easy temperament. Prenatal exposure to maternal depression predicted increasing probability of difficult toddler temperament. Maternal bone lead, a marker of cumulative exposure, also predicted difficult temperament. Prenatal lead exposure modified this association

  16. Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells. [X radiation, mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yunis, E.J.; Fernandes, G.; Smith, J.

    1976-12-01

    Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. The findings suggest that T cells, at an early stage of differentiation, are moremore » susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstitution and celular engineering without producing GVHD.« less

  17. Prenatal Estrogens and the Development of Homosexual Orientation.

    ERIC Educational Resources Information Center

    Meyer-Bahlburg, Heino F. L.; And Others

    1995-01-01

    Examines the hypothesis that prenatal estrogens contribute to the development of human sexual orientation. Several groups of women with a history of prenatal exposure to diethylstilbestrol (DES) were compared with several samples of control women. Findings showed that more DES-exposed women than controls were rated as bisexual or homosexual,…

  18. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin

    2013-03-15

    Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) inmore » the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.« less

  19. Prenatal stress and epigenetics.

    PubMed

    Cao-Lei, L; de Rooij, S R; King, S; Matthews, S G; Metz, G A S; Roseboom, T J; Szyf, M

    2017-05-18

    In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations. We also emphasized the advantage of using stressor from quasi-randomly assigned experiments. Furthermore, we discuss challenges that still need to be addressed in this field in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Prenatal programming of emotion regulation: neonatal reactivity as a differential susceptibility factor moderating the outcome of prenatal cortisol levels.

    PubMed

    Bolten, Margarete; Nast, Irina; Skrundz, Marta; Stadler, Christina; Hellhammer, Dirk H; Meinlschmidt, Gunther

    2013-10-01

    Hypothalamic-pituitary-adrenal (HPA) activation during pregnancy is linked to dysfunctional behavioral outcomes in the offspring. According to Belsky's differential susceptibility hypothesis, individuals vary regarding their developmental plasticity. Translating the differential susceptibility hypothesis to the field of fetal programming, we hypothesize that infants' temperament, as the constitutionally based reactivity to stimulation, moderates prenatal environmental effects on postnatal emotion regulation. Maternal HPA axis activity and stress-reactivity during pregnancy was estimated, by measuring cortisol concentrations in saliva, collected at 0, 30, 45 and 60 min after awakening and in blood, collected during a laboratory stress test (Trier Social Stress Test), respectively. Newborns reactivity to stimulation was evaluated between postnatal day 10 and 14 using the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Infant's self-quieting-activities, as an indicator of emotion regulation, were evaluated at the age of six months during the still face paradigm. Maternal cortisol reactivity to stress during pregnancy was associated with infant's emotion regulation at the age of six months. Whereas cortisol levels after awakening in mid and late pregnancy were not associated with emotion regulation. Furthermore, regression analyses revealed that in interaction with neonatal reactivity, both, prenatal maternal HPA activity as well as prenatal maternal HPA reactivity to stress predicted emotion regulation. The findings indicate that newborns' reactivity to stimulation is moderating the association between prenatal exposure to maternal glucocorticoids and emotion regulation in infancy. Data suggests that temperamental characteristics of the newborn are a relevant differential susceptibility factor with regard to prenatal effects on emotion regulation. © 2013.

  1. [Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

    PubMed

    Kojima, Shuji

    2006-10-01

    We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

  2. Plasmodium yoelii: induction of attenuated mutants by irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Waki, S.; Yonome, I.; Suzuki, M.

    When erythrocytic forms of Plasmodium yoelii nigeriensis, which is invariably fatal in mice, were exposed to X rays, the dose to reduce surviving parasites to one millionth was 100 gray (10 Krad). A suspension of 5 X 10(6) per ml of parasitized erythrocyte was irradiated at 100 gray, and 0.2 ml aliquots were inoculated into 22 mice. Eleven mice showed patent parasitemia, and in these the growth curves were less steep than that found in nonirradiated parasites. The infections of 8 mice of the 11 were self-resolving, and the attenuated feature of the parasites maintained following a limited number ofmore » blood passages. The parasites were slowly growing even in nude mice and cause self-resolving infections in intact mice. BALB/c mice immunized with the attenuated parasites were protected against subsequent challenge infections with the original virulent erythrocytic and sporogonic forms. These findings indicate that attenuated mutants of malaria parasites can be readily induced by this method.« less

  3. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    PubMed

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation.

  4. Informed Decision-Making in the Context of Prenatal Chromosomal Microarray.

    PubMed

    Baker, Jessica; Shuman, Cheryl; Chitayat, David; Wasim, Syed; Okun, Nan; Keunen, Johannes; Hofstedter, Renee; Silver, Rachel

    2018-03-07

    The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.

  5. Prenatal administration of retinoic acid upregulates connective tissue growth factor in the nitrofen CDH model.

    PubMed

    Ruttenstock, Elke Maria; Doi, Takashi; Dingemann, Jens; Puri, Prem

    2011-06-01

    Recent studies have suggested that retinoids may be involved in the molecular mechanisms of pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). Connective tissue growth factor (CTGF) plays a key role in foetal lung development and remodelling during later gestation. CTGF knockout mice exhibit PH with similar characteristics to the human and nitrofen-induced PH. Prenatal administration of retinoic acid (RA) has been shown to stimulate alveologenesis in nitrofen-induced PH. In vitro studies have revealed that RA can induce CTGF gene expression. We hypothesized that pulmonary gene expression of CTGF is downregulated during the later stages of lung development, and that prenatal administration of RA upregulates CTGF in the nitrofen CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Foetuses were harvested on D21 and divided into control, CDH, control + RA and CDH + RA group. Pulmonary CTGF gene and protein expression levels were determined using RT-PCR and immunohistochemistry. On D21, CTGF relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, expression levels of CTGF were significantly upregulated in CDH + RA and control + RA compared to the CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary CTGF gene and protein expression during later stages of lung development may interfere with normal alveologenesis in the nitrofen CDH model. Upregulation of CTGF pulmonary gene expression after prenatal RA treatment may promote lung growth by promoting alveologenesis in the nitrofen-induced CDH model.

  6. Prenatal screening: an ethical agenda for the near future.

    PubMed

    de Jong, Antina; de Wert, Guido M W R

    2015-01-01

    Prenatal screening for foetal abnormalities such as Down's syndrome differs from other forms of population screening in that the usual aim of achieving health gains through treatment or prevention does not seem to apply. This type of screening leads to no other options but the choice between continuing or terminating the pregnancy and can only be morally justified if its aim is to provide meaningful options for reproductive choice to pregnant women and their partners. However, this aim should not be understood as maximizing reproductive choice per se. Only if understood as allowing prospective parents to avoid suffering related to living with (a child with) serious disorders and handicaps can prenatal screening be a publicly or collectively funded programme. The alternative of moving prenatal testing outside the healthcare system into the private sector is problematic, as it makes these tests accessible only to those who can afford to pay for it. New developments in prenatal screening will have to be assessed in terms of whether and to what extent they either contribute to or undermine the stated aim of providing meaningful options for reproductive choice. In the light of this criterion, this article discusses the introduction of the new non-invasive prenatal test (NIPT), the tendency to widen the scope of follow-up testing, as well as the possible future scenarios of genome-wide screening and 'prenatal personalised medicine'. The article ends with recommendations for further debate, research and analysis. © 2014 John Wiley & Sons Ltd.

  7. Genetically mediated Nf1 loss in mice promotes diverse radiation-induced tumors modeling second malignant neoplasms

    PubMed Central

    Choi, Grace; Huang, Brian; Pinarbasi, Emile; Braunstein, Steve E.; Horvai, Andrew E.; Kogan, Scott; Bhatia, Smita; Faddegon, Bruce; Nakamura, Jean L.

    2013-01-01

    Second malignant neoplasms (SMNs) are therapy-induced malignancies and a growing problem in cancer survivors, particularly survivors of childhood cancers. The lack of experimental models of SMNs has limited understanding of their pathogenesis. It is currently not possible to predict or prevent this devastating late complication. Individuals with Neurofibromatosis I (NF1) are at increased risk of developing therapy-induced cancers for unclear reasons. To model SMNs, we replicated clinical radiotherapy and delivered fractionated abdominal irradiation to Nf1+/− and wildtype mice. Similar to irradiated cancer survivors, irradiated wildtype and Nf1+/− mice developed diverse in-field malignancies. In Nf1+/− mice, fractionated irradiation promoted both classical NF1-associated malignancies and malignancies unassociated with the NF1 syndrome but typical of SMNs. Nf1 heterozygosity potentiated the mutagenic effects of irradiation, as evidenced by the significantly reduced survival after irradiation and tumor development that was often characterized by synchronous primary tumors. Interestingly, diverse radiation-induced tumors arising in wildtype and Nf1+/− mice shared a genetic signature characterized by monoallelic loss of Nf1 and the adjacent Trp53 allele. These findings implicate Nf1 loss as mediating tumorigenesis in a broad range of cell types and organs extending beyond the classical NF1 tumor histologies. Examining clinical SMN samples, we found LOH of NF1 in SMNs from non-NF1 patients. Nf1 heterozygosity confers broad susceptibility to genotoxin-induced tumorigenesis and this paradigm serves as an experimental platform for future studies of SMNs. PMID:23071067

  8. Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

    PubMed Central

    Gaberman, Elena; Pinzur, Lena; Levdansky, Lilia; Tsirlin, Maria; Netzer, Nir; Aberman, Zami; Gorodetsky, Raphael

    2013-01-01

    Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×106 cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective “off the shelf” therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia. PMID:23823334

  9. Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells.

    PubMed

    Gaberman, Elena; Pinzur, Lena; Levdansky, Lilia; Tsirlin, Maria; Netzer, Nir; Aberman, Zami; Gorodetsky, Raphael

    2013-01-01

    Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×10(6) cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective "off the shelf" therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia.

  10. Prenatal expectations in Mexican American women: development of a culturally sensitive measure.

    PubMed

    Gress-Smith, Jenna L; Roubinov, Danielle S; Tanaka, Rika; Cmic, Keith; Cirnic, Keith; Gonzales, Nancy; Enders, Craig; Luecken, Linda J

    2013-08-01

    Prenatal expectations describe various domains a woman envisions in preparation for her role as a new mother and influence how women transition into the maternal role. Although the maternal role is strongly influenced by the prevailing familial and sociocultural context, research characterizing prenatal expectations in ethnic minority and low-income women is lacking. As part of the largest growing minority group in the USA, Latina mothers represent an important group to study. Two hundred and ten low-income Mexican American women were administered the Prenatal Experiences Scale for Mexican Americans (PESMA) that was adapted to capture specific cultural aspects of prenatal expectations. Measures of current support, prenatal depressive symptoms, and other sociodemographic characteristics were also completed to assess validity. Exploratory factor analysis identified three underlying factors of prenatal expectations: paternal support, family support, and maternal role fulfillment. Associations among these subscales and demographic and cultural variables were conducted to characterize women who reported higher and lower levels of expectations. The PESMA demonstrated good concurrent validity when compared to measures of social support, prenatal depressive symptoms, and other sociodemographic constructs. A culturally sensitive measure of prenatal expectations is an important step towards a better understanding of how Mexican American women transition to the maternal role and identify culturally specific targets for interventions to promote maternal health.

  11. The effect of picosecond laser pulses on redox-dependent processes in mice red blood cells studied in vivo

    NASA Astrophysics Data System (ADS)

    Voronova, Olga; Gening, Tatyana; Abakumova, Tatyana; Sysolyatin, Aleksey; Zolotovskiy, Igor; Antoneeva, Inna; Ostatochnikov, Vladimir; Gening, Snezhanna

    2014-02-01

    The study highlights the effect of different modes of in vivo laser irradiation of mice using a PFL8LA laser with λ = 1560 nm, pulse duration of 1,4•10-12 s, peak power of 3,72•103 W and average output power of 20•10-3 W on the lipid peroxidation parameters: conjugated dienes, ketodienes and conjugated trienes, malondialdehyde, Schiff bases and the activity of antioxidant enzymes - catalase, glutathione -S-transferase and superoxide dismutase in erythrocytes and plasma of mice. Two groups of mice received a total dose of 3.8 J/cm2 per group, but the 1st group was irradiated only once, while the 2nd - four times. Significant differences in the parameters of the 1st and 2nd groups indicate different effects of the irradiation modes on redox-dependent processes in red blood cells of mice.

  12. Conditioned medium from human bone marrow-derived mesenchymal stem cells promotes skin moisturization and effacement of wrinkles in UVB-irradiated SKH-1 hairless mice.

    PubMed

    Kwon, Tae-Rin; Oh, Chang Taek; Choi, Eun Ja; Kim, Soon Re; Jang, Yu-Jin; Ko, Eun Jung; Yoo, Kwang Ho; Kim, Beom Joon

    2016-05-01

    Mesenchymal stem cells (MSCs) are promising therapeutic agents for various diseases. To investigate the effects of conditioned medium from human bone marrow-derived mesenchymal stem cells (MSC-CdM) on pro-collagen production and wrinkle formation, we performed in vitro and in vivo experiments. We assessed the effects of MSC-CdM on proliferation and photo-aging in human dermal fibroblasts after UVB exposure using enzyme activity assays for collagen type I secretion and MMP-1. To determine the effect of topically applied MSC-CdM on wrinkle formation, MSC-CdM (1% and 10%) and vehicle (propylene glycol: ethanol, 7 : 3) were applied to the dorsal skin of UVB-irradiated hairless mice for 8 weeks. We examined the effects on wrinkle formation by assessing visual skin grading, replica, tape stripping, transepidermal water loss (TEWL), and skin hydration measurement. We also examined histology of the lesions using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. MSC-CdM markedly reduced UV-induced matrix metalloproteinase-1 expression and increased pro-collagen synthesis in a dose-dependent manner. Our findings suggest that MSC-CdM induces repair of dermal damage and effacement of wrinkles on UVB-irradiated hairless mice through protective effect of hydration. These results support an anti-wrinkle effect of MSC-CdM that involves increased collagen synthesis and suggest that MSC-CdM might be a potential candidate for preventing UV-induced skin damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Phenotypic Dichotomy Following Developmental Exposure to Perfluorooctanic Acid (PFOA) Exposure in CD-1 Mice: Low Doses Induce Elevated Serum, Leptin, Insulin, and Overweight in Mid-Life.

    EPA Science Inventory

    The synthetic surfactant, perfluorooctanoic acid (PFOA) is a proven developmental toxicant in mice, causing prenatal pregnancy loss, increased neonatal mortality, delayed eye opening, and abnormal mammary gland growth in animals exposed during fetal life. PFOA is found in the ser...

  14. Hydrogen-Rich Water Ameliorates Total Body Irradiation-Induced Hematopoietic Stem Cell Injury by Reducing Hydroxyl Radical

    PubMed Central

    Xue, Xiaolei; Han, Xiaodan; Li, Yuan; Lu, Lu; Li, Deguan

    2017-01-01

    We examined whether consumption of hydrogen-rich water (HW) could ameliorate hematopoietic stem cell (HSC) injury in mice with total body irradiation (TBI). The results indicated that HW alleviated TBI-induced HSC injury with respect to cell number alteration and to the self-renewal and differentiation of HSCs. HW specifically decreased hydroxyl radical (∙OH) levels in the c-kit+ cells of 4 Gy irradiated mice. Proliferative bone marrow cells (BMCs) increased and apoptotic c-kit+ cells decreased in irradiated mice uptaken with HW. In addition, the mean fluorescence intensity (MFI) of γ-H2AX and percentage of 8-oxoguanine positive cells significantly decreased in HW-treated c-kit+ cells, indicating that HW can alleviate TBI-induced DNA damage and oxidative DNA damage in c-kit+ cells. Finally, the cell cycle (P21), cell apoptosis (BCL-XL and BAK), and oxidative stress (NRF2, HO-1, NQO1, SOD, and GPX1) proteins were significantly altered by HW in irradiated mouse c-kit+ cells. Collectively, the present results suggest that HW protects against TBI-induced HSC injury. PMID:28243358

  15. Hydrogen-Rich Water Ameliorates Total Body Irradiation-Induced Hematopoietic Stem Cell Injury by Reducing Hydroxyl Radical.

    PubMed

    Zhang, Junling; Xue, Xiaolei; Han, Xiaodan; Li, Yuan; Lu, Lu; Li, Deguan; Fan, Saijun

    2017-01-01

    We examined whether consumption of hydrogen-rich water (HW) could ameliorate hematopoietic stem cell (HSC) injury in mice with total body irradiation (TBI). The results indicated that HW alleviated TBI-induced HSC injury with respect to cell number alteration and to the self-renewal and differentiation of HSCs. HW specifically decreased hydroxyl radical ( ∙ OH) levels in the c-kit + cells of 4 Gy irradiated mice. Proliferative bone marrow cells (BMCs) increased and apoptotic c-kit + cells decreased in irradiated mice uptaken with HW. In addition, the mean fluorescence intensity (MFI) of γ -H2AX and percentage of 8-oxoguanine positive cells significantly decreased in HW-treated c-kit + cells, indicating that HW can alleviate TBI-induced DNA damage and oxidative DNA damage in c-kit + cells. Finally, the cell cycle (P21), cell apoptosis (BCL-XL and BAK), and oxidative stress (NRF2, HO-1, NQO1, SOD, and GPX1) proteins were significantly altered by HW in irradiated mouse c-kit + cells. Collectively, the present results suggest that HW protects against TBI-induced HSC injury.

  16. Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

    1984-11-01

    The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly,more » as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.« less

  17. Human Prenatal Effects: Methodological Problems and Some Suggested Solutions

    ERIC Educational Resources Information Center

    Copans, Stuart A.

    1974-01-01

    Briefly reviews the relevant literature on human prenatal effects, describes some of the possible designs for such studies; and discusses some of the methodological problem areas: sample choice, measurement of prenatal variables, monitoring of labor and delivery, and neonatal assessment. (CS)

  18. Mitigating Prenatal Zika Virus Infection in the Americas.

    PubMed

    Ndeffo-Mbah, Martial L; Parpia, Alyssa S; Galvani, Alison P

    2016-10-18

    Because of the risk for Zika virus infection in the Americas and the links between infection and microcephaly, other serious neurologic conditions, and fetal death, health ministries across the region have advised women to delay pregnancy. However, the effectiveness of this policy in reducing prenatal Zika virus infection has yet to be quantified. To evaluate the effectiveness of pregnancy-delay policies on the incidence and prevalence of prenatal Zika virus infection. Vector-borne Zika virus transmission model fitted to epidemiologic data from 2015 to 2016 on Zika virus infection in Colombia. Colombia, August 2015 to July 2017. Population of Colombia, stratified by sex, age, and pregnancy status. Recommendations to delay pregnancy by 3, 6, 9, 12, or 24 months, at different levels of adherence. Weekly and cumulative incidence of prenatal infections and microcephaly cases. With 50% adherence to recommendations to delay pregnancy by 9 to 24 months, the cumulative incidence of prenatal Zika virus infections is likely to decrease by 17% to 44%, whereas recommendations to delay pregnancy by 6 or fewer months are likely to increase prenatal infections by 2% to 7%. This paradoxical exacerbation of prenatal Zika virus exposure is due to an elevated risk for pregnancies to shift toward the peak of the outbreak. Sexual transmission was not explicitly accounted for in the model because of limited data but was implicitly subsumed within the overall transmission rate, which was calibrated to observed incidence. Pregnancy delays can have a substantial effect on reducing cases of microcephaly but risks exacerbating the Zika virus outbreak if the duration is not sufficient. Duration of the delay, population adherence, and the timing of initiation of the intervention must be carefully considered. National Institutes of Health.

  19. Correction of X-linked immunodeficient mice by competitive reconstitution with limiting numbers of normal bone marrow cells.

    PubMed

    Rohrer, J; Conley, M E

    1999-11-15

    Gene therapy for inherited disorders is more likely to succeed if gene-corrected cells have a proliferative or survival advantage compared with mutant cells. We used a competitive reconstitution model to evaluate the strength of the selective advantage that Btk normal cells have in Btk-deficient xid mice. Whereas 2,500 normal bone marrow cells when mixed with 497,500 xid cells restored serum IgM and IgG3 levels to near normal concentrations in 3 of 5 lethally irradiated mice, 25,000 normal cells mixed with 475,000 xid cells reliably restored serum IgM and IgG3 concentrations and the thymus-independent antibody response in all transplanted mice. Reconstitution was not dependent on lethal irradiation, because sublethally irradiated mice all had elevated serum IgM and IgG3 by 30 weeks postreconstitution when receiving 25,000 normal cells. Furthermore, the xid defect was corrected with as few as 10% of the splenic B cells expressing a normal Btk. When normal donor cells were sorted into B220(+)/CD19(+) committed B cells and B220(-)/CD19(-) cell populations, only the B220(-)/CD19(-) cells provided long-term B-cell reconstitution in sublethally irradiated mice. These findings suggest that even inefficient gene therapy may provide clinical benefit for patients with XLA.

  20. Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

    PubMed Central

    2013-01-01

    Background Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. Methods Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. Results Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. Conclusion Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients. PMID:23672582