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  1. Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse

    SciTech Connect

    Morgan, J.E.; Hoffman, E.P.; Partridge, T.A. )

    1990-12-01

    Dystrophin deficiency in skeletal muscle of the x-linked dystrophic (mdx) mouse can be partially remedied by implantation of normal muscle precursor cells (mpc). However, it is difficult to determine whether this biochemical rescue results in any improvement in the structure or function of the treated muscle, because the vigorous regeneration of mdx muscle more than compensates for the degeneration. By using x-ray irradiation to prevent mpc proliferation, it is possible to study loss of mdx muscle fibers without the complicating effect of simultaneous fiber regeneration. Thus, improvements in fiber survival resulting from any potential therapy can be detected easily. Here, we have implanted normal mpc, obtained from newborn mice, into such preirradiated mdx muscles, finding that it is far more extensively permeated and replaced by implanted mpc than is nonirradiated mdx muscle; this is evident both from analysis of glucose-6-phosphate isomerase isoenzyme markers and from immunoblots and immunostaining of dystrophin in the treated muscles. Incorporation of normal mpc markedly reduces the loss of muscle fibers and the deterioration of muscle structure which otherwise occurs in irradiated mdx muscles. Surprisingly, the regenerated fibers are largely peripherally nucleated, whereas regenerated mouse skeletal muscle fibers are normally centrally nucleated. We attribute this regeneration of apparently normal muscle to the tendency of newborn mouse mpc to recapitulate their neonatal ontogeny, even when grafted into 3-wk-old degenerating muscle.

  2. Melatonin prevents learning disorders in brain-lesioned newborn mice.

    PubMed

    Bouslama, M; Renaud, J; Olivier, P; Fontaine, R H; Matrot, B; Gressens, P; Gallego, J

    2007-12-12

    Perinatal brain injuries often result in irreversible learning disabilities, which manifest in early childhood. These injuries are chiefly ascribable to marked susceptibility of the immature brain to glutamate-induced excitotoxicity. No treatments are available. One well-characterized model of perinatal brain injuries consists in injecting the glutamate analog ibotenate into the brain of 5-day-old mice. The resulting excitotoxic lesions resemble the hypoxic-ischemic gray-matter lesions seen in full-term and near-term newborns, as well as the white-matter lesions of preterm newborns. We previously reported that these lesions disrupted odor preference conditioning in newborn mice. The aim of this study was to assess the effectiveness of the neuroprotector melatonin in preventing learning disabilities in newborn mice with ibotenate-induced brain injury. In postnatal day (P) 6-P7 pups, we tested psychomotor reflexes, spontaneous preference for maternal odors as an index of memory, ultrasonic vocalization responses to stroking as an index of sensitivity to tactile stimuli, and conditioned preference for an odor previously paired with stroking as an index of learning abilities. Without melatonin, conditioning was abolished, whereas spontaneous odor preference, psychomotor reflexes, and sensitivity to tactile stimuli were normal. Thus, abolition of conditioning was not associated with sensorimotor impairments. Histological analysis confirmed the efficacy of melatonin in reducing white-matter lesions induced by ibotenate. Furthermore, treatment with melatonin protected the ability to develop conditioning. Thus, melatonin, which easily crosses the blood-brain barrier and has been proven safe in children, may be effective in preventing learning disabilities caused by perinatal brain injuries in human preterm infants. PMID:17950543

  3. Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf Whirler Mice.

    PubMed

    Chien, Wade W; Isgrig, Kevin; Roy, Soumen; Belyantseva, Inna A; Drummond, Meghan C; May, Lindsey A; Fitzgerald, Tracy S; Friedman, Thomas B; Cunningham, Lisa L

    2016-02-01

    Hereditary deafness is one of the most common disabilities affecting newborns. Many forms of hereditary deafness are caused by morphological defects of the stereocilia bundles on the apical surfaces of inner ear hair cells, which are responsible for sound detection. We explored the effectiveness of gene therapy in restoring the hair cell stereocilia architecture in the whirlin mouse model of human deafness, which is deaf due to dysmorphic, short stereocilia. Wild-type whirlin cDNA was delivered via adeno-associated virus (AAV8) by injection through the round window of the cochleas in neonatal whirler mice. Subsequently, whirlin expression was detected in infected hair cells (IHCs), and normal stereocilia length and bundle architecture were restored. Whirlin gene therapy also increased inner hair cell survival in the treated ears compared to the contralateral nontreated ears. These results indicate that a form of inherited deafness due to structural defects in cochlear hair cells is amenable to restoration through gene therapy.

  4. Mechanism of T cell mediated protection in newborn mice against a Chlamydia infection

    PubMed Central

    Pal, Sukumar; de la Maza, Luis M.

    2013-01-01

    To determine the immune components needed for protection of newborn mice against Chlamydia muridarum, animals born to Chlamydia-immunized and to sham-immunized dams were infected intranasally with C. muridarum at 2 post-natal days. T-cells isolated from immunized or sham-immunized adult mice were adoptively transferred to newborn mice at the time of infection. Also, to establish what cytokines are involved in protection, IFN-γ TNF-α, IL-10, and IL-12 were passively transferred to newborn mice. To assess the Chlamydia burden in the lungs mice were euthanized at 12 post-natal days. When T-cells from immunized adult mice were transferred, mice born to and fed by immunized dams were significantly protected as evidenced by the reduced number of Chlamydia isolated from the lungs compared to mice born to and fed by sham-immunized dams. Transfer of IFN-γ and TNF-α also significantly reduced the number of Chlamydia in the lungs of mice born to immunized dams. Transfer of IL-10 or IL-12 did not result in a significant reduction of Chlamydia. In vitro T-cell proliferation data suggest that neonatal antigen presenting cells can present Chlamydia antigens to adult T-cells. In conclusion, maternal antibodies and Chlamydia specific T-cells or Th1 cytokines are required for protection of neonates against this pathogen. PMID:23644176

  5. Mechanism of T-cell mediated protection in newborn mice against a Chlamydia infection.

    PubMed

    Pal, Sukumar; de la Maza, Luis M

    2013-01-01

    To determine the immune components needed for protection of newborn mice against Chlamydia muridarum, animals born to Chlamydia-immunized and to sham-immunized dams were infected intranasally with C. muridarum at 2 post-natal days. T-cells isolated from immunized or sham-immunized adult mice were adoptively transferred to newborn mice at the time of infection. Also, to establish what cytokines are involved in protection, IFN-γ, TNF-α, IL-10, and IL-12 were passively transferred to newborn mice. To assess the Chlamydia burden in the lungs mice were euthanized at 12 post-natal days. When T-cells from immunized adult mice were transferred, mice born to and fed by immunized dams were significantly protected as evidenced by the reduced number of Chlamydia isolated from the lungs compared to mice born to and fed by sham-immunized dams. Transfer of IFN-γ and TNF-α also significantly reduced the number of Chlamydia in the lungs of mice born to immunized dams. Transfer of IL-10 or IL-12 did not result in a significant reduction of Chlamydia. In vitro T-cell proliferation data suggest that neonatal antigen presenting cells can present Chlamydia antigens to adult T-cells. In conclusion, maternal antibodies and Chlamydia specific T-cells or Th1 cytokines are required for protection of neonates against this pathogen.

  6. MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice.

    PubMed

    Aguilo, Nacho; Uranga, Santiago; Marinova, Dessislava; Monzon, Marta; Badiola, Juan; Martin, Carlos

    2016-01-01

    Development of novel more efficient preventive vaccines against tuberculosis (TB) is crucial to achieve TB eradication by 2050, one of the Millennium Development Goals (MDG) for the current century. MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis developed as BCG-replacement strategy in newborns that has entered first-in-human adult clinical trials. In this work, we characterize the safety, immunogenicity and protective efficacy of MTBVAC in a model of newborn C57/BL6 mice. Our data clearly indicate that MTBVAC is safe for newborn mice, and does not affect animal growth or organ development. In addition, MTBVAC-vaccinated mice at birth showed enhanced immunogenicity and better protection against M. tuberculosis challenge in comparison with BCG.

  7. MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice

    PubMed Central

    Aguilo, Nacho; Uranga, Santiago; Marinova, Dessislava; Monzon, Marta; Badiola, Juan; Martin, Carlos

    2016-01-01

    Summary Development of novel more efficient preventive vaccines against tuberculosis (TB) is crucial to achieve TB eradication by 2050, one of the Millennium Development Goals (MDG) for the current century. MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis developed as BCG-replacement strategy in newborns that has entered first-in-human adult clinical trials. In this work, we characterize the safety, immunogenicity and protective efficacy of MTBVAC in a model of newborn C57/BL6 mice. Our data clearly indicate that MTBVAC is safe for newborn mice, and does not affect animal growth or organ development. In addition, MTBVAC-vaccinated mice at birth showed enhanced immunogenicity and better protection against M. tuberculosis challenge in comparison with BCG. PMID:26786657

  8. Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice.

    PubMed

    Ballot, Orlane; Joseph, Vincent; Soliz, Jorge

    2015-06-01

    We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency (fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (-25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (-37% in males, -59% in females) and VT (-38% in males, -47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia. PMID:25792712

  9. Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

    PubMed

    Tomatsu, Shunji; Montaño, Adriana M; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Gutiérrez, Monica L; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S

    2015-02-01

    We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice.

  10. Methylphenidate restores novel object recognition in DARPP-32 knockout mice.

    PubMed

    Heyser, Charles J; McNaughton, Caitlyn H; Vishnevetsky, Donna; Fienberg, Allen A

    2013-09-15

    Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate.

  11. Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice

    PubMed Central

    Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert; Navarro, Edwin; Jain, Noopur; Carandang, Francis; Peterson, Joanna; Mokres, Lucia; Milla, Carlos; Preuss, Stefanie; Alcazar, Miguel Alejandre; Khan, Suleman; Masumi, Juliet; Ferreira-Tojais, Nancy; Mujahid, Sana; Starcher, Barry; Rabinovitch, Marlene

    2014-01-01

    Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice. PMID:25539853

  12. Photochemical restoration of visual responses in blind mice

    PubMed Central

    Polosukhina, Aleksandra; Litt, Jeffrey; Tochitsky, Ivan; Nemargut, Joseph; Sychev, Yivgeny; De Kouchkovsky, Ivan; Huang, Tracy; Borges, Katharine; Trauner, Dirk; Van Gelder, Russell N.; Kramer, Richard H.

    2012-01-01

    Summary Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative blinding diseases caused by the death of rods and cones, leaving the remainder of the visual system intact but largely unable to respond to light. Here we show that, AAQ, a synthetic small molecule photoswitch, can restore light sensitivity to the retina and behavioral responses in vivo in mouse models of RP without exogenous gene delivery. Brief application of AAQ bestows prolonged light sensitivity on multiple types of retinal neurons, resulting in synaptically amplified responses and center-surround antagonism in arrays of retinal ganglion cells (RGCs). Intraocular injection of AAQ restores the pupillary light reflex and locomotory light avoidance responses in mice lacking retinal photoreceptors, indicating reconstitution of light signaling to brain circuits. AAQ and related photoswitch molecules present a new drug strategy for restoring retinal function in degenerative blinding diseases. PMID:22841312

  13. Chronic alcohol exposure is associated with decreased neurogenesis, aberrant integration of newborn neurons, and cognitive dysfunction in female mice

    PubMed Central

    Golub, Haleigh M.; Zhou, Qi-Gang; Zucker, Hannah; McMullen, Megan R.; Kokiko-Cochran, Olga Nicole; Ro, Eun Jeoung; Nagy, Laura E.; Suh, Hoonkyo

    2015-01-01

    Background Neurological deficits of alcohol use disorder (AUD) have been attributed to dysfunctions of specific brain structures. Studies of alcoholic patients and chronic alcohol exposure animal models consistently identify reduced hippocampal mass and cogntive dysfunctions as a key alcohol-induced brain adaptation. However, the precise substrate of chronic alcohol exposure that leads to structural and functional impairments of the hippocampus is largely unknown. Methods Using a calorie-matched alcohol feeding method, we tested whether chronic alcohol exposure targets neural stem cells and neurogenesis in the adult hippocampus. The effect of alcohol on proliferation of neural stem cells as well as cell fate determination and survival of newborn cells was evaluated via BrdU pulse and chase methods. A retrovirus-mediated single-cell labeling method was used to determine the effect of alcohol on the morphological development and circuitry incorporation of individual hippocampal newborn neurons. Finally, Novel Object Recognition and Y-maze tests were performed to examine whether disrupted neurogenesis is associated with hippocampus-dependent functional deficits in alcohol-fed mice. Results Chronic alcohol exposure reduced proliferation of neural stem cells and survival rate of newborn neurons; however, the fate determination of newborn cells remained unaltered. Moreover, the dendritic spine density of newborn neurons significantly decreased in alcohol-fed mice. Impaired spine formation indicates that alcohol interfered the synaptic connectivity of newborn neurons with excitatory neurons originating from a various areas of the brain. In the Novel Object Recognition test, alcohol-fed mice displayed deficits in the ability to discriminate the novel object. Conclusions Our study revealed that chronic alcohol exposure disrupted multiple steps of neurogenesis, including the production and development of newborn neurons. In addition, chronic alcohol exposure altered

  14. Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice

    PubMed Central

    Chen, Hsing-Jin; Chiang, Bor-Luen

    2015-01-01

    Background Preterm newborns that receive oxygen therapy often develop bronchopulmonary dysplasia (BPD), which is abnormal lung development characterized by impaired alveologenesis. Oxygen-mediated injury is thought to disrupt normal lung growth and development. However, the mechanism of hyperoxia-induced BPD has not been extensively investigated. We established a neonatal mouse model to investigate the effects of normobaric hyperoxia on retinoid metabolism and retinoid receptor expression. Methods Newborn mice were exposed to hyperoxic or normoxic conditions for 15 days. The concentration of retinol and retinyl palmitate in the lung was measured by HPLC to gauge retinoid metabolism. Retinoid receptor mRNA levels were assessed by real-time PCR. Proliferation and retinoid receptor expression in A549 cells were assessed in the presence and absence of exogenous vitamin A. Results Hyperoxia significantly reduced the body and lung weight of neonatal mice. Hyperoxia also downregulated expression of RARα, RARγ, and RXRγ in the lungs of neonatal mice. In vitro, hyperoxia inhibited proliferation and expression of retinoid receptors in A549 cells. Conclusion Hyperoxia disrupted retinoid receptor expression in neonatal mice. PMID:26509921

  15. CCAAT/enhancer binding protein alpha regulates p21 protein and hepatocyte proliferation in newborn mice.

    PubMed Central

    Timchenko, N A; Harris, T E; Wilde, M; Bilyeu, T A; Burgess-Beusse, B L; Finegold, M J; Darlington, G J

    1997-01-01

    CCAAT/enhancer binding protein alpha (C/EBP alpha) is expressed at high levels in quiescent hepatocytes and in differentiated adipocytes. In cultured cells, C/EBP alpha inhibits cell proliferation in part via stabilization of the p21 protein. The role of C/EBP alpha in regulating hepatocyte proliferation in vivo is presented herein. In C/EBP alpha knockout newborn mice, p21 protein levels are reduced in the liver, and the fraction of hepatocytes synthesizing DNA is increased. Greater than 30% of the hepatocytes in C/EBP alpha knockout animals continue to proliferate at day 17 of postnatal life when cell division in wild-type littermates is low (3%). p21 protein levels are relatively high in wild-type neonates but undetectable in C/EBP alpha knockout mice. The reduction of p21 protein in the highly proliferating livers that lack C/EBP alpha suggests that p21 is responsible for C/EBP alpha-mediated control of liver proliferation in newborn mice. During rat liver regeneration, the amounts of both C/EBP alpha and p21 proteins are decreased before DNA synthesis (6 to 12 h) and then return to presurgery levels at 48 h. Although C/EBP alpha controls p21 protein levels, p21 mRNA is not influenced by C/EBP alpha in liver. Using coimmunoprecipitation and a mammalian two-hybrid assay system, we have shown the interaction of C/EBP alpha and p21 proteins. Study of p21 stability in liver nuclear extracts showed that C/EBP alpha blocks proteolytic degradation of p21. Our data demonstrate that C/EBP alpha regulates hepatocyte proliferation in newborn mice and that in liver, the level of p21 protein is under posttranscriptional control, consistent with the hypothesis that protein-protein interaction with C/EBP alpha determines p21 levels. PMID:9372966

  16. In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice.

    PubMed

    Tree, Keda C; Scotto di Perretolo, Maud; Peyronnet, Julie; Cayetanot, Florence

    2014-07-01

    Cannabis is one of the most commonly used recreational drugs at ages highly correlated with potential pregnancy. Endocannabinoid signalling regulates important stages of neuronal development. When cannabinoid receptors, which are widely distributed through the nervous system, are activated by exogenous cannabinoids, breathing in adult rats is depressed. Here, we show that, in newborn mice, endocannabinoids, through the activation of cannabinoid receptor type 1 (CB1 R), participate in the modulation of respiration and its control. Blocking CB1 Rs at birth suppressed the brake exerted by endocannabinoids on ventilation in basal and in hypoxic conditions. The number of apnoeas and their duration were also minimized by activation of CB1 Rs in normoxic and in hypoxic conditions. However, prenatal cannabis intoxication, caused by a daily injection of WIN55,212-2, in pregnant mice durably modified respiration of the offspring, as shown by hyperventilation in basal conditions, an altered chemoreflex in response to hypoxia, and longer apnoeas. When CB1 Rs were blocked in WIN55,212-2 treated newborns, persistent hyperventilation was still observed, which could partly be explained by a perturbation of the central respiratory network. In fact, in vitro medullary preparations from WIN55,212-2 treated pups, free of peripheral or of supramedullary structures, showed an altered fictive breathing frequency. In conclusion, the endocannabinoid pathway at birth seems to modulate breathing and protect the newborn against apnoeas. However, when exposed prenatally to an excess of cannabinoid, the breathing neuronal network in development seems to be modified, probably rendering the newborn more vulnerable in the face of an unstable environment. PMID:24717006

  17. Human embryonic mesenchymal stem cells participate in differentiation of renal tubular cells in newborn mice

    PubMed Central

    Yuan, Li; Liu, Hou-Qi; Wu, Min-Juan

    2016-01-01

    Stem cells are used with increasing success in the treatment of renal tubular injury. However, whether mesenchymal stem cells (MSC) differentiate into renal tubular epithelial cells remains controversial. The aims of the present study were to observe the localization of human embryonic MSCs (hMSCs) in the kidneys of newborn mice, and to investigate hMSC differentiation into tubular epithelium. Primary culture hMSCs were derived from 4–7-week-old embryos and labeled with the cell membrane fluorescent dye PKH-26. The degree of apoptosis, cell growth, differentiation and localization of hMSCs with and without this label were then determined using immunohistochemical methods and flow cytometry. hMSCs and PKH26-labeled hMSCs were revealed to differentiate into chondrocytes and adipocytes, and were demonstrated to have similar proliferative capability. In the two cell types, the antigens CD34 and CD45, indicative of hematopoietic lineages, were not expressed; however, the expression of the mesenchymal markers CD29 and CD90 in MSCs, was significantly increased. During a 4-week culture period, laser confocal microscopy revealed that PKH26-labeled hMSCs in the kidneys of newborn mice gradually dispersed. Two weeks after the injection of the PKH26-labeled cells, the percentage of PKH26-labeled hMSCs localized to the renal tubules was 10±2.1%. In conclusion, PKH26 labeling has no effect on hMSC differentiation, proliferation and mesenchymal cell surface features, and hMSCs injected into the kidneys of newborn mice may transform to renal tubule epithelium. PMID:27446255

  18. Preferences of newborn mice for odours indicating closer genetic relatedness: is experience necessary?

    PubMed Central

    Todrank, Josephine; Busquet, Nicolas; Baudoin, Claude; Heth, Giora

    2005-01-01

    Evidence from studies with adult rodents indicates that individual recognition enables distinctions between familiar individuals irrespective of relatedness (but including close kin) and a separate mechanism enables discriminations based on genetic relatedness without prior familiarity. For example, adult mice could assess the extent of their genetic relatedness to unfamiliar individuals using perceptual similarities between their individual odours. The ontogeny of this genetic relatedness assessment mechanism, however, had not been investigated. Here, in two-choice tests, newborn mice differentially preferred odours of more genetically similar lactating females (paternal aunts to unrelated conspecific and conspecific to heterospecific) even without prior direct exposure to adults with the tested genotypes. The results provide a direct demonstration of genetic relatedness assessment abilities in newborns and show that experience with parental odours is not necessary for genetic relatedness distinctions. Future studies will be necessary to determine whether exposure to odours of other foetuses in the womb or littermates shortly after birth affects this genetic relatedness assessment process. PMID:16191620

  19. Spleen cells from adult mice given total lymphoid irradiation (TLI) or from newborn mice have similar regulatory effects in the mixed leukocyte reaction (MLR). II. Generation of antigen-specific suppressor cells in the MLR after the addition of spleen cells from newborn mice

    SciTech Connect

    Okada, S.; Strober, S.

    1982-11-01

    Spleen cells from newborn BALB/c mice were added to the mixed leukocyte reaction (MLR) between a variety of responder and stimulator cells. The newborn cells nonspecifically suppressed the uptake of (/sup 3/H)-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. Suppressor cell activity fell rapidly during the first 4 days after birth, and could not be detected by day 20. Newborn spleen cells inhibited the generation of nonspecific suppressor cells during the MLR but did not inhibit the generation of antigen-specific suppressor cells. Thus, newborn spleen cells exhibit a pattern of regulation of the MLR similar to that reported previously for spleen cells from adult mice given total lymphoid irradiation (TLI). These regulatory interactions provide a model that explains the ease of induction of transplantation tolerance in vivo in newborn mice and in TLI-treated adult mice.

  20. Orientation of newborn mice to lactating females: identifying biological substrates of semiochemical interest.

    PubMed

    Al Aïn, Syrina; Chraïti, Amal; Schaal, Benoist; Patris, Bruno

    2013-03-01

    Among mammals, odor-based communication between females and infants is decisive for neonatal survival. So far, the nature of odor substrates involved in the localization of the mother and their nipples is unknown in mice. The present study aims: (1) to evaluate the specific attractive value of lactating females to newborn mice, (2) to localize the abdominal region that is most attractive to pups, and (3) to identify odor substrates that support such attraction. Results showed that 5-6-day-old mice roam preferentially over the abdomen of lactating females than the abdomen of non-lactating females. In lactating females, pups are more attracted to abdominal areas comprising nipples. The blend of odor substrates from nipples, as well as separate sources presumed to compose it, viz. milk, maternal saliva and pup saliva, were detectable and equivalently attractive to pups. The equivalent attraction of these different odor substrates may derive either from overlap in chemical constituents, or from associative learning during nursing.

  1. Uptake of mercury by the hair of methylmercury-treated newborn mice

    SciTech Connect

    Shi, Chenyang; Lane, A.T.; Clarkson, T.W. )

    1990-04-01

    Human hair has unique advantages in monitoring environmental exposures to methyl-mercury. Using newborn Balb/c mice as a model system, the incorporation of methylmercury into the hair was studied and compared with methylmercury distributions in other tissues. Newborn mice were given intraperitoneal injections of {sup 203}Hg-labeled methylmercury at designated times according to hair growth stages of the mouse. Animals were sacrificed 2 days after dosing. Distribution of mercury in pelt and other tissues was measured. The level of mercury in pelt was found to correlate with hair growth. The amount of mercury in pelt peaked when hair growth was most rapid and the total amount of mercury in pelt was significantly higher than that in other tissues, constituting 40% of the whole body burden. However, when the hair ceased growing, the amount of mercury in pelt dramatically dropped to 4% of whole body burden and mercury concentrations in other tissues except brain were elevated. Autoradiographic studies with tritium-labeled methylmercury demonstrated that methylmercury concentrated in hair follicles in the skin. Within hair follicles and hairs, methylmercury accumulated in regions that are rich in high-sulfur proteins. The uptake of inorganic mercury (administered as HgCl{sub 2}) by pelt was also compared with that of methylmercury. The amount of inorganic mercury found in pelt was less than one-half that of methylmercury in animals with growing hair. Cessation of hair growth did not decrease the inorganic mercury level in pelt to the same extent as in the case of methylmercury.

  2. Effects of Allogeneic Hematopoietic Stem Cell Transplantation Plus Thymus Transplantation on Malignant Tumors: Comparison Between Fetal, Newborn, and Adult Mice

    PubMed Central

    Zhang, Yuming; Hosaka, Naoki; Cui, Yunze; Shi, Ming

    2011-01-01

    We have recently shown that allogeneic intrabone marrow–bone marrow transplantation + adult thymus transplantation (TT) is effective for hosts with malignant tumors. However, since thymic and hematopoietic cell functions differ with age, the most effective age for such intervention needed to be determined. We performed hematopoietic stem cell transplantation (HSCT) using the intrabone marrow method with or without TT from fetal, newborn, and adult B6 mice (H-2b) into BALB/c mice (H-2d) bearing Meth-A sarcoma (H-2d). The mice treated with all types of HSCT + TT showed more pronounced regression and longer survival than those treated with HSCT alone in all age groups. Those treated with HSCT + TT showed increased numbers of CD4+ and CD8+ T cells but decreased numbers of Gr-1/Mac-1 myeloid suppressor cells and decreased percentages of FoxP3 cells in CD4+ T cells, compared with those treated with HSCT alone. In all mice, those treated with fetal liver cell (as fetal HSCs) transplantation + fetal TT or with newborn liver cell (as newborn HSCs) transplantation (NLT) + newborn TT (NTT) showed the most regression, and the latter showed the longest survival. The number of Gr-1/Mac-1 cells was the lowest, whereas the percentage of CD62L−CD44+ effector memory T cells and the production of interferon γ (IFN-γ) were highest in the mice treated with NLT + NTT. These findings indicate that, at any age, HSCT + TT is more effective against cancer than HSCT alone and that NLT + NTT is most effective. PMID:20672991

  3. In vivo proliferative regeneration of balance hair cells in newborn mice

    PubMed Central

    Burns, Joseph C.; Cox, Brandon C.; Thiede, Benjamin R.; Zuo, Jian; Corwin, Jeffrey T.

    2012-01-01

    The regeneration of mechanoreceptive hair cells occurs throughout life in non-mammalian vertebrates and allows them to recover from hearing and balance deficits that affect humans and other mammals permanently. The irreversibility of comparable deficits in mammals remains unexplained, but often has been attributed to steep embryonic declines in cellular production. However, recent results suggest that gravity-sensing hair cells in murine utricles may increase in number during neonatal development, raising the possibility that young mice might retain sufficient cellular plasticity for mitotic hair cell regeneration. To test for this we used neomycin to kill hair cells in utricles cultured from mice of different ages and found that proliferation increased ten-fold in damaged utricles from the youngest neonates. To kill hair cells in vivo, we generated a novel mouse model that uses an inducible, hair-cell-specific CreER allele to drive expression of diptheria toxin fragment A (DTA). In newborns, induction of DTA expression killed hair cells and resulted in significant, mitotic hair cell replacement in vivo, which occurred days after the normal cessation of developmental mitoses that produce hair cells. DTA expression induced in five-day-old mice also caused hair cell loss, but no longer evoked mitotic hair cell replacement. These findings show that regeneration limits arise in vivo during the postnatal period when the mammalian balance epithelium’s supporting cells differentiate unique cytological characteristics and lose plasticity, and they support the notion that the differentiation of those cells may directly inhibit regeneration or eliminate an essential, but as yet unidentified pool of stem cells. PMID:22573679

  4. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

    PubMed

    Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development. PMID:24819605

  5. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

    PubMed

    Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

  6. Epidermal growth factor inhibits radioiodine uptake but stimulates deoxyribonucleic acid synthesis in newborn rat thyroids grown in nude mice

    SciTech Connect

    Ozawa, S.; Spaulding, S.W. )

    1990-08-01

    We have studied the effect of altering the level of circulating epidermal growth factor (EGF) on the function and growth of newborn rat thyroids transplanted into nude mice. Preliminary studies confirmed that sialoadenectomy reduced circulating EGF levels in nude mice (from 0.17 +/- 0.02 to 0.09 +/- 0.02 ng/ml), and that ip injection of 5 micrograms EGF raised EGF levels (the peak level of 91.7 +/- 3.3 ng/ml was achieved at 30 min, with a subsequent half-life of about 1 h). The radioiodine uptake by newborn rat thyroid transplants in the sialoadenectomized and sham-operated animals correlated inversely with the circulating EGF levels determined when the mice were killed (r = -0.99). Low-dose TSH treatment (0.1 microU/day) generally stimulated the radioiodine uptake, but high-dose TSH groups (100 microU/day) were not significantly different from the control group. The 5-day nuclear (3H)thymidine labeling index was 6.8 +/- 0.5% IN newborn rat thyroid transplants grown in sialoadenectomized animals, 13.1 +/- 0.3% in sham-operated animals, and 16.8 +/- 0.5% in nude mice receiving 5 micrograms EGF ip daily. In general, both low-dose and high-dose TSH promoted DNA synthesis under low EGF conditions but were ineffective in the presence of higher levels of EGF. Adult rat thyroid transplants showed no significant responses. Although sialoadenectomy may alter other factors besides EGF, it appears that changes in the levels of circulating EGF within the physiological range affect the function and growth of newborn rat thyroid transplants. Circulating EGF may play a role in thyroid maturation and may also be involved in the regulation of thyroid function throughout life.

  7. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice.

    PubMed

    Yang, Yang; Wang, Lili; Bell, Peter; McMenamin, Deirdre; He, Zhenning; White, John; Yu, Hongwei; Xu, Chenyu; Morizono, Hiroki; Musunuru, Kiran; Batshaw, Mark L; Wilson, James M

    2016-03-01

    Many genetic liver diseases in newborns cause repeated, often lethal, metabolic crises. Gene therapy using nonintegrating viruses such as adeno-associated virus (AAV) is not optimal in this setting because the nonintegrating genome is lost as developing hepatocytes proliferate. We reasoned that newborn liver may be an ideal setting for AAV-mediated gene correction using CRISPR-Cas9. Here we intravenously infuse two AAVs, one expressing Cas9 and the other expressing a guide RNA and the donor DNA, into newborn mice with a partial deficiency in the urea cycle disorder enzyme, ornithine transcarbamylase (OTC). This resulted in reversion of the mutation in 10% (6.7-20.1%) of hepatocytes and increased survival in mice challenged with a high-protein diet, which exacerbates disease. Gene correction in adult OTC-deficient mice was lower and accompanied by larger deletions that ablated residual expression from the endogenous OTC gene, leading to diminished protein tolerance and lethal hyperammonemia on a chow diet.

  8. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice

    PubMed Central

    Yang, Yang; Wang, Lili; Bell, Peter; McMenamin, Deirdre; He, Zhenning; White, John; Yu, Hongwei; Xu, Chenyu; Morizono, Hiroki; Musunuru, Kiran; Batshaw, Mark L.; Wilson, James M.

    2016-01-01

    Many genetic liver diseases present in newborns with repeated, often lethal, metabolic crises. Gene therapy using non-integrating viruses such as AAV is not optimal in this setting because the non-integrating genome is lost as developing hepatocytes proliferate1,2. We reasoned that newborn liver may be an ideal setting for AAV-mediated gene correction using CRISPR/Cas9. Here we intravenously infuse two AAVs, one expressing Cas9 and the other expressing a guide RNA and the donor DNA, into newborn mice with a partial deficiency in the urea cycle disorder enzyme, ornithine transcarbamylase (OTC). This resulted in reversion of the mutation in 10% (6.7% – 20.1%) of hepatocytes and increased survival in mice challenged with a high-protein diet, which exacerbates disease. Gene correction in adult OTC-deficient mice was lower and accompanied by larger deletions that ablated residual expression from the endogenous OTC gene, leading to diminished protein tolerance and lethal hyperammonemia on a chow diet. PMID:26829317

  9. Conditioned medium from Bifidobacteria infantis protects against Cronobacter sakazakii-induced intestinal inflammation in newborn mice.

    PubMed

    Weng, Meiqian; Ganguli, Kriston; Zhu, Weishu; Shi, Hai Ning; Walker, W Allan

    2014-05-01

    Necrotizing enterocolitis (NEC) is associated with a high morbidity and mortality in very low birth weight infants. Several hypotheses regarding the pathogenesis of NEC have been proposed but to date no effective treatment is available. Previous studies suggest that probiotic supplementation is protective. We recently reported that probiotic (Bifidobacterium infantis) conditioned medium (PCM) has an anti-inflammatory effect in cultured fetal human intestinal cells (H4) and fetal intestine explants. In this study, we tested in vivo whether PCM protects neonatal mice from developing intestinal inflammation induced by exposure to Cronobacter sakazakii (C. sakazakii), an opportunistic pathogen associated with NEC. We found that infected neonatal mice had a significantly lower body weight than control groups. Infection led to ileal tissue damage including villous rupture, disruption of epithelial cell alignment, intestinal inflammation, apoptotic cell loss, and decreased mucus production. Pretreatment with PCM prevented infection caused decrease in body weight, attenuated enterocyte apoptotic cell death, mitigated reduced mucin production, and maintained ileal structure. Infected ileum expressed reduced levels of IκBα, which could be restored upon pretreatment with PCM. We also observed a nuclear translocation of NF-κB p65 in H4 cells exposed to C. sakazakii, which was prevented in PCM-pretreated cells. Finally, treatment of neonatal mice with PCM prior to infection sustained the capacity of ileal epithelial proliferation. This study suggests that an active component(s) released into the culture medium by B. infantis may prevent ileal damage by a pathogen linked to NEC.

  10. Cerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation

    PubMed Central

    Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M.; Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3′-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3′-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development. PMID:24819605

  11. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    PubMed

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  12. Failure-to-Thrive Syndrome Associated with Tumor Formation by Madin–Darby Canine Kidney Cells in Newborn Nude Mice

    PubMed Central

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-01-01

    Tumors that formed in newborn nude mice that were inoculated with 107 Madin–Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 102.8 to 107.5); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor–derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  13. Analysis of physiological and behavioural parameters in mice after toe clipping as newborns.

    PubMed

    Schaefer, Dagmar C; Asner, Igor N; Seifert, Burkhardt; Bürki, Kurt; Cinelli, Paolo

    2010-01-01

    In this study, we have investigated the short- and long-term impact of toe clipping, a commonly used method for marking and simultaneously taking biopsies of pups, which is controversially discussed because of its potentially negative impact on animals. Furthermore, we have analysed animal welfare aspects such as health, behaviour, development, stress and detrimental effects in young animals and in adults after toe clipping at postnatal days 3 (P3) and 7 (P7). Our findings indicate that for both P3 and P7 pups amputations at the second phalange of one toe of each paw do not have any negative effects on growth and physical development and that the clipped pups do not suffer from rejection by their mother. Our data indicate that even though at both ages no abnormalities have been detected in histology, clipping at P7 is the preferable age for an adequate marking mostly because of the small size of the toes at P3. This was also confirmed by grip tests at the age of 12 weeks where P3 animals had lower grip strength than control animals, whereas P7 pups did not show any impairment. Hotplate tests indicated that toe clipping performed at P3 and P7 did not cause hyperalgesia at the amputation stump. Serum corticosterone analysis directly performed on P7 pups after clipping indicated that major stress was provoked mainly through the handling and not because of the clipping itself. Taken together, these data lead to the conclusion that toe clipping is from a morphological, physiological and welfare point of view an acceptable method for marking and genotyping newborn mice.

  14. [Study of the metanephros of fetuses, newborn and 2-month-old mice developing under conditions of kidney damage to the females by nephrocytotoxic serum].

    PubMed

    Averkina, R F; Suchkova, N I

    1976-01-01

    In the metanephros of foetuses beginning from the 14 days of development and in the newborn mice from females with injured kidneys, marked defects of proximal convoluted tubules and less marked defects of glomeruli were noted what corresponded to the character of kidney injury in their mothers. At the same time the diameter of glomeruli and convoluted tubules, the height and width of their cells increased, but the diameter of their nuclei decreased. These changes are accompanied by distrophic changes, mainly in the cells of convoluted tubules, the most markedly expressed in the newborn mice. No marked histological changes were found in the metanephros of two months old experimental mice.

  15. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment.

    PubMed

    Wulf-Goldenberg, Annika; Keil, Marlen; Fichtner, Iduna; Eckert, Klaus

    2012-04-01

    In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34(+) cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation. Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34(+) cord blood stem cell preparations.

  16. Brief dark exposure restored ocular dominance plasticity in aging mice and after a cortical stroke.

    PubMed

    Stodieck, Sophia Katharina; Greifzu, Franziska; Goetze, Bianka; Schmidt, Karl-Friedrich; Löwel, Siegrid

    2014-12-01

    In the primary visual cortex (V1), monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons towards the open eye (Wiesel and Hubel, 1963; Gordon and Stryker, 1996). In V1 of C57Bl/6J mice, this OD-plasticity is maximal in juveniles, declines in adults and is absent beyond postnatal day (PD) 110 (Lehmann and Löwel, 2008) if mice are raised in standard cages. Since it was recently shown that brief dark exposure (DE) restored OD-plasticity in young adult rats (PD70-100) (He et al., 2006), we wondered whether DE would restore OD-plasticity also in adult and old mice and after a cortical stroke. To this end, we raised mice in standard cages until adulthood and transferred them to a darkroom for 10-14 days. Using intrinsic signal optical imaging we demonstrate that short-term DE can restore OD-plasticity after MD in both adult (PD138) and old mice (PD535), and that OD-shifts were mediated by an increase of open eye responses in V1. Interestingly, restored OD-plasticity after DE was accompanied by a reduction of both parvalbumin expressing cells and perineuronal nets and was prevented by increasing intracortical inhibition with diazepam. DE also maintained OD-plasticity in adult mice (PD150) after a stroke in the primary somatosensory cortex. In contrast, short-term DE did not affect basic visual parameters as measured by optomotry. In conclusion, short-term DE was able to restore OD-plasticity in both adult and aging mice and even preserved plasticity after a cortical stroke, most likely mediated by reducing intracortical inhibition.

  17. Immunogenicity and protective efficacy of an EV71 virus-like particle vaccine against lethal challenge in newborn mice.

    PubMed

    Sun, Shiyang; Gao, Fan; Mao, Qunying; Shao, Jie; Jiang, Liping; Liu, Dawei; Wang, Yiping; Yao, Xin; Wu, Xing; Sun, Bo; Zhao, Dandan; Ma, Youlei; Lu, Jingcai; Kong, Wei; Jiang, Chunlai; Liang, Zhenglun

    2015-01-01

    Enterovirus 71(EV71) has caused severe epidemics of hand, foot and mouth disease (HFMD) in the Asia Pacific in recent years, particularly in infants and pre-school children. It has become a serious public health threat, as currently there are no approved vaccines or antiviral drugs for EV71 infection. Many EV71 vaccines have been under development worldwide, however the main focus is inactivated EV71 vaccines. For example, the inactivated EV71 vaccine has recently finished phase III clinical trial in Mainland China. There have been very few studies on EV71 virus like particles (VLPs). In this study, the immunogenicity and protective potency of the EV71 VLPs produced in insect cells were evaluated in mice with different dosages. Our results showed that EV71 VLPs could elicit high titers of neutralizing antibodies (NTAbs) in a dose-dependent manner and NTAbs were sustained after the second injection with an average GMT (geometric mean titer) level from 19 to 2960 in immunized mice. Survival rates were 100%, 100%, 85%, and 40% after challenge with 15 LD50 (median lethal dose) of EV71 in these newborn mice, respectively. ED50 (50% effective dose) of VLPs was 0.20 μg/dose in newborn mice, while NTAb titer under this dosage was about 50. Passive protection was determined with 2 methods and demonstrated that the survival rates were positively correlated with NTAb titers, which at 24 and 54 induced 50% survival rates in experimental animals. The ED50 of VLP vaccines and the passive NTAb titers were also analyzed. The maternal NTAb titer was similar as the passive NTAb titer in the mouse model challenged with our lethal mouse EV71 strain. Hence, our work has provided preliminary data on the protection potency of VLPs as a vaccine candidate and would facilitate future VLP vaccine development.

  18. Connexin32 can restore hearing in connexin26 deficient mice.

    PubMed

    Degen, Joachim; Schütz, Melanie; Dicke, Nikolai; Strenzke, Nicola; Jokwitz, Melanie; Moser, Tobias; Willecke, Klaus

    2011-10-01

    Functional gap junction channels composed of certain connexin proteins are essential for the function of the cochlea. Homozygous deficiency in the Gjb2 (mice) or GJB2 (human) gene coding for connexin26 (Cx26) in the cochlea leads to hearing impairment in mice and humans, respectively. Here we have studied the functional equivalence of Cx26 and connexin32 (Cx32) isoforms in the cochlea. We analyzed a conditional mouse mutant in which the Gjb2 coding DNA was exchanged by LacZ DNA coding for the reporter protein beta-galactosidase. This allowed us to follow the unrestricted and cell type specific expression of Gjb2 promoter activity. After inner ear specific, Otogelin-Cre recombinase mediated deletion of the loxP-site-flanked LacZ coding DNA, transcription of the Gjb1 gene, coding for Cx32 was activated by the Gjb2 promoter. Interbreeding of these mice with conditional Gjb2 null mice resulted in animals in which Cx32 instead of Cx26 protein is expressed in the non-sensory epithelial network of the cochlea. When we analyzed the auditory function in these mice, we found that the expression of Cx32 protein is sufficient to support hearing in the absence of Cx26. Thus Cx32 can functionally replace Cx26 in the mouse cochlea resulting in almost normal hearing. PMID:21813206

  19. Peroxisome deficiency-induced ER stress and SREBP-2 pathway activation in the liver of newborn PEX2 knock-out mice.

    PubMed

    Kovacs, Werner J; Charles, Khanichi N; Walter, Katharina M; Shackelford, Janis E; Wikander, Thomas M; Richards, Michael J; Fliesler, Steven J; Krisans, Skaidrite K; Faust, Phyllis L

    2012-06-01

    Disruption of the Pex2 gene leads to peroxisome deficiency and widespread metabolic dysfunction. We previously demonstrated that peroxisomes are critical for maintaining cholesterol homeostasis, using peroxisome-deficient Pex2(-/-) mice on a hybrid Swiss Webster×129S6/SvEv (SW/129) genetic background. Peroxisome deficiency activates hepatic endoplasmic reticulum (ER) stress pathways, leading to dysregulation of the endogenous sterol response mechanism. Herein, we demonstrate a more profound dysregulation of cholesterol homeostasis in newborn Pex2(-/-) mice congenic on a 129S6/SvEv (129) genetic background, and substantial differences between newborn versus postnatal Pex2(-/-) mice in factors that activate ER stress. These differences extend to relationships between activation of genes regulated by SREBP-2 versus PPARα. The SREBP-2 pathway is induced in neonatal Pex2(-/-) livers from 129 and SW/129 strains, despite normal hepatic cholesterol levels. ER stress markers are increased in newborn 129 Pex2(-/-) livers, which occurs in the absence of hepatic steatosis or accumulation of peroxins in the ER. Moreover, the induction of SREBP-2 and ER stress pathways is independent of PPARα activation in livers of newborn 129 and SW/129 Pex2(-/-) mice. Two-week-old wild-type mice treated with the peroxisome proliferator WY-14,643 show strong induction of PPARα-regulated genes and decreased expression of SREBP-2 and its target genes, further demonstrating that SREBP-2 pathway induction is not dependent on PPARα activation. Lastly, there is no activation of either SREBP-2 or ER stress pathways in kidney and lung of newborn Pex2(-/-) mice, suggesting a parallel induction of these pathways in peroxisome-deficient mice. These findings establish novel associations between SREBP-2, ER stress and PPARα pathway inductions.

  20. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet.

    PubMed

    Clemmensen, Christoffer; Chabenne, Joseph; Finan, Brian; Sullivan, Lorraine; Fischer, Katrin; Küchler, Daniela; Sehrer, Laura; Ograjsek, Teja; Hofmann, Susanna M; Schriever, Sonja C; Pfluger, Paul T; Pinkstaff, Jason; Tschöp, Matthias H; Dimarchi, Richard; Müller, Timo D

    2014-04-01

    We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog in combination with exendin-4 or FGF21. However, the return of leptin action required discontinuation of high-fat diet (HFD) exposure. Here we assess whether a single peptide possessing balanced coagonism at the glucagon-like peptide 1 (GLP-1) and glucagon receptors can restore leptin responsiveness in DIO mice maintained on a HFD. DIO mice were treated with PEG-GLP-1/glucagon (30 nmol/kg every fourth day) to induce an ∼15% body weight loss, upon which they were randomized to continue PEG-GLP-1/glucagon therapy or reassigned to receive supplemental daily PEG-leptin (185 nmol/kg/day). The addition of PEG-leptin to PEG-GLP-1/glucagon resulted in an ∼18% greater weight loss as compared with PEG-GLP-1/glucagon alone and was accompanied by further decreases in food intake and improved glucose and lipid metabolism. The beneficial effect of PEG-leptin supplementation occurred after an initial body weight loss similar to what we previously reported following reduced dietary fat along with PEG-leptin and exendin-4 or FGF21 cotreatment. In summary, we report that GLP-1/glucagon coagonism restores leptin responsiveness in mice maintained on a HFD, thus emphasizing the translational value of this polypharmacotherapy for the treatment of obesity and diabetes. PMID:24379349

  1. Orexin Gene Therapy Restores the Timing and Maintenance of Wakefulness in Narcoleptic Mice

    PubMed Central

    Kantor, Sandor; Mochizuki, Takatoshi; Lops, Stefan N.; Ko, Brian; Clain, Elizabeth; Clark, Erika; Yamamoto, Mihoko; Scammell, Thomas E.

    2013-01-01

    Study Objectives: Narcolepsy is caused by selective loss of the orexin/hypocretin-producing neurons of the hypothalamus. For patients with narcolepsy, chronic sleepiness is often the most disabling symptom, but current therapies rarely normalize alertness and do not address the underlying orexin deficiency. We hypothesized that the sleepiness of narcolepsy would substantially improve if orexin signaling were restored in specific brain regions at appropriate times of day. Design: We used gene therapy to restore orexin signaling in a mouse model of narcolepsy. In these Atx mice, expression of a toxic protein (ataxin-3) selectively kills the orexin neurons. Interventions: To induce ectopic expression of the orexin neuropeptides, we microinjected an adeno-associated viral vector coding for prepro-orexin plus a red fluorescence protein (AAV-orexin) into the mediobasal hypothalamus of Atx and wild-type mice. Control mice received an AAV coding only for red fluorescence protein. Two weeks later, we recorded sleep/wake behavior, locomotor activity, and body temperature and examined the patterns of orexin expression. Measurements and Results: Atx mice rescued with AAV-orexin produced long bouts of wakefulness and had a normal diurnal pattern of arousal, with the longest bouts of wake and the highest amounts of locomotor activity in the first hours of the night. In addition, AAV-orexin improved the timing of rapid eye movement sleep and the consolidation of nonrapid eye movement sleep in Atx mice. Conclusions: These substantial improvements in sleepiness and other symptoms of narcolepsy demonstrate the effectiveness of orexin gene therapy in a mouse model of narcolepsy. Additional work is needed to optimize this approach, but in time, AAV-orexin could become a useful therapeutic option for patients with narcolepsy. Citation: Kantor S; Mochizuki T; Lops SN; Ko B; Clain E; Clark E; Yamamoto M; Scammell TE. Orexin gene therapy restores the timing and maintenance of wakefulness

  2. Modified Aloe Polysaccharide Restores Chronic Stress-Induced Immunosuppression in Mice

    PubMed Central

    Lee, Youngjoo; Im, Sun-A; Kim, Jiyeon; Lee, Sungwon; Kwon, Junghak; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2016-01-01

    Chronic stress generally experienced in our daily lives; is known to augment disease vulnerability by suppressing the host immune system. In the present study; the effect of modified Aloe polysaccharide (MAP) on chronic stress-induced immunosuppression was studied; this Aloe compound was characterized in our earlier study. Mice were orally administered with MAP for 24 days and exposed to electric foot shock (EFS; duration; 3 min; interval; 10 s; intensity; 2 mA) for 17 days. The stress-related immunosuppression and restorative effect of MAP were then analyzed by measuring various immunological parameters. MAP treatment alleviated lymphoid atrophy and body weight loss. The numbers of lymphocyte subsets were significantly normalized in MAP-treated mice. Oral administration of MAP also restored the proliferative activities of lymphocytes; ovalbumin (OVA)-specific T cell proliferation; antibody production; and the cell killing activity of cytotoxic T lymphocytes. In summary; oral administration of MAP ameliorated chronic EFS stress-induced immunosuppression. PMID:27706024

  3. Non-neuronal, but atropine-sensitive ileal contractile responses to short-chain fatty acids: age-dependent desensitization and restoration under inflammatory conditions in mice.

    PubMed

    Yajima, Masako; Kimura, Shunsuke; Karaki, Shinichiro; Nio-Kobayashi, Junko; Tsuruta, Takeshi; Kuwahara, Atsukazu; Yajima, Takaji; Iwanaga, Toshihiko

    2016-04-01

    Intestinal epithelial cells sense short-chain fatty acids (SCFAs) to secrete non-neuronal acetylcholine (ACh). However, the roles of luminalSCFAs and epithelialACh under normal and pathological conditions remain unknown. We examined ileal contractile responses toSCFAs at different ages and their mucosal cholinergic alterations under inflammatory conditions. Ileal contractile responses toSCFAs in 1-day-old pups to 7-week-old mice were compared using an isotonic transducer, and responses to an intraperitoneal injection of lipopolysaccharide (LPS) were analyzed in 7-week-old mice. ThemRNAexpression levels of aSCFAactivate free fatty acid receptor, acetylcholinesterase (AChE), choline acetyltransferase (Chat), and choline transporter-like protein 4 (CTL4) were measured using real-time quantitativeRT-PCRAChE was analyzed by histochemical and optical enzymatic assays. Atropine-sensitive ileal contractile responses toSCFAs occurred in all 1-day-old pups, but were frequently desensitized after the weaning period. These contractile responses were not inhibited by tetrodotoxin and did not appear when the mucosal layer had been scraped off. Contractile desensitization in 7-week-old mice was abolished in the presence of theAChE inhibitor, eserine, which was consistent with increasedAChE activity after weaning. Ileal contractions toSCFAs in adult mice were restored byLPS, which significantly increased the epithelialmRNAexpression of Chat andCTL4. Atropine-sensitive ileal contractile responses toSCFAs constitutively occur in the newborn period, and are desensitized during developmental stages following the up-regulated expression ofAChE in the villous mucosa, but are restored under inflammatory conditions possibly via the release of epithelialACh. PMID:27053293

  4. Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice

    PubMed Central

    Proulx, Steven T.; Dillard, Miriam E.; Johnson, Nicole; Detmar, Michael

    2016-01-01

    Prox1 heterozygous mice have a defective lymphatic vasculature and develop late-onset obesity. Chyle abnormally leaks from those vessels, accumulates in the surrounding tissues, and causes an increase in adipose tissue. We characterized the lymphatics of Prox1+/– mice to determine whether the extent of obesity correlated with the severity of lymphatic defects. The lymphatic vasculature in Prox1+/– mice exhibited reduced tracer clearance from the ear skin, dysfunctional perfusion of the lower legs, and reduced tracer uptake into the deep lymphatic collectors during mechanostimulation prior to the onset of obesity. Ear lymphatic vessels and leg collectors in Prox1+/– mice were disorganized and irregular, further confirming that defective lymphatic vessels are associated with obesity in Prox1+/– mice. We now provide conclusive in vivo evidence that demonstrates that leaky lymphatics mediate obesity in Prox1+/– mice, as restoration of lymphatic vasculature function was sufficient to rescue the obesity features in Prox1+/– mice. Finally, depth-lipomic profiling of lymph contents showed that free fatty acids induce adipogenesis in vitro. PMID:26973883

  5. Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice.

    PubMed

    Tam, Bjorn T; Pei, Xiao M; Yung, Benjamin Y; Yip, Shea P; Chan, Lawrence W; Wong, Cesar S; Siu, Parco M

    2015-12-01

    Impairment of insulin signaling in skeletal muscle detrimentally affects insulin-stimulated disposal of glucose. Restoration of insulin signaling in skeletal muscle is important as muscle is one of the major sites for disposal of blood glucose. Recently, unacylated ghrelin (UnAG) has received attention in diabetic research due to its favorable actions on improving glucose tolerance, glycemic control, and insulin sensitivity. The investigation of UnAG has entered phase Ib clinical trial in type 2 diabetes and phase II clinical trial in hyperphagia in Prader-Willi syndrome. Nonetheless, the precise mechanisms responsible for the anti-diabetic actions of UnAG remain incompletely understood. In this study, we examined the effects of UnAG on restoring the impaired insulin signaling in skeletal muscle of db/db diabetic mice. Our results demonstrated that UnAG effectively restored the impaired insulin signaling in diabetic muscle. UnAG decreased insulin receptor substrate (IRS) phosphorylation, increased protein kinase B (Akt) phosphorylation, and, hence, suppressed mTOR signaling. Consequently, UnAG enhanced Glut4 localization and increased PDH activity in the diabetic skeletal muscle. Intriguingly, our data indicated that UnAG normalized the suppressed autophagic signaling in diabetic muscle. In conclusion, our findings illustrated that UnAG restored the impaired insulin and autophagic signaling in skeletal muscle of diabetic mice, which are valuable to understand the underlying mechanisms of the anti-diabetic action of UnAG at peripheral skeletal muscle level. PMID:26228926

  6. Sources, sinks, and spatial ecology of cotton mice in longleaf pine stands undergoing restoration

    USGS Publications Warehouse

    Sharp, N.W.; Mitchell, M.S.; Grand, J.B.

    2009-01-01

    The Fire and Fire Surrogate studya replicated, manipulative experimentsought the most economically and ecologically efficient way to restore the nation's fire-maintained ecosystems. As part of this study, we conducted a 3-year markrecapture study, comprising 105,000 trap-nights, to assess demographic responses of cotton mice (Peromyscus gossypinus) to Fire and Fire Surrogate treatments at the Gulf Coastal Plain site, where longleaf pine was the ecosystem to be restored. We compared competing models to evaluate restoration effects on variation in apparent survival and recruitment over time, space, and treatment, and incorporated measures of available source habitat for cotton mice with reverse-time modeling to infer immigration from outside the study area. The top-ranked survival model contained only variation over time, but the closely ranked 2nd and 3rd models included variation over space and treatment, respectively. The top 4 recruitment models all included effects for availability of source habitat and treatments. Burning appeared to degrade habitat quality for cotton mice, showing demographic characteristics of a sink, but treatments combining fire with thinning of trees or application of herbicide to the understory appeared to improve habitat quality, possibly creating sources. Bottomland hardwoods outside the study also acted as sources by providing immigrants to experimental units. Models suggested that population dynamics operated over multiple spatial scales. Treatments applied to 15-ha stands probably only caused local variation in vital rates within the larger population. ?? 2009 American Society of Mammalogists.

  7. Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.

    PubMed

    Koike, Kengo; Ishigami, Akihito; Sato, Yasunori; Hirai, Toyohiro; Yuan, Yiming; Kobayashi, Etsuko; Tobino, Kazunori; Sato, Tadashi; Sekiya, Mitsuaki; Takahashi, Kazuhisa; Fukuchi, Yoshinosuke; Maruyama, Naoki; Seyama, Kuniaki

    2014-02-01

    Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

  8. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice.

    PubMed

    Aso, Kazuyoshi; Tsuruhara, Akitoshi; Takagaki, Kentaro; Oki, Katsuyuki; Ota, Megumi; Nose, Yasuhiro; Tanemura, Hideki; Urushihata, Naoki; Sasanuma, Jinichi; Sano, Masayuki; Hirano, Atsuyuki; Aso, Rio; McGhee, Jerry R; Fujihashi, Kohtaro

    2016-01-01

    It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice. PMID:26840058

  9. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice

    PubMed Central

    Aso, Kazuyoshi; Tsuruhara, Akitoshi; Takagaki, Kentaro; Oki, Katsuyuki; Ota, Megumi; Nose, Yasuhiro; Tanemura, Hideki; Urushihata, Naoki; Sasanuma, Jinichi; Sano, Masayuki; Hirano, Atsuyuki; Aso, Rio; McGhee, Jerry R.; Fujihashi, Kohtaro

    2016-01-01

    It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer’s patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice. PMID:26840058

  10. Monoaminergic control of spinal locomotor networks in SOD1G93A newborn mice

    PubMed Central

    Milan, Léa; Barrière, Grégory; De Deurwaerdère, Philippe; Cazalets, Jean-René; Bertrand, Sandrine S.

    2014-01-01

    Mutations in the gene that encodes Cu/Zn-superoxide dismutase (SOD1) are the cause of approximately 20% of familial forms of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. While ALS symptoms appear in adulthood, spinal motoneurons exhibit functional alterations as early as the embryonic and postnatal stages in the murine model of ALS, the SOD1 mice. Monoaminergic – i.e., dopaminergic (DA), serotoninergic (5-HT), and noradrenergic (NA) – pathways powerfully control spinal networks and contribute significantly to their embryonic and postnatal maturation. Alterations in monoaminergic neuromodulation during development could therefore lead to impairments in the motoneuronal physiology. In this study, we sought to determine whether the monoaminergic spinal systems are modified in the early stages of development in SOD1 mice. Using a post-mortem analysis by high performance liquid chromatography (HPLC), monoaminergic neuromodulators and their metabolites were quantified in the lumbar spinal cord of SOD1 and wild-type (WT) mice aged one postnatal day (P1) and P10. This analysis underscores an increased content of DA in the SOD1 lumbar spinal cord compared to that of WT mice but failed to reveal any modification of the other monoaminergic contents. In a next step, we compared the efficiency of the monoaminergic compounds in triggering and modulating fictive locomotion in WT and SOD1 mice. This study was performed in P1–P3 SOD1 mice and age-matched control littermates using extracellular recordings from the lumbar ventral roots in the in vitro isolated spinal cord preparation. This analysis revealed that the spinal networks of SOD1G93A mice could generate normal locomotor activity in the presence of NMA-5-HT. Interestingly, we also observed that SOD1 spinal networks have an increased sensitivity to NA compared to WT spinal circuits but exhibited similar DA responses. PMID:25071458

  11. Concentrations of DDT, PVBs, HCB, and HCH isomers in the liver and adipose tissue of newborn mice receiving an extract of human milk

    SciTech Connect

    Sitarska, E.; Gorski, T.; Ludwick, J.K.

    1987-11-01

    Persistent organic chlorine compounds, such as DDT and its metabolites, hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) circulate in the food chain of the ecosystem. Most data on the toxicity and accumulation of organic chlorine compounds have been obtained from animal experiments after chronic or acute poisoning with marketed preparations or standards of the used components of these preparations. In food products of animal origin and in human milk these compounds and their metabolites are present after multiple metabolic steps in varying proportions and concentrations. Their variable amounts are passed to newborns with mother's milk. The purpose of the present study was to investigate in an experimental model of newborn mice the degree of accumulation of these compounds in the liver and adipose tissue after long-standing feeding them with an extract of human milk with added organic chlorine compounds in doses received by human newborns with milk. In the assessment of the relationship between the degree of accumulation of various compounds in the tissues of newborn mice and the daily dose concentrations were used similar to those found in human milk.

  12. Immune response of newborn BALB/c mice to Cryptosporidium infection.

    PubMed

    Ahmadian, Nasser; Pashaei-Asl, Roghiyeh; Ahmadian, Masomeh; Rahmati-Yamchi, Mohammad; Shahabi, Saed; Vazini, Hossein

    2016-09-01

    Cryptosporidium parvum is a protozoan parasite which causes diarrheal in human and animals worldwide. Infection transmission has reported through oral-fecal by infectious objects through foods and drinks. In this study we explored the immune response pathway in animal model for C. parvum to develop the new treatment way. Oocysts collected from fecal positive for C. parvum and diluted about 1:5 in sucrose solution. New born BALB/c mice (3 days) divided to 2 different groups. Control group hadn't received any oocyst, the test groups received 5 × 10(5) oocysts. 5 mice selected for each control group and 11 mice chosen for each test group. Blood collected from heart bleeds in days of 6, 9, 12 and 16. Protein concentrations determined by bio-photometer. Dot blotting used to find out total antibody concentrations oocyst antigen. Among the test and the control groups, blots appeared in test group which means antibody production, but not any blot observed in the control groups. The non-characteristic proteins in serum were measured by the biophotometer. In this study, we investigated antibody serum production against C. parvum oocysts in new born BALB/c mice. The detected antibody through dot blot technique was our aims which had conjugated to our characteristic antiserum. The recorded numbers for the controls by biophotometer related to the non characteristic proteins in serum. The results of this study can used to produce polyclonal or monoclonal antibodies against cryptosporidiosis. PMID:27605838

  13. Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM.

    PubMed

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

    2008-01-01

    The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-gamma and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans. PMID:17705143

  14. Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM.

    PubMed

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

    2008-01-01

    The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-gamma and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans.

  15. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain.

    PubMed

    Allam, Ahmed A; Maodaa, Salah N; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns.

  16. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain

    PubMed Central

    Allam, Ahmed A.; Maodaa, Salah N.; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns. PMID:26966507

  17. Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology

    PubMed Central

    Yang, Sujeong; Cacquevel, Matthias; Saksida, Lisa M.; Bussey, Timothy J.; Schneider, Bernard L.; Aebischer, Patrick; Melani, Riccardo; Pizzorusso, Tommaso; Fawcett, James W.; Spillantini, Maria Grazia

    2015-01-01

    Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau hyperphosphorylation, aggregation and neurodegeneration: a transgenic mouse model in which the mutant P301S tau is expressed in neurons (Tg P301S), and a model in which an adeno-associated virus expressing P301S tau (AAV-P301S) was injected in the perirhinal cortex, a region critical for object recognition (OR) memory. Both models show profound loss of OR memory despite only 15% neuronal loss in the Tg P301S and 26% in AAV-P301S-injected mice. Recordings from perirhinal cortex slices of 3 month-old P301S transgenic mice showed a diminution in synaptic transmission following temporal stimulation. Chondroitinase ABC (ChABC) can reactivate plasticity and affect memory through actions on perineuronal nets. ChABC was injected into the perirhinal cortex and animals were tested for OR memory 1 week later, demonstrating restoration of OR memory to normal levels. Synaptic transmission indicated by fEPSP amplitude was restored to control levels following ChABC treatment. ChABC did not affect the progression of neurodegenerative tauopathy. These findings suggest that increasing plasticity by manipulation of perineuronal nets offers a novel therapeutic approach to the treatment of memory loss in neurodegenerative disorders. PMID:25483398

  18. Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology.

    PubMed

    Yang, Sujeong; Cacquevel, Matthias; Saksida, Lisa M; Bussey, Timothy J; Schneider, Bernard L; Aebischer, Patrick; Melani, Riccardo; Pizzorusso, Tommaso; Fawcett, James W; Spillantini, Maria Grazia

    2015-03-01

    Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau hyperphosphorylation, aggregation and neurodegeneration: a transgenic mouse model in which the mutant P301S tau is expressed in neurons (Tg P301S), and a model in which an adeno-associated virus expressing P301S tau (AAV-P301S) was injected in the perirhinal cortex, a region critical for object recognition (OR) memory. Both models show profound loss of OR memory despite only 15% neuronal loss in the Tg P301S and 26% in AAV-P301S-injected mice. Recordings from perirhinal cortex slices of 3month-old P301S transgenic mice showed a diminution in synaptic transmission following temporal stimulation. Chondroitinase ABC (ChABC) can reactivate plasticity and affect memory through actions on perineuronal nets. ChABC was injected into the perirhinal cortex and animals were tested for OR memory 1week later, demonstrating restoration of OR memory to normal levels. Synaptic transmission indicated by fEPSP amplitude was restored to control levels following ChABC treatment. ChABC did not affect the progression of neurodegenerative tauopathy. These findings suggest that increasing plasticity by manipulation of perineuronal nets offers a novel therapeutic approach to the treatment of memory loss in neurodegenerative disorders.

  19. Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

    PubMed Central

    Nishiguchi, Koji M.; Carvalho, Livia S.; Rizzi, Matteo; Powell, Kate; Holthaus, Sophia-Martha kleine; Azam, Selina A.; Duran, Yanai; Ribeiro, Joana; Luhmann, Ulrich F. O.; Bainbridge, James W. B.; Smith, Alexander J.; Ali, Robin R.

    2015-01-01

    The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice. PMID:25613321

  20. Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after a Stroke in the Somatosensory Cortex

    PubMed Central

    Kalogeraki, Evgenia; Pielecka-Fortuna, Justyna; Hüppe, Janika M.; Löwel, Siegrid

    2016-01-01

    The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in V1 declines with age and is compromised by a lesion in adjacent and distant cortical regions. In contrast, mice raised in an enriched environment (EE), exhibit lifelong OD plasticity and are protected from losing OD plasticity after a stroke-lesion in the somatosensory cortex. Since SC mice with an access to a running wheel (RW) displayed preserved OD plasticity during aging, we investigated whether physical exercise might also provide a plasticity promoting effect after a cortical stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity after stroke and also if short-term running after stroke restored OD plasticity to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD plasticity even after stroke, and a 2 weeks RW experience after stroke already restored lost OD plasticity. Additionally, the experience-enabled increase of the spatial frequency and contrast threshold of the optomotor reflex of the open eye, normally lost after a stroke, was restored in both groups of RW mice. Our data suggest that physical exercise alone can not only preserve visual plasticity into old age, but also restore it after a cortical stroke. PMID:27708575

  1. Overstimulation of newborn mice leads to behavioral differences and deficits in cognitive performance

    PubMed Central

    Christakis, D. A.; Ramirez, J. S. B.; Ramirez, J. M.

    2012-01-01

    Observational studies in humans have found associations between overstimulation in infancy via excessive television viewing and subsequent deficits in cognition and attention. We developed and tested a mouse model of overstimulation whereby p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for six hours per day for a total of 42 days. 10 days later cognition and behavior were tested using the following tests: Light Dark Latency, Elevated Plus Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated mice performed significantly worse compared to controls suggesting increased activity and risk taking, diminished short term memory, and decreased cognitive function. These findings suggest that excessive non-normative stimulation during critical periods of brain development can have demonstrable untoward effects on subsequent neurocognitive function. PMID:22855702

  2. Erythropoietin restores C-fiber function and prevents pressure ulcer formation in diabetic mice.

    PubMed

    Demiot, Claire; Sarrazy, Vincent; Javellaud, James; Gourloi, Loriane; Botelle, Laurent; Oudart, Nicole; Achard, Jean-Michel

    2011-11-01

    Pressure-induced vasodilatation (PIV), a cutaneous physiological neurovascular (C-fiber/endothelium) mechanism, is altered in diabetes and could possibly contribute to pressure ulcer development. We wanted to determine whether recombinant human erythropoietin (rhEPO), which has protective neurovascular effects, could prevent PIV alteration and pressure ulcer formation. We developed a skin pressure ulcer model in mice by applying two magnetic plates to the dorsal skin. This induced significant stage 2 ulcers (assessed visually and histologically) in streptozotocin-treated mice with 8 weeks of diabetes compared with very few in controls. Control and streptozotocin mice received either no treatment or systematic rhEPO (3,000 UI kg(-1) intraperitoneally, twice a week) during the last 2 weeks of diabetes. After 8 weeks of diabetes, we assessed ulcer development, PIV, endothelium-dependent vasodilation, C-fiber-mediated nociception threshold, and skin innervation density. Pretreatment with rhEPO fully prevented ulcer development in streptozotocin mice and also fully restored C-fiber nociception, skin innervation density, and significantly improved PIV, but had no effect on endothelium-dependent vasodilation. Our finding that rhEPO treatment protects the skin against pressure-induced ulcers in diabetic mice encourages evaluation of the therapeutic potential for non-hematopoietic analogs of EPO in preventing neuropathic diabetic ulcers.

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Reif, A.E.

    1985-01-01

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

  5. Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice.

    PubMed

    Diao, Fan; Jiang, Chen; Wang, Xiu-Xing; Zhu, Rui-Lou; Wang, Qiang; Yao, Bing; Li, Chao-Jun

    2016-01-01

    Spermatogenesis in adulthood depends on the successful neonatal establishment of the spermatogonial stem cell (SSC) pool and gradual differentiation during puberty. The stage-dependent changes in protein prenylation in the seminiferous epithelium might be important during the first round of spermatogenesis before sexual maturation, but the mechanisms are unclear. We have previous found that altered prenylation in Sertoli cells induced spermatogonial apoptosis in the neonatal testis, resulting in adult infertility. Now we further explored the role of protein prenylation in germ cells, using a conditional deletion of geranylgeranyl diphosphate synthase (Ggpps) in embryonic stage and postmeiotic stage respectively. We observed infertility of Ggpps(-/-) Ddx4-Cre mice that displayed a Sertoli-cell-only syndrome phenotype, which resulted from abnormal spermatogonial differentiation and SSC depletion during the prepubertal stage. Analysis of morphological characteristics and cell-specific markers revealed that spermatogonial differentiation was enhanced from as early as the 7(th) postnatal day in the first round of spermatogenesis. Studies of the molecular mechanisms indicated that Ggpps deletion enhanced Rheb farnesylation, which subsequently activated mTORC1 and facilitated spermatogonial differentiation. In conclusion, the prenylation balance in germ cells is crucial for spermatogonial differentiation fate decision during the prepubertal stage, and the disruption of this process results in primary infertility. PMID:27374985

  6. Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice

    PubMed Central

    Diao, Fan; Jiang, Chen; Wang, Xiu-Xing; Zhu, Rui-Lou; Wang, Qiang; Yao, Bing; Li, Chao-Jun

    2016-01-01

    Spermatogenesis in adulthood depends on the successful neonatal establishment of the spermatogonial stem cell (SSC) pool and gradual differentiation during puberty. The stage-dependent changes in protein prenylation in the seminiferous epithelium might be important during the first round of spermatogenesis before sexual maturation, but the mechanisms are unclear. We have previous found that altered prenylation in Sertoli cells induced spermatogonial apoptosis in the neonatal testis, resulting in adult infertility. Now we further explored the role of protein prenylation in germ cells, using a conditional deletion of geranylgeranyl diphosphate synthase (Ggpps) in embryonic stage and postmeiotic stage respectively. We observed infertility of Ggpps−/− Ddx4-Cre mice that displayed a Sertoli-cell-only syndrome phenotype, which resulted from abnormal spermatogonial differentiation and SSC depletion during the prepubertal stage. Analysis of morphological characteristics and cell-specific markers revealed that spermatogonial differentiation was enhanced from as early as the 7th postnatal day in the first round of spermatogenesis. Studies of the molecular mechanisms indicated that Ggpps deletion enhanced Rheb farnesylation, which subsequently activated mTORC1 and facilitated spermatogonial differentiation. In conclusion, the prenylation balance in germ cells is crucial for spermatogonial differentiation fate decision during the prepubertal stage, and the disruption of this process results in primary infertility. PMID:27374985

  7. Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice.

    PubMed

    Persson, Karin; Rekling, Jens C

    2011-05-15

    The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8AM loaded brainstem-spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem-spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools.

  8. Dosimetry of a set-up for the exposure of newborn mice to 2.45-GHZ WiFi frequencies.

    PubMed

    Pinto, R; Lopresto, V; Galloni, P; Marino, C; Mancini, S; Lodato, R; Pioli, C; Lovisolo, G A

    2010-08-01

    This work describes the dosimetry of a two waveguide cell system designed to expose newborn mice to electromagnetic fields associated with wireless fidelity signals in the frequency band of 2.45 GHz. The dosimetric characterisation of the exposure system was performed both numerically and experimentally. Specific measures were adopted with regard to the increase in both weight and size of the biological target during the exposure period. The specific absorption rate (SAR, W kg(-1)) for 1 W of input power vs. weight curve was assessed. The curve evidenced an SAR pattern varying from <1 W kg(-1) to >6 W kg(-1) during the first 5 weeks of the life of mice, with a peak resonance phenomenon at a weight around 5 g. This curve was used to set the appropriate level of input power during experimental sessions to expose the growing mice to a defined and constant dose.

  9. Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia.

    PubMed

    Hnasko, Thomas S; Perez, Francisco A; Scouras, Alex D; Stoll, Elizabeth A; Gale, Samuel D; Luquet, Serge; Phillips, Paul E M; Kremer, Eric J; Palmiter, Richard D

    2006-06-01

    A line of dopamine-deficient (DD) mice was generated to allow selective restoration of normal dopamine signaling to specific brain regions. These DD floxed stop (DDfs) mice have a nonfunctional Tyrosine hydroxylase (Th) gene because of insertion of a NeoR gene flanked by lox P sites targeted to the first intron of the Th gene. DDfs mice have trace brain dopamine content, severe hypoactivity, and aphagia, and they die without intervention. However, they can be maintained by daily treatment with l-3,4-dihydroxyphenylalanine (L-dopa). Injection of a canine adenovirus (CAV-2) engineered to express Cre recombinase into the central caudate putamen restores normal Th gene expression to the midbrain dopamine neurons that project there because CAV-2 efficiently transduces axon terminals and is retrogradely transported to neuronal cell bodies. Bilateral injection of Cre recombinase into the central caudate putamen restores feeding and normalizes locomotion in DDfs mice. Analysis of feeding behavior by using lickometer cages revealed that virally rescued DDfs mice are hyperphagic and have modified meal structures compared with control mice. The virally rescued DDfs mice are also hyperactive at night, have reduced motor coordination, and are thigmotactic compared with controls. These results highlight the critical role for dopamine signaling in the dorsal striatum for most dopamine-dependent behaviors but suggest that dopamine signaling in other brain regions is important to fine-tune these behaviors. This approach offers numerous advantages compared with previous models aimed at examining dopamine signaling in discrete dopaminergic circuits.

  10. Increasing testicular temperature by exposure to elevated ambient temperatures restores spermatogenesis in adult Utp14b (jsd) mutant (jsd) mice.

    PubMed

    Comish, P B; Liang, L Y; Yamauchi, Y; Weng, C C; Shetty, G; Naff, K A; Ward, M A; Meistrich, M L

    2015-03-01

    Because mutations in the human UTP14C gene are associated with male infertility, we sought to develop a method for fertility restoration in azoospermic mice with a mutation in the orthologous Utp14b(jsd) (jsd) gene that have spermatogonial arrest. The method is based on our observation that elevation of testicular temperatures restores spermatogonial differentiation in jsd mutant mice. To non-surgically raise intrascrotal temperatures we placed these mice in incubators at different elevated ambient temperatures. Exposure of jsd/jsd mice to ambient temperatures of 34.5 °C or 35.5 °C for 24 days increased the proportion of tubules with spermatocytes from 0% in untreated controls to over 80%. As those higher temperatures interfere with spermatid differentiation, the mice were then transferred to incubators at 32-32.5 °C for the next 24 days. These environments allowed differentiation to progress, resulting in up to 42% of tubules having late spermatids and about half of the mutant mice having spermatozoa in testicular suspensions. When these spermatozoa were used in intracytoplasmic sperm injection, all gave rise to viable healthy offspring with normal weight gain and fertility. The successful restoration of fertility in Utp14b mutant mice suggests that transient testicular warming might also be useful for spermatogenesis recovery in infertile men with UTP14C gene mutations.

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

    SciTech Connect

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

    2011-10-15

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

  12. Original Research: The expression of MMP2 and MMP9 in the hippocampus and cerebral cortex of newborn mice under maternal lead exposure.

    PubMed

    Li, Ning; Li, Xing; Li, Li; Zhang, Pingan; Qiao, Mingwu; Zhao, Qiuyan; Song, Lianjun; Yu, Zengli

    2016-10-01

    The current study focused on the MMP2 and MMP9 expression in cerebral cortex and hippocampus of newborn mice under maternal lead exposure. Lead exposure was initiated from gestation to weaning. Lead acetate was dissolved in deionized water with concentration of 0.1, 0.2, and 0.5% and was absorbed through daily drinking. On day 21 after birth, lead in blood and tissue levels was examined by Graphite Furnace Atomic Absorption Spectrum (GFAAS). The protein expressions of MMP2 and MMP9 in hippocampus and cerebral cortex tissues were tested by western blotting and immunohistochemistry. Compared to the control group, blood, cerebral cortex, and hippocampus lead levels of newborn mice in 0.1, 0.2, and 0.5% lead exposure groups were markedly high (P < 0.05), and mice within the 0.2 and 0.5% lead exposure groups performed much worse than that of the control group in Water Maze test (P < 0.05). Compared with the control group, MMP2 and MMP9 expressions in hippocampus were up-regulated in the lead exposure groups (P < 0.05), and the MMP2 and MMP9 expressions in cerebral cortex were also higher (P < 0.05). The increased expression of MMP2 and MMP9 in the hippocampus and cerebral cortex may lead to the neurotoxicity in the context of maternal lead exposure. PMID:27190262

  13. Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin.

    PubMed

    Song, Imane; Patel, Oelfah; Himpe, Eddy; Muller, Christo J F; Bouwens, Luc

    2015-01-01

    One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The

  14. Quantitative evaluation of ontogenetic change in heart rate and its autonomic regulation in newborn mice with the use of a noninvasive piezoelectric sensor.

    PubMed

    Sato, Shinichi

    2008-04-01

    A reliable basal heart rate (HR) measurement in freely moving newborn mice was accomplished for the first time by using a novel noninvasive piezoelectric transducer (PZT) sensor. The basal HR was approximately 320 beats/min at postnatal day (P)0 and increased with age to approximately 690 beats/min at P14. Contribution of autonomic control to HR was then assessed. Sympathetic blockade with metoprolol significantly reduced basal HR at both P6 (-236 +/- 23 beats/min; mean +/- SE) and P12 (-105 +/- 8 beats/min), but atropine was without effect, indicating the predominant tonic adrenergic stimulation and absence of vagal control for basal HR in newborn mice. In contrast to stable basal HR during 5-min recording, HR measured by ECG (ECG-HR) was markedly decreased because of the restraint stress of attaching ECG electrodes, with accompanying freezing behavior. ECG-HR lowered and further decreased gradually during 5 min (slow cardiodeceleration) at P0-P3 and rapidly decreased and gradually recovered within 5 min (transient bradycardia) at P9-P14. The response was not uniform in P4-P8 mice: they showed either of these two patterns or sustained bradycardia (9-29%), and the number of mice that showed transient bradycardia increased with age (30-100%) during the period. Studies with autonomic blockade suggest that the slow cardiodeceleration and transient bradycardia are mediated mainly by withdrawal of adrenergic stimulation and phasic vagal activation, respectively, and the autonomic control of HR response to restraint stress is likely to change from the withdrawal of adrenergic stimulation to the phasic vagal activation at different stages during P4-P8 in individual mice. The PZT sensor may offer excellent opportunities to monitor basal HR of small animals noninvasively.

  15. Newborn jaundice

    MedlinePlus

    Jaundice of the newborn; Neonatal hyperbilirubinemia; Bili lights - jaundice; Infant - yellow skin; Newborn - yellow skin ... lasts 1 to 2 days. Sometimes special blue lights are used on infants whose levels are very ...

  16. Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia

    PubMed Central

    Bindels, Laure B; Neyrinck, Audrey M; Claus, Sandrine P; Le Roy, Caroline I; Grangette, Corinne; Pot, Bruno; Martinez, Inés; Walter, Jens; Cani, Patrice D; Delzenne, Nathalie M

    2016-01-01

    Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia. PMID:26613342

  17. Pre- and post-conditioning hormesis in elderly mice, rats, and humans: its loss and restoration.

    PubMed

    Calabrese, Edward J

    2016-08-01

    This paper assessed differences and similarities in the capacity for preconditioning (PC) and post-conditioning (PostC) to prevent ischemic reperfusion (IR) damage to the heart in the old/elderly as compared to young adult mice, rats, and humans. While PC reliably reduces myocardial ischemia-induced heart damage by about 30-60 % in young adult (2-3 months old) mice and rats, such protection begins to diminish in middle age (1 year old) and is fully lost in the old and elderly (≥18 months). Common rearing practices (i.e., no exercise; ad libitum feeding) are strongly associated with the loss of PC to prevent IR damage to the heart in old/elderly rodents. Substantial restoration of lost PC in old/elderly animal models is affected via various types of exercise and exercise protocols, several types of dietary interventions and pharmacological means. Evidence of PC-mediated cardioprotection in old/elderly humans via epidemiological investigations has been reported using multiple research protocols. These findings suggest the need for animal studies to better reflect human dietary, exercise and lifestyle patterns to enhance their extrapolative relevance. PMID:27075594

  18. Glycolipid Metabolism Disorder in the Liver of Obese Mice Is Improved by TUDCA via the Restoration of Defective Hepatic Autophagy

    PubMed Central

    Guo, Qinyue; Shi, Qindong; Li, Huixia; Liu, Jiali; Wu, Shufang; Sun, Hongzhi; Zhou, Bo

    2015-01-01

    Objective. Tauroursodeoxycholic acid (TUDCA) has been considered an important regulator of energy metabolism in obesity. However, the mechanism underlying how TUDCA is involved in insulin resistance is not fully understood. We tested the effects of TUDCA on autophagic dysfunction in obese mice. Material and Methods. 500 mg/kg of TUDCA was injected into obese mice, and metabolic parameters, autophagy markers, and insulin signaling molecular were assessed by Western blotting and real-time PCR. Results. The TUDCA injections in the obese mice resulted in a reduced body weight gain, lower blood glucose, and improved insulin sensitivity compared with obese mice that were injected with vehicle. Meanwhile, TUDCA treatment not only reversed autophagic dysfunction and endoplasmic reticulum stress, but also improved the impaired insulin signaling in the liver of obese mice. Additionally, the same results obtained with TUDCA were evident in obese mice treated with the adenoviral Atg7. Conclusions. We found that TUDCA reversed abnormal autophagy, reduced ER stress, and restored insulin sensitivity in the liver of obese mice and that glycolipid metabolism disorder was also improved via the restoration of defective hepatic autophagy. PMID:26681941

  19. Human melanopsin-AAV2/8 transfection to retina transiently restores visual function in rd1 mice

    PubMed Central

    Liu, Ming-Ming; Dai, Jia-Man; Liu, Wen-Yi; Zhao, Cong-Jian; Lin, Bin; Yin, Zheng-Qin

    2016-01-01

    AIM To explore whether ectopic expression of human melanopsin can effectively and safely restore visual function in rd1 mice. METHODS Hematoxylin-eosin staining of retinal sections from rd1 mice was used to detect the thickness of the outer nuclear layer to determine the timing of surgery. We constructed a human melanopsin-AAV2/8 viral vector and injected it into the subretinal space of rd1 mice. The Phoenix Micron IV system was used to exclude the aborted injections, and immunohistochemistry was used to validate the ectopic expression of human melanopsin. Furthermore, visual electrophysiology and behavioral tests were used to detect visual function 30 and 45d after the injection. The structure of the retina was compared between the human melanopsin-injected group and phosphate buffer saline (PBS)-injected group. RESULTS Retinas of rd1 mice lost almost all of their photoreceptors on postnatal day 28 (P28). We therefore injected the human melanopsin-adeno-associated virus (AAV) 2/8 viral vector into P30 rd1 mice. After excluding aborted injections, we used immunohistochemistry of the whole mount retina to confirm the ectopic expression of human melanopsin by co-expression of human melanopsin and YFP that was carried by a viral vector. At 30d post-injection, visual electrophysiology and the behavioral test significantly improved. However, restoration of vision disappeared 45d after human melanopsin injection. Notably, human melanopsin-injected mice did not show any structural differences in their retinas compared with PBS-injected mice. CONCLUSION Ectopic expression of human melanopsin effectively and safely restores visual function in rd1 mice. PMID:27275417

  20. Mouse otocyst transuterine gene transfer restores hearing in mice with connexin 30 deletion-associated hearing loss.

    PubMed

    Miwa, Toru; Minoda, Ryosei; Ise, Momoko; Yamada, Takao; Yumoto, Eiji

    2013-06-01

    Although numerous causative genes for hereditary hearing loss have been identified, there are no fundamental treatments for this condition. Herein, we describe a novel potential treatment for genetic hearing loss. Because mutations or deletions in the connexin (Cx) genes are common causes of profound congenital hearing loss in both humans and mice, we investigated whether gene supplementation therapy using the wild-type Cx gene could cure hearing loss. We first generated inner ear-specific connexin 30 (Cx30)-deficient mice via the transuterine transfer of Cx30-targeted short hairpin RNA (shRNA-Cx30) into otocysts. The inner ear-specific Cx30-deficient mice mimicked homozygous Cx30-deficient mice both histologically and physiologically. Subsequently, we cotransfected the shRNA-Cx30 and the wild-type Cx30 gene. The cotransfected mice exhibited Cx30 expression in the cochleae and displayed normal auditory functions. Next, we performed the transuterine transfer of the wild-type Cx30 gene into the otocysts of homozygous Cx30-deficient mice, thereby rescuing the lack of Cx30 expression in the cochleae and restoring auditory functioning. These results demonstrate that supplementation therapy with wild-type genes can restore postnatal auditory functioning. Moreover, this is the first report to show that Cx-related genetic hearing loss is treatable by in vivo gene therapy.

  1. Hyaluronic acid-bound letrozole nanoparticles restore sensitivity to letrozole-resistant xenograft tumors in mice.

    PubMed

    Nair, Hareesh B; Huffman, Steven; Veerapaneni, Poornachand; Kirma, Nameer B; Binkley, Peter; Perla, Rao P; Evans, Dean B; Tekmal, Rajeshwar R

    2011-05-01

    Letrozole is a potent aromatase inhibitor and superior to other defined selective estrogen receptor modulators such as tamoxifen in treating hormone-responsive postmenopausal breast cancer patients. Patients who receive this drug may become insensitive to the effects of estrogen deprivation induced by letrozole. Letrozole has known side effects on bone metabolism due to systemic ablation of estrogen production. The purpose of this study was to examine the therapeutic efficacy of hyaluronic acid-bound letrozole nanoparticles (HA-Letr-NPs) in restoring sensitivity to letrozole-resistant (LTLT-Ca) cells. To target letrozole to LTLT-Ca cells, hyaluronic acid-bound letrozole nanoparticles were prepared by nanoprecipitation using biodegradable PLGA-PEG co-polymer. Binding specificity of HA to CD44 on the cell surface was analyzed in vitro using FITC-CD44 Ab and CD44 siRNA by flow cytometry. Effects on in vitro cytotoxicity and aromatase enzymatic activity of HA-Letr-NPs were performed in MCF-7 breast cancer cells, MCF-7 cells over-expressing aromatase (MCF-7/Aro), and LTLT-Ca cells resistant to letrozole. Preclinical efficacy of HA-Letr-NPs was examined in mice using LTLT-Ca xenograft tumors. HA-Letr-NPs were restricted to a maximum size of 100 nm. The in vitro drug release assay showed that the highest released concentration of letrozole occurred after 23 hours at 37 degrees C in phosphate-buffered saline. HA-Letr-NPs on MCF-7/Aro and LTLT-Ca cells showed an IC50 of 2 microM and 5 microM, respectively. HA-Letr-NPs were more efficacious in inhibiting tumor growth, reducing in vitro cellular and in vivo tumor aromatase enzyme activity more than the corresponding Letr-NPs or letrozole. HA-Letr-NPs restored and maintained a prolonged sensitivity and targeted delivery of letrozole in letrozole-resistant tumors in vivo. PMID:21780370

  2. GABAB RECEPTORS CONTRIBUTE TO THE RESTORATION OF BALANCE DURING VESTIBULAR COMPENSATION IN MICE

    PubMed Central

    Heskin-Sweezie, Raquel; Titley, Heather K.; Baizer, Joan S.; Broussard, Dianne M.

    2010-01-01

    Following unilateral vestibular damage (UVD), vestibular compensation restores both static and dynamic vestibular reflexes. The cerebellar cortex provides powerful GABAergic inhibitory input to the vestibular nuclei which is necessary for compensation. Metabotropic GABA type B (GABAB) receptors in the vestibular nuclei are thought to be involved. However, the contribution of GABAB receptors may differ between static and dynamic compensation. We tested static and dynamic postural reflexes and gait in young mice, while they compensated for unilateral vestibular damage (UVD) caused by injection of air into the vestibular labyrinth. The effects of an agonist (baclofen), an antagonist (CGP56433A) and a positive allosteric modulator (CGP7930) of the GABAB receptor were evaluated during compensation. Static postural reflexes recovered very rapidly in our model, and baclofen slightly accelerated recovery. However, CGP56433A significantly impaired static compensation. Dynamic reflexes were evaluated by balance-beam performance and by gait; both showed significant decrements following UVD and performance improved over the next 2 days. Both CGP56433A and baclofen temporarily impaired the ability to walk on a balance beam after UVD. Two days later, there were no longer any significant effects of drug treatments on balance-beam performance. Baclofen slightly accelerated the recovery of stride length on a flat surface, but CGP7930 worsened the gait impairment following UVD. Using immunohistochemistry, we confirmed that GABAB receptors are abundantly expressed on the vestibulospinal neurons of Deiters in mice. Our results suggest that GABAB receptors contribute to the compensation of static vestibular reflexes following unilateral peripheral damage. We also conclude that impairment of the first stage of compensation, static recovery, does not necessarily result in an impairment of dynamic recovery in the long term. PMID:20394801

  3. Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia

    PubMed Central

    Morimoto, M; Lee, E-Y; Zhang, X; Inaba, Y; Inoue, H; Ogawa, M; Shirasawa, T; Yokosuka, O; Miki, T

    2016-01-01

    Background/Objective: Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial. Methods: We examined the antidiabetic effect of EPA in insulin receptor mutant (InsrP1195L/+) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia. Results: EPA supplementation was found to alleviate hyperglycemia of InsrP1195L/+ mice fed HFD (InsrP1195L/+/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in InsrP1195L/+ mice but not in wild-type mice, suggesting that InsrP1195L/+ mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of InsrP1195L/+ mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia. Conclusions: EPA exerts an antidiabetic effect in InsrP1195L/+/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia. PMID:27348201

  4. Treatment with garlic restores membrane thiol content and ameliorates lead induced early death of erythrocytes in mice.

    PubMed

    Sarkar, Avik; Sengupta, Dipanwita; Mandal, Samir; Sen, Gargi; Dutta Chowdhury, Kaustav; Chandra Sadhukhan, Gobinda

    2015-04-01

    Sequelae of chronic lead (Pb(2+) ) toxicity includes anemia that is partially due to early death of erythrocytes characterized by excess accumulation of ROS and downregulation of antioxidant system causing oxidative stress and externalization of phosphatidylserine. In this study, pathophysiological based therapeutic application of garlic was evaluated against erythrocyte death. Results suggest that garlic administration prevents oxidative stress, restored the antioxidant balance in erythrocytes of Pb(2+) exposed mice. Moreover, in vitro studies revealed that activity of both scramblase and aminophospholipid translocase could be changed by modifying the critical sulfhydryl groups in presence of dithiothreitol during Pb(2+) exposure. Data also indicated that garlic treatment in Pb(2+) exposed mice exhibited sharp decline in PS exposure and increase in erythrocyte membrane thiol group followed by increase in aminophospholipid translocase activity and decline in scramblase activity. Findings indicated that garlic has the ability to restore the lifespan of erythrocytes during Pb(2+) exposure.

  5. MPTP Impairs Dopamine D1 Receptor-Mediated Survival of Newborn Neurons in Ventral Hippocampus to Cause Depressive-Like Behaviors in Adult Mice

    PubMed Central

    Zhang, Tingting; Hong, Juan; Di, Tingting; Chen, Ling

    2016-01-01

    Parkinson’s disease (PD) is characterized by motor symptoms with depression. We evaluated the influence of dopaminergic depletion on hippocampal neurogenesis process to explore mechanisms of depression production. Five consecutive days of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection in mice (MPTP-mice) reduced dopaminergic fibers in hippocampal dentate gyrus (DG). MPTP-mice exhibited depressive-like behaviors later for 2–3 weeks. BrdU was injected 4 h after last-injection of MPTP. BrdU-positive (BrdU+) cells in dorsal (d-DG) and ventral (v-DG) DG were examined on day 1 (D1), 7 (D7), 14 (D14) and 21 (D21) after BrdU injection. Fewer D7-, D14- and D21-BrdU+ cells or BrdU+/NeuN+ cells, but not D1-BrdU+ cells, were found in v-DG of MPTP-mice than in controls. However, the number of BrdU+ cells in d-DG did not differ between the both. Loss of doublecortin-positive (DCX+) cells was observed in v-DG of MPTP-mice. Protein kinase A (PKA) and Ca2+/cAMP-response element binding protein (CREB) phosphorylation were reduced in v-DG of MPTP-mice, which were reversed by D1-like receptor (D1R) agonist SKF38393, but not D2R agonist quinpirole. The treatment of MPTP-mice with SKF38393 on days 2–7 after BrdU-injection reduced the loss of D7- and D21-BrdU+ cells in v-DG and improved the depressive-like behaviors; these changes were sensitive to PKA inhibitor H89. Moreover, the v-DG injection of SKF38393 in MPTP-mice could reduce the loss of D21-BrdU+ cells and relieve the depressive-like behaviors. In control mice, the blockade of D1R by SCH23390 caused the reduction of D21-BrdU+ cells in v-DG and the depressive-like behaviors. Our results indicate that MPTP-reduced dopaminergic depletion impairs the D1R-mediated early survival of newborn neurons in v-DG, producing depressive-like behaviors. PMID:27790091

  6. Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice.

    PubMed

    Fleming, Sherry D; Egan, Ryan P; Chai, Chunyan; Girardi, Guillermina; Holers, V Michael; Salmon, Jane; Monestier, Marc; Tsokos, George C

    2004-12-01

    Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether anti-phospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage. PMID:15557203

  7. β-Sarcoglycan gene transfer decreases fibrosis and restores force in LGMD2E mice.

    PubMed

    Pozsgai, E R; Griffin, D A; Heller, K N; Mendell, J R; Rodino-Klapac, L R

    2016-01-01

    Limb-girdle muscular dystrophy type 2E (LGMD2E) results from mutations in the β-sarcoglycan (SGCB) gene causing loss of functional protein and concomitant loss of dystrophin-associated proteins. The disease phenotype is characterized by muscle weakness and wasting, and dystrophic features including muscle fiber necrosis, inflammation and fibrosis. The Sgcb-null mouse recapitulates the clinical phenotype with significant endomysial fibrosis providing a relevant model to test whether gene replacement will be efficacious. We directly addressed this question using a codon optimized human β-sarcoglycan gene (hSGCB) driven by a muscle-specific tMCK promoter (scAAVrh74.tMCK.hSGCB). Following isolated limb delivery (5 × 10(11) vector genome (vg)), 91.2% of muscle fibers in the lower limb expressed β-sarcoglycan, restoring assembly of the sarcoglycan complex and protecting the membrane from Evans blue dye leakage. Histological outcomes were significantly improved including decreased central nucleation, normalization of muscle fiber size, decreased macrophages and inflammatory mononuclear cells, and an average of a 43% reduction in collagen deposition in treated muscle compared with untreated muscle at end point. These measures correlated with improvement of tetanic force and resistance to eccentric contraction. In 6-month-old mice, as indicated by collagen staining, scAAVrh74.tMCK.hSGCB treatment reduced fibrosis by 42%. This study demonstrates the potential for gene replacement to reverse debilitating fibrosis, typical of muscular dystrophy, thereby providing compelling evidence for movement to clinical gene replacement for LGMD2E.

  8. Mifepristone (RU486) restores humoral and T cell-mediated immune response in endotoxin immunosuppressed mice.

    PubMed

    Rearte, B; Maglioco, A; Balboa, L; Bruzzo, J; Landoni, V I; Laborde, E A; Chiarella, P; Ruggiero, R A; Fernández, G C; Isturiz, M A

    2010-12-01

    Sepsis and septic shock can be caused by Gram-positive and -negative bacteria and other microorganisms. In the case of Gram-negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, interferon (IFN)-γ and the concomitant induction of anti-inflammatory mediators such as IL-10, transforming growth factor (TGF)-β or glucocorticoids, which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the main cause of the non-specific humoral and cellular immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that mifepristone (RU486), a known glucocorticoid receptor antagonist, could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, suggesting the involvement of endogenous glucocorticoids in this phenomenon. On the other hand, using cyclophosphamide and gemcitabine, we demonstrated that regulatory/suppressor CD4(+) CD25(+) forkhead boxP3(+) and GR-1(+) CD11b(+) cells do not play a major role in the establishment or the maintenance of endotoxin tolerance, a central mechanism for inducing an immunosuppression state. PMID:20964639

  9. Cyclosporine A prevents the generation of single positive (Lyt2+ L3T4-, Lyt2- L3T4+) mature T cells, but not single positive (Lyt2+ T3-) Immature thymocytes, in newborn mice.

    PubMed

    Heeg, K; Bendigs, S; Wagner, H

    1989-12-01

    The influence of cyclosporine A (CsA) on T-cell maturation was investigated in newborn mice. CsA treatment during the pre- and postnatal periods resulted in a hypoplasia of peripheral lymphatic organs, and absence of mature T3+ T cells in lymph nodes and spleens; no functional T-cell reactivity was observed. In thymuses of CsA-treated mice, no T3+ single positive Lyt2+ or T3+L3T4+ thymocytes could be found, but double positive (DP) cells were readily detected. A thymocyte subset with the phenotype Lyt2+L3T4-T3- was still discernible; this population was non-functional in vitro. The data show that the maturation of single positive (SP) T cells is critically influenced by CsA; under the conditions used here we found no evidence that 'leaky' autoreactive SP T cells develop in CsA-treated newborn mice.

  10. Selenium supplementation restores the decreased albumin level of peripheral blood mononuclear cells in streptozotocin-induced diabetic mice

    PubMed Central

    AHN, Taeho; BAE, Chun-Sik; YUN, Chul-Ho

    2016-01-01

    Previously, it has been suggested that the phenotypic level of albumin in peripheral blood mononuclear cells (PBMC) decreased in streptozotocin (STZ)-induced diabetic rats. Concomitantly, the production of oxidative stresses was also elevated in the diabetic PBMC compared to that of normal control. These results suggest the close relationship between PBMC-albumin and its antioxidant roles. Here, we expanded the previous studies and investigated the effect of selenium supplementation as inorganic (sodium selenate) forms on the levels of albumin expression and oxidative stress in PBMC of STZ-induced diabetic mice. Selenium intake recovered the decreased albumin levels to those of normal mice and reduced the production of reactive oxygen species (ROS). These results support that selenium intake may alleviate the etiology and pathology of PBMC in type 1 diabetic mice by restoring the decrease in albumin contents and the production of ROS. PMID:26726102

  11. The effect of Coriandrum sativum seed extract on the learning of newborn mice by electric shock: interaction with caffeine and diazepam.

    PubMed

    Zargar-Nattaj, Seyed Sadegh; Tayyebi, Pooya; Zangoori, Vahid; Moghadamnia, Yasaman; Roodgari, Hasan; Jorsaraei, Seyed Gholamali; Moghadamnia, Ali Akbar

    2011-01-01

    Coriander has been recommended for the relief of pain, anxiety, flatulence, and loss of appetite. In traditional medicine, it is believed that coriander can induce some degree of amnesia in a child when his/her mother uses coriander during the pregnancy. We evaluated the effect of Coriandrum sativum seed extract on learning in second-generation mice. Ethanolic extract (2%) of coriander (100 mg/kg intraperitoneal) was dissolved in sunflower oil (oil) as a vehicle and injected into the control group mother mice during breastfeeding for 25 days at 5-day intervals. After feeding the newborn mice, their learning was evaluated using a step-through passive avoidance task with 0.4 mA electric shock for 2 or 4 seconds. While coriander extract showed a negative effect in the short term (1 hour) after the training session, it potentiated the mice's learning in later assessments (24 hours post-training [P = 0.022] and 1 week post-training [P = 0.002] by a 4-second shock). Low-dose caffeine (25 mg/kg ip after training) improved the learning after 1 hour (P = 0.024); while diazepam (1 mg/kg ip) suppressed learning at all time points after the 4-second shock training (1 hour, P = 0.022; 24 hours, P = 0.002; and 1 week, P = 0.008). No modification in the pain threshold was elicited by electric stimuli both in coriander and control groups. In conclusion, coriander does not improve learning within a short period of time after training; however, learning after coriander administration can be improved in the long term.

  12. An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs

    PubMed Central

    Voss, Daniel; Petsch, Benjamin; Baumhof, Patrick; Kramps, Thomas; Stitz, Lothar

    2016-01-01

    Rabies is a zoonotic infectious disease of the central nervous system (CNS). In unvaccinated or untreated subjects, rabies virus infection causes severe neurological symptoms and is invariably fatal. Despite the long-standing existence of effective vaccines, vaccine availability remains insufficient, with high numbers of fatal infections mostly in developing countries. Nucleic acid based vaccines have proven convincingly as a new technology for the fast development of vaccines against newly emerging pathogens, diseases where no vaccine exists or for replacing already existing vaccines. We used an optimized non-replicating rabies virus glycoprotein (RABV-G) encoding messenger RNA (mRNA) to induce potent neutralizing antibodies (VN titers) in mice and domestic pigs. Functional antibody titers were followed in mice for up to one year and titers remained stable for the entire observation period in all dose groups. T cell analysis revealed the induction of both, specific CD4+ as well as CD8+ T cells by RABV-G mRNA, with the induced CD4+ T cells being higher than those induced by a licensed vaccine. Notably, RABV-G mRNA vaccinated mice were protected against lethal intracerebral challenge infection. Inhibition of viral replication by vaccination was verified by qRT-PCR. Furthermore, we demonstrate that CD4+ T cells are crucial for the generation of neutralizing antibodies. In domestic pigs we were able to induce VN titers that correlate with protection in adult and newborn pigs. This study demonstrates the feasibility of a non-replicating mRNA rabies vaccine in small and large animals and highlights the promises of mRNA vaccines for the prevention of infectious diseases. PMID:27336830

  13. An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs.

    PubMed

    Schnee, Margit; Vogel, Annette B; Voss, Daniel; Petsch, Benjamin; Baumhof, Patrick; Kramps, Thomas; Stitz, Lothar

    2016-06-01

    Rabies is a zoonotic infectious disease of the central nervous system (CNS). In unvaccinated or untreated subjects, rabies virus infection causes severe neurological symptoms and is invariably fatal. Despite the long-standing existence of effective vaccines, vaccine availability remains insufficient, with high numbers of fatal infections mostly in developing countries. Nucleic acid based vaccines have proven convincingly as a new technology for the fast development of vaccines against newly emerging pathogens, diseases where no vaccine exists or for replacing already existing vaccines. We used an optimized non-replicating rabies virus glycoprotein (RABV-G) encoding messenger RNA (mRNA) to induce potent neutralizing antibodies (VN titers) in mice and domestic pigs. Functional antibody titers were followed in mice for up to one year and titers remained stable for the entire observation period in all dose groups. T cell analysis revealed the induction of both, specific CD4+ as well as CD8+ T cells by RABV-G mRNA, with the induced CD4+ T cells being higher than those induced by a licensed vaccine. Notably, RABV-G mRNA vaccinated mice were protected against lethal intracerebral challenge infection. Inhibition of viral replication by vaccination was verified by qRT-PCR. Furthermore, we demonstrate that CD4+ T cells are crucial for the generation of neutralizing antibodies. In domestic pigs we were able to induce VN titers that correlate with protection in adult and newborn pigs. This study demonstrates the feasibility of a non-replicating mRNA rabies vaccine in small and large animals and highlights the promises of mRNA vaccines for the prevention of infectious diseases. PMID:27336830

  14. Restoration of synaptic plasticity and learning in young and aged NCAM-deficient mice by enhancing neurotransmission mediated by GluN2A-containing NMDA receptors.

    PubMed

    Kochlamazashvili, Gaga; Bukalo, Olena; Senkov, Oleg; Salmen, Benedikt; Gerardy-Schahn, Rita; Engel, Andreas K; Schachner, Melitta; Dityatev, Alexander

    2012-02-15

    Neural cell adhesion molecule (NCAM) is the predominant carrier of the unusual glycan polysialic acid (PSA). Deficits in PSA and/or NCAM expression cause impairments in hippocampal long-term potentiation and depression (LTP and LTD) and are associated with schizophrenia and aging. In this study, we show that impaired LTP in adult NCAM-deficient (NCAM(-/-)) mice is restored by increasing the activity of the NMDA subtype of glutamate receptor (GluN) through either reducing the extracellular Mg2+ concentration or applying d-cycloserine (DCS), a partial agonist of the GluN glycine binding site. Pharmacological inhibition of the GluN2A subtype reduced LTP to the same level in NCAM(-/-) and wild-type (NCAM(+/+)) littermate mice and abolished the rescue by DCS in NCAM(-/-) mice, suggesting that the effects of DCS are mainly mediated by GluN2A. The insufficient contribution of GluN to LTD in NCAM(-/-) mice was also compensated for by DCS. Furthermore, impaired contextual and cued fear conditioning levels were restored in NCAM(-/-) mice by administration of DCS before conditioning. In 12-month-old NCAM(-/-), but not NCAM(+/+) mice, there was a decline in LTP compared with 3-month-old mice that could be rescued by DCS. In 24-month-old mice of both genotypes, there was a reduction in LTP that could be fully restored by DCS in NCAM(+/+) mice but only partially restored in NCAM(-/-) mice. Thus, several deficiencies of NCAM(-/-) mice can be ameliorated by enhancing GluN2A-mediated neurotransmission with DCS.

  15. Anemia in the Newborn

    MedlinePlus

    ... Video) Meconium Aspiration Syndrome Additional Content Medical News Anemia in the Newborn By Arthur E. Kopelman, MD ... Prematurity (ROP) Necrotizing Enterocolitis (NEC) Jaundice in Newborns Anemia in the Newborn Polycythemia in the Newborn Thyroid ...

  16. Thrush in newborns

    MedlinePlus

    Candidiasis - oral - newborn; Oral thrush - newborn; Fungal infection - mouth - newborn; Candida - oral - newborn ... thrush. You paint this medicine on your baby's mouth and tongue. If you have a yeast infection on your nipples, your doctor may recommend an ...

  17. Virally-expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice

    PubMed Central

    Yu, Qing; Wang, Yunfeng; Chang, Qing; Wang, Jianjun; Gong, Shushen; Li, Huawei; Lin, Xi

    2013-01-01

    Mutations in GJB2, which codes for the gap junction protein connexin26, are the most common causes of human nonsyndromic hereditary deafness. We inoculated modified adeno-associated viral vectors into the scala media of early postnatal conditional Gjb2 knockout mice to drive exogenous connexin26 expression. We found extensive virally-expressed connexin26 in cells lining the scala media, and intercellular gap junction network was re-established in the organ of Corti of mutant mouse cochlea. Widespread ectopic connexin26 expression neither formed ectopic gap junctions nor affected normal hearing thresholds in wild type mice, suggesting that autonomous cellular mechanisms regulate proper membrane trafficking of exogenously-expressed connexin26 and govern the functional manifestation of them. Functional recovery of gap-junction-mediated coupling among the supporting cells was observed. We found that both cell death in the organ of Corti and degeneration of spiral ganglion neurons in the cochlea of mutant mice were substantially reduced, although auditory brainstem responses did not show significant hearing improvement. This is the first report demonstrating that virally-mediated gene therapy restored extensive gap junction intercellular network among cochlear non-sensory cells in vivo. Such a treatment performed at early postnatal stages resulted in a partial rescue of disease phenotypes in the cochlea of the mutant mice. PMID:24225640

  18. Comparative Hair Restorer Efficacy of Medicinal Herb on Nude (Foxn1nu) Mice

    PubMed Central

    Begum, Shahnaz; Lee, Mi Ra; Gu, Li Juan; Hossain, Md. Jamil; Kim, Hyun Kyoung; Sung, Chang Keun

    2014-01-01

    Eclipta alba (L.) Hassk, Asiasarum sieboldii (Miq.) F. Maek (Asiasari radix), and Panax ginseng C. A. Mey (red ginseng) are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly (P > 0.001) than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs). The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss. PMID:25478567

  19. Comparative hair restorer efficacy of medicinal herb on nude (Foxn1nu) mice.

    PubMed

    Begum, Shahnaz; Lee, Mi Ra; Gu, Li Juan; Hossain, Md Jamil; Kim, Hyun Kyoung; Sung, Chang Keun

    2014-01-01

    Eclipta alba (L.) Hassk, Asiasarum sieboldii (Miq.) F. Maek (Asiasari radix), and Panax ginseng C. A. Mey (red ginseng) are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly (P>0.001) than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs). The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss. PMID:25478567

  20. Effect of resveratrol on restoring spermatogenesis in experimental cryptorchid mice and analysis of related differentially expressed proteins.

    PubMed

    Li, Enzhong; Guo, Yuping; Wang, Gailing; Chen, Fujia; Li, Qingwang

    2015-06-01

    The present study aimed to evaluate the effect of trans-Resveratrol on spermatogenesis. Male Kunming suckling mice (10 days old) were surgically rendered cryptorchid and subcutaneously injected with trans-Resveratrol at doses of 5, 10, 20, and 40 µg/g/day as groups I, II, III, and IV, respectively, for 35 days. Animals in the control group received 10 µL/mouse/day of olive oil. Serum estradiol, testosterone, FSH, and LH levels were measured on day 45. Tissue analysis and sperm morphological abnormalities analysis were done. Results showed that in the control group and group I only spermatogonia and primary spermatocytes were present, whereas spermatogenesis was totally restored in groups II, III, and IV. Sperm counts in groups III and IV were remarkably higher than the control group (P<0.05). The morphological abnormalities in resveratrol-treated groups were higher than the mature mice. Serum estradiol levels in the resveratrol-treated groups were not significantly different from the control group, but were lower than the mature mice (P<0.05). There was no significant difference in serum testosterone levels between the resveratrol-treated groups and mature mice, but the levels in the resveratrol-treated groups was significantly lower than the control group (P<0.05). No significant influence of trans-Resveratrol was observed on serum FSH levels in all cryptorchid mice. Serum LH levels in groups I, II, and III were higher than the control group. These results indicate that trans-Resveratrol restores spermatogenesis in cryptorchid mice. In addition, proteomic analysis between the 20 μg/g/day resveratrol-treated group and the control group was carried out, and five kinds of proteins (BAF250, ZFP261, CHD1L, RBBP9, and SOHLH2) were identified. The expression of SOHLH2 increased, while that of BAF250, ZFP261, CHD1L, and RBBP9 decreased in the 20 µg/g/day resveratrol-treated group, indicating that SOHLH2 may contribute to testicular germ cell differentiation.

  1. Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice.

    PubMed

    Madsen, Kirsten; Reddy, Ramesh N; Price, S Russ; Williams, Clintoria R; Gooch, Jennifer L

    2013-01-01

    Mice lacking the α isoform of the catalytic subunit of calcineurin (CnAα) were first reported in 1996 and have been an important model to understand the role of calcineurin in the brain, immune system, bones, muscle, and kidney. Research using the mice has been limited, however, by failure to thrive and early lethality of most null pups. Work in our laboratory led to the rescue of CnAα-/- mice by supplemental feeding to compensate for a defect in salivary enzyme secretion. The data revealed that, without intervention, knockout mice suffer from severe caloric restriction. Since nutritional deprivation is known to significantly alter development, it is imperative that previous conclusions based on CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development and function persist in adult CnAα-/- mice including a significant decrease in glomerular filtration rate and an increase in blood urea nitrogen levels. These data indicate that impaired renal development we previously reported was not due to caloric restriction but rather a specific role for CnAα in renal development and function. In contrast, we find that rather than being hypoglycemic, rescued mice are mildly hyperglycemic and insulin resistant. Examination of muscle fiber types shows that previously reported reductions in type I muscle fibers are no longer evident in rescued null mice. Rather, loss of CnAα likely alters insulin response due to a reduction in insulin receptor substrate-2 (IRS2) expression and signaling in muscle. This study illustrates the importance of re-examining the phenotypes of CnAα-/- mice and the advances that are now possible with the use of adult, rescued knockout animals. PMID:23638102

  2. Restoration of cocaine stimulation and reward by reintroducing wild type dopamine transporter in adult knock-in mice with a cocaine-insensitive dopamine transporter.

    PubMed

    Wu, Haiyin; O'Neill, Brian; Han, Dawn D; Thirtamara-Rajamani, Keerthi; Wang, Yanlin; Gu, Howard H

    2014-11-01

    In previous studies, we generated knock-in mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) and found cocaine does not stimulate locomotion or produce reward in these mice, indicating DAT inhibition is necessary for cocaine stimulation and reward. However, DAT uptake is reduced in DAT-CI mice and thus the lack of cocaine responses could be due to adaptive changes. To test this, we used adeno-associated virus (AAV) to reintroduce the cocaine-sensitive wild type DAT (AAV-DATwt) back into adult DAT-CI mice, which restores cocaine inhibition of DAT in affected brain regions but does not reverse the adaptive changes. In an earlier study we showed that AAV-DATwt injections in regions covering the lateral nucleus accumbens (NAc) and lateral caudate-putamen (CPu) restored cocaine stimulation but not cocaine reward. In the current study, we expanded the AAV-DATwt infected areas to cover the olfactory tubercle (Tu) and the ventral midbrain (vMB) containing the ventral tegmental area (VTA) and substantia nigra (SN) in addition to CPu and NAc with multiple injections. These mice displayed the restoration of both locomotor stimulation and cocaine reward. We further found that AAV-DATwt injection in the vMB alone was sufficient to restore both cocaine stimulation and reward in DAT-CI mice. AAV injected in the VTA and SN resulted in DATwt expression and distribution to the DA terminal regions. In summary, cocaine induced locomotion and reward can be restored in fully developed DAT-CI mice, and cocaine inhibition of DAT expressed in dopaminergic neurons originated from the ventral midbrain mediates cocaine reward and stimulation.

  3. Restoration of Cocaine Stimulation and Reward by Reintroducing Wild Type Dopamine Transporter in Adult Knock-in Mice with a Cocaine-Insensitive Dopamine Transporter

    PubMed Central

    Wu, Haiyin; O’Neill, Brian; Han, Dawn D.; Thirtamara-Rajamani, Keerthi; Wang, Yanlin; Gu, Howard H.

    2014-01-01

    In previous studies, we generated knock-in mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) and found cocaine does not stimulate locomotion or produce reward in these mice, indicating DAT inhibition is necessary for cocaine stimulation and reward. However, DAT uptake is reduced in DAT-CI mice and thus the lack of cocaine responses could be due to adaptive changes. To test this, we used adeno-associated virus (AAV) to reintroduce the cocaine-sensitive wild type DAT (AAV-DATwt) back into adult DAT-CI mice, which restores cocaine inhibition of DAT in affected brain regions but does not reverse the adaptive changes. In an earlier study we showed that AAV-DATwt injections in regions covering the lateral nucleus accumbens (NAc) and lateral caudate-putamen (CPu) restored cocaine stimulation but not cocaine reward. In the current study, we expanded the AAV-DATwt infected areas to cover the olfactory tubercle (Tu) and the ventral midbrain (vMB) containing the ventral tegmental area (VTA) and substantia nigra (SN) in addition to CPu and NAc with multiple injections. These mice displayed the restoration of both locomotor stimulation and cocaine reward. We further found that AAV-DATwt injection in the vMB alone was sufficient to restore both cocaine stimulation and reward in DAT-CI mice. AAV injected in the VTA and SN resulted in DATwt expression and distribution to the DA terminal regions. In summary, cocaine induced locomotion and reward can be restored in fully developed DAT-CI mice, and cocaine inhibition of DAT expressed in dopaminergic neurons originated from the ventral midbrain mediates cocaine reward and stimulation. PMID:24835281

  4. Restoration of Retarded Influenza Virus-specific Immunoglobulin Class Switch in Aged Mice

    PubMed Central

    Zhang, Yongxin; Wang, Ying; Zhang, Monica; Liu, Lin; Mbawuike, Innocent N

    2016-01-01

    Objective The declined immune response to infection causes significant higher morbidity and mortality in aging in spite of the coexisted hyperimmunoglobulinemia (HIG). This study is to reveal the cellular basis of HIG and mechanism of weakened HA-specific IgG response in aged mice and to test cell therapy in the treatment of age-related IgG antibody production deficiency with immunocyte adoptive transfer. Methods BALB/c mice was immunized with Influenza A/Taiwan vaccine and challenged with the same strain of virus. ELISA was used to assess the levels of total immunoglobulins and antigen specific antibody response. The flow cytometry and ELISPOT were used to evaluate the frequencies of total immunoglobulin- and specific antibody-producing and secreting B lymphocytes. In vitro expanded mononuclear cells, CD4+ T lymphocytes and CD20+ B lymphocytes from old and young mice were adoptively transferred into influenza virus-challenged aged mice, and HA-specific IgG responses were observed. Results It is found that old mice exhibited higher levels of total serum IgG, IgM and IgA, higher frequencies of IgG+, IgM+ and IgA+ cells, and greater antigen-specific IgM and IgA responses to influenza infection, in comparison to young mice. However, influenza antigen- specific IgG and its subclass responses in old mice were significantly lower. Conclusion The retarded specific IgG response could be attributed to an insufficiency of immunoglobulin class switch in aging. Correlation analysis indicated that HIG and deficient specific IgG production in aged mice could be independent to each other in their pathogenesis. Correction of deficient specific IgG production by adoptive transfer of in vitro expanded and unexpanded CD4+ cells from immunized young mice suggests the CD4+ cell dysfunction contributes to the insufficiency of immunoglobulin class switch in aged mice. The transfusion of in vitro expanded lymphocytes could be a potential effective therapy for the age

  5. Ghrelin Inhibition Restores Glucose Homeostasis in Hepatocyte Nuclear Factor-1α (MODY3)-Deficient Mice.

    PubMed

    Brial, François; Lussier, Carine R; Belleville, Karine; Sarret, Philippe; Boudreau, François

    2015-09-01

    Hepatocyte nuclear factor-1α (HNF1α) is a transcription factor expressed in tissues of endoderm origin. Mutations in HNF1A are associated with maturity-onset diabetes of the young 3 (MODY3). Mice deficient for Hnf1α are hyperglycemic, with their pancreatic β-cells being defective in glucose-sensing insulin secretion. The specific mechanisms involved in this defect are unclear. Gut hormones control glucose homeostasis. Our objective was to explore whether changes in these hormones play a role in glucose homeostasis in the absence of Hnf1α. An increase in ghrelin gene transcript and a decrease in glucose-dependent insulinotropic polypeptide (GIP) gene transcripts were observed in the gut of Hnf1α-null mice. These changes correlated with an increase of ghrelin and a decrease of GIP-labeled cells. Ghrelin serological levels were significantly induced in Hnf1α-null mice. Paradoxically, GIP levels were also induced in these mice. Treatment of Hnf1α-null mice with a ghrelin antagonist led to a recovery of the diabetic symptoms. We conclude that upregulation of ghrelin in the absence of Hnf1α impairs insulin secretion and can be reversed by pharmacological inhibition of ghrelin/GHS-R interaction. These observations open up on future strategies to counteract ghrelin action in a program that could become beneficial in controlling non-insulin-dependent diabetes. PMID:25979074

  6. Pyridostigmine Restores Cardiac Autonomic Balance after Small Myocardial Infarction in Mice

    PubMed Central

    Durand, Marina T.; Becari, Christiane; de Oliveira, Mauro; do Carmo, Jussara M.; Aguiar Silva, Carlos Alberto; Prado, Cibele M.; Fazan, Rubens; Salgado, Helio C.

    2014-01-01

    The effect of pyridostigmine (PYR) - an acetylcholinesterase inhibitor - on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1st week, while the sympathetic tone was increased in the 1st and 4th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1st week, but enhanced it in the 4th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice. PMID:25133392

  7. Zileuton restores memory impairments and reverses amyloid and tau pathology in aged AD mice

    PubMed Central

    Di Meco, Antonio; Lauretti, Elisabetta; Vagnozzi, Alana N.; Praticò, Domenico

    2014-01-01

    The enzyme 5-lipoxygenase (5LO) is up-regulated in Alzheimer’s disease (AD), and its pharmacological blockade with zileuton slows down the development of the AD-like phenotype in young AD mice. However, its efficacy after the AD pathology is established is unknown. To this end, starting at 12-months of age triple transgenic mice (3xTg) received zileuton, a selective 5LO inhibitor, or placebo for 3 months, and then the effect of this treatment on behavior, amyloid and tau pathology assessed. While mice on placebo showed worsening of their memory, treated mice performed even better than at baseline. Compared with placebo, treated mice had significant less Aβ deposits and tau phosphorylation secondary to reduced γ-secretase and CDK-5 activation, respectively. Our data provide novel insights into the disease-modifying action of pharmacologically inhibiting 5LO as a viable AD therapeutic approach. They represent the successful completion of preclinical studies for the development of this class of drug as clinically applicable therapy for the disease. PMID:24973121

  8. Post-training reward partially restores chronic stress induced effects in mice.

    PubMed

    Dalm, Sergiu; de Kloet, E Ron; Oitzl, Melly S

    2012-01-01

    Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact) over the course of two weeks. Following novelty exploration, (non-) spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1) the effects of chronic stress persisted beyond the period of the actual rat exposure. (2) Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3) in stressed mice sugar partially "normalized" the impaired performance to the level of controls without sugar. Chronic stress (4) increased behavioral inhibition in response to novelty; (5) induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6) increased the intake of sucrose and water. (7) Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory.

  9. Suberoylanilide Hydroxamic Acid Restores Estrogen Reduced-cTnI Expression in Neonatal Hearts of Mice.

    PubMed

    Peng, Chang; Luo, Xiaomei; Xing, Qianlu; Sun, Huichao; Huang, Xupei

    2016-10-01

    Diastolic cardiac dysfunction can be caused by abnormality in cTnI expression during cardiogenesis. In this study, we investigated the effects of estrogen on the abnormal expression of cTnI in the hearts of neonatal mice and its potential epigenetic mechanisms. We then evaluated suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, as a new target treatment of diastolic cardiac dysfunction. Postnatal day 0.5 C57BL/6 mice were injected with estrogen for 1 week, then the hearts of 7-day-old neonatal mice were retrieved for examination. The activities of HDAC and HAT were assayed by colorimetry, and the interaction of cTnI with HDAC5 in mice hearts were examined using chromatin immunoprecipitation assays. The expression of cTnI was tested by quantitative real-time RT-PCR and Western blot. Estrogen treated groups displayed a significantly increased HDAC activity in the hearts of neonatal mice while HAT activity remained unchanged. Additionally, HDAC5 was higher at the cTnI promoter, as compared to the saline treated control groups. The acetylation of histone H3K9ac on cTnI promoter significantly decreased in the hearts of neonatal mice treated with estrogen, and the expression of cTnI at transcriptional and protein levels also decreased. SAHA was shown to increase the acetylation of histone H3K9ac and upregulate the expression of cTnI. The data demonstrated that SAHA can correct cTnI expression abnormality caused by estrogen through inhibiting the binding of HDAC5 to the promoter of cTnI. J. Cell. Biochem. 117: 2377-2384, 2016. © 2016 Wiley Periodicals, Inc. PMID:27379430

  10. Newborn transition.

    PubMed

    Graves, Barbara W; Haley, Mary Mumford

    2013-01-01

    The transition from intrauterine to extrauterine life is a complex adaptation. Although, in a sense, the entire time in utero is in preparation for this transition, there are many specific anatomic and physiologic changes that take place in the weeks and days leading up to labor that facilitate a healthy transition. Some, including increasing pulmonary vasculature and blood flow, are part of an ongoing process of maturation. Others, such as a reversal in the lung from secreting fluid to absorbing fluid and the secretion of pulmonary surfactant, are associated with the hormonal milieu that occurs when spontaneous labor is impending. Interventions such as elective cesarean birth or induction of labor may interfere with this preparation for birth. Postnatal interventions such as immediate clamping of the umbilical cord and oropharyngeal suction may also compromise the normal process of newborn transition. This article reviews the physiology of the fetal to newborn transition and explores interventions that may facilitate or hinder the optimal process.

  11. Transgenerational inheritance of enhanced susceptibility to radiation-induced medulloblastoma in newborn Ptch1+/− mice after paternal irradiation

    PubMed Central

    Tanno, Barbara; Meschini, Roberta; Cordelli, Eugenia; Benassi, Barbara; Longobardi, Maria Grazia; Izzotti, Alberto; Pulliero, Alessandra; Mancuso, Mariateresa; Pacchierotti, Francesca

    2015-01-01

    The hypothesis of transgenerational induction of increased cancer susceptibility after paternal radiation exposure has long been controversial because of inconsistent results and the lack of a mechanistic interpretation. Here, exploiting Ptch1 heterozygous knockout mice, susceptible to spontaneous and radiation-induced medulloblastoma, we show that exposure of paternal germ cells to 1 Gy X-rays, at the spermatogonial stage, increased by a considerable 1.4-fold the offspring susceptibility to medulloblastoma induced by neonatal irradiation. This effect gained further biological significance thanks to a number of supporting data on the immunohistochemical characterization of the target tissue and preneoplastic lesions (PNLs). These results altogether pointed to increased proliferation of cerebellar granule cell precursors and PNLs cells, which favoured the development of frank tumours. The LOH analysis of tumor DNA showed Ptch1 biallelic loss in all tumor samples, suggesting that mechanisms other than interstitial deletions, typical of radiation-induced medulloblastoma, did not account for the observed increased cancer risk. This data was supported by comet analysis showing no differences in DNA damage induction and repair in cerebellar cells as a function of paternal irradiation. Finally, we provide biological plausibility to our results offering evidence of a possible epigenetic mechanism of inheritance based on radiation-induced changes of the microRNA profile of paternal sperm. PMID:26452034

  12. Vertical sleeve gastrectomy restores glucose homeostasis in apolipoprotein A-IV KO mice.

    PubMed

    Pressler, Josh W; Haller, April; Sorrell, Joyce; Wang, Fei; Seeley, Randy J; Tso, Patrick; Sandoval, Darleen A

    2015-02-01

    Bariatric surgery is the most successful strategy for treating obesity, yet the mechanisms for this success are not clearly understood. Clinical literature suggests that plasma levels of apolipoprotein A-IV (apoA-IV) rise with Roux-en-Y gastric bypass (RYGB). apoA-IV is secreted from the intestine postprandially and has demonstrated benefits for both glucose and lipid homeostasis. Because of the parallels in the metabolic improvements seen with surgery and the rise in apoA-IV levels, we hypothesized that apoA-IV was necessary for obtaining the metabolic benefits of bariatric surgery. To test this hypothesis, we performed vertical sleeve gastrectomy (VSG), a surgery with clinical efficacy very similar to that for RYGB, in whole-body apoA-IV knockout (KO) mice. We found that VSG reduced body mass and improved both glucose and lipid homeostasis similarly in wild-type mice compared with apoA-IV KO mice. In fact, VSG normalized the impairment in glucose tolerance and caused a significantly greater improvement in hepatic triglyceride storage in the apoA-IV KO mice. Last, independent of surgery, apoA-IV KO mice had a significantly reduced preference for a high-fat diet. Altogether, these data suggest that apoA-IV is not necessary for the metabolic improvements shown with VSG, but also suggest an interesting role for apoA-IV in regulating macronutrient preference and hepatic triglyceride levels. Future studies are necessary to determine whether this is the case for RYGB as well.

  13. Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob/ob) mice.

    PubMed

    Favero, Gaia; Stacchiotti, Alessandra; Castrezzati, Stefania; Bonomini, Francesca; Albanese, Massimo; Rezzani, Rita; Rodella, Luigi Fabrizio

    2015-10-01

    The increasing incidence of obesity, leading to metabolic complications, is now recognized as a major public health problem. The adipocytes are not merely energy-storing cells, but they play crucial roles in the development of the so-called metabolic syndrome due to the adipocyte-derived bioactive factors such as adipokines, cytokines, and growth factors. The dysregulated production and secretion of adipokines seen in obesity is linked to the pathogenesis of the metabolic disease processes. In this study, we hypothesized that dietary melatonin administration would support an anti-inflammatory response and play an important role in energy metabolism in subcutaneous and visceral adipose tissues of obese mice and so may counteract some of the disruptive effects of obesity. Lean and obese mice (ob/ob) received melatonin or vehicle in drinking water for 8 weeks. Thereafter, they were evaluated for morphologic alteration, inflammatory cell infiltration, and the adipokine patterns in visceral and subcutaneous white fat depots. In obese mice treated with vehicle, we observed a significant increase in fat depots, inflammation, and a dysregulation of the adipokine network. In particular, we measured a significant reduction of adiponectin and an increase of tumor necrosis factor α, resistin, and visfatin in adipose tissue deposits. These changes were partially reversed when melatonin was supplemented to obese mice. Melatonin supplementation by regulating inflammatory infiltration ameliorates obesity-induced adipokine alteration, whereas melatonin administration in lean mice was unaffected. Thus, it is likely that melatonin would be provided in supplement form to control some of the disruptive effects on the basis of obesity pathogenic process.

  14. Bifidobacterium animalis ssp. lactis CNCM-I2494 Restores Gut Barrier Permeability in Chronically Low-Grade Inflamed Mice

    PubMed Central

    Martín, Rebeca; Laval, Laure; Chain, Florian; Miquel, Sylvie; Natividad, Jane; Cherbuy, Claire; Sokol, Harry; Verdu, Elena F.; van Hylckama Vlieg, Johan; Bermudez-Humaran, Luis G.; Smokvina, Tamara; Langella, Philippe

    2016-01-01

    Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis ssp. lactis CNCM-I2494, a strain used in fermented dairy products. A chronic dinitrobenzene sulfonic acid (DNBS)-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability, and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations, and colonic cytokines were found to be altered. B. animalis ssp. lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations, and cytokine levels. Furthermore, tight junction (TJ) proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4+ lymphocyte alterations in both spleen and mesenteric lymphoid nodes. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4+ Th1 cells) by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5, and IL-10). Altogether, these data suggest that B. animalis ssp. lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability. PMID:27199937

  15. Bifidobacterium animalis ssp. lactis CNCM-I2494 Restores Gut Barrier Permeability in Chronically Low-Grade Inflamed Mice.

    PubMed

    Martín, Rebeca; Laval, Laure; Chain, Florian; Miquel, Sylvie; Natividad, Jane; Cherbuy, Claire; Sokol, Harry; Verdu, Elena F; van Hylckama Vlieg, Johan; Bermudez-Humaran, Luis G; Smokvina, Tamara; Langella, Philippe

    2016-01-01

    Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis ssp. lactis CNCM-I2494, a strain used in fermented dairy products. A chronic dinitrobenzene sulfonic acid (DNBS)-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability, and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations, and colonic cytokines were found to be altered. B. animalis ssp. lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations, and cytokine levels. Furthermore, tight junction (TJ) proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4(+) lymphocyte alterations in both spleen and mesenteric lymphoid nodes. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4(+) Th1 cells) by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5, and IL-10). Altogether, these data suggest that B. animalis ssp. lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability. PMID:27199937

  16. Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary-gonadal axis in Akita diabetic mice and restores male fertility.

    PubMed

    Schoeller, Erica L; Albanna, Gabriella; Frolova, Antonina I; Moley, Kelle H

    2012-07-01

    The mechanism responsible for poor reproductive outcomes in type 1 diabetic males is not well understood. In light of new evidence that the Sertoli cells of the testis secrete insulin, it is currently unclear whether diabetic subfertility is the result of deficiency of pancreatic insulin, testicular insulin, or both. In this study, the Akita mouse diabetic model, which expresses a mutant, nonfunctional form of ins2 in testes and pancreas, was used to distinguish between systemic and local effects of insulin deficiency on the process of spermatogenesis and fertility. We determined that Akita homozygous male mice are infertile and have reduced testis size and abnormal morphology. Spermatogonial germ cells are still present but are unable to mature into spermatocytes and spermatids. Exogenous insulin treatment regenerates testes and restores fertility, but this plasma insulin cannot pass through the blood-testis barrier. We conclude that insulin does not rescue fertility through direct interaction with the testis; instead, it restores function of the hypothalamic-pituitary-gonadal axis and, thus, normalizes hormone levels of luteinizing hormone and testosterone. Although we show that the Sertoli cells of the testis secrete insulin protein, this insulin does not appear to be critical for fertility.

  17. Innocuous IFNγ induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production

    PubMed Central

    Jain, Renu; Tartar, Danielle M.; Gregg, Randal K.; Divekar, Rohit D.; Bell, J. Jeremiah; Lee, Hyun-Hee; Yu, Ping; Ellis, Jason S.; Hoeman, Christine M.; Franklin, Craig L.; Zaghouani, Habib

    2008-01-01

    The role of Th17 cells in type I diabetes (TID) remains largely unknown. Glutamic acid decarboxylase (GAD) sequence 206–220 (designated GAD2) represents a late-stage epitope, but GAD2-specific T cell receptor transgenic T cells producing interferon γ (IFNγ) protect against passive TID. Because IFNγ is known to inhibit Th17 cells, effective presentation of GAD2 peptide under noninflammatory conditions may protect against TID at advanced disease stages. To test this premise, GAD2 was genetically incorporated into an immunoglobulin (Ig) molecule to magnify tolerance, and the resulting Ig-GAD2 was tested against TID at different stages of the disease. The findings indicated that Ig-GAD2 could not prevent TID at the preinsulitis phase, but delayed TID at the insulitis stage. More importantly, Ig-GAD2 sustained both clearance of pancreatic cell infiltration and β-cell division and restored normoglycemia when given to hyperglycemic mice at the prediabetic stage. This was dependent on the induction of splenic IFNγ that inhibited interleukin (IL)-17 production. In fact, neutralization of IFNγ led to a significant increase in the frequency of Th17 cells, and the treatment became nonprotective. Thus, IFNγ induced by an adjuvant free antigen, contrary to its usual inflammatory function, restores normoglycemia, most likely by localized bystander suppression of pathogenic IL-17–producing cells. PMID:18195074

  18. Parvovirus minute virus of mice strain i multiplication and pathogenesis in the newborn mouse brain are restricted to proliferative areas and to migratory cerebellar young neurons.

    PubMed Central

    Ramírez, J C; Fairén, A; Almendral, J M

    1996-01-01

    Newborn BALB/c mice intranasally inoculated at birth with a lethal dose of the immunosuppressive strain of the parvovirus minute virus of mice (MVMi) developed motor disabilities and intention tremors with a high incidence by the day 6 postinfection (dpi). These neurological syndromes paralleled the synthesis of virus intermediate DNA replicative forms and yield of infectious particles in the brain, with kinetics that peaked by this time. The preferred virus replicative sites in the brain were established early in the infection (2 dpi) and at the onset of clinical symptoms (6 dpi) and were compared with major regions of cellular proliferative activity found after intraperitoneal injection of bromodeoxyuridine 24 h before encephalons were subjected to immunohistochemistry detection. At 2 dpi, viral capsid antigen was located in the laterodorsal thalamic and the pontine nuclei but not in the extensive proliferative regions of the mouse brain at this postnatal day. At 6 dpi, however, the neurotropism of the MVMi was highlighted by its ability to target the subventricular zone of the ventricles, the subependymal zone of the olfactory bulb, and the dentate gyrus of the hippocampus, which are the three main germinal centers of the cerebrum in mouse postbirth neurogenesis. Unexpectedly, in the cerebellum, the MVMi capsid antigen was confined exclusively to cells that have undergone mitosis and have migrated to the internal granular layer (IGL) and not to the proliferative external granular layer (EGL), which was stained with antiproliferative cell nuclear antigen antibody and is the main target in other parvovirus infections. This result implies temporal or differentiation coupling between MVMi cycle and neuroblast morphogenesis, since proliferative granules of the EGL should primarily be infected but must migrate in a virus carrier state into the IGL in order to express the capsid proteins. During migration, many cells undergo destruction, accounting for the marked

  19. Oral putrescine restores virulence of ornithine decarboxylase-deficient Leishmania donovani in mice

    PubMed Central

    Olenyik, Tamara; Gilroy, Caslin; Ullman, Buddy

    2011-01-01

    Administration of putrescine as a 1% solution in the drinking water ameliorated the profound loss of virulence exhibited by ornithine decarboxylase (ODC) deficient Leishmania donovani in mice. Furthermore, supplying α-difluoromethylornithine, an ODC inhibitor, at 2% in the drinking water reduced but did not eliminate infection with wild type L. donovani in the mouse model. Taken collectively, these findings: 1) demonstrate that oral putrescine can access the phagolysosome of macrophages in which the parasite resides in mice; 2) establish that the loss of virulence due to the Δodc lesion is a consequence of the inability of the mutant parasite to synthesize sufficient polyamines de novo; 3) imply that the L. donovani amastigote cannot access host polyamines in sufficient amounts for survival and growth; 4) and validate ODC as a drug target, although oral administration of DFMO is an unlikely therapeutic paradigm for visceral leishmaniasis. PMID:21182873

  20. Hippocampal BDNF signaling restored with chronic asiaticoside treatment in depression-like mice.

    PubMed

    Luo, Liu; Liu, Xiao-Long; Mu, Rong-Hao; Wu, Yong-Jing; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

    2015-05-01

    Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of depression in the brain. Recently, increasing studies have focused on the antidepressant-like mechanism of BDNF and its downstream signaling pathway. A previous study has shown that asiaticoside produced an antidepressant-like action in the mouse tail suspension test and forced swimming test. However, the neurotrophic mechanism that is affected by asiaticoside is unclear. Our present study aimed to verify whether asiaticoside produces an antidepressant-like effect through the activation of BDNF signaling in chronic unpredictable mild stress (CUMS). The results showed that mice treated with asiaticoside for four weeks reversed the decreased sucrose preference and increased immobility time that was observed in CUMS mice. In addition, we found that asiaticoside up-regulated BDNF, PSD-95 and synapsin I expression only in the hippocampus but not in the frontal cortex in both non-stressed and CUMS mice. However, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), completely abolished the antidepressant-like effect of asiaticoside. Moreover, the expression of hippocampal BDNF, PSD-95 and synapsin I that had increased with asiaticoside also declined with K252a pretreatment. In conclusion, our study implies that it is possible that asiaticoside exerts its antidepressant-like action by activating BDNF signaling in the hippocampus.

  1. Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice.

    PubMed

    Wang, Ming-Xing; Liu, Yang-Liu; Yang, Ying; Zhang, Dong-Mei; Kong, Ling-Dong

    2015-01-15

    Nuciferine, a major aporphine alkaloid of the leaves of Nelumbo nucifera, was found to decrease serum urate levels and improved kidney function, as well as inhibited system and renal interleukin-1β (IL-1β) secretion in potassium oxonate-induced hyperuricemic mice. Furthermore, nuciferine reversed expression alteration of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette, subfamily G, membrane 2 (ABCG2), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), and organic cation/carnitine transporters 1/2 (OCTN1/2) in hyperuricemic mice. More importantly, nuciferine suppressed renal activation of Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB (TLR4/MyD88/NF-κB) signaling and NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome to reduce serum and renal IL-1β levels in hyperuricemic mice with renal inflammation reduction. The anti-inflammatroy effect of nuciferine was also confirmed in human proximal renal tubular epithelial cells (HK-2 cells) incubated with 4mg/dl uric acid for 24h. This study firstly reported the anti-hyperuricemic and anti-inflammatory effects of nuciferine by regulating renal organic ion transporters and inflammatory signaling in hyperuricemia. These results suggest that a dietary supplement of nuciferine rich in lotus leaf may be potential for the prevention and treatment of hyperuricemia with kidney inflammation.

  2. Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice.

    PubMed

    Wang, Ming-Xing; Liu, Yang-Liu; Yang, Ying; Zhang, Dong-Mei; Kong, Ling-Dong

    2015-01-15

    Nuciferine, a major aporphine alkaloid of the leaves of Nelumbo nucifera, was found to decrease serum urate levels and improved kidney function, as well as inhibited system and renal interleukin-1β (IL-1β) secretion in potassium oxonate-induced hyperuricemic mice. Furthermore, nuciferine reversed expression alteration of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette, subfamily G, membrane 2 (ABCG2), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), and organic cation/carnitine transporters 1/2 (OCTN1/2) in hyperuricemic mice. More importantly, nuciferine suppressed renal activation of Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB (TLR4/MyD88/NF-κB) signaling and NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome to reduce serum and renal IL-1β levels in hyperuricemic mice with renal inflammation reduction. The anti-inflammatroy effect of nuciferine was also confirmed in human proximal renal tubular epithelial cells (HK-2 cells) incubated with 4mg/dl uric acid for 24h. This study firstly reported the anti-hyperuricemic and anti-inflammatory effects of nuciferine by regulating renal organic ion transporters and inflammatory signaling in hyperuricemia. These results suggest that a dietary supplement of nuciferine rich in lotus leaf may be potential for the prevention and treatment of hyperuricemia with kidney inflammation. PMID:25499818

  3. Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice.

    PubMed

    Li, Haixiao; Sun, Jing; Wang, Fangyan; Ding, Guoqiang; Chen, Wenqian; Fang, Renchi; Yao, Ye; Pang, Mengqi; Lu, Zhong-Qiu; Liu, Jiaming

    2016-07-01

    Sodium butyrate (SB) has been widely used to treat cerebral diseases. The aim of the present study is to examine the neuroprotective effects of SB on early TBI in mice and to explore the underlying mechanisms of these effects. TBI was induced using a modified weight-drop method. Neurological deficits were evaluated according to the neurological severity score (NSS), brain oedema was measured by brain water content, and blood-brain barrier (BBB) permeability was evaluated by Evans blue (EB) dye extravasation. Neuronal injury was assessed by hematoxylin and eosin (H&E) staining and Fluoro-Jade C staining. The expression of tight junction-associated proteins, such as occludin and zonula occludens-1 (ZO-1), was analysed by western blotting and immunofluorescence. Our results showed that mice subjected to TBI exhibited worsened NSS, brain oedema, neuronal damage and BBB permeability. However, these were all attenuated by SB. Moreover, SB reversed the decrease in occludin and ZO-1 expression induced by TBI. These findings suggest that SB might attenuate neurological deficits, brain oedema, neuronal change and BBB damage, as well as increase occludin and ZO-1 expression in the brain to protect against TBI. The protective effect of SB may be correlated with restoring the BBB following its impairment. PMID:27017959

  4. Inhibition of B-cell death does not restore T-cell-dependent immune responses in CD40-deficient mice

    PubMed Central

    Merino, Jesús; Díez, Miguel A; Muñiz, María; Buelta, Luis; Núñez, Gabriel; López-Hoyos, Marcos; Merino, Ramón

    2003-01-01

    Signalling through CD40 is essential for the development of immunoglobulin G (IgG) antibody responses, germinal centres and B-cell memory against T-dependent antigens. In addition, engagement of CD40 in B cells promotes cell survival by inducing the expression of anti-apoptotic members of the bcl-2 family of cell-death regulators. In the present study we analysed whether T-dependent immune responses can be developed in mice deficient in CD40 if the anti-apoptotic activity mediated by the engagement of CD40 in B cells is compensated by the constitutive over-expression of anti-apoptotic genes of the bcl-2 family. We showed that the over-expression of either hbcl-2 or hbcl-xL transgenes in B cells is not sufficient to restore IgG antibody responses and germinal centre formation in CD40-deficient mice. These results indicate that CD40 functions, other than those mediated through survival, are required for the establishment of T-dependent B-cell responses. PMID:12871216

  5. Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis

    PubMed Central

    Rachel, Rivka A.; May-Simera, Helen L.; Veleri, Shobi; Gotoh, Norimoto; Choi, Byung Yoon; Murga-Zamalloa, Carlos; McIntyre, Jeremy C.; Marek, Jonah; Lopez, Irma; Hackett, Alice N.; Brooks, Matthew; den Hollander, Anneke I.; Beales, Philip L.; Li, Tiansen; Jacobson, Samuel G.; Sood, Raman; Martens, Jeffrey R.; Liu, Paul; Friedman, Thomas B.; Khanna, Hemant; Koenekoop, Robert K.; Kelley, Matthew W.; Swaroop, Anand

    2012-01-01

    Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects, and complex interactions exist among ciliopathy-associated proteins. Mutations of the centrosomal protein 290 kDa (CEP290) lead to distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness due to photoreceptor degeneration. Mice homozygous for a mutant Cep290 allele (Cep290rd16 mice) exhibit LCA-like early-onset retinal degeneration that is caused by an in-frame deletion in the CEP290 protein. Here, we show that the domain deleted in the protein encoded by the Cep290rd16 allele directly interacts with another ciliopathy protein, MKKS. MKKS mutations identified in patients with the ciliopathy Bardet-Biedl syndrome disrupted this interaction. In zebrafish embryos, combined subminimal knockdown of mkks and cep290 produced sensory defects in the eye and inner ear. Intriguingly, combinations of Cep290rd16 and Mkksko alleles in mice led to improved ciliogenesis and sensory functions compared with those of either mutant alone. We propose that altered association of CEP290 and MKKS affects the integrity of multiprotein complexes at the cilia transition zone and basal body. Amelioration of the sensory phenotypes caused by specific mutations in one protein by removal of an interacting domain/protein suggests a possible novel approach for treating human ciliopathies. PMID:22446187

  6. Normocaloric Diet Restores Weight Gain and Insulin Sensitivity in Obese Mice

    PubMed Central

    Lombardo, Giovanni Enrico; Arcidiacono, Biagio; De Rose, Roberta Francesca; Lepore, Saverio Massimo; Costa, Nicola; Montalcini, Tiziana; Brunetti, Antonio; Russo, Diego; De Sarro, Giovambattista; Celano, Marilena

    2016-01-01

    An increased incidence of obesity is registered worldwide, and its association with insulin resistance and type 2 diabetes is closely related with increased morbidity and mortality for cardiovascular diseases. A major clinical problem in the management of obesity is the non-adherence or low adherence of patients to a hypocaloric dietetic restriction. In this study, we evaluated in obese mice the effects of shifting from high-calorie foods to normal diet on insulin sensitivity. Male C57BL/6JOlaHsd mice (n = 20) were fed with high fat diet (HFD) for a 24-week period. Afterward, body weight, energy, and food intake were measured in all animals, together with parameters of insulin sensitivity by homeostatic model assessment of insulin resistance and plasma glucose levels in response to insulin administration. Moreover, in half of these mice, Glut4 mRNA levels were measured in muscle at the end of the high fat treatment, whereas the rest of the animals (n = 10) were shifted to normocaloric diet (NCD) for 10 weeks, after which the same analyses were carried out. A significant reduction of body weight was found after the transition from high to normal fat diet, and this decrease correlated well with an improvement in insulin sensitivity. In fact, we found a reduction in serum insulin levels and the recovery of insulin responsiveness in terms of glucose disposal measured by insulin tolerance test and Glut4 mRNA and protein expression. These results indicate that obesity-related insulin resistance may be rescued by shifting from HFD to NCD. PMID:27303363

  7. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

    PubMed

    D'Antonio, Maurizio; Musner, Nicolò; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M Laura; Wrabetz, Lawrence

    2013-04-01

    P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

  8. Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract.

    PubMed

    Ishikawa, Satoru; Matsui, Yasunori; Wachi, Satoshi; Yamaguchi, Hiroshi; Harashima, Nanae; Harada, Mamoru

    2016-08-01

    Because cancer is associated with aging, immunological features in the aged should be considered in anticancer immunotherapy. In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific CTLs from vaccinated aged mice. Analyses on tumor-infiltrating immune cells as early as day 5 after CT26 inoculation revealed that monocytic and granulocytic MDSCs preferentially infiltrated into tumor sites in aged mice compared with young mice. Alternatively, oral administration of Lentinula edodes mycelia (L.E.M.) extract, which has the potential to suppress inflammation in tumor-bearing hosts, decreased the serum levels of IL-6 in aged mice. When administration of L.E.M. extract was started 1 week earlier, CT26 growth was retarded in aged mice and the in vivo priming of tumor-specific CTLs was improved in CT26-vaccinated aged mice. These results indicate early infiltration of MDSCs is related to impaired immunity of aged hosts and that oral administration of L.E.M. extract can mitigate the impairment.

  9. Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract.

    PubMed

    Ishikawa, Satoru; Matsui, Yasunori; Wachi, Satoshi; Yamaguchi, Hiroshi; Harashima, Nanae; Harada, Mamoru

    2016-08-01

    Because cancer is associated with aging, immunological features in the aged should be considered in anticancer immunotherapy. In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific CTLs from vaccinated aged mice. Analyses on tumor-infiltrating immune cells as early as day 5 after CT26 inoculation revealed that monocytic and granulocytic MDSCs preferentially infiltrated into tumor sites in aged mice compared with young mice. Alternatively, oral administration of Lentinula edodes mycelia (L.E.M.) extract, which has the potential to suppress inflammation in tumor-bearing hosts, decreased the serum levels of IL-6 in aged mice. When administration of L.E.M. extract was started 1 week earlier, CT26 growth was retarded in aged mice and the in vivo priming of tumor-specific CTLs was improved in CT26-vaccinated aged mice. These results indicate early infiltration of MDSCs is related to impaired immunity of aged hosts and that oral administration of L.E.M. extract can mitigate the impairment. PMID:27312060

  10. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

    PubMed Central

    Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

    2010-01-01

    The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

  11. Nearby Newborns

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site] Figure 1

    This image shows six of the three-dozen 'ultraviolet luminous galaxies' spotted in our corner of the universe by NASA's Galaxy Evolution Explorer. These massive galaxies greatly resemble newborn galaxies that were common in the early universe. The discovery came as a surprise, because astronomers had thought that the universe's 'birth-rate' had declined, and that massive galaxies were no longer forming.

    The galaxies, located in the center of each panel, were discovered after the Galaxy Evolution Explorer scanned a large portion of the sky with its highly sensitive ultraviolet-light detectors. Because young stars pack most of their light into ultraviolet wavelengths, young galaxies appear to the Galaxy Evolution Explorer like diamonds in a field of stones. Astronomers mined for these rare 'gems' before, but missed them because they weren't able to examine a large enough slice of the sky. The Galaxy Evolution Explorer surveyed thousands of nearby galaxies before finding three-dozen newborns.

    While still relatively close in astronomical terms, these galaxies are far enough away to appear small to the Galaxy Evolution Explorer. Clockwise beginning from the upper left, they are called: GALEX_J232539.24+004507.1, GALEX_J231812.98-004126.1, GALEX_J015028.39+130858.5, GALEX_J021348.52+125951.3, GALEX_J143417.15+020742.5, GALEX_J020354.02-092452.5.

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

    PubMed

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

    2011-01-01

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

  13. Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice

    PubMed Central

    Agrawal, Vijayendra; Maharjan, Sony; Kim, Kyeojin; Kim, Nam-Jung; Son, Jimin; Lee, Keunho; Choi, Hyun-Jung; Rho, Seung-Sik; Ahn, Sunjoo; Won, Moo-Ho; Ha, Sang-Jun; Koh, Gou Young; Kim, Young-Myeong; Suh, Young-Ger; Kwon, Young-Guen

    2014-01-01

    Tumor blood vessels are leaky and immature, which causes inadequate blood supply to tumor tissues resulting in hypoxic microenvironment and promotes metastasis. Here we have explored tumor vessel modulating activity of Sac-1004, a recently developed molecule in our lab, which directly potentiates VE-cadherin-mediated endothelial cell junction. Sac-1004 could enhance vascular junction integrity in tumor vessels and thereby inhibit vascular leakage and enhance vascular perfusion. Improved perfusion enabled Sac-1004 to have synergistic anti-tumor effect on cisplatin-mediated apoptosis of tumor cells. Interestingly, characteristics of normalized blood vessels namely reduced hypoxia, improved pericyte coverage and decreased basement membrane thickness were readily observed in tumors treated with Sac-1004. Remarkably, Sac-1004 was also able to inhibit lung and lymph node metastasis in MMTV and B16BL6 tumor models. This was in correlation with a reduction in epithelial-to-mesenchymal transition of tumor cells with considerable diminution in expression of related transcription factors. Moreover, cancer stem cell population dropped substantially in Sac-1004 treated tumor tissues. Taken together, our results showed that direct restoration of vascular junction could be a significant strategy to induce normalization of tumor blood vessels and reduce metastasis. PMID:24811731

  14. Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice.

    PubMed

    Agrawal, Vijayendra; Maharjan, Sony; Kim, Kyeojin; Kim, Nam-Jung; Son, Jimin; Lee, Keunho; Choi, Hyun-Jung; Rho, Seung-Sik; Ahn, Sunjoo; Won, Moo-Ho; Ha, Sang-Jun; Koh, Gou Young; Kim, Young-Myeong; Suh, Young-Ger; Kwon, Young-Guen

    2014-05-15

    Tumor blood vessels are leaky and immature, which causes inadequate blood supply to tumor tissues resulting in hypoxic microenvironment and promotes metastasis. Here we have explored tumor vessel modulating activity of Sac-1004, a recently developed molecule in our lab, which directly potentiates VE-cadherin-mediated endothelial cell junction. Sac-1004 could enhance vascular junction integrity in tumor vessels and thereby inhibit vascular leakage and enhance vascular perfusion. Improved perfusion enabled Sac-1004 to have synergistic anti-tumor effect on cisplatin-mediated apoptosis of tumor cells. Interestingly, characteristics of normalized blood vessels namely reduced hypoxia, improved pericyte coverage and decreased basement membrane thickness were readily observed in tumors treated with Sac-1004. Remarkably, Sac-1004 was also able to inhibit lung and lymph node metastasis in MMTV and B16BL6 tumor models. This was in correlation with a reduction in epithelial-to-mesenchymal transition of tumor cells with considerable diminution in expression of related transcription factors. Moreover, cancer stem cell population dropped substantially in Sac-1004 treated tumor tissues. Taken together, our results showed that direct restoration of vascular junction could be a significant strategy to induce normalization of tumor blood vessels and reduce metastasis. PMID:24811731

  15. Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice.

    PubMed

    Sun, Linjie; Wang, Yan; Song, Yu; Cheng, Xiang-Rong; Xia, Shufang; Rahman, Md Ramim Tanver; Shi, Yonghui; Le, Guowei

    2015-02-27

    Circadian rhythmic disorders induced by high-fat diet are associated with metabolic diseases. Resveratrol could improve metabolic disorder, but few reports focused on its effects on circadian rhythm disorders in a variety of studies. The aim of the present study was to analyze the potential effects of resveratrol on high-fat diet-induced disorders about the rhythmic expression of clock genes and clock-controlled lipid metabolism. Male C57BL/6 mice were divided into three groups: a standard diet control group (CON), a high-fat diet (HFD) group and HFD supplemented with 0.1% (w/w) resveratrol (RES). The body weight, fasting blood glucose and insulin, plasma lipids and leptin, whole body metabolic status and the expression of clock genes and clock-controlled lipogenic genes were analyzed at four different time points throughout a 24-h cycle (8:00, 14:00, 20:00, 2:00). Resveratrol, being associated with rhythmic restoration of fasting blood glucose and plasma insulin, significantly decreased the body weight in HFD mice after 11 weeks of feeding, as well as ameliorated the rhythmities of plasma leptin, lipid profiles and whole body metabolic status (respiratory exchange ratio, locomotor activity, and heat production). Meanwhile, resveratrol modified the rhythmic expression of clock genes (Clock, Bmal1 and Per2) and clock-controlled lipid metabolism related genes (Sirt1, Pparα, Srebp-1c, Acc1 and Fas). The response pattern of mRNA expression for Acc1 was similar to the plasma triglyceride. All these results indicated that resveratrol reduced lipogenesis and ultimately normalized rhythmic expression of plasma lipids, possibly via its action on clock machinery.

  16. Restoration of autophagy alleviates hepatic ER stress and impaired insulin signalling transduction in high fructose-fed male mice.

    PubMed

    Wang, Hao; Sun, Ruo-Qiong; Zeng, Xiao-Yi; Zhou, Xiu; Li, Songpei; Jo, Eunjung; Molero, Juan C; Ye, Ji-Ming

    2015-01-01

    High-carbohydrate (mainly fructose) consumption is a major dietary factor for hepatic insulin resistance, involving endoplasmic reticulum (ER) stress and lipid accumulation. Because autophagy has been implicated in ER stress, the present study investigated the role of autophagy in high-fructose (HFru) diet-induced hepatic ER stress and insulin resistance in male C57BL/6J mice. The results show that chronic HFru feeding induced glucose intolerance and impaired insulin signaling transduction in the liver, associated with ER stress and the accumulation of lipids. Intriguingly, hepatic autophagy was suppressed as a result of activation of mammalian target of rapamycin. The suppressed autophagy was detected within 6 hours after HFru feeding along with activation of both inositol-requiring enzyme 1 and protein kinase RNA-like endoplasmic reticulum kinase pathways. These events occurred prior to lipid accumulation or lipogenesis and were sufficient to blunt insulin signaling transduction with activation of c-Jun N-terminal kinase/inhibitory-κB kinase and serine phosphorylation of insulin receptor substrate 1. The stimulation of autophagy attenuated ER stress- and c-Jun N-terminal kinase/inhibitory-κB kinase-associated impairment in insulin signaling transduction in a mammalian target of rapamycin -independent manner. Taken together, our data suggest that restoration of autophagy functions disrupted by fructose is able to alleviate ER stress and improve insulin signaling transduction.

  17. Behavior of knock-in mice with a cocaine-insensitive dopamine transporter after virogenetic restoration of cocaine sensitivity in the striatum

    PubMed Central

    O'Neill, Brian; Tilley, Michael R.; Han, Dawn D.; Thirtamara-Rajamani, Keerthi; Hill, Erik R.; Bishop, Georgia A.; Zhou, Fu-Ming; During, Matthew J.; Gu, Howard H.

    2014-01-01

    Cocaine's main pharmacological actions are the inhibition of the dopamine, serotonin, and norepinephrine transporters. Its main behavioral effects are reward and locomotor stimulation, potentially leading to addiction. Using knock-in mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) we have shown previously that inhibition of the dopamine transporter (DAT) is necessary for both of these behaviors. In this study, we sought to determine brain regions in which DAT inhibition by cocaine stimulates locomotor activity and/or produces reward. We used adeno-associated viral vectors to reintroduce the cocaine-sensitive wild-type DAT in specific brain regions of DAT-CI mice, which otherwise only express a cocaine-insensitive DAT globally. Viral-mediated expression of wild-type DAT in the rostrolateral striatum restored cocaine-induced locomotor stimulation and sensitization in DAT-CI mice. In contrast, the expression of wild-type DAT in the dorsal striatum, or in the medial nucleus accumbens, did not restore cocaine-induced locomotor stimulation. These data help to determine cocaine's molecular actions and anatomical loci that cause hyperlocomotion. Interestingly, cocaine did not produce significant reward – as measured by conditioned place-preference – in any of the three cohorts of DAT-CI mice with the virus injections. Therefore, the locus or loci underlying cocaine-induced reward remain underdetermined. It is possible that multiple dopamine-related brain regions are involved in producing the robust rewarding effect of cocaine. PMID:24412674

  18. Hepcidin and 1,25(OH)2D3 effectively restore Ca2+ transport in β-thalassemic mice: reciprocal phenomenon of Fe2+ and Ca2+ absorption.

    PubMed

    Kraidith, Kamonshanok; Svasti, Saovaros; Teerapornpuntakit, Jarinthorn; Vadolas, Jim; Chaimana, Rattana; Lapmanee, Sarawut; Suntornsaratoon, Panan; Krishnamra, Nateetip; Fucharoen, Suthat; Charoenphandhu, Narattaphol

    2016-07-01

    Previously, β-thalassemia, an inherited anemic disorder with iron overload caused by loss-of-function mutation of β-globin gene, has been reported to induce osteopenia and impaired whole body calcium metabolism, but the pathogenesis of aberrant calcium homeostasis remains elusive. Herein, we investigated how β-thalassemia impaired intestinal calcium absorption and whether it could be restored by administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or hepcidin, the latter of which was the liver-derived antagonist of intestinal iron absorption. The results showed that, in hemizygous β-globin knockout (BKO) mice, the duodenal calcium transport was lower than that in wild-type littermates, and severity was especially pronounced in female mice. Both active and passive duodenal calcium fluxes in BKO mice were found to be less than those in normal mice. This impaired calcium transport could be restored by 7-day 1,25(OH)2D3 treatment. The 1,25(OH)2D3-induced calcium transport was diminished by inhibitors of calcium transporters, e.g., L-type calcium channel, NCX1, and PMCA1b, as well as vesicular transport inhibitors. Interestingly, the duodenal calcium transport exhibited an inverse correlation with transepithelial iron transport, which was markedly enhanced in thalassemic mice. Thus, 3-day subcutaneous hepcidin injection and acute direct hepcidin exposure in the Ussing chamber were capable of restoring the thalassemia-associated impairment of calcium transport; however, the positive effect of hepcidin on calcium transport was completely blocked by proteasome inhibitors MG132 and bortezomib. In conclusion, both 1,25(OH)2D3 and hepcidin could be used to alleviate the β-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in β-thalassemia. PMID:27245334

  19. BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.

    PubMed

    Crispino, Giulia; Di Pasquale, Giovanni; Scimemi, Pietro; Rodriguez, Laura; Galindo Ramirez, Fabian; De Siati, Romolo Daniele; Santarelli, Rosa Maria; Arslan, Edoardo; Bortolozzi, Mario; Chiorini, John A; Mammano, Fabio

    2011-01-01

    The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans. PMID:21876744

  20. Targeting Channelrhodopsin-2 to ON-bipolar Cells With Vitreally Administered AAV Restores ON and OFF Visual Responses in Blind Mice

    PubMed Central

    Macé, Emilie; Caplette, Romain; Marre, Olivier; Sengupta, Abhishek; Chaffiol, Antoine; Barbe, Peggy; Desrosiers, Mélissa; Bamberg, Ernst; Sahel, Jose-Alain; Picaud, Serge; Duebel, Jens; Dalkara, Deniz

    2015-01-01

    Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of retinal neurons mediated by adeno-associated virus (AAV) gene therapy has the potential to restore vision regardless of patient-specific mutations. The challenge for clinical translatability is to restore a vision as close to natural vision as possible, while using a surgically safe delivery route for the fragile degenerated retina. To preserve the visual processing of the inner retina, we targeted ON bipolar cells, which are still present at late stages of disease. For safe gene delivery, we used a recently engineered AAV variant that can transduce the bipolar cells after injection into the eye's easily accessible vitreous humor. We show that AAV encoding channelrhodopsin under the ON bipolar cell–specific promoter mediates long-term gene delivery restricted to ON-bipolar cells after intravitreal administration. Channelrhodopsin expression in ON bipolar cells leads to restoration of ON and OFF responses at the retinal and cortical levels. Moreover, light-induced locomotory behavior is restored in treated blind mice. Our results support the clinical relevance of a minimally invasive AAV-mediated optogenetic therapy for visual restoration. PMID:25095892

  1. Mold-casted non-degradable, islet macro-encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice.

    PubMed

    Rios, Peter Daniel; Zhang, Xiaomin; Luo, Xunrong; Shea, Lonnie D

    2016-11-01

    Islet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three-dimensional microenvironment conducive to survival of transplanted islets to extend graft function. Herein, we present a novel macroencapsulation device, composed of PEG hydrogel, that combines encapsulation with lithography techniques to generate polydimethylsiloxane (PDMS) molds. PEG solutions are mixed with islets, which are then cast into PDMS molds for subsequent crosslinking. The molds can also be employed to provide complex architectures, such as microchannels that may allow vascular ingrowth through pre-defined regions of the hydrogel. PDMS molds allowed for the formation of stable gels with encapsulation of islets, and in complex architectures. Hydrogel devices with a thickness of 600 μm containing 500 islets promoted normoglycemia within 12 days following transplantation into the epididymal fat pad, which was sustained over the two-month period of study until removal of the device. The inclusion of microchannels, which had a similar minimum distance between islets and the hydrogel surface, similarly promoted normoglycemia. A glucose challenge test indicated hydrogel devices achieved normoglycemia 90 min post-dextrose injections, similar to control mice with native pancreata. Histochemical staining revealed that transplanted islets, identified as insulin positive, were viable and isolated from host tissue at 8 weeks post-transplantation, yet devices with microchannels had tissue and vascular ingrowth within the channels. Taken together, these results demonstrate a system for creating non-degradable hydrogels with complex geometries for encapsulating islets capable of restoring normoglycemia, which may expand islet transplantation as a treatment option for diabetic patients. Biotechnol. Bioeng. 2016;113: 2485-2495. © 2016 Wiley

  2. Skin findings in newborns

    MedlinePlus

    Newborn skin characteristics; Infant skin characteristics; Neonatal care - skin ... the first few weeks of the baby's life. Newborn skin will vary, depending on the length of the pregnancy. Premature infants have thin, transparent skin. The skin of a ...

  3. Feeding Your Newborn

    MedlinePlus

    ... you choose to breastfeed or formula feed. About Breastfeeding Breastfeeding your newborn has many advantages. Perhaps most ... to care for her newborn. continue Limitations of Breastfeeding With all the good things known about breastfeeding, ...

  4. Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine.

    PubMed

    Gattoni-Celli, Sebastiano; Young, M Rita I

    2016-01-01

    Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products. Mice with established GL261 brain gliomas were vaccinated subcutaneously with H-2(b) GL261 glioma cells fused with H-2(d) RAG-neo cells or with a mock vaccine of phosphate-buffered saline. The results of these analyses show that the presence of GL261 tumor-conditioned medium resulted in increased production of Th1, inflammatory and inhibitory cytokines by spleen cells from control mice and from vaccinated glioma-bearing mice. In contrast, spleen cells of tumor-bearing, mock-vaccinated mice produced lower levels of cytokines in the presence of tumor-conditioned media. However, these results also show that there was not a heightened level of cytokine production in the presence of tumor-conditioned medium by spleen cells of vaccinated mice over the production by spleen cells of control mice. Overall, these results show that vaccination slows growth of the GL261 tumors to the point where GL261-vaccinated mice do not show the signs of morbidly or splenic dysfunction exhibited by unvaccinated, late stage glioma-bearing mice. PMID:27598146

  5. Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine

    PubMed Central

    Gattoni-Celli, Sebastiano; Young, M. Rita I.

    2016-01-01

    Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products. Mice with established GL261 brain gliomas were vaccinated subcutaneously with H-2b GL261 glioma cells fused with H-2d RAG-neo cells or with a mock vaccine of phosphate-buffered saline. The results of these analyses show that the presence of GL261 tumor-conditioned medium resulted in increased production of Th1, inflammatory and inhibitory cytokines by spleen cells from control mice and from vaccinated glioma-bearing mice. In contrast, spleen cells of tumor-bearing, mock-vaccinated mice produced lower levels of cytokines in the presence of tumor-conditioned media. However, these results also show that there was not a heightened level of cytokine production in the presence of tumor-conditioned medium by spleen cells of vaccinated mice over the production by spleen cells of control mice. Overall, these results show that vaccination slows growth of the GL261 tumors to the point where GL261-vaccinated mice do not show the signs of morbidly or splenic dysfunction exhibited by unvaccinated, late stage glioma-bearing mice. PMID:27598146

  6. Topical mechlorethamine restores autoimmune-arrested follicular activity in mice with an alopecia areata-like disease by targeting infiltrated lymphocytes.

    PubMed

    Tang, Liren; Cao, Liping; Bernardo, Olga; Chen, Yongliang; Sundberg, John P; Lui, Harvey; Chung, Stephen; Shapiro, Jerry

    2003-03-01

    Alopecia areata is an autoimmune disease targeted at hair follicles with infiltrated T lymphocytes probably playing an important role in the pathogenesis. It was reported in 1985 that mechlorethamine was effective on alopecia areata patients. This has never been confirmed since. The aims of the study were to investigate the effects of mechlorethamine on balding C3H/HeJ mice affected with an alopecia-areata-like disease and to study the underlying mechanisms. Mice were treated on half of the dorsal skin with mechlorethamine and the contralateral side was treated with the vehicle ointment. After 10 wk of mechlorethamine therapy, a full pelage of hair covered the treated side in all the mice and was maintained during the study, whereas the vehicle-treated sides showed either no change or continued hair loss. Immunohistochemistry revealed that infiltrated CD4+ and CD8+ lymphocytes were eliminated from the treated side. In vitro cell viability assay showed that lymphocytes were much more sensitive to the cytotoxic effects of mechlorethamine than skin and hair follicular cells. RNase protection assay and real-time reverse transcription polymerase chain reaction showed that tumor necrosis factor alpha/beta, interleukin-12, and interferon-gamma were inhibited by mechlorethamine upon successful treatment. Our findings support that mechlorethamine restores follicular activity by selectively targeting infiltrated lymphocytes in vivo in alopecia-areata-affected mice.

  7. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

    SciTech Connect

    Sadler, Natalie C.; Angel, Thomas E.; Lewis, Michael P.; Pederson, Leeanna M.; Chauvigne-Hines, Lacie M.; Wiedner, Susan D.; Zink, Erika M.; Smith, Richard D.; Wright, Aaron T.

    2012-10-24

    High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD or if the mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar or elevated relative to standard diet (SD) mice, thereby IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice.

  8. Restoration of Lysosomal pH in RPE Cells from Cultured Human and ABCA4−/− Mice: Pharmacologic Approaches and Functional Recovery

    PubMed Central

    Liu, Ji; Lu, Wennan; Reigada, David; Nguyen, Jonathan; Laties, Alan M.; Mitchell, Claire H.

    2008-01-01

    Purpose Degradation of engulfed material is primarily mediated by lysosomal enzymes that function optimally within a narrow range of acidic pH values. RPE cells are responsible for daily degradation of photoreceptor outer segments and are thus particularly susceptible to perturbations in lysosomal pH. The authors hypothesized that elevated lysosomal pH levels could slow enzyme activity and encourage accumulation of partially digested material. Consequently, treatment to lower perturbed lysosomal pH levels may enhance degradative activity. Methods A high-throughput screening assay was developed to quantify the lysosomal pH of fresh mouse and cultured ARPE-19 cells. The effect of lysosomal pH on outer segment clearance was determined. Results Lysosomal pH is elevated in RPE cells from ABCA4 knockout mice and in cultured human ARPE-19 cells exposed to N-retinylidene-N-retinylethanolamine (A2E), tamoxifen, or chloroquine. The lysosomal pH of fresh RPE cells from ABCA4−/− mice and of chemically compromised RPE cells was reacidified by elevating intracellular cAMP directly. Compromised lysosomal pH was also restored by stimulating A2A adenosine or β-adrenergic receptors, consistent with Gs-protein coupling of these receptors. Restoring lysosomal pH with these treatments enhanced photoreceptor outer segment clearance, demonstrating functional relevance consistent with an enhancement of degradative enzyme activity. Conclusions Elevation of lysosomal pH in RPE cells interferes with the degradation of outer segments and may contribute to the pathologies associated with A2E. Pharmacologic elevation of cAMP can restore an acid pH and improve degradative function. PMID:18235027

  9. Troxerutin improves hepatic lipid homeostasis by restoring NAD(+)-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice.

    PubMed

    Zhang, Zi-Feng; Fan, Shao-Hua; Zheng, Yuan-Lin; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin

    2014-09-01

    Recent evidences suggest that NAD(+) depletion leads to abnormal hepatic lipid metabolism in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD); however, the contributing mechanism is not well understood. Our previous study showed that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, effectively inhibited obesity, and normalized hyperglycemia and hyperlipidemia in high-cholesterol diet-induced diabetic mice. Here we investigated whether troxerutin improved hepatic lipid metabolism via preventing NAD(+) depletion in HFD-induced NAFLD mouse model and the mechanisms underlying these effects. Our results showed that troxerutin markedly prevented obesity, liver steatosis and injury in HFD-fed mice. Troxerutin largely suppressed oxidative stress-mediated NAD(+)-depletion by increasing nicotinamide phosphoribosyltransferase (NAMPT) protein expression and decreasing poly (ADP-ribose) polymerase-1 (PARP1) protein expression and activity in HFD-treated mouse livers. Consequently, troxerutin remarkably restored Silent mating type information regulation 2 homolog1 (SirT1) protein expression and activity in HFD-treated mouse livers. Therefore, troxerutin promoted SirT1-mediated AMP-activated protein kinase (AMPK) activation to inhibit mammalian target of rapamycin complex 1 (mTORC1) signaling, which enhanced nuclear lipin 1 localization, lowered cytoplasmic lipin 1 localization and the ratio of hepatic Lpin 1β/α. Ultimately, troxerutin improved lipid homeostasis by enhancing fatty acid oxidation and triglyceride secretion, and suppressing lipogenesis in HFD-fed mouse livers. In conclusion, troxerutin displayed beneficial effects on hepatic lipid homeostasis in HFD-induced NAFLD by blocking oxidative stress to restore NAD(+)-depletion-mediated dysfunction of lipin 1 signaling. This study provides novel mechanistic insights into NAFLD pathogenesis and indicates that troxerutin is a candidate for pharmacological intervention of NAFLD

  10. Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells

    PubMed Central

    Tochitsky, Ivan; Polosukhina, Aleksandra; Degtyar, Vadim E.; Gallerani, Nicholas; Smith, Caleb M.; Friedman, Aaron; Van Gelder, Russell N.; Trauner, Dirk; Kaufer, Daniela; Kramer, Richard H.

    2014-01-01

    Summary Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. Here we report a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight. A single intraocular injection of DENAQ photosensitizes the blind retina for days, restoring electrophysiological and behavioral responses with no toxicity. Experiments on mouse strains with functional, non-functional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated photoreceptors. DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD. PMID:24559673

  11. Toward gene therapy of premature ovarian failure: intraovarian injection of adenovirus expressing human FSH receptor restores folliculogenesis in FSHR(−/−) FORKO mice

    PubMed Central

    Ghadami, M.; El-Demerdash, E.; Salama, S.A.; Binhazim, A.A.; Archibong, A.E.; Chen, X.; Ballard, B.R.; Sairam, M.R.; Al-Hendy, A.

    2010-01-01

    A homozygous missense mutation, C566T, in the follicle stimulation hormone receptor (FSHR) gene has been linked to premature ovarian failure. The disease leads to infertility in a normal karyotype female with an elevated follicle stimulating hormone (FSH) and decreased serum estrogen level. Female mice carrying mutated FSHR gene, called follitropin receptor knockout (FORKO), display similar phenotype and are sterile because of a folliculogenesis block at a primary stage. We investigated the effects of bilateral intra-ovarian injection of an adenovirus expressing a normal copy of human FSHR on the reproductive system of 6–10 weeks female FORKO mice. Ad-LacZ was injected directly into each ovary of the control group. Animals were sacrificed at 2, 4, 8 and 12 weeks post-injection and tissues collected for evaluation. Treated mice showed estrogenic changes in daily vaginal smear whereas control animals remained fixated in the diestrus stage. Histological evaluation showed on average 26 ± 4 follicles/ovary in treated group with 8 ± 2 follicles at the antral stage compared with only 5 ± 2 with zero follicles at antral stage in Ad-LacZ control mice. There was no significant change in serum level of progesterone, however, estrogen level increased 2–3-fold (P < 0.02) and FSH decreased by up to 50% (P < 0.04) in treated animals. FSHR mRNA was detected in the ovaries of the treated group. In conclusion, intra-ovarian injection of an adenovirus expressing human FSHR gene is able to restore FSH responsiveness and reinitiate ovarian folliculogenesis as well as resume estrogen production in female FORKO mice. Ad-LacZ injections indicate the absence of systemic viral dissemination or germ line transmission of adenovirus DNA to offspring. PMID:20086006

  12. Age-dependent effects of esculetin on mood-related behavior and cognition from stressed mice are associated with restoring brain antioxidant status.

    PubMed

    Martín-Aragón, Sagrario; Villar, Ángel; Benedí, Juana

    2016-02-01

    Dietary antioxidants might exert an important role in the aging process by relieving oxidative damage, a likely cause of age-associated brain dysfunctions. This study aims to investigate the influence of esculetin (6,7-dihydroxycoumarin), a naturally occurring antioxidant in the diet, on mood-related behaviors and cognitive function and its relation with age and brain oxidative damage. Behavioral tests were employed in 11-, 17- and 22-month-old male C57BL/6J mice upon an oral 35day-esculetin treatment (25mg/kg). Activity of antioxidant enzymes, GSH and GSSG levels, GSH/GSSG ratio, and mitochondrial function were analyzed in brain cortex at the end of treatment in order to assess the oxidative status related to mouse behavior. Esculetin treatment attenuated the increased immobility time and enhanced the diminished climbing time in the forced swim task elicited by acute restraint stress (ARS) in the 11- and 17-month-old mice versus their counterpart controls. Furthermore, ARS caused an impairment of contextual memory in the step-through passive avoidance both in mature adult and aged mice which was partially reversed by esculetin only in the 11-month-old mice. Esculetin was effective to prevent the ARS-induced oxidative stress mostly in mature adult mice by restoring antioxidant enzyme activities, augmenting the GSH/GSSG ratio and increasing cytochrome c oxidase (COX) activity in cortex. Modulation of the mood-related behavior and cognitive function upon esculetin treatment in a mouse model of ARS depends on age and is partly due to the enhancement of redox status and levels of COX activity in cortex.

  13. Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.

    PubMed

    Yuan, Xusheng; Tong, Bei; Dou, Yannong; Wu, Xin; Wei, Zhifeng; Dai, Yue

    2016-02-01

    Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR. PMID:26640276

  14. Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.

    PubMed

    Yuan, Xusheng; Tong, Bei; Dou, Yannong; Wu, Xin; Wei, Zhifeng; Dai, Yue

    2016-02-01

    Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR.

  15. Conjunctivitis (Pink Eye) in Newborns

    MedlinePlus

    ... Antibiotics Work Adenovirus Non-Polio Enterovirus Parent Portal Conjunctivitis (Pink Eye) in Newborns Language: English Español (Spanish) ... can be very serious. Symptoms and Causes of Conjunctivitis in Newborns Newborns with conjunctivitis develop drainage from ...

  16. Dipeptidyl peptidase-4 inhibitor MK-626 restores insulin secretion through enhancing autophagy in high fat diet-induced mice.

    PubMed

    Liu, Limei; Liu, Jian; Yu, Xiaoxing

    2016-02-12

    Autophagy is cellular machinery for maintenance of β-cell function and mass. The current study aimed to investigate the regulatory effects of MK-626, a dipeptidyl peptidase-4 inhibitor, on insulin secretion through the activation of autophagy in high fat diet-induced obese mice. C57BL/6 mice were fed with a rodent diet containing 45 kcal% fat for 16 weeks to induce obesity and then were received either vehicle or MK-626 (3 mg/kg/day) orally during the final 4 weeks. Mouse islets were isolated. Phosphorylation of serine/threonine-protein kinase mTOR and levels of light chain 3B I (LC3B I), LC3B II, sequestosome-1 (SQSTM1/p62) and autophagy-related protein-7 (Atg7) were examined by Western blotting. Glucagon like-peptide-1 (GLP-1) level and insulin secretion were measured by ELISA. GLP-1 level in plasma was decreased in obese mice, which was elevated by dipeptidyl peptidase-4 inhibitor MK-626. In the islets of obese mice, phosphorylation of mTOR, ratio of LC3B I and LC3B II, and level of p62 were elevated and the expression of Atg7 and insulin secretion were reduced compared to those of C57BL/6 mice. However, such effects were reversed by MK-626. Autophagy activator rapamycin stimulated insulin secretion in obese mice but autophagy inhibitor chloroquine treatment inhibited insulin secretion in obese mice administrated by MK-626. Furthermore, the beneficial effects of MK-626 were inhibited by GLP-1 receptor antagonist exendin 9-39. The present study reveals the activation of autophagy to mediate the anti-diabetic effect of GLP-1.

  17. Communication and Your Newborn

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Communication and Your Newborn KidsHealth > For Parents > Communication and Your Newborn Print A A A Text ... first smile — a welcome addition to your baby's communication skills! continue What Should I Do? As soon ...

  18. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    PubMed Central

    Silva, Marcondes A. B.; Bruder-Nascimento, Thiago; Cau, Stefany B. A.; Lopes, Rheure A. M.; Mestriner, Fabiola L. A. C.; Fais, Rafael S.; Touyz, Rhian M.; Tostes, Rita C.

    2015-01-01

    Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db)] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+) mice] received spironolactone (50 mg/kg body weight/day) or vehicle (ethanol 1%) via oral per gavage for 6 weeks. Spironolactone treatment abolished endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177) in arteries from db/db mice, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 and catalase expression, improved sodium nitroprusside and BAY 41-2272-induced relaxation, and increased soluble guanylyl cyclase (sGC) β subunit expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes. PMID:26500555

  19. Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+ T-Lymphocyte-Depleted Mice

    PubMed Central

    Samuelson, D. R.; Assouline, B.; Morre, M.; Shellito, J. E.

    2015-01-01

    Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+ T lymphocytes are critical for host defense against this infection, but in the absence of CD4+ T lymphocytes, CD8+ T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense against Pneumocystis and accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected with Pneumocystis, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response to Pneumocystis murina and that administration of rhIL-7 markedly enhanced clearance of Pneumocystis in CD4-depleted mice. Additionally, we observed increased recruitment of CD8+ T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8+ T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-γ)-positive CD8+ central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murine Pneumocystis pneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8+ T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8+ T lymphocytes. PMID:26483405

  20. Delineation of biochemical, molecular, and physiological changes accompanying bile acid pool size restoration in Cyp7a1−/− mice fed low levels of cholic acid

    PubMed Central

    Jones, Ryan D.; Repa, Joyce J.; Russell, David W.; Dietschy, John M.

    2012-01-01

    Cholesterol 7α-hydroxylase (CYP7A1) is the initiating and rate-limiting enzyme in the neutral pathway that coverts cholesterol to primary bile acids (BA). CYP7A1-deficient (Cyp7a1−/−) mice have a depleted BA pool, diminished intestinal cholesterol absorption, accelerated fecal sterol loss, and increased intestinal cholesterol synthesis. To determine the molecular and physiological effects of restoring the BA pool in this model, adult female Cyp7a1−/− mice and matching Cyp7a1+/+ controls were fed diets containing cholic acid (CA) at modest levels [0.015, 0.030, and 0.060% (wt/wt)] for 15–18 days. A level of just 0.03% provided a CA intake of ∼12 μmol (4.8 mg) per day per 100 g body wt and was sufficient in the Cyp7a1−/− mice to normalize BA pool size, fecal BA excretion, fractional cholesterol absorption, and fecal sterol excretion but caused a significant rise in the cholesterol concentration in the small intestine and liver, as well as a marked inhibition of cholesterol synthesis in these organs. In parallel with these metabolic changes, there were marked shifts in intestinal and hepatic expression levels for many target genes of the BA sensor farnesoid X receptor, as well as genes involved in cholesterol transport, especially ATP-binding cassette (ABC) transporter A1 (ABCA1) and ABCG8. In Cyp7a1+/+ mice, this level of CA supplementation did not significantly disrupt BA or cholesterol metabolism, except for an increase in fecal BA excretion and marginal changes in mRNA expression for some BA synthetic enzymes. These findings underscore the importance of using moderate dietary BA levels in studies with animal models. PMID:22628034

  1. Manipulation of mtDNA heteroplasmy in all striated muscles of newborn mice by AAV9-mediated delivery of a mitochondria-targeted restriction endonuclease.

    PubMed

    Bacman, S R; Williams, S L; Duan, D; Moraes, C T

    2012-11-01

    Mitochondrial diseases are frequently caused by heteroplasmic mitochondrial DNA (mtDNA) mutations. As these mutations express themselves only at high relative ratios, any approach able to manipulate mtDNA heteroplasmy can potentially be curative. In this study, we developed a system to manipulate mtDNA heteroplasmy in all skeletal muscles from neonate mice. We selected muscle because it is one of the most clinically affected tissues in mitochondrial disorders. A mitochondria-targeted restriction endonuclease (mito-ApaLI) expressed from AAV9 particles was delivered either by intraperitoneal or intravenous injection in neonate mice harboring two mtDNA haplotypes, only one of which was susceptible to ApaLI digestion. A single injection was able to elicit a predictable and marked change in mtDNA heteroplasmy in all striated muscles analyzed, including heart. No health problems or reduction in mtDNA levels were observed in treated mice, suggesting that this approach could have clinical applications for mitochondrial myopathies.

  2. Short-Term Pharmacological Suppression of the Hyperprolactinemia of Infertile hCG-Overproducing Female Mice Persistently Restores Their Fertility

    PubMed Central

    Ratner, Laura D.; Gonzalez, Betina; Ahtiainen, Petteri; Di Giorgio, Noelia P.; Poutanen, Matti; Calandra, Ricardo S.; Huhtaniemi, Ilpo T.

    2012-01-01

    Female infertility is often associated with deregulation of hormonal networks, and hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis affecting the reproductive functions. We have shown previously that transgenic female mice overexpressing human chorionic gonadotropin β-subunit (hCGβ+ mice), and producing elevated levels of bioactive LH/hCG, exhibit increased production of testosterone and progesterone, are overweight and infertile, and develop hyperprolactinemia associated with pituitary lactotrope adenomas in adult age. In the present study, we analyzed the influence of the hyperprolactinemia of hCGβ+ females on their reproductive phenotype by treating them with the dopamine agonists, bromocriptine and cabergoline. Long-term bromocriptine treatment of adult mice was effective in the control of obesity, pituitary growth, and disturbances in the hormone profile, demonstrating that hyperprolactinemia was the main cause of the hCGβ+ female phenotype. Interestingly, short-term treatment (1 wk) with cabergoline applied on 5-wk-old mice corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, prevented pituitary overgrowth, normalized gonadal function, and recovered fertility of adult hCGβ+ females after hormone-induced and natural ovulation. The same cabergoline treatment in the short term applied on 3-month-old hCGβ+ females failed to recover their reproductive function. Hence, we demonstrated that the short-term cabergoline treatment applied at a critical early stage of the phenotype progression effectively prevented the hyperprolactinemia-associated reproductive dysfunction of hCG-overproducing females. PMID:23117930

  3. Short-term pharmacological suppression of the hyperprolactinemia of infertile hCG-overproducing female mice persistently restores their fertility.

    PubMed

    Ratner, Laura D; Gonzalez, Betina; Ahtiainen, Petteri; Di Giorgio, Noelia P; Poutanen, Matti; Calandra, Ricardo S; Huhtaniemi, Ilpo T; Rulli, Susana B

    2012-12-01

    Female infertility is often associated with deregulation of hormonal networks, and hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis affecting the reproductive functions. We have shown previously that transgenic female mice overexpressing human chorionic gonadotropin β-subunit (hCGβ+ mice), and producing elevated levels of bioactive LH/hCG, exhibit increased production of testosterone and progesterone, are overweight and infertile, and develop hyperprolactinemia associated with pituitary lactotrope adenomas in adult age. In the present study, we analyzed the influence of the hyperprolactinemia of hCGβ+ females on their reproductive phenotype by treating them with the dopamine agonists, bromocriptine and cabergoline. Long-term bromocriptine treatment of adult mice was effective in the control of obesity, pituitary growth, and disturbances in the hormone profile, demonstrating that hyperprolactinemia was the main cause of the hCGβ+ female phenotype. Interestingly, short-term treatment (1 wk) with cabergoline applied on 5-wk-old mice corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, prevented pituitary overgrowth, normalized gonadal function, and recovered fertility of adult hCGβ+ females after hormone-induced and natural ovulation. The same cabergoline treatment in the short term applied on 3-month-old hCGβ+ females failed to recover their reproductive function. Hence, we demonstrated that the short-term cabergoline treatment applied at a critical early stage of the phenotype progression effectively prevented the hyperprolactinemia-associated reproductive dysfunction of hCG-overproducing females.

  4. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

    PubMed Central

    Stutchfield, Benjamin M.; Antoine, Daniel J.; Mackinnon, Alison C.; Gow, Deborah J.; Bain, Calum C.; Hawley, Catherine A.; Hughes, Michael J.; Francis, Benjamin; Wojtacha, Davina; Man, Tak Y.; Dear, James W.; Devey, Luke R.; Mowat, Alan M.; Pollard, Jeffrey W.; Park, B. Kevin; Jenkins, Stephen J.; Simpson, Kenneth J.; Hume, David A.; Wigmore, Stephen J.; Forbes, Stuart J.

    2015-01-01

    Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients

  5. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

    PubMed

    Lees, Emma K; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W; Delibegovic, Mirela

    2014-10-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans. PMID:24935677

  6. Newborn Respiratory Distress.

    PubMed

    Hermansen, Christian L; Mahajan, Anand

    2015-12-01

    Newborn respiratory distress presents a diagnostic and management challenge. Newborns with respiratory distress commonly exhibit tachypnea with a respiratory rate of more than 60 respirations per minute. They may present with grunting, retractions, nasal flaring, and cyanosis. Common causes include transient tachypnea of the newborn, respiratory distress syndrome, meconium aspiration syndrome, pneumonia, sepsis, pneumothorax, persistent pulmonary hypertension of the newborn, and delayed transition. Congenital heart defects, airway malformations, and inborn errors of metabolism are less common etiologies. Clinicians should be familiar with updated neonatal resuscitation guidelines. Initial evaluation includes a detailed history and physical examination. The clinician should monitor vital signs and measure oxygen saturation with pulse oximetry, and blood gas measurement may be considered. Chest radiography is helpful in the diagnosis. Blood cultures, serial complete blood counts, and C-reactive protein measurement are useful for the evaluation of sepsis. Most neonates with respiratory distress can be treated with respiratory support and noninvasive methods. Oxygen can be provided via bag/mask, nasal cannula, oxygen hood, and nasal continuous positive airway pressure. Ventilator support may be used in more severe cases. Surfactant is increasingly used for respiratory distress syndrome. Using the INSURE technique, the newborn is intubated, given surfactant, and quickly extubated to nasal continuous positive airway pressure. Newborns should be screened for critical congenital heart defects via pulse oximetry after 24 hours but before hospital discharge. Neonatology consultation is recommended if the illness exceeds the clinician's expertise and comfort level or when the diagnosis is unclear in a critically ill newborn. PMID:26760414

  7. Inhibitory Interneuron Progenitor Transplantation Restores Normal Learning and Memory in ApoE4 Knock-In Mice without or with Aβ Accumulation

    PubMed Central

    Tong, Leslie M.; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K.; Yoon, Seo Yeon; Wang, Max M.; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L.R.; Alvarez-Buylla, Arturo

    2014-01-01

    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. PMID:25031394

  8. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

    PubMed

    Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

    2014-07-16

    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. PMID:25031394

  9. Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3−/−/Nrl−/− mice, an all-cone model of CNGA3 achromatopsia†

    PubMed Central

    Du, Wei; Tao, Ye; Deng, Wen-Tao; Zhu, Ping; Li, Jie; Dai, Xufeng; Zhang, Yuxin; Shi, Wei; Liu, Xuan; Chiodo, Vince A.; Ding, Xi-Qin; Zhao, Chen; Michalakis, Stylianos; Biel, Martin; Zhang, Zuoming; Qu, Jia; Hauswirth, William W.; Pang, Ji-jing

    2015-01-01

    The CNGA3−/−/Nrl−/− mouse is a cone-dominant model with Cnga3 channel deficiency, which partially mimics the all cone foveal structure of human achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector administration can transfect retinal cells efficiently, the injection-induced retinal detachment can cause retinal damage, particularly when SR vector bleb includes the fovea. We therefore explored whether cone function–structure could be rescued in CNGA3−/−/Nrl−/− mice by intravitreal (IVit) delivery of tyrosine to phenylalanine (Y-F) capsid mutant AAV8. We find that AAV-mediated CNGA3 expression can restore cone function and rescue structure following IVit delivery of AAV8 (Y447, 733F) vector. Rescue was assessed by restoration of the cone-mediated electroretinogram (ERG), optomotor responses, and cone opsin immunohistochemistry. Demonstration of gene therapy in a cone-dominant mouse model by IVit delivery provides a potential alternative vector delivery mode for safely transducing foveal cones in achromatopsia patients and in other human retinal diseases affecting foveal function. PMID:25855802

  10. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

    PubMed

    Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

    2014-07-16

    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases.

  11. Vesicular stomatitis virus-based vaccines expressing EV71 virus-like particles elicit strong immune responses and protect newborn mice from lethal challenges.

    PubMed

    Yan, Qin; Wu, Linjuan; Chen, Longyun; Qin, Yali; Pan, Zishu; Chen, Mingzhou

    2016-07-29

    Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus-like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71. Second, we inserted P1 and 3CD into one VSV backbone to generate an rVSV expressing P1 and 3CD together (mP1-3CD). When P1 and 3CD were expressed in the cells either co-infected with mP1 and m3CD (mP1/m3CD) or infected with mP1-3CD, P1 was cleaved by 3CD and produced VP1, VP3, and VP0 to form VLPs. Furthermore, mice immunized with mP1/m3CD or mP1-3CD showed higher humoral and cellular immunity responses than mice immunized with mVP1. Finally, the rVSVs expressing the EV71 proteins were evaluated in mice to determine their potential to protect against a lethal EV71 virus challenge, and among all the rVSVs, the mP1-3CD was shown to be the most promising vaccine candidate for EV71 protection. PMID:27373596

  12. Vesicular stomatitis virus-based vaccines expressing EV71 virus-like particles elicit strong immune responses and protect newborn mice from lethal challenges.

    PubMed

    Yan, Qin; Wu, Linjuan; Chen, Longyun; Qin, Yali; Pan, Zishu; Chen, Mingzhou

    2016-07-29

    Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus-like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71. Second, we inserted P1 and 3CD into one VSV backbone to generate an rVSV expressing P1 and 3CD together (mP1-3CD). When P1 and 3CD were expressed in the cells either co-infected with mP1 and m3CD (mP1/m3CD) or infected with mP1-3CD, P1 was cleaved by 3CD and produced VP1, VP3, and VP0 to form VLPs. Furthermore, mice immunized with mP1/m3CD or mP1-3CD showed higher humoral and cellular immunity responses than mice immunized with mVP1. Finally, the rVSVs expressing the EV71 proteins were evaluated in mice to determine their potential to protect against a lethal EV71 virus challenge, and among all the rVSVs, the mP1-3CD was shown to be the most promising vaccine candidate for EV71 protection.

  13. Newborn health: everybody's business.

    PubMed

    Darmstadt, Gary L; Munar, Wolfgang; Henry, Sarah K

    2014-01-01

    Despite advances in issue-attention and in evidence of what works to save newborn lives (e.g., kangaroo mother care, antenatal corticosteroids, immediate and exclusive breastfeeding), we are still falling short on impact. To advance the unfinished newborn survival agenda, newborns must become an integral priority in developing countries where the burden of neonatal mortality is highest. Interventions must be adapted to local contexts and cultures and integrated into packages along the continuum of care delivered through the primary health-care systems that countries have at their disposal. PMID:24953532

  14. Newborn health: everybody's business.

    PubMed

    Darmstadt, Gary L; Munar, Wolfgang; Henry, Sarah K

    2014-01-01

    Despite advances in issue-attention and in evidence of what works to save newborn lives (e.g., kangaroo mother care, antenatal corticosteroids, immediate and exclusive breastfeeding), we are still falling short on impact. To advance the unfinished newborn survival agenda, newborns must become an integral priority in developing countries where the burden of neonatal mortality is highest. Interventions must be adapted to local contexts and cultures and integrated into packages along the continuum of care delivered through the primary health-care systems that countries have at their disposal.

  15. Newborn screening: current status.

    PubMed

    Arn, Pamela H

    2007-01-01

    Newborn screening, which represents one of the major advances in child health of the past century, has been carried out in all fifty U.S. states since the 1970s. Newborn screening programs are state-run, and decisions are left to the individual states regarding the conditions to be screened for, the mechanism for confirmatory testing, follow-up care, and financing of the programs. Laboratory advances in tandem mass spectrometry make it possible to screen newborns for many rare inborn errors of metabolism. This raises many policy issues including screening's cost-effectiveness, ethics, quality, and oversight.

  16. Gene dysregulation is restored in the Parkinson’s disease MPTP neurotoxic mice model upon treatment of the therapeutic drug CuII(atsm)

    PubMed Central

    Cheng, Lesley; Quek, Camelia Y. J.; Hung, Lin W.; Sharples, Robyn A.; Sherratt, Nicki A.; Barnham, Kevin J.; Hill, Andrew F.

    2016-01-01

    The administration of MPTP selectively targets the dopaminergic system resulting in Parkinsonism-like symptoms and is commonly used as a mice model of Parkinson’s disease. We previously demonstrated that the neuroprotective compound CuII(atsm) rescues nigral cell loss and improves dopamine metabolism in the MPTP model. The mechanism of action of CuII(atsm) needs to be further defined to understand how the compound promotes neuronal survival. Whole genome transcriptomic profiling has become a popular method to examine the relationship between gene expression and function. Substantia nigra samples from MPTP-lesioned mice were evaluated using whole transcriptome sequencing to investigate the genes altered upon CuII(atsm) treatment. We identified 143 genes affected by MPTP lesioning that are associated with biological processes related to brain and cognitive development, dopamine synthesis and perturbed synaptic neurotransmission. Upon CuII(atsm) treatment, the expression of 40 genes involved in promoting dopamine synthesis, calcium signaling and synaptic plasticity were restored which were validated by qRT-PCR. The study provides the first detailed whole transcriptomic analysis of pathways involved in MPTP-induced Parkinsonism. In addition, we identify key therapeutic pathways targeted by a potentially new class of neuroprotective agents which may provide therapeutic benefits for other neurodegenerative disorders. PMID:26928495

  17. The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL-15/IL-15Rα treatment

    PubMed Central

    Nair, Savita; Fang, Min; Sigal, Luis J

    2015-01-01

    Immune dysfunctions in the elderly result in increased susceptibility to infectious diseases, cancer, and autoimmune diseases. Natural killer (NK) cells are bone marrow-derived lymphocytes crucial for host defense against several infections and cancer. We have previously shown that compared to young, aged C57BL/6 mice have decreased numbers of mature NK cells in the blood, spleen, and bone marrow, resulting in susceptibility to mousepox, a lethal disease caused by ectromelia virus. Here, we describe further age-related defects in NK cells including reduced proliferation in vivo, additional signs of immaturity, and dysregulated expression of activating and inhibitory receptors. Aging also alters the expression of collagen-binding integrins in conventional NK cells and the frequency and phenotype of liver tissue-resident NK cells. We additionally show that the defect in NK maturation is the consequence of deficient maturational cues provided by bone marrow stromal cells. Moreover, we demonstrate that in aged mice, treatment with complexes of the cytokine IL-15 and IL-15Rα induce massive expansion of the NK cells, but most of these NK cells remain immature and are unable to restore resistance to mousepox. The use of rodent model to understand immunosenescence may help the development of treatments to improve the immune fitness of the aged. Our work with NK cells should contribute toward this goal. PMID:25399821

  18. Reconstitution of B-cell-depleted mice with B cells restores Th2-type immune responses during Plasmodium chabaudi chabaudi infection.

    PubMed Central

    Taylor-Robinson, A W; Phillips, R S

    1996-01-01

    In mice depleted of B cells from birth by treatment with anti-immunoglobulin M(mu) antibodies, progression from a Th1- to a Th2-regulated immune response during primary infection with Plasmodium chabaudi chabaudi fails to occur. While Th1-type immunity limits parasitemia, in the absence of B cells, chronic low-grade infections persist. Here, we show that reconstituting immune, and to a lesser extent naive, B cells to mice rendered deficient in B-cell function through anti-immunoglobulin M(mu) pretreatment restores the CD4+ T-cell response to the Th2 type later in P. c. chabaudi infection and with it the capacity to eliminate infection. This finding provides clear evidence that B cells are required for switching the balance of immune regulation between CD4+ T cells from Th1 to Th2 during P.c. chabaudi infection and supports the concept that B cells, through antibody production, are needed for effective antimalarial immunity. PMID:8557367

  19. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes

    PubMed Central

    Marinić, Jelena; Broznić, Dalibor; Milin, Čedomila

    2016-01-01

    Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2. PMID:26925195

  20. The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL-15/IL-15Rα treatment.

    PubMed

    Nair, Savita; Fang, Min; Sigal, Luis J

    2015-04-01

    Immune dysfunctions in the elderly result in increased susceptibility to infectious diseases, cancer, and autoimmune diseases. Natural killer (NK) cells are bone marrow-derived lymphocytes crucial for host defense against several infections and cancer. We have previously shown that compared to young, aged C57BL/6 mice have decreased numbers of mature NK cells in the blood, spleen, and bone marrow, resulting in susceptibility to mousepox, a lethal disease caused by ectromelia virus. Here, we describe further age-related defects in NK cells including reduced proliferation in vivo, additional signs of immaturity, and dysregulated expression of activating and inhibitory receptors. Aging also alters the expression of collagen-binding integrins in conventional NK cells and the frequency and phenotype of liver tissue-resident NK cells. We additionally show that the defect in NK maturation is the consequence of deficient maturational cues provided by bone marrow stromal cells. Moreover, we demonstrate that in aged mice, treatment with complexes of the cytokine IL-15 and IL-15Rα induce massive expansion of the NK cells, but most of these NK cells remain immature and are unable to restore resistance to mousepox. The use of rodent model to understand immunosenescence may help the development of treatments to improve the immune fitness of the aged. Our work with NK cells should contribute toward this goal.

  1. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes.

    PubMed

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  2. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    PubMed Central

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  3. Bifidobacterium pseudocatenulatum CECT 7765 Reduces Obesity-Associated Inflammation by Restoring the Lymphocyte-Macrophage Balance and Gut Microbiota Structure in High-Fat Diet-Fed Mice

    PubMed Central

    Moya-Pérez, Angela; Neef, Alexander; Sanz, Yolanda

    2015-01-01

    Background/Objectives The role of intestinal dysbiosis in obesity-associated systemic inflammation via the cross-talk with peripheral tissues is under debate. Our objective was to decipher the mechanisms by which intervention in the gut ecosystem with a specific Bifidobacterium strain reduces systemic inflammation and improves metabolic dysfunction in obese high-fat diet (HFD) fed mice. Methods Adult male wild-type C57BL-6 mice were fed either a standard or HFD, supplemented with placebo or Bifidobacterium pseudocatenulatum CECT 7765, for 14 weeks. Lymphocytes, macrophages and cytokine/chemokine concentrations were quantified in blood, gut, liver and adipose tissue using bead-based multiplex assays. Biochemical parameters in serum were determined by ELISA and enzymatic assays. Histology was assessed by hematoxylin-eosin staining. Microbiota was analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. Results B. pseudocatenulatum CECT 7765 reduced obesity-associated systemic inflammation by restoring the balance between regulatory T cells (Tregs) and B lymphocytes and reducing pro-inflammatory cytokines of adaptive (IL-17A) and innate (TNF-α) immunity and endotoxemia. In the gut, the bifidobacterial administration partially restored the HFD-induced alterations in microbiota, reducing abundances of Firmicutes and of LPS-producing Proteobacteria, paralleled to reductions in B cells, macrophages, and cytokines (IL-6, MCP-1, TNF-α, IL-17A), which could contribute to systemic effects. In adipose tissue, bifidobacterial administration reduced B cells whereas in liver the treatment increased Tregs and shifted different cytokines (MCP-1 plus ILP-10 in adipose tissue and INF-γ plus IL-1β in liver). In both tissues, the bifidobacteria reduced pro-inflammatory macrophages and, TNF-α and IL-17A concentrations. These effects were accompanied by reductions in body weight gain and in serum cholesterol, triglyceride, glucose and insulin levels and improved oral glucose

  4. Adult hippocampal neurogenesis and mRNA expression are altered by perinatal arsenic exposure in mice and restored by brief exposure to enrichment.

    PubMed

    Tyler, Christina R; Allan, Andrea M

    2013-01-01

    Arsenic is a common and pervasive environmental contaminant found in drinking water in varying concentrations depending on region. Exposure to arsenic induces behavioral and cognitive deficits in both human populations and in rodent models. The Environmental Protection Agency (EPA) standard for the allotment of arsenic in drinking water is in the parts-per-billion range, yet our lab has shown that 50 ppb arsenic exposure during development can have far-reaching consequences into adulthood, including deficits in learning and memory, which have been linked to altered adult neurogenesis. Given that the morphological impact of developmental arsenic exposure on the hippocampus is unknown, we sought to evaluate proliferation and differentiation of adult neural progenitor cells in the dentate gyrus after 50 ppb arsenic exposure throughout the perinatal period of development in mice (equivalent to all three trimesters in humans) using a BrdU pulse-chase assay. Proliferation of the neural progenitor population was decreased by 13% in arsenic-exposed mice, but was not significant. However, the number of differentiated cells was significantly decreased by 41% in arsenic-exposed mice compared to controls. Brief, daily exposure to environmental enrichment significantly increased proliferation and differentiation in both control and arsenic-exposed animals. Expression levels of 31% of neurogenesis-related genes including those involved in Alzheimer's disease, apoptosis, axonogenesis, growth, Notch signaling, and transcription factors were altered after arsenic exposure and restored after enrichment. Using a concentration previously considered safe by the EPA, perinatal arsenic exposure altered hippocampal morphology and gene expression, but did not inhibit the cellular neurogenic response to enrichment. It is possible that behavioral deficits observed during adulthood in animals exposed to arsenic during development derive from the lack of differentiated neural progenitor cells

  5. Adult Hippocampal Neurogenesis and mRNA Expression are Altered by Perinatal Arsenic Exposure in Mice and Restored by Brief Exposure to Enrichment

    PubMed Central

    Tyler, Christina R.; Allan, Andrea M.

    2013-01-01

    Arsenic is a common and pervasive environmental contaminant found in drinking water in varying concentrations depending on region. Exposure to arsenic induces behavioral and cognitive deficits in both human populations and in rodent models. The Environmental Protection Agency (EPA) standard for the allotment of arsenic in drinking water is in the parts-per-billion range, yet our lab has shown that 50 ppb arsenic exposure during development can have far-reaching consequences into adulthood, including deficits in learning and memory, which have been linked to altered adult neurogenesis. Given that the morphological impact of developmental arsenic exposure on the hippocampus is unknown, we sought to evaluate proliferation and differentiation of adult neural progenitor cells in the dentate gyrus after 50 ppb arsenic exposure throughout the perinatal period of development in mice (equivalent to all three trimesters in humans) using a BrdU pulse-chase assay. Proliferation of the neural progenitor population was decreased by 13% in arsenic-exposed mice, but was not significant. However, the number of differentiated cells was significantly decreased by 41% in arsenic-exposed mice compared to controls. Brief, daily exposure to environmental enrichment significantly increased proliferation and differentiation in both control and arsenic-exposed animals. Expression levels of 31% of neurogenesis-related genes including those involved in Alzheimer’s disease, apoptosis, axonogenesis, growth, Notch signaling, and transcription factors were altered after arsenic exposure and restored after enrichment. Using a concentration previously considered safe by the EPA, perinatal arsenic exposure altered hippocampal morphology and gene expression, but did not inhibit the cellular neurogenic response to enrichment. It is possible that behavioral deficits observed during adulthood in animals exposed to arsenic during development derive from the lack of differentiated neural progenitor

  6. Infant and Newborn Care

    MedlinePlus

    ... Newborns have many needs, like frequent feedings and diaper changes. Babies can have health issues that are different from older children and adults, like diaper rash and cradle cap. Your baby will go ...

  7. Senses and Your Newborn

    MedlinePlus

    ... especially mom's and dad's, are a baby's favorite "music." Your baby already knows that this is where ... your baby react to soft lullabies or other music? Even if your child passed the newborn hearing ...

  8. Transient tachypnea - newborn

    MedlinePlus

    TTN; Wet lungs - newborns; Retained fetal lung fluid; Transient RDS; Prolonged transition; Neonatal - transient tachypnea ... As the baby grows in the womb, the lungs make a special fluid. This fluid fills the ...

  9. Sleep and Newborns

    MedlinePlus

    ... KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say Vaccines: Which ... Your Newborn Sleep Establishing a bedtime routine (bathing, reading, singing) will help your baby relax and sleep ...

  10. Investigation of Newborn Hyperbilirubinemia

    PubMed Central

    Rachlis, Val; Petryshen, Patricia

    1992-01-01

    The trend to early neonatal discharge underscores the need to detect and manage neonatal hyperbilirubinemia. In a retrospective study, 84 charts from newborns were audited for clinical hyperbilirubinemia. Jaundice was recorded for 29% of the newborns, 92% of cases appearing after the second day. Audits of additional 257 charts indicated that neonates delivered by cesarean section were twice as likely to develop jaundice. PMID:21229120

  11. Transgenerational inheritance of enhanced susceptibility to radiation-induced medulloblastoma in newborn Ptch1⁺/⁻ mice after paternal irradiation.

    PubMed

    Paris, Lorena; Giardullo, Paola; Leonardi, Simona; Tanno, Barbara; Meschini, Roberta; Cordelli, Eugenia; Benassi, Barbara; Longobardi, Maria Grazia; Izzotti, Alberto; Pulliero, Alessandra; Mancuso, Mariateresa; Pacchierotti, Francesca

    2015-11-01

    The hypothesis of transgenerational induction of increased cancer susceptibility after paternal radiation exposure has long been controversial because of inconsistent results and the lack of a mechanistic interpretation. Here, exploiting Ptch1 heterozygous knockout mice, susceptible to spontaneous and radiation-induced medulloblastoma, we show that exposure of paternal germ cells to 1 Gy X-rays, at the spermatogonial stage, increased by a considerable 1.4-fold the offspring susceptibility to medulloblastoma induced by neonatal irradiation. This effect gained further biological significance thanks to a number of supporting data on the immunohistochemical characterization of the target tissue and preneoplastic lesions (PNLs). These results altogether pointed to increased proliferation of cerebellar granule cell precursors and PNLs cells, which favoured the development of frank tumours. The LOH analysis of tumor DNA showed Ptch1 biallelic loss in all tumor samples, suggesting that mechanisms other than interstitial deletions, typical of radiation-induced medulloblastoma, did not account for the observed increased cancer risk. This data was supported by comet analysis showing no differences in DNA damage induction and repair in cerebellar cells as a function of paternal irradiation. Finally, we provide biological plausibility to our results offering evidence of a possible epigenetic mechanism of inheritance based on radiation-induced changes of the microRNA profile of paternal sperm. PMID:26452034

  12. A Special Extract of Bacopa monnieri (CDRI-08) Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit GluN2B in the Brain of Scopolamine-Induced Amnesic Mice

    PubMed Central

    Rai, Rakesh; Singh, Hemant K.; Prasad, S.

    2015-01-01

    In the present communication, we have investigated effects of the CDRI-08, a well characterized extract of Bacopa monnieri, on expression of the GluN2B subunit of NMDAR in various brain regions of the scopolamine-induced amnesic mice. Our behavioral data reveal that scopolamine-treated amnesic mice exhibit significant decline in the spatial memory compared to the normal control mice. Our RT-PCR and immunoblotting data revealed that the scopolamine treatment resulted in a significant downregulation of the NMDAR GluN2B subunit expression in prefrontal cortex and hippocampus. Our enzyme assay data revealed that scopolamine caused a significant increase in the acetylcholinesterase activity in both the brain regions. Further, oral administration of the CDRI-08 to scopolamine-treated amnesic mice restored the spatial memory which was found to be associated with significant upregulation of the GluN2B subunit expression and decline in the acetylcholinesterase activity in prefrontal cortex as well as hippocampus towards their levels in the normal control mice. Our study provides the evidence for the mechanism underlying role of the Bacopa monnieri extract (CDRI-08) in restoring spatial memory in amnesic mice, which may have therapeutic implications. PMID:26413117

  13. Cyclooxygenase-2 in newborn hyperoxic lung injury.

    PubMed

    Britt, Rodney D; Velten, Markus; Tipple, Trent E; Nelin, Leif D; Rogers, Lynette K

    2013-08-01

    Supraphysiological O2 concentrations, mechanical ventilation, and inflammation significantly contribute to the development of bronchopulmonary dysplasia (BPD).Exposure of newborn mice to hyperoxia causes inflammation and impaired alveolarization similar to that seen in infants with BPD.Previously, we demonstrated that pulmonary cyclooxygenase-2 (COX-2) protein expression is increased in hyperoxia-exposed newborn mice.The present studies were designed to define the role of COX-2 in newborn hyperoxic lung injury.We tested the hypothesis that attenuation of COX-2 activity would reduce hyperoxia-induced inflammation and improve alveolarization.Newborn C3H/HeN micewere injected daily with vehicle, aspirin (nonselective COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor) for the first 7 days of life.Additional studies utilized wild-type (C57Bl/6, COX-2(+/+)), heterozygous (COX-2(+/-)), and homozygous (COX-2(-/-)) transgenic mice.Micewere exposed to room air (21% O2) or hyperoxia (85% O2) for 14 days.Aspirin-injected and COX-2(-/-) pups had reduced levels of monocyte chemoattractant protein (MCP-1) in bronchoalveolar lavage fluid (BAL).Both aspirin and celecoxib treatment reduced macrophage numbers in the alveolar walls and air spaces.Aspirin and celecoxib treatment attenuated hyperoxia-induced COX activity, including altered levels of prostaglandin (PG)D2 metabolites.Decreased COX activity, however, did not prevent hyperoxia-induced lung developmental deficits.Our data suggest thatincreased COX-2 activity may contribute to proinflammatory responses, including macrophage chemotaxis, during exposure to hyperoxia.Modulation of COX-2 activity may be a useful therapeutic target to limit hyperoxia-induced inflammation in preterm infants at risk of developing BPD. PMID:23624331

  14. Lower hepatic iron storage associated with obesity in mice can be restored by decreasing body fat mass through feeding a low-fat diet.

    PubMed

    Chung, Hak; Wu, Dayong; Smith, Donald; Meydani, Simin Nikbin; Han, Sung Nim

    2016-09-01

    High-fat diet (HFD)-induced obesity has been reported to result in low hepatic iron storage. In the current study, we tested the hypothesis that these obesity-related changes in hepatic iron status could be reversed by decreasing adiposity by feeding a low-fat diet. Five-week-old C57BL/6 mice were assigned to 3 groups: the LL group was fed a control diet for 31 weeks, the HH group was fed a HFD for 31 weeks, and the HL group was fed the HFD for 15 weeks and then switched to the control diet for 16 weeks. The fat mass of the HL group decreased by 3.2 g from the 14th to the 30th weeks. Fat mass was significantly different among the groups (11.4, 15.8, and 37.5 g in the LL, HH, and HL groups, respectively; P< .001). The liver iron concentration of the HL group was similar to that of the LL group, which was about 30% higher than that of the HH group (74.2, 72.7, and 55.7 μg/g in the LL, HL, and HH groups, respectively; P< .05). Duodenal cytochrome b messenger RNA (mRNA) levels were higher in the HL group than in the HH group. Although bone morphogenetic protein 6 (Bmp6) mRNA levels showed no significant differences in the liver, duodenal Bmp6 mRNA levels were significantly lower in the HH group compared with the LL and HL groups. Liver Smad1/5 proteins were differentially activated: the HH group had significantly less phosphorylated Smads than did the LL and HL groups. Our data demonstrate that hepatic iron storage levels are closely related to body adiposity, and reducing body fat mass through feeding a lower-fat diet to HFD-induced obese mice restores liver iron storage.

  15. A Novel Arginase Inhibitor Derived from Scutellavia indica Restored Endothelial Function in ApoE-Null Mice Fed a High-Cholesterol Diet.

    PubMed

    Hwang, Hye Mi; Lee, Jeong Hyung; Min, Byung Sun; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong; Ryoo, Sungwoo

    2015-10-01

    Elevated endothelial arginase activity decreases nitric oxide (NO) production by competing with the substrate l-arginine, previously reported, and reciprocally regulating endothelial nitric oxide synthase (eNOS) activity. Thus, arginase inhibitors may help treat vascular diseases associated with endothelial dysfunction. A screening of metabolites from medicinal plants revealed that (2S)-5,2',5'-trihydroxy-7,8-dimethoxy flavanone (TDF) was a noncompetitive inhibitor of arginase. We investigated whether TDF reciprocally regulated endothelial NO production and its possible mechanism. TDF noncompetitively inhibited arginase I and II activity in a dose-dependent manner. TDF incubation decreased arginase activity and increased NO production in human umbilical vein endothelial cells and isolated mouse aortic vessels and reduced reactive oxygen species (ROS) generation in the endothelium of the latter. These TDF-mediated effects were associated with increased eNOS phosphorylation and dimerization but not with changes in protein content. Endothelium-dependent vasorelaxant responses to acetylcholine (Ach) were significantly increased in TDF-incubated aortic rings and attenuated by incubation with soluble guanylyl cyclase inhibitor. Phenylephrine-induced vasoconstrictor responses were markedly attenuated in TDF-treated vessels from wild-type mice. In atherogenic-prone ApoE(-/-) mice, TDF attenuated the high-cholesterol diet (HCD)-induced increase in arginase activity, which was accompanied by restoration of NO production and reduction of ROS generation. TDF incubation induced eNOS dimerization and phosphorylation at Ser1177. In addition, TDF improved Ach-dependent vasorelaxation responses and attenuated U46619-dependent contractile responses but did not change sodium nitroprusside-induced vasorelaxation or N-NAME-induced vasoconstriction. The findings suggest that TDF may help treat cardiovascular diseases by reducing pathophysiology derived from HCD-mediated endothelial

  16. Lower hepatic iron storage associated with obesity in mice can be restored by decreasing body fat mass through feeding a low-fat diet.

    PubMed

    Chung, Hak; Wu, Dayong; Smith, Donald; Meydani, Simin Nikbin; Han, Sung Nim

    2016-09-01

    High-fat diet (HFD)-induced obesity has been reported to result in low hepatic iron storage. In the current study, we tested the hypothesis that these obesity-related changes in hepatic iron status could be reversed by decreasing adiposity by feeding a low-fat diet. Five-week-old C57BL/6 mice were assigned to 3 groups: the LL group was fed a control diet for 31 weeks, the HH group was fed a HFD for 31 weeks, and the HL group was fed the HFD for 15 weeks and then switched to the control diet for 16 weeks. The fat mass of the HL group decreased by 3.2 g from the 14th to the 30th weeks. Fat mass was significantly different among the groups (11.4, 15.8, and 37.5 g in the LL, HH, and HL groups, respectively; P< .001). The liver iron concentration of the HL group was similar to that of the LL group, which was about 30% higher than that of the HH group (74.2, 72.7, and 55.7 μg/g in the LL, HL, and HH groups, respectively; P< .05). Duodenal cytochrome b messenger RNA (mRNA) levels were higher in the HL group than in the HH group. Although bone morphogenetic protein 6 (Bmp6) mRNA levels showed no significant differences in the liver, duodenal Bmp6 mRNA levels were significantly lower in the HH group compared with the LL and HL groups. Liver Smad1/5 proteins were differentially activated: the HH group had significantly less phosphorylated Smads than did the LL and HL groups. Our data demonstrate that hepatic iron storage levels are closely related to body adiposity, and reducing body fat mass through feeding a lower-fat diet to HFD-induced obese mice restores liver iron storage. PMID:27632915

  17. Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth.

    PubMed

    McPherson, Nicole O; Bakos, Hassan W; Owens, Julie A; Setchell, Brian P; Lane, Michelle

    2013-01-01

    Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.

  18. Pharmacological inhibitors of TRPV4 channels reduce cytokine production, restore endothelial function and increase survival in septic mice

    PubMed Central

    Dalsgaard, Thomas; Sonkusare, Swapnil K.; Teuscher, Cory; Poynter, Matthew E.; Nelson, Mark T.

    2016-01-01

    Sepsis is characterized by systemic inflammation, edema formation and hypo-perfusion leading to organ dysfunction and ultimately death. Activation of the transient receptor potential vanilloid type 4 (TRPV4) channel is associated with edema formation and circulatory collapse. Here, we show that TRPV4 channels are involved in the hyper-inflammatory response and mortality associated with sepsis. Pharmacological inhibition of TRPV4 channels in mice reduced mortality in lipopolysaccharide and cecal-ligation-and-puncture models of sepsis, but not in a tumor necrosis factor-α (TNFα)-induced sepsis model. These protective effects of TRPV4 channel inhibition were attributable to prevention of the sepsis-induced surge of a broad spectrum of pro-inflammatory cytokines, including TNFα, interleukin (IL)-1 and IL-6, and subsequent preservation of endothelial cell function, including Ca2+ signaling, integrity and endothelium-dependent vasodilation. These results suggest that TRPV4 antagonists may be of therapeutic utility in the management of sepsis. PMID:27653046

  19. Learning, Play, and Your Newborn

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Learning, Play, and Your Newborn KidsHealth > For Parents > Learning, ... juega su recién nacido What Is My Newborn Learning? Play is the chief way that infants learn ...

  20. Clostridium butyricum combined with Bifidobacterium infantis probiotic mixture restores fecal microbiota and attenuates systemic inflammation in mice with antibiotic-associated diarrhea.

    PubMed

    Ling, Zongxin; Liu, Xia; Cheng, Yiwen; Luo, Yueqiu; Yuan, Li; Li, Lanjuan; Xiang, Charlie

    2015-01-01

    Antibiotic-associated diarrhea (AAD) is one of the most common complications of most types of antibiotics. Our aim was to determine the efficacy of Clostridium butyricum, Bifidobacterium infantis, and their mixture for AAD treatment in mice. AAD models were administered with single probiotic strain and probiotic mixture for short term and long term to evaluate the changes of the composition and diversity of intestinal microbiota, histopathology of the colon, and the systemic inflammation. Our data indicated that long-term probiotic therapy, but not short-term course, exerted beneficial effects on the restoration of the intestinal microbiota, the recovery of the tissue architecture, and attenuation of systemic inflammation. All predominant fecal bacteria reached normal level after the long-term probiotic mixture treatment, while IL-10, IFN-γ, and TNF-α also returned to normal level. However, the efficacy for AAD was time dependent and probiotic strain specific. Short-term administration of probiotic strains or mixture showed no apparent positive effects for AAD. In addition, the beneficial effects of C. butyricum combined with B. infantis probiotic mixture were superior to their single strain. This research showed that supplementation with C. butyricum combined with B. infantis probiotic mixture may be a simple and effective method for AAD treatment.

  1. What's New with Newborn Screening

    ERIC Educational Resources Information Center

    Exceptional Parent, 2008

    2008-01-01

    Newborn screening is the process of testing and screening newborns shortly after birth for certain, potentially dangerous, conditions and/or impairments--conditions that include everything from inborn errors of metabolism and other genetic disorders to hearing impairment. Early detection through newborn screening is paramount, often allowing the…

  2. Newborn Black Holes

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Scientists using NASA's Swift satellite say they have found newborn black holes, just seconds old, in a confused state of existence. The holes are consuming material falling into them while somehow propelling other material away at great speeds. "First comes a blast of gamma rays followed by intense pulses of x-rays. The energies involved are much…

  3. Growth and Your Newborn

    MedlinePlus

    ... somewhere between 5 pounds, 8 ounces (2,500 grams) and 8 pounds, 13 ounces (4,000 grams). A newborn who is lighter or heavier than ... less than 5 pounds, 8 ounces (2,500 grams) at birth. That's the case for about 1 ...

  4. Body perception in newborns.

    PubMed

    Filippetti, Maria Laura; Johnson, Mark H; Lloyd-Fox, Sarah; Dragovic, Danica; Farroni, Teresa

    2013-12-01

    Body ownership and awareness has recently become an active topic of research in adults using paradigms such as the "rubber hand illusion" and "enfacement" [1-11]. These studies show that visual, tactile, postural, and anatomical information all contribute to the sense of body ownership in adults [12]. While some hypothesize body perception from birth [13], others have speculated on the importance of postnatal experience [14, 15]. Through studying body perception in newborns, we can directly investigate the factors involved prior to significant postnatal experience. To address this issue, we measured the looking behavior of newborns presented with visual-tactile synchronous and asynchronous cues, under conditions in which the visual information was either an upright (body-related stimulus; experiment 1) or inverted (non-body-related stimulus; experiment 2) infant face. We found that newborns preferred to look at the synchronous condition compared to the asynchronous condition, but only when the visual stimulus was body related. These results are in line with findings from adults and demonstrate that human newborns detect intersensory synchrony when related to their own bodies, consistent with the basic processes underlying body perception being present at birth. PMID:24268410

  5. Mutations in the Schmallenberg Virus Gc Glycoprotein Facilitate Cellular Protein Synthesis Shutoff and Restore Pathogenicity of NSs Deletion Mutants in Mice

    PubMed Central

    Pinto, Rute Maria; Caporale, Marco; Piras, Ilaria M.; Taggart, Aislynn; Seehusen, Frauke; Hahn, Kerstin; Janowicz, Anna; de Souza, William Marciel; Baumgärtner, Wolfgang; Shi, Xiaohong

    2016-01-01

    ABSTRACT Serial passage of viruses in cell culture has been traditionally used to attenuate virulence and identify determinants of viral pathogenesis. In a previous study, we found that a strain of Schmallenberg virus (SBV) serially passaged in tissue culture (termed SBVp32) unexpectedly displayed increased pathogenicity in suckling mice compared to wild-type SBV. In this study, we mapped the determinants of SBVp32 virulence to the viral genome M segment. SBVp32 virulence is associated with the capacity of this virus to reach high titers in the brains of experimentally infected suckling mice. We also found that the Gc glycoprotein, encoded by the M segment of SBVp32, facilitates host cell protein shutoff in vitro. Interestingly, while the M segment of SBVp32 is a virulence factor, we found that the S segment of the same virus confers by itself an attenuated phenotype to wild-type SBV, as it has lost the ability to block the innate immune system of the host. Single mutations present in the Gc glycoprotein of SBVp32 are sufficient to compensate for both the attenuated phenotype of the SBVp32 S segment and the attenuated phenotype of NSs deletion mutants. Our data also indicate that the SBVp32 M segment does not act as an interferon (IFN) antagonist. Therefore, SBV mutants can retain pathogenicity even when they are unable to fully control the production of IFN by infected cells. Overall, this study suggests that the viral glycoprotein of orthobunyaviruses can compensate, at least in part, for the function of NSs. In addition, we also provide evidence that the induction of total cellular protein shutoff by SBV is determined by multiple viral proteins, while the ability to control the production of IFN maps to the NSs protein. IMPORTANCE The identification of viral determinants of pathogenesis is key to the development of prophylactic and intervention measures. In this study, we found that the bunyavirus Gc glycoprotein is a virulence factor. Importantly, we show that

  6. Newborn male circumcision.

    PubMed

    Sorokan, S Todd; Finlay, Jane C; Jefferies, Ann L

    2015-01-01

    The circumcision of newborn males in Canada has become a less frequent practice over the past few decades. This change has been significantly influenced by past recommendations from the Canadian Paediatric Society and the American Academy of Pediatrics, who both affirmed that the procedure was not medically indicated. Recent evidence suggesting the potential benefit of circumcision in preventing urinary tract infection and some sexually transmitted infections, including HIV, has prompted the Canadian Paediatric Society to review the current medical literature in this regard. While there may be a benefit for some boys in high-risk populations and circumstances where the procedure could be considered for disease reduction or treatment, the Canadian Paediatric Society does not recommend the routine circumcision of every newborn male.

  7. Newborn male circumcision

    PubMed Central

    Sorokan, S Todd; Finlay, Jane C; Jefferies, Ann L

    2015-01-01

    The circumcision of newborn males in Canada has become a less frequent practice over the past few decades. This change has been significantly influenced by past recommendations from the Canadian Paediatric Society and the American Academy of Pediatrics, who both affirmed that the procedure was not medically indicated. Recent evidence suggesting the potential benefit of circumcision in preventing urinary tract infection and some sexually transmitted infections, including HIV, has prompted the Canadian Paediatric Society to review the current medical literature in this regard. While there may be a benefit for some boys in high-risk populations and circumstances where the procedure could be considered for disease reduction or treatment, the Canadian Paediatric Society does not recommend the routine circumcision of every newborn male. PMID:26435672

  8. Gingival Cyst of Newborn.

    PubMed

    Moda, Aman

    2011-01-01

    Gingival cyst of newborn is an oral mucosal lesion of transient nature. Although it is very common lesion within 3 to 6 weeks of birth, it is very rare to visualize the lesion thereafter. Presented here is a case report of gingival cyst, which was visible just after 15 days of birth. Clinical diagnoses of these conditions are important in order to avoid unnecessary therapeutic procedure and provide suitable information to parents about the nature of the lesion.

  9. Retinal hemorrhages in newborn.

    PubMed

    Govind, A; Kumari, S; Lath, N K

    1989-02-01

    Two hundred and fifty eight newborn babies were studied for the presence of retinal hemorrhages between 1-3 days of birth. The overall incidence of retinal hemorrhages was found to be 18.9%. It was observed that the incidence of retinal hemorrhages was higher in unassisted vaginal deliveries than in assisted births. Also, a two fold higher incidence was noted in term infants as compared to preterm babies. No association was seen with birth asphyxia.

  10. Newborn jaundice - what to ask your doctor

    MedlinePlus

    ... your doctor; What to ask your doctor about newborn jaundice ... What causes jaundice in a newborn child? How common is newborn jaundice? Will the jaundice harm my child? What are the treatments for jaundice? How long does ...

  11. River restoration

    NASA Astrophysics Data System (ADS)

    Wohl, Ellen; Angermeier, Paul L.; Bledsoe, Brian; Kondolf, G. Mathias; Macdonnell, Larry; Merritt, David M.; Palmer, Margaret A.; Poff, N. Leroy; Tarboton, David

    2005-10-01

    River restoration is at the forefront of applied hydrologic science. However, many river restoration projects are conducted with minimal scientific context. We propose two themes around which a research agenda to advance the scientific basis for river restoration can be built. First, because natural variability is an inherent feature of all river systems, we hypothesize that restoration of process is more likely to succeed than restoration aimed at a fixed end point. Second, because physical, chemical, and biological processes are interconnected in complex ways across watersheds and across timescales, we hypothesize that restoration projects are more likely to be successful in achieving goals if undertaken in the context of entire watersheds. To achieve restoration objectives, the science of river restoration must include (1) an explicit recognition of the known complexities and uncertainties, (2) continued development of a theoretical framework that enables us to identify generalities among river systems and to ask relevant questions, (3) enhancing the science and use of restoration monitoring by measuring the most effective set of variables at the correct scales of measurement, (4) linking science and implementation, and (5) developing methods of restoration that are effective within existing constraints. Key limitations to river restoration include a lack of scientific knowledge of watershed-scale process dynamics, institutional structures that are poorly suited to large-scale adaptive management, and a lack of political support to reestablish delivery of the ecosystem amenities lost through river degradation. This paper outlines an approach for addressing these shortcomings.

  12. Leucine metabolism in human newborns

    SciTech Connect

    Denne, S.C.; Kalhan, S.C. )

    1987-12-01

    The present study was designed to (1) determine whether a relationship exists between newborn birth weight and leucine metabolism and (2) compare leucine and energy metabolism in a period of rapid growth and development (i.e., newborn) with a constant nongrowth period (i.e., adult). Leucine kinetics and energy expenditure were measured in the postabsorptive state in 12 normal full-term newborns in early neonatal life and in 11 normal adults using a primed constant L-(1-{sup 13}C)leucine infusion combined with respiratory calorimetry. A significant positive correlation between newborn birth weight and leucine flux was observed. These data suggest the following. (1) A relationship exists between newborn birth weight and protein metabolism, as reflected by the correlation between leucine flux when expressed as micromoles per kilogram per hour and birth weight. (2) The high rate of leucine flux measured in newborns probably reflects the rapid remodeling of protein that occurs in this period of development, even during fasting. (3) The similar values in newborns and adults of leucine kinetics and energy expenditure when normalized to metabolic body weight and the nearly equivalent allometric exponents relating body weight to leucine flux and energy expenditure support a close relationship between leucine and energy metabolism, at least at the extremes of human growth.

  13. Newborn Physiological Immaturity

    PubMed Central

    Fabrellas-Padrés, Núria; Delgado-Hito, Pilar; Hurtado-Pardos, Bárbara; Martí-Cavallé, Montserrat; Gironès-Nogué, Marta; García-Berman, Rosa-Maria; Alonso-Fernandez, Sergio

    2015-01-01

    Background: Most standardized nursing care plans for healthy neonates include multiple nursing diagnoses to reflect nurses' judgments on the infant's status; however scientific literature concerning this issue is scarce. Newborn physiological immaturity is a concept in the ATIC terminology (architecture, terminology, interface, information, nursing [infermeria], and knowledge [coneixement]) to represent the natural status of vulnerability of the healthy neonate. Purpose: To identify the essential attributes of the concept and provide its conceptual and operational definition, using the Wilsonian approach. Findings: The concept under analysis embeds a natural cluster of vulnerabilities and environmental interactions that enhance the evolving maturation process. Implications for Practice: The use of this diagnosis may simplify the process of charting the nursing care plans and reduce time needed for documentation while maintaining the integrity of the information. Implications for Research: Consistent development and use of nursing concepts is essential for knowledge building. Studies on the actual use of nursing diagnoses are needed to inform decision making. PMID:25822514

  14. Healthy Start, Grow Smart: Your Newborn.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This booklet offers guidance to parents in caring for their newborn babies. Advice is given on the following topics: (1) newborn health screening; (2) what a healthy newborn looks like; (3) newborn reflexes; (4) baby checkups; (5) fathers' role; (6) the baby blues; (7) sleeping position; (8) breast milk; (9) breast feeding; (10) bottle feeding;…

  15. Preservation & Restoration.

    ERIC Educational Resources Information Center

    Online-Offline, 2000

    2000-01-01

    This theme issue on preservation and restoration presents selected resources for elementary and secondary education that include Web sites, CD-ROM and software, videos, books, magazines, and professional resources as well as classroom activities. Age levels are specified for most materials. I Sidebars discuss restoring a masterpiece, a bug's life,…

  16. A primer on newborn screening.

    PubMed

    Bryant, Kristin Gatrell; Horns, Kimberly M; Longo, Nicola; Schiefelbein, Julieanne

    2004-10-01

    Metabolic disorders are individually rare, but when considered together as a disease entity are relatively frequent, occurring in 1 in 1000 to 1 in 3000 infants. Some disorders can have devastating and irreversible outcomes if not diagnosed early and treated promptly. Newborn screening is a vital step in identifying infants with inborn metabolic disorders, hemoglobinopathies, infectious processes, and congenital endocrinopathies; the goal is early recognition and treatment. This article summarizes the critical aspects of newborn screening, comparing and contrasting current national screening practices, and identifying key considerations for clinical care, parental education, and support. To prevent morbidity and mortality, healthcare providers must understand the purpose and guidelines for newborn screening. Providers are also responsible for informing parents about the implications of newborn screening to improve awareness and understanding.

  17. ApoA-1 mimetic restores adiponectin expression and insulin sensitivity independent of changes in body weight in female obese mice

    PubMed Central

    Marino, J S; Peterson, S J; Li, M; Vanella, L; Sodhi, K; Hill, J W; Abraham, N G

    2012-01-01

    Background: We examined the ability of the apolipoprotein AI mimetic peptide L-4F to improve the metabolic state of female and male ob mice and the mechanisms involved. Methods: Female and male lean and obese (ob) mice were administered L-4F or vehicle for 6 weeks. Body weight was measured weekly. Fat distribution, serum cytokines and markers of cardiovascular dysfunction were determined at the end of treatment. Results: L-4F significantly decreased serum interleukin (IL)-6, tumor necrosis factor-α and IL-1β. L-4F improved vascular function, and increased serum adiponectin levels and insulin sensitivity compared with untreated mice. In addition, L-4F treatment increased heme oxygenase (HO)-1, pAKT and pAMPK levels in kidneys of ob animals. pAKT and pAMPK levels were significantly reduced in the presence of an HO inhibitor. Interestingly, L4F did not alter body weight in female mice, but caused a significant reduction in males. Conclusions: L-4F treatments reduced cardiovascular risk factors and improved insulin sensitivity in female ob mice independent of body fat changes. Reduced inflammatory cytokine levels accompanied by increased HO activity, serum adiponectin and improved insulin sensitivity suggest that L-4F may promote the conversion of visceral fat to a healthier phenotype. Therefore, L-4F appears to be a promising therapeutic strategy for treating both cardiovascular risk factors and insulin resistance in obese patients of either gender. PMID:23169576

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

    PubMed Central

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

    2013-01-01

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

  19. Pain Management in Newborns

    PubMed Central

    Hall, Richard W.; Anand, Kanwaljeet J. S.

    2014-01-01

    Effective pain management is a desirable standard of care for preterm and term newborns and may potentially improve their clinical and neurodevelopmental outcomes. Neonatal pain should be assessed routinely using context-specific, validated and objective pain methods, despite the limitations of currently available tools. Reducing invasive procedures, and using pharmacological, behavioral or environmental measures can be used to manage neonatal pain. Non-pharmacologic approaches include kangaroo care, facilitated tucking, non-nutritive sucking, sucrose and other sweeteners, massage and acupuncture therapy. They are used for procedures causing acute, transient, or mild pain, or as adjunctive therapy for moderate or severe pain. Local and topical anesthetics can reduce the acute pain caused by skin-breaking or mucosa-injuring procedures. Opioids form the mainstay for treatment of severe pain; morphine and fentanyl are the most commonly used drugs, although other opioids are also available. Non-opioid drugs include various sedatives and anesthetic agents, mostly used as adjunctive therapy in ventilated neonates. Acetaminophen, ibuprofen and other drugs are used for neonates, although their efficacy and safety remains unproven. Approaches for implementing an effective pain management program in the Neonatal ICU are summarized, together with practical protocols for procedural, postoperative, and mechanical ventilation-associated neonatal pain and stress. PMID:25459780

  20. Thrombosis in newborn infants.

    PubMed

    Bacciedoni, Viviana; Attie, Myriam; Donato, Hugo

    2016-04-01

    The incidence of thrombosis is higher among newborn infants than in any other stage of pediatric development. This fact is the consequence of labile characteristics of the neonatal hemostatic system, in addition to exposure to multiple risk factors and the wide use of vascular catheters. Venous thromboses, which mainly affect the limbs, the right atrium and renal veins, are more frequently seen than arterial thromboses. A stroke may be caused by the occlusion of the arterial flow entering the brain or by occlusion of its venous drainage system. Purpura fulminans is a very severe condition that should be treated as a medical emergency, and is secondary to severe protein C deficiency or, less frequently, protein S or antithrombin deficiency. Most thrombotic events should be managed with antithrombotic therapy, which is done with unfractionated and/or low molecular weight heparins. Purpura fulminans requires protein C replacement and/or fresh frozen plasma infusion. Thrombolytic therapy is done using tissue plasminogen activator and should only be used for life-, or limb-, or organ-threatening thrombosis.

  1. Thrombosis in newborn infants.

    PubMed

    Bacciedoni, Viviana; Attie, Myriam; Donato, Hugo

    2016-04-01

    The incidence of thrombosis is higher among newborn infants than in any other stage of pediatric development. This fact is the consequence of labile characteristics of the neonatal hemostatic system, in addition to exposure to multiple risk factors and the wide use of vascular catheters. Venous thromboses, which mainly affect the limbs, the right atrium and renal veins, are more frequently seen than arterial thromboses. A stroke may be caused by the occlusion of the arterial flow entering the brain or by occlusion of its venous drainage system. Purpura fulminans is a very severe condition that should be treated as a medical emergency, and is secondary to severe protein C deficiency or, less frequently, protein S or antithrombin deficiency. Most thrombotic events should be managed with antithrombotic therapy, which is done with unfractionated and/or low molecular weight heparins. Purpura fulminans requires protein C replacement and/or fresh frozen plasma infusion. Thrombolytic therapy is done using tissue plasminogen activator and should only be used for life-, or limb-, or organ-threatening thrombosis. PMID:27079395

  2. Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

    NASA Astrophysics Data System (ADS)

    Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

    2016-05-01

    Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

  3. Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study.

    PubMed

    Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K; Akar, Furuzan; Ulak, Güner

    2016-05-15

    Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, C=O/lipid, CH3/lipid, CH2/lipid, PO(-)2/lipid, COO(-)/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

  4. Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study.

    PubMed

    Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K; Akar, Furuzan; Ulak, Güner

    2016-05-15

    Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, C=O/lipid, CH3/lipid, CH2/lipid, PO(-)2/lipid, COO(-)/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development. PMID:26952787

  5. A prospective strategy to restore the tissue damage in malaria infection: Approach with chitosan-trypolyphosphate conjugated nanochloroquine in Swiss mice.

    PubMed

    Tripathy, Satyajit; Das, Sabyasachi; Dash, Sandeep Kumar; Mahapatra, Santanu Kar; Chattopadhyay, Sourav; Majumdar, Subrata; Roy, Somenath

    2014-08-15

    Accumulating evidence indicates that wide range of polymer based nanoconjugated drug have the ability to overcome the microbial infection. The present study was to evaluate the effects of nanoconjugated chloroquine (Nch) against Plasmodium berghei NK65 (P. berghei) infection on selective makers of oxidative damage, antioxidant status, pro-inflammatory and anti-inflammatory cytokines in liver and spleen. P. berghei infected Swiss mice were treated with Nch (250mg/kg bw for 15 days) compared with chloroquine. The stress markers, pro-inflammatory cytokines were increased significantly (P<0.05) and the anti-oxidant enzymes level, redox ratio (GSH/GSSG), anti-inflammatory markers were decreased significantly (P<0.05) in liver and spleen of infected mice compared with uninfected mice. Chloroquine and Nch effectively decreased the stress markers, pro-inflammatory cytokines, as well as, increased antioxidants level in liver and spleen of the infected mice. Moreover, the favorable effect Nch is better than the chloroquine defending the tissue damage during malarial infection. These findings suggested that the potential use and prospective role of Nch than only chloroquine against P. berghei induced pathology as well as oxidative damage in liver and spleen.

  6. (-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus.

    PubMed

    Jia, Ning; Han, Kun; Kong, Jing-Jing; Zhang, Xiu-Mei; Sha, Sha; Ren, Gui-Ru; Cao, Yun-Peng

    2013-08-01

    Alzheimer's disease (AD) fundamentally represents a metabolic disease associated with brain insulin resistance. TNF-α/c-Jun N-terminal kinase (JNK) signaling plays a central role in serine phosphorylation of insulin receptor substrate-1 (IRS-1). (-)-Epigallocatechin-3-gallate (EGCG), a potent antioxidant, has been verified to attenuate peripheral insulin resistance by reducing IRS-1 signaling blockage. This study aimed to investigate the effects and possible mechanisms of EGCG on central IRS-1 signaling in vivo. APP/PS1 mice were treated with EGCG, and spatial memory was assessed by the Morris water maze test. Levels of soluble and insoluble Aβ42 in the hippocampus were determined by ELISA. The activation of NF-α/JNK and IRS signaling was detected by immunohistochemistry and Western blot analysis. Our results showed that EGCG ameliorated the impaired learning and memory in APP/PS1 mice. Notably, we found a significant reduction of IRS-1pS636 level accompanied with decreased Aβ42 levels in the hippocampus of 13-month-old female APP/PS1 mice after treatment with EGCG (2 or 6 mg/kg/day) for 4 weeks. Furthermore, EGCG treatment inhibited TNF-α/JNK signaling and increased the phosphorylation of Akt and glycogen synthase kinase-3β in the hippocampus of APP/PS1 mice. In conclusion, our study provides evidence that long-term consumption of EGCG may alleviate AD-related cognitive deficits by effectively attenuating central insulin resistance.

  7. Newborn Screening and the Obstetrician

    PubMed Central

    Dolan, Siobhan M

    2012-01-01

    Newborn screening is the largest genetic screening program in the United States, with approximately four million infants screened yearly. It has been available and in continuous development for over 50 years. Each state manages, funds, and maintains its own individual program, which encompasses newborn screening as well as the diagnosis and coordination of care for affected infants and children. The ideal disorder for screening is one in which newborn intervention prevents later disabilities or death for infants who may appear normal at birth. There are 31 core conditions that are currently recommended for incorporation into state screening programs. To obtain a sample, several drops of blood are collected from the newborn’s heel and applied to filter paper. Although testing for core disorders is fairly standardized, more extensive screening varies by state and the rigorous evaluation of new disorders for inclusion in state screening panels is ongoing. As genomic medicine becomes more accessible, screening newborns for chronic diseases that may affect their long-term health will need to be addressed, as well the use of the residual blood spots for research. Obstetric providers should, at some time during pregnancy, review the basic process of newborn screening with parents to prepare them for this testing in the neonatal period. This information can be reviewed as it best suits incorporation in an individual’s practice; verbal discussion and the distribution of written materials with resources for further information is encouraged. PMID:22996108

  8. The ethics of newborn resuscitation.

    PubMed

    Mercurio, Mark R

    2009-12-01

    It is widely believed in neonatology and obstetrics that there are situations in which it is inappropriate to attempt newborn resuscitation, and other times when newborn resuscitation is obligatory despite parental refusal. In each case, an ethical justification for the decision needs to be identified. This essay is intended to provide guidance in deciding when resuscitation should be attempted, and in identifying ethical considerations that should be taken into account. It specifically addresses the issue of extreme prematurity, including an analysis of current recommendations, the data, relevant rights of patient and parents, and a discussion of the relative merits of withholding resuscitation vs providing resuscitation and possibly withdrawing intensive care later. In addition to extreme prematurity, the considerations presented are also relevant to a wider spectrum of newborn problems, including Trisomy 13, Trisomy 18, and severe congenital anomalies.

  9. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    PubMed

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans. PMID:27096360

  10. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    PubMed

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  11. How Are Newborn Screening Tests Done?

    MedlinePlus

    ... Clinical Trials Resources and Publications How are newborn screening tests done? Skip sharing on social media links Share this: Page Content Newborn screening typically consists of a blood test and a ...

  12. Vitamin K deficiency bleeding of the newborn

    MedlinePlus

    Vitamin K deficiency bleeding of the newborn (VKDB) is a bleeding disorder in babies. It most often ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often ...

  13. Can Newborns Discriminate between Their Own Cry and the Cry of Another Newborn Infant?

    ERIC Educational Resources Information Center

    Dondi, Marco; Simion, Francesca; Caltran, Giovanna

    1999-01-01

    Two experiments tested whether newborns could discriminate their own and another newborn's cry. Results indicated that awake newborns expressed facial distress more frequently and longer to another newborn's cry than to their own. Sucking decreased significantly between pretest phase and first minute of another infant's cry. Asleep infants'…

  14. Gliomatosis cerebri in a newborn.

    PubMed

    Barth, P G; Stam, F C; Hack, W; Delemarre-van de Waal, H A

    1988-11-01

    A newborn is reported with diffuse gliomatosis involving the cerebral hemispheres, the brainstem and the cerebellum. The presenting signs were paucity of spontaneous movements except for multifocal clonic seizures, absent response to sensory stimuli and optic atrophy. A CT scan suggested agyria. The child expired on the seventh day. Autopsy disclosed diffuse gliomatosis affecting both cerebral hemispheres, the brainstem and the whole cerebellum, but excluding the spinal cord. Neuronal loss was unusually severe in all the affected areas. The genitals were ambiguous, an association not explained by the cerebral pathology. The karyotype was 46XY (male pseudohermaphroditism). This is probably the first reported instance of gliomatosis cerebri in a newborn.

  15. Craniocerebral gunshot injury in newborn

    PubMed Central

    Dabdoub, CB; Serra, SM; da Cunha, AH; Silveira, EN; Lopez, A; Azevedo-Filho, H

    2012-01-01

    Head wounds caused by firearms in newborns are an under-studied phenomenon in Latin America due to either the low frequency of such events or inadequate documentation. Nonetheless, a progressive increase is noted, with different frequencies reported for different geographic areas. We present the case of a 28-day-old newborn who suffered traumatic brain injury from a gunshot wound stemming from urban violence. This is one of the youngest patients reported with this type of head trauma in the literature. PMID:24960794

  16. Acute inhibition of central c-Jun N-terminal kinase restores hypothalamic insulin signalling and alleviates glucose intolerance in diabetic mice.

    PubMed

    Benzler, J; Ganjam, G K; Legler, K; Stöhr, S; Krüger, M; Steger, J; Tups, A

    2013-05-01

    The hypothalamus has been identified as a main insulin target tissue for regulating normal body weight and glucose metabolism. Recent observations suggest that c-Jun-N-terminal kinase (JNK)-signalling plays a crucial role in the development of obesity and insulin resistance because neuronal JNK-1 ablation in the mouse prevented high-fat diet-induced obesity (DIO) and increased energy expenditure, as well as insulin sensitivity. In the present study, we investigated whether central JNK inhibition is associated with sensitisation of hypothalamic insulin signalling in mice fed a high-fat diet for 3 weeks and in leptin-deficient mice. We determined whether i.c.v. injection of a pharmacological JNK-inhibitor (SP600125) improved impaired glucose homeostasis. By immunohistochemistry, we first observed that JNK activity was increased in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH) in both mouse models, relative to normoglycaemic controls. This suggests that up-regulation of JNK in these regions is associated with glucose intolerance and obesity, independent of leptin levels. Acute i.c.v. injection of SP600125 ameliorated glucose tolerance within 30 min in both leptin-deficient and DIO mice. Given the acute nature of i.c.v. injections, these effects cannot be attributed to changes in food intake or energy balance. In a hypothalamic cell line, and in the ARC and VMH of leptin-deficient mice, JNK inhibition by SP600125 consistently improved impaired insulin signalling. This was determined by a reduction of phospho-insulin receptor substrate-1 [IRS-1(Ser612)] protein in a hypothalamic cell line and a decline in the number of pIRS-1(Ser612) immunoreactive cells in the ARC and VMH. Serine 612 phosphorylation of IRS-1 is assumed to negatively regulate insulin signalling. In leptin-deficient mice, in both nuclei, central inhibition of JNK increased the number of cells immunoreactive for phospho-Akt (Ser473) and phospho-GSK-3β (Ser9), which are important

  17. Newborns' Head Orientation toward Sounds Within Hemifields.

    ERIC Educational Resources Information Center

    Fenwick, Kimberley; And Others

    This experiment examined the accuracy with which newborn infants orient their heads toward a sound positioned off midline within hemifields. The study also evaluated newborns' ability to update the angle of their head turn to match a change in localization of an ongoing sound. Alert newborns were held in a supine position and presented a sound at…

  18. Newborn Screening: Characteristics of State Programs.

    ERIC Educational Resources Information Center

    Toiv, Helene F.; Austin, Janina; Gardiner, Emily Gamble; Tynan, Ann; Hill, Ariel; Milne, Kevin; Moon, Cindy; Lawes, Susan

    Each year, state newborn screening programs test 4 million newborns for disorders that require early detection and treatment to prevent serious illness or death. The U.S. General Accounting Office (GAO) was asked to provide Congress with information on variations among state newborn screening programs. Based on surveys of such programs in all 50…

  19. NICHD Research Initiative in Newborn Screening

    ERIC Educational Resources Information Center

    Alexander, Duane; Hanson, James W.

    2006-01-01

    Recent changes in genetics research have created new opportunities to improve the scope and quality of newborn screening services. Changes in newborn screening should be supported and directed by an organized program of research. The NICHD Research Initiative in Newborn Screening includes the development of systematic methods to identify…

  20. 42 CFR 435.117 - Newborn children.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Newborn children. 435.117 Section 435.117 Public..., Children Under 8, and Newborn Children § 435.117 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  1. 42 CFR 435.117 - Newborn children.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Newborn children. 435.117 Section 435.117 Public..., Children Under 8, and Newborn Children § 435.117 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  2. 42 CFR 435.117 - Newborn children.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Newborn children. 435.117 Section 435.117 Public..., AND AMERICAN SAMOA Mandatory Coverage Mandatory Coverage of Pregnant Women, Children Under 19, and Newborn Children § 435.117 Newborn children. (a) The agency must provide Medicaid eligibility to a...

  3. 42 CFR 435.117 - Newborn children.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Newborn children. 435.117 Section 435.117 Public..., AND AMERICAN SAMOA Mandatory Coverage Mandatory Coverage of Pregnant Women, Children Under 19, and Newborn Children § 435.117 Newborn children. (a) The agency must provide Medicaid eligibility to a...

  4. 42 CFR 435.117 - Newborn children.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Newborn children. 435.117 Section 435.117 Public..., Children Under 8, and Newborn Children § 435.117 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  5. Natural restoration

    SciTech Connect

    Kamlet, K.S.

    1993-02-01

    After a company pays millions of dollars to clean up contaminated site, its liability may not be over. It may have to spend tens of millions more to restore damaged natural resources under an oft-overlooked Superfund program. Examples of liability are cited in this report from the Exxon Valdez oil spill and a pcb leak which contaminated a harbor.

  6. Newborn Infants Orient to Sounds.

    ERIC Educational Resources Information Center

    Muir, Darwin; Field, Jeffrey

    1979-01-01

    In two experiments, the majority of 21 newborn infants who were maintained in an alert state consistently turned their heads toward a continuous sound source presented 90 degrees from midline. For most infants, this orientation response was rather slow, taking median latencies of 2.5 seconds to begin and 5.5 seconds to end. (JMB)

  7. Hemolytic disease of the newborn

    MedlinePlus

    ... is a blood disorder in a fetus or newborn infant. In some infants, it can be life threatening. Normally, red blood cells last for about 120 days in the body. In this disorder, red blood cells in the blood are destroyed earlier than normal.

  8. Pilot Programs in Newborn Screening

    ERIC Educational Resources Information Center

    Pass, Kenneth; Green, Nancy S.; Lorey, Fred; Sherwin, John; Comeau, Anne Marie

    2006-01-01

    The term "pilot study" has been used over the years to describe the evaluation of the many elements involved in deciding whether a proposed condition should be added to a newborn screening (NBS) panel, and until recently, was unilaterally used to describe the evaluation of the assay to be used before the condition was officially adopted by a state…

  9. Newborns' Mooney-Face Perception

    ERIC Educational Resources Information Center

    Leo, Irene; Simion, Francesca

    2009-01-01

    The aim of this study is to investigate whether newborns detect a face on the basis of a Gestalt representation based on first-order relational information (i.e., the basic arrangement of face features) by using Mooney stimuli. The incomplete 2-tone Mooney stimuli were used because they preclude focusing both on the local features (i.e., the fine…

  10. Protecting Your Newborn. Instructor's Guide.

    ERIC Educational Resources Information Center

    Bhatia, Esha

    This guide is intended to help instructors educate new and expectant parents about safely transporting their newborn babies. The guide accompanies a 27-minute video, developed by the National Traffic Safety Administration, which introduces some of the key safety issues that new parents should consider during their baby's first 6 months of life.…

  11. The Amelioration of Hepatic Steatosis by Thyroid Hormone Receptor Agonists Is Insufficient to Restore Insulin Sensitivity in Ob/Ob Mice

    PubMed Central

    Cimini, Stephanie L.; Webb, Paul; Phillips, Kevin J.

    2015-01-01

    Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered. PMID:25849936

  12. Restoring Ancestral Language, Restoring Identity.

    ERIC Educational Resources Information Center

    Bannon, Kay T.

    1999-01-01

    Describes the Cherokee Language Renewal Program that was designed to help Cherokee elementary school children learn to function in the dominant culture without sacrificing their own cultural heritage. Explains how the program got started, and reports on how it helps restore a cultural identify to a people who are at risk of losing their identity.…

  13. Restoration Process

    NASA Technical Reports Server (NTRS)

    1979-01-01

    In the accompanying photos, a laboratory technician is restoring the once-obliterated serial number of a revolver. The four-photo sequence shows the gradual progression from total invisibility to clear readability. The technician is using a new process developed in an applications engineering project conducted by NASA's Lewis Research Center in conjunction with Chicago State University. Serial numbers and other markings are frequently eliminated from metal objects to prevent tracing ownership of guns, motor vehicles, bicycles, cameras, appliances and jewelry. To restore obliterated numbers, crime laboratory investigators most often employ a chemical etching technique. It is effective, but it may cause metal corrosion and it requires extensive preparatory grinding and polishing. The NASA-Chicago State process is advantageous because it can be applied without variation to any kind of metal, it needs no preparatory work and number recovery can be accomplished without corrosive chemicals; the liquid used is water.

  14. Spherical nucleic acid targeting microRNA-99b enhances intestinal MFG-E8 gene expression and restores enterocyte migration in lipopolysaccharide-induced septic mice.

    PubMed

    Wang, Xiao; Hao, Liangliang; Bu, Heng-Fu; Scott, Alexander W; Tian, Ke; Liu, Fangyi; De Plaen, Isabelle G; Liu, Yulan; Mirkin, Chad A; Tan, Xiao-Di

    2016-01-01

    Milk fat globule-EGF factor 8 (MFG-E8) maintains the intestinal homeostasis by enhancing enterocyte migration and attenuating inflammation. We previously reported that sepsis is associated with down-regulation of intestinal MFG-E8 and impairment of enterocyte migration. Here, we showed that impairment of intestinal epithelial cell migration occurred in lipopolysaccharide (LPS)-induced septic mice. Treatment of RAW264.7 cells (a murine macrophage-like cell line) with LPS increased expression of miR-99b, a microRNA that is predicted to target mouse MFG-E8 3'UTR. Using a luciferase assay, we showed that miR-99b mimic suppressed the activity of a reporter containing MFG-E8 3'UTR. This suggests the role of miR-99b in inhibition of MFG-E8 gene expression. In addition, we developed an anti-miR99b spherical nucleic acid nanoparticle conjugate (SNA-NC(anti-miR99b)). Treatment of both naïve and LPS-challenged cells with SNA-NC(anti-miR99b) enhanced MFG-E8 expression in the cells. Administration of SNA-NC(anti-miR99b) rescued intestinal MFG-E8 expression in LPS-induced septic mice and attenuated LPS inhibitory effects on intestinal epithelial cell migration along the crypt-villus axis. Collectively, our study suggests that LPS represses MFG-E8 expression and disrupts enterocyte migration via a miR-99b dependent mechanism. Furthermore, this work shows that SNA-NC(anti-miR99b) is a novel nanoparticle-conjugate capable of rescuing MFG-E8 gene expression and maintaining intestinal epithelial homeostasis in sepsis. PMID:27538453

  15. Spherical nucleic acid targeting microRNA-99b enhances intestinal MFG-E8 gene expression and restores enterocyte migration in lipopolysaccharide-induced septic mice

    PubMed Central

    Wang, Xiao; Hao, Liangliang; Bu, Heng-Fu; Scott, Alexander W.; Tian, Ke; Liu, Fangyi; De Plaen, Isabelle G.; Liu, Yulan; Mirkin, Chad A.; Tan, Xiao-Di

    2016-01-01

    Milk fat globule-EGF factor 8 (MFG-E8) maintains the intestinal homeostasis by enhancing enterocyte migration and attenuating inflammation. We previously reported that sepsis is associated with down-regulation of intestinal MFG-E8 and impairment of enterocyte migration. Here, we showed that impairment of intestinal epithelial cell migration occurred in lipopolysaccharide (LPS)-induced septic mice. Treatment of RAW264.7 cells (a murine macrophage-like cell line) with LPS increased expression of miR-99b, a microRNA that is predicted to target mouse MFG-E8 3′UTR. Using a luciferase assay, we showed that miR-99b mimic suppressed the activity of a reporter containing MFG-E8 3′UTR. This suggests the role of miR-99b in inhibition of MFG-E8 gene expression. In addition, we developed an anti-miR99b spherical nucleic acid nanoparticle conjugate (SNA-NCanti-miR99b). Treatment of both naïve and LPS-challenged cells with SNA-NCanti-miR99b enhanced MFG-E8 expression in the cells. Administration of SNA-NCanti-miR99b rescued intestinal MFG-E8 expression in LPS-induced septic mice and attenuated LPS inhibitory effects on intestinal epithelial cell migration along the crypt-villus axis. Collectively, our study suggests that LPS represses MFG-E8 expression and disrupts enterocyte migration via a miR-99b dependent mechanism. Furthermore, this work shows that SNA-NCanti-miR99b is a novel nanoparticle-conjugate capable of rescuing MFG-E8 gene expression and maintaining intestinal epithelial homeostasis in sepsis. PMID:27538453

  16. [THE COMPARATIVE CHARACTERISTIC OF KAOLIN-ACTIVATED THROMBOELASTOGRAPHY IN HEALTHY NEWBORNS AND NEWBORNS WITH HEART AILMENTS].

    PubMed

    Leonov, N P; Karas'kov, A M; Litasova, E E; Strunin, O V; Karmadonova, N A; Akopov, G D; Vishegorodtseva, L I

    2016-02-01

    The study was carried out to diferentiate reference values for kaolin-activated thromboelastography in newborns with congenital heart disease. The study included two groups ofpatients. The first one consisted of 62 newborns with congenital heart disease and the second one consisted of 35 healthy newborns. The results of kaolin-activated thromboelastography implemented in groups are evaluated as condition of normal coagulation. The valuable diferences of homeostasis system in healthy newborns and newborns with congenital heart disease (without severe concomitant pathology) are not established. They have similar indicators of kaolin-activated thromboelastography. The derived results can be applied as standards in full-term newborns with congenital heart disease. PMID:27455561

  17. Congenital epulis of the newborn.

    PubMed

    Kumar, R Mahesh; Bavle, Radhika M; Umashankar, D N; Sharma, Rashi

    2015-01-01

    Congenital epulis, a benign tumor of the oral cavity, is an extremely rare condition in newborn. It may lead to mechanical obstruction, therefore resulting in respiratory distress and difficulty in feeding. Addressing the problem may need a multidisciplinary team approach at the time of birth. Antenatal ultrasonography and perinatal magnetic resonance imaging are an adjunct to treatment planning. Prenatal diagnosis remains difficult as the findings are nonspecific due to the late development of the tumor. Surgical excision is, therefore, the treatment of choice. Our report discusses this condition and the treatment thereafter on a newborn, with an epulis originating from the upper alveolar ridge discovered at birth. Histological examination confirmed the diagnosis of large polygonal granular cells. The mass was excised under general anesthesia, and the outcome was good after surgery allowing regular feeds on the second postoperative day. PMID:26980979

  18. Congenital epulis of the newborn

    PubMed Central

    Kumar, R Mahesh; Bavle, Radhika M; Umashankar, DN; Sharma, Rashi

    2015-01-01

    Congenital epulis, a benign tumor of the oral cavity, is an extremely rare condition in newborn. It may lead to mechanical obstruction, therefore resulting in respiratory distress and difficulty in feeding. Addressing the problem may need a multidisciplinary team approach at the time of birth. Antenatal ultrasonography and perinatal magnetic resonance imaging are an adjunct to treatment planning. Prenatal diagnosis remains difficult as the findings are nonspecific due to the late development of the tumor. Surgical excision is, therefore, the treatment of choice. Our report discusses this condition and the treatment thereafter on a newborn, with an epulis originating from the upper alveolar ridge discovered at birth. Histological examination confirmed the diagnosis of large polygonal granular cells. The mass was excised under general anesthesia, and the outcome was good after surgery allowing regular feeds on the second postoperative day. PMID:26980979

  19. Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.

    PubMed

    Schmouth, J-F; Banks, K G; Mathelier, A; Gregory-Evans, C Y; Castellarin, M; Holt, R A; Gregory-Evans, K; Wasserman, W W; Simpson, E M

    2012-04-01

    Nr2e1 encodes a stem cell fate determinant of the mouse forebrain and retina. Abnormal regulation of this gene results in retinal, brain, and behavioral abnormalities in mice. However, little is known about the functionality of human NR2E1. We investigated this functionality using a novel knock-in humanized-mouse strain carrying a single-copy bacterial artificial chromosome (BAC). We also documented, for the first time, the expression pattern of the human BAC, using an NR2E1-lacZ reporter strain. Unexpectedly, cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. These results correlated with an absence of NR2E1-lacZ reporter expression in the dorsal pallium of embryos and proliferative cells of adult brains. Surprisingly, retinal histology and electroretinograms demonstrated complete correction of the retina-null phenotype. These results correlated with appropriate expression of the NR2E1-lacZ reporter in developing and adult retina. We conclude that the human BAC contained all the elements allowing correction of the mouse-null phenotype in the retina, while missing key regulatory regions important for proper spatiotemporal brain expression. This is the first time a separation of regulatory mechanisms governing NR2E1 has been demonstrated. Furthermore, candidate genomic regions controlling expression in proliferating cells during neurogenesis were identified.

  20. Moringa oleifera Lam. leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet.

    PubMed

    Das, Nilanjan; Sikder, Kunal; Ghosh, Santinath; Fromenty, Bernard; Dey, Sanjit

    2012-06-01

    Consumption of high-fat diet (HFD) induces nonalcoholic fatty liver disease (NAFLD) and may lead to multiple complications affecting human health. In the present study, effect of Moringa oleifera leaf extract (MoLE) in alleviating HFD induced liver injury in mice has been reported. Liver histology and serum activity of hepatic marker enzymes i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) have been studied. Lipid peroxidation (LPO), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) were also estimated using liver homogenate. Results of the study suggested that MoLE treatment protected HFD-induced liver damage as indicated by histopathology and liver enzyme activity compared to only-HFD fed group (P < 0.05). Interestingly, early signs of HFD-induced fatty liver were also alleviated by MoLE. Moreover, significant increase in endogenous antioxidant parameters and lower lipid peroxidation were found in liver of all MoLE treated groups. Results of the study indicated that MoLE has both preventive as also curative hepatoprotective activity. PMID:22734251

  1. Moringa oleifera Lam. leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet.

    PubMed

    Das, Nilanjan; Sikder, Kunal; Ghosh, Santinath; Fromenty, Bernard; Dey, Sanjit

    2012-06-01

    Consumption of high-fat diet (HFD) induces nonalcoholic fatty liver disease (NAFLD) and may lead to multiple complications affecting human health. In the present study, effect of Moringa oleifera leaf extract (MoLE) in alleviating HFD induced liver injury in mice has been reported. Liver histology and serum activity of hepatic marker enzymes i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) have been studied. Lipid peroxidation (LPO), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) were also estimated using liver homogenate. Results of the study suggested that MoLE treatment protected HFD-induced liver damage as indicated by histopathology and liver enzyme activity compared to only-HFD fed group (P < 0.05). Interestingly, early signs of HFD-induced fatty liver were also alleviated by MoLE. Moreover, significant increase in endogenous antioxidant parameters and lower lipid peroxidation were found in liver of all MoLE treated groups. Results of the study indicated that MoLE has both preventive as also curative hepatoprotective activity.

  2. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice

    PubMed Central

    Xu, Jian; Kurup, Pradeep; Baguley, Tyler D.; Foscue, Ethan; Ellman, Jonathan A.; Nairn, Angus C.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we characterize the regulation of BDNF expression by STEP61, utilizing PCP-treated cortical culture and PCP-treated mice. PCP-treated cortical neurons showed both an increase in STEP61 levels and a decrease in BDNF expression. The reduction in BDNF expression was prevented by STEP61 knockdown or use of the STEP inhibitor, TC-2153. The PCP-induced increase in STEP61 expression was associated with the inhibition of CREB-dependent BDNF transcription. Similarly, both genetic and pharmacologic inhibition of STEP prevented the PCP-induced reduction in BDNF expression in vivo and normalized PCP-induced hyperlocomotion and cognitive deficits. These results suggest a mechanism by which STEP61 regulates BDNF expression, with implications for cognitive functioning in CNS disorders. PMID:26450419

  3. Newborn Screening for Biliary Atresia

    PubMed Central

    Wang, Kasper S.

    2016-01-01

    Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child’s native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States. PMID:26620065

  4. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

    PubMed

    Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

    2013-02-15

    During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

  5. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

    PubMed

    Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

    2013-02-15

    During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states. PMID:23233542

  6. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.; Wentz, Anna E.; André d'Avignon, D.

    2013-01-01

    During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1+/− mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states. PMID:23233542

  7. Hepatitis B virus HBx protein localized to the nucleus restores HBx-deficient virus replication in HepG2 cells and in vivo in hydrodynamically-injected mice

    SciTech Connect

    Keasler, Victor V.; Hodgson, Amanda J.; Madden, Charles R.; Slagle, Betty L.

    2009-07-20

    Identifying the requirements for the regulatory HBx protein in hepatitis B virus (HBV) replication is an important goal. A plasmid-based HBV replication assay was used to evaluate whether HBx subcellular localization influences its ability to promote virus replication, as measured by real time PCR quantitation of viral capsid-associated DNA. HBx targeted to the nucleus by a nuclear localization signal (NLS-HBx) was able to restore HBx-deficient HBV replication, while HBx containing a nuclear export signal (NES-HBx) was not. Both NLS-HBx and NES-HBx were expressed at similar levels (by immunoprecipitation and Western blotting), and proper localization of the signal sequence-tagged proteins was confirmed by deconvolution microscopy using HBx, NLS-HBx, and NES-HBx proteins fused to GFP. Importantly, these findings were confirmed in vivo by hydrodynamic injection into mice. Our results demonstrate that in these HBV replication assays, at least one function of HBx requires its localization to the nucleus.

  8. The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice

    PubMed Central

    Rossi, F; Bellini, G; Torella, M; Tortora, C; Manzo, I; Giordano, C; Guida, F; Luongo, L; Papale, F; Rosso, F; Nobili, B; Maione, S

    2014-01-01

    Background and Purpose Osteoporosis is a condition characterized by a decrease in bone density, which decreases its strength and results in fragile bones. The endocannabinoid/endovanilloid system has been shown to be involved in the regulation of skeletal remodelling. The aim of this study was to investigate the possible modulation of bone mass mediated by the transient receptor potential vanilloid type 1 channel (TRPV1) in vivo and in vitro. Experimental Approach A multidisciplinary approach, including biomolecular, biochemical and morphological analysis, was used to investigate the involvement of TRPV1 in changes in bone density in vivo and osteoclast activity in vitro, in wild-type and Trpv1−/− mice, that had undergone ovariectomy or had a sham operation. Key Results Genetic deletion of Trpv1 as well as pharmacological inhibition/desensitization of TRPV1 signalling dramatically reduced the osteoclast activity in vitro and prevented the ovariectomy-induced bone loss in vivo, whereas the expression of cannabinoid type 2 (CB2) receptors was increased. Conclusions and Implications These findings highlight the pivotal role TRPV1 channels play in bone resorption and suggest a possible cross-talk between TRPV1 and CB2 receptors. Based on these results, hybrid compounds acting on both TRPV1 and CB2 receptors in an opposite manner could provide a future pharmacological tool for the treatment of diseases associated with disturbances in the bone remodelling process. Linked Articles This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-10 PMID:24308803

  9. Hospital stay for healthy term newborn infants.

    PubMed

    Benitz, William E

    2015-05-01

    The hospital stay of the mother and her healthy term newborn infant should be long enough to allow identification of problems and to ensure that the mother is sufficiently recovered and prepared to care for herself and her newborn at home. The length of stay should be based on the unique characteristics of each mother-infant dyad, including the health of the mother, the health and stability of the newborn, the ability and confidence of the mother to care for herself and her newborn, the adequacy of support systems at home, and access to appropriate follow-up care in a medical home. Input from the mother and her obstetrical care provider should be considered before a decision to discharge a newborn is made, and all efforts should be made to keep a mother and her newborn together to ensure simultaneous discharge.

  10. Cystic Fibrosis Diagnosis and Newborn Screening.

    PubMed

    Rosenfeld, Margaret; Sontag, Marci K; Ren, Clement L

    2016-08-01

    The diagnosis of cystic fibrosis (CF) has evolved over the past decade as newborn screening has become universal in the United States and elsewhere. The heterogeneity of phenotypes associated with CF transmembrane conductance regulator (CFTR) dysfunction and mutations in the CFTR gene has become clearer, ranging from classic pancreatic-insufficient CF to manifestations in only 1 organ system to indeterminate diagnoses identified by newborn screening. The tools available for diagnosis have also expanded. This article reviews the newest diagnostic criteria for CF, newborn screening, prenatal screening and diagnosis, and indeterminate diagnoses in newborn-screened infants and symptomatic adults. PMID:27469178

  11. Newborn and Four-Week Retest on a Normative Population Using the Brazelton Newborn Assessment Procedure.

    ERIC Educational Resources Information Center

    Horowitz, Frances Degan; And Others

    A survey of assessment procedures of the newborn and of the infant during the first month of life was conducted; the survey indicated that there were instruments for evaluating the newborn and for evaluating the four-week-old infant, but there was no single procedure which included an evaluation of both the newborn and the four-week-old infant.…

  12. State of the World's Newborns: A Report from Saving Newborn Lives.

    ERIC Educational Resources Information Center

    Costello, Anthony; Francis, Victoria; Byrne, Ali; Puddephatt, Claire

    There has been little change in newborn mortality in the past 20 years, even through proven, cost-effective solutions exist to save many of these young lives. This report reviews the most recent data on the newborn, revealing the alarming poor health and quality of health care for mothers and newborns in virtually all impoverished countries. The…

  13. Newborn Screening (NBS): Answers to Frequently Asked Questions

    MedlinePlus

    ... FREE ADDITONAL NEWBORN SCREENING PACKETS What is Newborn Screening (NBS)? NBS is a system that helps tell ... the condition. What are the benefits of Newborn Screening? Early detection of disorders and conditions detectable through ...

  14. Isolated penile torsion in newborns

    PubMed Central

    Eroglu, Egemen; Gundogdu, Gokhan

    2015-01-01

    Introduction: We reported on the incidence of isolated penile torsion among our healthy children and our approach to this anomaly. Methods: Between 2011 and 2014, newborn babies with penile torsion were classified according to the angle of torsion. Surgical correction (penile degloving and reattachment for moderate cases and dorsal dartos flap technique in case of resistance) after 6 months was advised to the babies with rotations more than 45°. Results: Among 1000 newborn babies, 200 isolated penile torsions were found, and among these, 43 had torsions more than 45°, and 4 of these had angles greater than 90°. The mean angle of the rotations was found 30.45° (median: 20°). In total, 8 children with 60° torsions were previously circumcised. Surgery was performed on 19 patients, with a mean patient age of 12 ± 2 months. Of these 19, 13 babies were corrected with degloving and reattachment. This technique was not enough on the remaining 6 patients; therefore, derotational dorsal dartos flap was added to correct the torsion. After a mean of 15.6 ± 9.8 months, residual penile rotation, less than 15°, was found only in 2 children. Conclusion: The incidence of isolated penile torsion is 20% in newborns. However, rotation more than 45° angles are seen in 4.3% of male babies. Correction is not necessary in mild degrees, and penile degloving with reattachment is enough in most cases. If the initial correction is insufficient, dorsal dartos flap rotation is easy and effective. Prior circumcision neither disturbs the operative procedure nor affects the outcomes. PMID:26600889

  15. Update: newborn screening for endocrinopathies.

    PubMed

    Pass, Kenneth A; Neto, Eurico Carmago

    2009-12-01

    Congenital hypothyroidism and congenital adrenal hyperplasia are included in many newborn screening (NBS) panels worldwide and in all state-sponsored programs in the United States. Both conditions meet the fundamental prerequisites for NBS: high incidence in the population; biomarkers in the dried blood specimen that are easily detected; and, effective therapies to lessen, if not prevent, the sequelae of late or no treatment. In this review, the history of NBS is discussed for these 2 conditions. The technologies and protocols used in their detection, and related subjects such as genetics, and treatment and outcomes, are also discussed. PMID:19944295

  16. Newborn screening in southeastern Europe.

    PubMed

    Groselj, Urh; Tansek, Mojca Zerjav; Smon, Andraz; Angelkova, Natalija; Anton, Dana; Baric, Ivo; Djordjevic, Maja; Grimci, Lindita; Ivanova, Maria; Kadam, Adil; Kotori, Vjosa Mulliqi; Maksic, Hajrija; Marginean, Oana; Margineanu, Otilia; Milijanovic, Olivera; Moldovanu, Florentina; Muresan, Mariana; Murko, Simona; Nanu, Michaela; Lampret, Barbka Repic; Samardzic, Mira; Sarnavka, Vladimir; Savov, Aleksei; Stojiljkovic, Maja; Suzic, Biljana; Tincheva, Radka; Tahirovic, Husref; Toromanovic, Alma; Usurelu, Natalia; Battelino, Tadej

    2014-01-01

    The aim of our study was to assess the current state of newborn screening (NBS) in the region of southeastern Europe, as an example of a developing region, focusing also on future plans. Responses were obtained from 11 countries. Phenylketonuria screening was not introduced in four of 11 countries, while congenital hypothyroidism screening was not introduced in three of them; extended NBS programs were non-existent. The primary challenges were identified. Implementation of NBS to developing countries worldwide should be considered as a priority. PMID:25174966

  17. Iodine supplementation in the newborn.

    PubMed

    Ghirri, Paolo; Lunardi, Sara; Boldrini, Antonio

    2014-01-01

    Iodine deficiency can be defined as the world's greatest single cause of preventable brain damage. Fetal and neonatal hypothyroidism, caused by iodine deficiency can be prevented prior to conception and then during pregnancy and lactation when an adequate iodine supplementation is ensured. Extremely low birth weight preterm babies risk having a negative iodine balance status in the first weeks of life, exacerbating the hypothyroxinaemia of the prematurity. It is important to ensure that these babies are provided with an adequate iodine intake from the first days of life. Mothers and newborns should avoid environmental iodine excess during pregnancy or lactation.

  18. Newborn intraabdominal cystic lymphatic malformations.

    PubMed

    Lin, J I; Fisher, J; Caty, M G

    2000-08-01

    Cystic lymphatic malformations are rare causes of abdominal masses in the newborn. Also known as mesenteric, omental, or retroperitoneal cysts, they can present in a variety of ways including, intestinal obstruction, volvulus, nonspecific abdominal pain, intracystic hemorrhage, or as an asymptomatic abdominal mass. Abdominal ultrasound scan provides a definitive diagnosis in most suspected cases. Complete resection is possible in most patients except those with extensive retroperitoneal involvement. Recurrence is unusual when complete resection is accomplished. Because most case series with complete data suggest that these entities are lymphatic malformations, the authors suggest the more specific term, cystic lymphatic malformations, be used to describe these lesions.

  19. Hypoxic ventilatory response in Tac1-/- neonatal mice following exposure to opioids.

    PubMed

    Berner, J; Shvarev, Y; Zimmer, A; Wickstrom, R

    2012-12-01

    Morphine is the dominating analgetic drug used in neonates, but opioid-induced respiratory depression limits its therapeutic use. In this study, we examined acute morphine effects on respiration during intermittent hypoxia in newborn Tac1 gene knockout mice (Tac1-/-) lacking substance P and neurokinin A. In vivo, plethysmography revealed a blunted hypoxic ventilatory response (HVR) in Tac1-/- mice. Morphine (10 mg/kg) depressed the HVR in wild-type animals through an effect on respiratory frequency, whereas it increased tidal volumes in Tac1-/- during hypoxia, resulting in increased minute ventilation. Apneas were reduced during the first hypoxic episode in both morphine-exposed groups, but were restored subsequently in Tac1-/- mice. Morphine did not affect ventilation or apnea prevalence during baseline conditions. In vitro, morphine (50 nM) had no impact on anoxic response of brain stem preparations of either strain. In contrast, it suppressed the inspiratory rhythm during normoxia and potentiated development of posthypoxic neuronal arrest, especially in Tac1-/-. Thus this phenotype has a higher sensitivity to the depressive effects of morphine on inspiratory rhythm generation, but morphine does not modify the reactivity to oxygen deprivation. In conclusion, although Tac1-/- mice are similar to wild-type animals during normoxia, they differed by displaying a reversed pattern with an improved HVR during intermittent hypoxia both in vivo and in vitro. These data suggest that opioids and the substance P-ergic system interact in the HVR, and that reducing the activity in the tachykinin system may alter the respiratory effects of opioid treatment in newborns.

  20. Newborn Screening for Fragile X Syndrome

    ERIC Educational Resources Information Center

    Bailey, Donald B., Jr.

    2004-01-01

    Newborn screening for fragile X syndrome (FXS) is technically possible, and in the relatively near future accurate and inexpensive screening technologies are likely to be available. When that happens, will America's public health system adopt newborn screening for fragile X syndrome? This article addresses this issue by first placing screening for…

  1. 42 CFR 436.124 - Newborn children.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Newborn children. 436.124 Section 436.124 Public... the Categorically Needy § 436.124 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  2. 42 CFR 436.124 - Newborn children.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Newborn children. 436.124 Section 436.124 Public... the Categorically Needy § 436.124 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  3. 42 CFR 436.124 - Newborn children.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Newborn children. 436.124 Section 436.124 Public... the Categorically Needy § 436.124 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  4. 42 CFR 436.124 - Newborn children.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Newborn children. 436.124 Section 436.124 Public... the Categorically Needy § 436.124 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  5. 42 CFR 436.124 - Newborn children.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Newborn children. 436.124 Section 436.124 Public... the Categorically Needy § 436.124 Newborn children. (a) The agency must provide Medicaid eligibility to a child born to a woman who has applied for, has been determined eligible and is...

  6. [Premature newborn: a case presentation].

    PubMed

    Pastor Rodríguez, Jesús David; Pastor Bravo, María Del Mar; López García, Visitación; Cotes Teruel, María Isabel; Mellado, Jesús Eulogio; Cárceles, José Jara

    2010-01-01

    A case is presented of a premature newborn of 27 weeks gestation and weighing 420 grams who was delivered as a result of a maternal pre-eclampsia and retarded intra-uterine growth. During the 125 days of hospitalisation, an individual care plan based on the Virginia Henderson model was devised and applied to both the child and her parents using NANDA diagnostics, interventions according to the NIC classification, and the expected results according to the NOC classification. The Marjory Gordon functional patterns were used for the initial assessment. By applying the pre-term newborn (PTNB) plan, all their needs were provided and were modified throughout the hospital stay, with new needs that were added to the established ones. These required a continuous assessment with the subsequent adapting of the care plan. Likewise, the care required by the parents varied from the initial grief due to the possible loss of their child to learning the alarm signs and the home care that their child would need. The child was finally discharged weighing 2900 grams and with normal neurological and psychomotor development, although with a lower weight appropriate to her age. Currently, at 2 years old, the child has a normal neurological and psychomotor development, but with weight and size lower than the P(3) percentile. She requires speech therapy treatment due to paralysis of the right vocal cord.

  7. Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

    PubMed

    De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

    2014-01-01

    Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

  8. Newborn cord care practices in Haiti.

    PubMed

    Walsh, Susan; Norr, Kathleen; Sankar, Girija; Sipsma, Heather

    2015-10-01

    Newborn cord infections commonly lead to neonatal sepsis and death, particularly in low-resource countries where newborns may receive unhygienic cord care. Topical application of chlorhexidine to the newborn's cord has been shown to prevent infection. Such benefits may be particularly important in Haiti. We explored current cord care practices by conducting a qualitative study using five focus groups among key community stakeholders (mothers of newborns/children under age two years, pregnant women, traditional birth attendants, community health workers, traditional healers) in Petit-Goâve, Haiti. Data collection was guided by the Health Belief Model. Results suggest community stakeholders recognise that infants are susceptible to cord infection and that cord infection is a serious threat to newborns. Long-held traditional cord care practices are potential barriers to adopting a new cord care intervention. However, all groups acknowledged that traditional practices could be harmful to the newborn while expressing a willingness to adopt practices that would protect the newborn. Results demonstrate potential acceptability for altering traditional cord care practices among neonatal caretakers in Haiti. An informational campaign designed to educate local health workers and new mothers to eliminate unhygienic cord applications while promoting chlorhexidine application may be a strong approach for preventing neonatal cord infections.

  9. EPIDERMOLYSIS BULLOSA IN THE NEWBORN.

    PubMed

    2016-01-01

    We present the case of a new-born baby girl who was delivered at term to a young primigravida mother. The pregnancy was booked late and had no antenatal medical or surgical complications. The baby was born vaginally and had a normal initial examination. However after three hours of birth the baby started to develop skin blisters after minor trauma/friction. The baby was seen by a Dermatologist who diagnosed the condition to be Epidermolysis Bullosa. This hereditary condition is extremely rare, and even rarer is such an early presentation in a neonate. It is caused by mutations in the genes coding for the structural proteins of the skin and is characterized by development of vesicles and blisters. The mainstay of management is supportive care. The baby was discharged on request of the parents on second day of life without any complications. PMID:27323591

  10. Producing Newborn Synchronous Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  11. Newborn screening for congenital hypothyroidism.

    PubMed

    Büyükgebiz, Atilla

    2006-11-01

    Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets. PMID:17220056

  12. Preventing herpes simplex virus in the newborn.

    PubMed

    Pinninti, Swetha G; Kimberlin, David W

    2014-12-01

    Genital herpes simplex virus (HSV) infections are very common worldwide. Approximately 22% of pregnant women are infected genitally with HSV, and most of them are unaware of this. The most devastating consequence of maternal genital herpes is HSV disease in the newborn. Although neonatal HSV infections remain uncommon, due to the significant morbidity and mortality associated with the infection, HSV infection in the newborn is often considered in the differential diagnosis of ill neonates. This review summarizes the epidemiology and management of neonatal HSV infections and discusses strategies to prevent HSV infection in the newborn.

  13. General characteristics and viral susceptibility of a newborn pig kidney (NPK) continuous culture.

    PubMed

    Ferrari, M; Losio, M N; Gualandi, G L; Di Lernia, R; Manocchio, I

    1989-10-01

    We have developed a fibroblastic-like continuous culture of newborn pig kidney (NPK). The current cell line was serially passaged 160 times and appeared to be well suited for production and assay of a number of viruses affecting pigs, such as pig parvovirus, pseudorabies and transmissible gastroenteritis. The cell line appeared aneuploid, with a modal chromosome number of 36 and induced tumors, classified as fibrosarcoma, in athymic mice. PMID:2555655

  14. Zika Linked to Deformed Limbs in Newborns

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160324.html Zika Linked to Deformed Limbs in Newborns Cause isn' ... 2016 TUESDAY, Aug. 9, 2016 (HealthDay News) -- The Zika virus has already been linked to serious birth ...

  15. Crying in Newborn and Young Infants.

    ERIC Educational Resources Information Center

    Michelsson, Katarina

    1988-01-01

    Discusses the reasons that newborns and young infants cry, the communicative effect and perception of crying, crying in sick and healthy infants, the sound spectograph, and crying for the use of clinical diagnostics. (RJC)

  16. Warmth is Analgesic in Healthy Newborns

    PubMed Central

    Lang, Colleen W.; Porges, Stephen W.

    2014-01-01

    This study identifies a behavioral and nonpharmacologic means of preventing and reducing newborn pain. Our objective was to determine whether warmth is analgesic in newborn infants undergoing vaccination—a routine painful hospital procedure. We used a prospective randomized controlled trial of 47 healthy full-term newborn infants. Infants were randomized into one of three conditions prior to vaccination: warmth exposure, pacifier suckling, or sucrose taste. Crying, grimacing, and heart rate differences were analyzed between groups before, during, and after vaccination as outcome measures. Warmer infants cried significantly less than sucrose taste or pacifier suckling after vaccination. Heart rate patterns reflected this analgesia. Core temperature did not differ between study groups. Providing natural warmth to newborn infants during a painful procedure decreases the crying and grimacing on par with the “gold” standard treatments of sucrose or pacifier. PMID:22424877

  17. The interfacility transport of critically ill newborns

    PubMed Central

    Whyte, Hilary EA; Jefferies, Ann L

    2015-01-01

    The practice of paediatric/neonatal interfacility transport continues to expand. Transport teams have evolved into mobile intensive care units capable of delivering state-of-the-art critical care during paediatric and neonatal transport. While outcomes are best for high-risk infants born in a tertiary care setting, high-risk mothers often cannot be safely transferred. Their newborns may then have to be transported to a higher level of care following birth. The present statement reviews issues relating to transport of the critically ill newborn population, including personnel, team competencies, skills, equipment, systems and processes. Six recommendations for improving interfacility transport of critically ill newborns are highlighted, emphasizing the importance of regionalized care for newborns. PMID:26175564

  18. The interfacility transport of critically ill newborns.

    PubMed

    Whyte, Hilary Ea; Jefferies, Ann L

    2015-01-01

    The practice of paediatric/neonatal interfacility transport continues to expand. Transport teams have evolved into mobile intensive care units capable of delivering state-of-the-art critical care during paediatric and neonatal transport. While outcomes are best for high-risk infants born in a tertiary care setting, high-risk mothers often cannot be safely transferred. Their newborns may then have to be transported to a higher level of care following birth. The present statement reviews issues relating to transport of the critically ill newborn population, including personnel, team competencies, skills, equipment, systems and processes. Six recommendations for improving interfacility transport of critically ill newborns are highlighted, emphasizing the importance of regionalized care for newborns.

  19. National Newborn Screening and Genetics Resource Center

    MedlinePlus

    ... GENERAL INFORMATION Conditions Screened by US Programs General Resources Genetics Birth Defects Hearing Screening FOR PROFESSIONALS ACT Sheets(ACMG) General Resources Newborn Screening Genetics Birth Defects FOR FAMILIES FAQs ...

  20. Artificially reared mice exhibit anxiety-like behavior in adulthood.

    PubMed

    Yasuda, Hidemi; Harauma, Akiko; Kato, Maki; Ootomo, Yuki; Hatanaka, Erisa; Moriguchi, Toru

    2016-07-29

    It is important to establish experimental animal techniques that are applicable to the newborn and infant phases for nutrition and pharmacological studies. Breeding technology using the artificial suckling method without breast milk is very effective for the study of newborn nutrition. Using this method, we separated newborn mice from dams within 48 h of birth and provided them with artificial milk. We evaluated mouse anxiety levels after early postnatal maternal separation. Artificially reared mice were subjected to elevated plus-maze tests to assess emotional behavior at 9 weeks of age. Artificially reared mice showed a significantly lower frequency of entries and dipping into the open arms of the maze compared with dam-reared mice. This result indicates that the anxiety level of artificially reared mice was higher than that of dam-reared mice. Moreover, the concentration of monoamines in the brain was determined after the behavioral experiment. The hippocampal norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in the artificially reared mice were significantly higher than those of the dam-reared mice. These results suggest that maternal-offspring interactions are extremely important for the emotional development of newborn infants during the lactation period. In future studies, it is necessary to consider the environmental factors and conditions that minimize the influence of artificial rearing on emotional behavior.

  1. Artificially reared mice exhibit anxiety-like behavior in adulthood

    PubMed Central

    Yasuda, Hidemi; Harauma, Akiko; Kato, Maki; Ootomo, Yuki; Hatanaka, Erisa; Moriguchi, Toru

    2016-01-01

    It is important to establish experimental animal techniques that are applicable to the newborn and infant phases for nutrition and pharmacological studies. Breeding technology using the artificial suckling method without breast milk is very effective for the study of newborn nutrition. Using this method, we separated newborn mice from dams within 48 h of birth and provided them with artificial milk. We evaluated mouse anxiety levels after early postnatal maternal separation. Artificially reared mice were subjected to elevated plus-maze tests to assess emotional behavior at 9 weeks of age. Artificially reared mice showed a significantly lower frequency of entries and dipping into the open arms of the maze compared with dam-reared mice. This result indicates that the anxiety level of artificially reared mice was higher than that of dam-reared mice. Moreover, the concentration of monoamines in the brain was determined after the behavioral experiment. The hippocampal norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels in the artificially reared mice were significantly higher than those of the dam-reared mice. These results suggest that maternal-offspring interactions are extremely important for the emotional development of newborn infants during the lactation period. In future studies, it is necessary to consider the environmental factors and conditions that minimize the influence of artificial rearing on emotional behavior. PMID:26948536

  2. Development of Newborn and Infant Vaccines

    PubMed Central

    Sanchez-Schmitz, Guzman; Levy, Ofer

    2014-01-01

    Vaccines for early-life immunization are a crucial biomedical intervention to reduce global morbidity and mortality, yet their developmental path has been largely ad hoc, empiric, and inconsistent. Immune responses of human newborns and infants are distinct and cannot be predicted from those of human adults or animal models. Therefore, understanding and modeling age-specific human immune responses will be vital to the rational design and development of safe and effective vaccines for newborns and infants. PMID:21734174

  3. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

    PubMed Central

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss; Wiese, Maria; Lundsager, Mia; Buschard, Karsten Stig; Hansen, Axel Kornerup; Frøkiær, Hanne

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice. PMID:26783537

  4. Newborn screening for Krabbe's disease.

    PubMed

    Orsini, Joseph J; Saavedra-Matiz, Carlos A; Gelb, Michael H; Caggana, Michele

    2016-11-01

    Live newborn screening for Krabbe's disease (KD) was initiated in New York on August 7, 2006, and started in Missouri in August, 2012. As of August 7, 2015, nearly 2.5 million infants had been screened, and 443 (0.018%) infants had been referred for followup clinical evaluation; only five infants had been determined to have KD. As of August, 2015, the combined incidence of infantile KD in New York and Missouri is ∼1 per 500,000; however, patients who develop later-onset forms of KD may still emerge. This Review provides an overview of the processes used to develop the screening and followup algorithms. It also includes updated results from screening and discussion of observations, lessons learned, and suggested areas for improvement that will reduce referral rates and the number of infants defined as at risk for later-onset forms of KD. Although current treatment options for infants with early-infantile Krabbe's disease are not curative, over time treatment options should improve; in the meantime, it is essential to evaluate the lessons learned and to ensure that screening is completed in the best possible manner until these improvements can be realized. © 2016 Wiley Periodicals, Inc. PMID:27638592

  5. Inflammatory cytokines in newborn infants.

    PubMed Central

    Sarandakou, A; Giannaki, G; Malamitsi-Puchner, A; Rizos, D; Hourdaki, E; Protonotariou, E; Phocas, I

    1998-01-01

    Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes. PMID:9883964

  6. Inflammatory cytokines in newborn infants.

    PubMed

    Sarandakou, A; Giannaki, G; Malamitsi-Puchner, A; Rizos, D; Hourdaki, E; Protonotariou, E; Phocas, I

    1998-01-01

    Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

  7. Behavioral fever in newborn rabbits

    NASA Technical Reports Server (NTRS)

    Satinoff, E.; Mcewen, G. N., Jr.; Williams, B. A.

    1976-01-01

    New Zealand white rabbit pups aged 12 to 72 hr were divided into three groups and given an intraperitoneal injection of Pseudomonas polysaccharide, a saline vehicle alone, and no treatment, respectively. The animals injected with pyrogen and maintained at an ambient temperature of 32 C for 2 hr did not develop fever. When placed in a thermally graded alleyway, the animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline. Further stay at selected positions for 5 min caused a considerable increase in the rectal temperature of the pyrogen-injected pups but not that of controls. The results support the hypothesis that newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen if the opportunity for thermoregulatory behavior is present. No fever develops if the pups must rely solely on internal thermoregulatory mechanisms. The behavioral system for producing a fever is mature at birth, but an adequate system of internal reflexes does not appear to develop for some days.

  8. The Clinical Aspects of Newborn Screening: Importance of Newborn Screening Follow-Up

    ERIC Educational Resources Information Center

    James, Philip M.; Levy, Harvey L.

    2006-01-01

    The aim of newborn screening is to identify presymptomatic healthy infants that will develop significant metabolic or endocrine derangements if left undiagnosed and untreated. The goal of ultimately reducing or eliminating irreversible sequelae is reached by maximizing test sensitivity of the primary newborn screening that measures specific…

  9. Restoration technology branch

    USGS Publications Warehouse

    ,

    2007-01-01

    The mission of Leetown Science Center (LSC), Restoration Technology Branch (RTB) is to conduct research needed to restore or protect the chemical, physical and biological integrity of desirable aquatic systems.

  10. [Lung ultrasound in the newborn].

    PubMed

    Yousef, N

    2016-03-01

    Lung ultrasound (LU) is becoming a bedside point-of-care technique in critical care and emergency medicine as it is performed and immediately interpreted by the clinician. LU is quick, easy, relatively inexpensive, and provides accurate diagnostic information when compared with conventional lung imaging methods, such as CT scans and chest radiographs, with the additional advantage of being non-irradiating, adapted to bedside use, and easily repeatable with no side effects for the patient. LU is easy to learn, does not require sophisticated ultrasound machines or settings, and shows low intra- and interobserver variability when a standardized approach is used. A comprehensive and standardized ultrasound semiology has been described and validated in both adults and children. In summary, LU allows for quick easy recognition of a normally aerated lung in contrast to an interstitial or alveolar pattern. Recognition of these patterns may be even easier in neonates due to their small size and the absence of obesity and heavy musculature. Specific LU findings have been described for some types of neonatal lung injury, such as neonatal respiratory distress syndrome, transient tachypnea of the neonate, meconium aspiration syndrome, and neonatal pneumonia. In the newborn, LU has proved its usefulness in predicting the need for hospital admission and/or intubation based on simple LU patterns. A recently proposed LU score, adapted for the neonate, correlates well with oxygenation status, independently of gestational age and underlying respiratory condition. The score reliably predicts the need for surfactant treatment in preterm babies less than 34 weeks gestation treated with nasal CPAP from birth. LU is a promising tool with numerous potential applications that warrant future studies. However, like every technique, LU has its limitations and should not completely replace standard radiography. LU can nevertheless largely reduce exposure to ionizing radiation by limiting the

  11. Linking restoration ecology with coastal dune restoration

    NASA Astrophysics Data System (ADS)

    Lithgow, D.; Martínez, M. L.; Gallego-Fernández, J. B.; Hesp, P. A.; Flores, P.; Gachuz, S.; Rodríguez-Revelo, N.; Jiménez-Orocio, O.; Mendoza-González, G.; Álvarez-Molina, L. L.

    2013-10-01

    Restoration and preservation of coastal dunes is urgently needed because of the increasingly rapid loss and degradation of these ecosystems because of many human activities. These activities alter natural processes and coastal dynamics, eliminate topographic variability, fragment, degrade or eliminate habitats, reduce diversity and threaten endemic species. The actions of coastal dune restoration that are already taking place span contrasting activities that range from revegetating and stabilizing the mobile substrate, to removing plant cover and increasing substrate mobility. Our goal was to review how the relative progress of the actions of coastal dune restoration has been assessed, according to the ecosystem attributes outlined by the Society of Ecological Restoration: namely, integrity, health and sustainability and that are derived from the ecological theory of succession. We reviewed the peer reviewed literature published since 1988 that is listed in the ISI Web of Science journals as well as additional references, such as key books. We exclusively focused on large coastal dune systems (such as transgressive and parabolic dunefields) located on natural or seminatural coasts. We found 150 articles that included "coastal dune", "restoration" and "revegetation" in areas such as title, keywords and abstract. From these, 67 dealt specifically with coastal dune restoration. Most of the studies were performed in the USA, The Netherlands and South Africa, during the last two decades. Restoration success has been assessed directly and indirectly by measuring one or a few ecosystem variables. Some ecosystem attributes have been monitored more frequently (ecosystem integrity) than others (ecosystem health and sustainability). Finally, it is important to consider that ecological succession is a desirable approach in restoration actions. Natural dynamics and disturbances should be considered as part of the restored system, to improve ecosystem integrity, health and

  12. Common respiratory conditions of the newborn

    PubMed Central

    Gallacher, David J.; Hart, Kylie

    2016-01-01

    Key points Respiratory distress is a common presenting feature among newborn infants. Prompt investigation to ascertain the underlying diagnosis and appropriate subsequent management is important to improve outcomes. Many of the underlying causes of respiratory distress in a newborn are unique to this age group. A chest radiograph is crucial to assist in diagnosis of an underlying cause. Educational aims To inform readers of the common respiratory problems encountered in neonatology and the evidence-based management of these conditions. To enable readers to develop a framework for diagnosis of an infant with respiratory distress. The first hours and days of life are of crucial importance for the newborn infant as the infant adapts to the extra-uterine environment. The newborn infant is vulnerable to a range of respiratory diseases, many unique to this period of early life as the developing fluid-filled fetal lungs adapt to the extrauterine environment. The clinical signs of respiratory distress are important to recognise and further investigate, to identify the underlying cause. The epidemiology, diagnostic features and management of common neonatal respiratory conditions are covered in this review article aimed at all healthcare professionals who come into contact with newborn infants. PMID:27064402

  13. Ending preventable newborn deaths in a generation.

    PubMed

    Akseer, Nadia; Lawn, Joy E; Keenan, William; Konstantopoulos, Andreas; Cooper, Peter; Ismail, Zulkifli; Thacker, Naveen; Cabral, Sergio; Bhutta, Zulfiqar A

    2015-10-01

    The end of the Millennium Development Goal (MDG) era was marked in 2015, and while maternal and child mortality have been halved, MGD 4 and MDG 5 are off-track at the global level. Reductions in neonatal death rates (age <1 month) lag behind those for post-neonates (age 1-59 months), and stillbirth rates (omitted from the MDGs) have been virtually unchanged. Hence, almost half of under-five deaths are newborns, yet about 80% of these are preventable using cost-effective interventions. The Every Newborn Action Plan has been endorsed by the World Health Assembly and ratified by many stakeholders and donors to reduce neonatal deaths and stillbirths to 10 per 1000 births by 2035. The plan provides an evidence-based framework for scaling up of essential interventions across the continuum of care with the potential to prevent the deaths of approximately three million newborns, mothers, and stillbirths every year. Two million stillbirths and newborns could be saved by care at birth and care of small and sick newborns, giving a triple return on investment at this key time. Commitment, investment, and intentional leadership from global and national stakeholders, including all healthcare professionals, can make these ambitious goals attainable.

  14. Disorders of mineral metabolism in the newborn.

    PubMed

    Tuchman, Shamir

    2014-01-01

    Disorders of calcium and phosphorus homeostasis present both acute and chronic clinical consequences for newborns. The etiologies responsible range from iatrogenic, idiopathic, and inherited metabolic abnormalities. Maintenance of physiologically normal serum calcium and phosphorus requires complex interactions between the kidneys, gastrointestinal tract, and bone. Calciotropic hormones such as vitamin D and parathyroid hormone, as well as hormones controlling phosphorus homeostasis, such as fibroblast growth factor-23 (FGF-23), are essential in controlling these interactions. In newborns, calcium and phosphorus balance must necessarily be positive in order to provide the requisite building blocks for growth and maturation. Renal tubular handling of these minerals is a key control point in regulating the overall body balance in calcium and phosphorus. Adaptive changes in renal calcium and phosphorus reabsorption in newborns explain how a net positive total body balance of these minerals is achieved. Monogenetic disorders leading to abnormal renal handling of calcium and/or phosphorus have immediate clinical consequences in terms of complications associated with high or low levels of these minerals. Perhaps more importantly, chronic abnormalities of calcium and/or phosphorus, without treatment, may have serious consequences for growth and development of the growing skeleton. This article serves to review calcium and phosphorus regulation in the human body, describe differences in handling of these minerals by the newborn, and review the conditions, both acquired and congenital, that may present with abnormalities in calcium and/or phosphorus in the newborn period. PMID:25088267

  15. Ending preventable newborn deaths in a generation.

    PubMed

    Akseer, Nadia; Lawn, Joy E; Keenan, William; Konstantopoulos, Andreas; Cooper, Peter; Ismail, Zulkifli; Thacker, Naveen; Cabral, Sergio; Bhutta, Zulfiqar A

    2015-10-01

    The end of the Millennium Development Goal (MDG) era was marked in 2015, and while maternal and child mortality have been halved, MGD 4 and MDG 5 are off-track at the global level. Reductions in neonatal death rates (age <1 month) lag behind those for post-neonates (age 1-59 months), and stillbirth rates (omitted from the MDGs) have been virtually unchanged. Hence, almost half of under-five deaths are newborns, yet about 80% of these are preventable using cost-effective interventions. The Every Newborn Action Plan has been endorsed by the World Health Assembly and ratified by many stakeholders and donors to reduce neonatal deaths and stillbirths to 10 per 1000 births by 2035. The plan provides an evidence-based framework for scaling up of essential interventions across the continuum of care with the potential to prevent the deaths of approximately three million newborns, mothers, and stillbirths every year. Two million stillbirths and newborns could be saved by care at birth and care of small and sick newborns, giving a triple return on investment at this key time. Commitment, investment, and intentional leadership from global and national stakeholders, including all healthcare professionals, can make these ambitious goals attainable. PMID:26433505

  16. Newborn Analgesia Mediated by Oxytocin during Delivery

    PubMed Central

    Mazzuca, Michel; Minlebaev, Marat; Shakirzyanova, Anastasia; Tyzio, Roman; Taccola, Giuliano; Janackova, Sona; Gataullina, Svetlana; Ben-Ari, Yehezkel; Giniatullin, Rashid; Khazipov, Rustem

    2011-01-01

    The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth. PMID:21519396

  17. Applying Genomic Analysis to Newborn Screening

    PubMed Central

    Solomon, B.D.; Pineda-Alvarez, D.E.; Bear, K.A.; Mullikin, J.C.; Evans, J.P.

    2012-01-01

    Large-scale genomic analysis such as whole-exome and whole-genome sequencing is becoming increasingly prevalent in the research arena. Clinically, many potential uses of this technology have been proposed. One such application is the extension or augmentation of newborn screening. In order to explore this application, we examined data from 3 children with normal newborn screens who underwent whole-exome sequencing as part of research participation. We analyzed sequence information for 151 selected genes associated with conditions ascertained by newborn screening. We compared findings with publicly available databases and results from over 500 individuals who underwent whole-exome sequencing at the same facility. Novel variants were confirmed through bidirectional dideoxynucleotide sequencing. High-density microarrays (Illumina Omni1-Quad) were also performed to detect potential copy number variations affecting these genes. We detected an average of 87 genetic variants per individual. After excluding artifacts, 96% of the variants were found to be reported in public databases and have no evidence of pathogenicity. No variants were identified that would predict disease in the tested individuals, which is in accordance with their normal newborn screens. However, we identified 6 previously reported variants and 2 novel variants that, according to published literature, could result in affected offspring if the reproductive partner were also a mutation carrier; other specific molecular findings highlight additional means by which genomic testing could augment newborn screening. PMID:23112750

  18. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

    PubMed

    Panfoli, Isabella; Ravera, Silvia; Podestà, Marina; Cossu, Claudia; Santucci, Laura; Bartolucci, Martina; Bruschi, Maurizio; Calzia, Daniela; Sabatini, Federica; Bruschettini, Matteo; Ramenghi, Luca Antonio; Romantsik, Olga; Marimpietri, Danilo; Pistoia, Vito; Ghiggeri, Gianmarco; Frassoni, Francesco; Candiano, Giovanni

    2016-04-01

    Exosomes are secreted nanovesicles that are able to transfer RNA and proteins to target cells. The emerging role of mesenchymal stem cell (MSC) exosomes as promoters of aerobic ATP synthesis restoration in damaged cells, prompted us to assess whether they contain an extramitochondrial aerobic respiration capacity. Exosomes were isolated from culture medium of human MSCs from umbilical cord of ≥37-wk-old newborns or between 28- to 30-wk-old newborns (i.e.,term or preterm infants). Characterization of samples was conducted by cytofluorometry. Oxidative phosphorylation capacity was assessed by Western blot analysis, oximetry, and luminometric and fluorometric analyses. MSC exosomes express functional respiratory complexes I, IV, and V, consuming oxygen. ATP synthesis was only detectable in exosomes from term newborns, suggestive of a specific mechanism that is not completed at an early gestational age. Activities are outward facing and comparable to those detected in mitochondria isolated from term MSCs. MSC exosomes display an unsuspected aerobic respiratory ability independent of whole mitochondria. This may be relevant for their ability to rescue cell bioenergetics. The differential oxidative metabolism of pretermvs.term exosomes sheds new light on the preterm newborn's clinical vulnerability. A reduced ability to repair damaged tissue and an increased capability to cope with anoxic environment for preterm infants can be envisaged.-Panfoli, I., Ravera, S., Podestà, M., Cossu, C., Santucci, L., Bartolucci, M., Bruschi, M., Calzia, D., Sabatini, F., Bruschettini, M., Ramenghi, L. A., Romantsik, O., Marimpietri, D., Pistoia, V., Ghiggeri, G., Frassoni, F., Candiano, G. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

  19. Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation.

    PubMed

    Fu, Qiuli; Vankelecom, Hugo

    2012-12-10

    In a recent study, we showed that the adult pituitary gland is capable of regenerating transgenically ablated growth hormone-producing (GH(+)) somatotropes. Here, we investigated whether the gland's regenerative capacity is more general and also applies to the other major hormonal cell type, the prolactin-producing (PRL(+)) lactotropes. We set up the transgenic PRLCre/inducible diphtheria toxin receptor (iDTR) mouse model, in which the PRL promoter drives expression of Cre that induces DTR in lactotropes. Injection of female mice with DT for different periods causes a gradual ablation of PRL(+) cells, reaching a maximum of 70% after 10-day DT treatment. During the following weeks, lactotropes progressively reappear achieving a 60% restoration after 6 weeks. The Sox2(+) stem/progenitor cell compartment displays a prompt reaction to the DT-triggered cell ablation injury, including expansion of the marginal-zone niche and coexpression of PRL, the latter only very rarely observed in control pituitary. Throughout the regeneration period (2-6 weeks), Sox2(+) as well as double Sox2(+)/PRL(+) cells continue to be more abundant than in control pituitary. In addition to this stem cell reaction, surviving or newborn lactotropes increase their proliferative activity, and bihormonal PRL(+)/GH(+) cells become detectable suggesting somatotrope-to-lactotrope transdifferentiation. In conclusion, the adult pituitary gland is capable of restoring lactotrope cells after destruction, further confirming its regenerative competence. Repair of lactotropes appears to be driven by a combination of mechanisms, including recruitment from stem cells, proliferation of lactotropes, and transdifferentiation of somatotropes.

  20. Neurotransmitter properties of the newborn human retina

    SciTech Connect

    Hollyfield, J.G.; Frederick, J.M.; Rayborn, M.E.

    1983-07-01

    Human retinal tissue from a newborn was examined autoradiographically for the presence of high-affinity uptake and localization of the following putative neurotransmitters: dopamine, glycine, GABA, aspartate, and glutamate. In addition, the dopamine content of this newborn retina was measured by high pressure liquid chromatography. Our study reveals that specific uptake mechanisms for /sup 3/H-glycine, /sup 3/H-dopamine, and /sup 3/H-GABA are present at birth. However, the number and distribution of cells labeled with each of these /sup 3/H-transmitters are not identical to those observed in adult human retinas. Furthermore, the amount of endogenous dopamine in the newborn retina is approximately 1/20 the adult level. Photoreceptor-specific uptake of /sup 3/H-glutamate and /sup 3/H-aspartate are not observed. These findings indicate that, while some neurotransmitter-specific properties are present at birth, significant maturation of neurotransmitter systems occurs postnatally.

  1. Oxidative Stress Related Diseases in Newborns

    PubMed Central

    Aykac, Kubra

    2016-01-01

    We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229

  2. Oxidative Stress Related Diseases in Newborns.

    PubMed

    Ozsurekci, Yasemin; Aykac, Kubra

    2016-01-01

    We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229

  3. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney

    PubMed Central

    Smith, Francine G.; Wade, Andrew W.; Lewis, Megan L.; Qi, Wei

    2012-01-01

    This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function. PMID:24281306

  4. Zika May Persist for Months in Newborns, Study Shows

    MedlinePlus

    ... news/fullstory_160594.html Zika May Persist for Months in Newborns, Study Shows Brazilian infant appeared outwardly ... cause damage in newborns for at least two months after birth. The report, published online Aug. 24 ...

  5. Newborn care practices in Pemba Island (Tanzania) and their implications for newborn health and survival.

    PubMed

    Thairu, Lucy; Pelto, Gretel

    2008-07-01

    Newborn mortality accounts for about one-third of deaths in children under five. Neglecting this problem may undermine the fourth Millennium Development Goal of reducing child mortality by two-thirds by 2015. This study was conducted in Tanzania, where an estimated 32/1000 infants die within the first 28 days. Our objective was to describe newborn care practices and their potential impact on newborn health. We interviewed two purposive samples of mothers from Pemba Island, a predominantly Muslim community of Arab-African ethnicity, and one of Tanzania's poorest. The first sample of mothers (n = 12) provided descriptive data; the second (n = 26) reported actual practice. We identified cultural beliefs and practices that promote early initiation of breastfeeding and bonding, including 'post-partum seclusion'. We also identified practices which are potentially harmful for newborn health, such as bathing newborns immediately after delivery, a practice motivated by concerns about 'ritual pollution', which may lead to newborn hypothermia and premature breast milk supplementation (e.g. with water and other fluids) which may expose newborns to pathogens. Some traditional practices to treat illness, such as exposing sick newborns to medicinal smoke from burning herbs, are also of concern. It is unclear whether the practice of massaging newborns with coconut oil is harmful or beneficial. Interventions to reduce neonatal mortality need to identify and address the cultural rationales that underlie negative practices, as well as reinforce and protect the beliefs that support positive practices. The results suggest the need to improve use of health services through improving health worker communication skills and social management of patients, as well as by lowering healthcare costs. PMID:18582353

  6. Newborn care practices in Pemba Island (Tanzania) and their implications for newborn health and survival.

    PubMed

    Thairu, Lucy; Pelto, Gretel

    2008-07-01

    Newborn mortality accounts for about one-third of deaths in children under five. Neglecting this problem may undermine the fourth Millennium Development Goal of reducing child mortality by two-thirds by 2015. This study was conducted in Tanzania, where an estimated 32/1000 infants die within the first 28 days. Our objective was to describe newborn care practices and their potential impact on newborn health. We interviewed two purposive samples of mothers from Pemba Island, a predominantly Muslim community of Arab-African ethnicity, and one of Tanzania's poorest. The first sample of mothers (n = 12) provided descriptive data; the second (n = 26) reported actual practice. We identified cultural beliefs and practices that promote early initiation of breastfeeding and bonding, including 'post-partum seclusion'. We also identified practices which are potentially harmful for newborn health, such as bathing newborns immediately after delivery, a practice motivated by concerns about 'ritual pollution', which may lead to newborn hypothermia and premature breast milk supplementation (e.g. with water and other fluids) which may expose newborns to pathogens. Some traditional practices to treat illness, such as exposing sick newborns to medicinal smoke from burning herbs, are also of concern. It is unclear whether the practice of massaging newborns with coconut oil is harmful or beneficial. Interventions to reduce neonatal mortality need to identify and address the cultural rationales that underlie negative practices, as well as reinforce and protect the beliefs that support positive practices. The results suggest the need to improve use of health services through improving health worker communication skills and social management of patients, as well as by lowering healthcare costs.

  7. Primary care role in expanded newborn screening

    PubMed Central

    Hayeems, Robin Z.; Miller, Fiona A.; Carroll, June C.; Little, Julian; Allanson, Judith; Bytautas, Jessica P.; Chakraborty, Pranesh; Wilson, Brenda J.

    2013-01-01

    Abstract Objective To examine the role of primary care providers in informing and supporting families who receive positive screening results. Design Cross-sectional survey. Setting Ontario. Participants Family physicians, pediatricians, and midwives involved in newborn care. Main outcome measures Beliefs, practices, and barriers related to providing information to families who receive positive screening results for their newborns. Results A total of 819 providers participated (adjusted response rate of 60.9%). Of the respondents, 67.4% to 81.0% agreed that it was their responsibility to provide care to families of newborns who received positive screening results, and 64.2% to 84.8% agreed they should provide brochures or engage in general discussions about the identified conditions. Of the pediatricians, 67.3% endorsed having detailed discussions with families, but only 24.1% of family physicians and 27.6% of midwives endorsed this practice. All provider groups reported less involvement in information provision than they believed they should have. This discrepancy was most evident for family physicians: most stated that they should provide brochures (64.2%) or engage in general discussions (73.5%), but only a minority did so (15.3% and 27.7%, respectively). Family physicians reported insufficient time (42.2%), compensation (52.2%), and training (72.3%) to play this role, and only a minority agreed they were up to date (18.5%) or confident (16.5%) regarding newborn screening. Conclusion Providers of primary newborn care see an information-provision role for themselves in caring for families who receive positive newborn screening results. Efforts to further define the scope of this role combined with efforts to mitigate existing barriers are warranted. PMID:23946032

  8. Reevaluation of the newborn thyroid dose from radioiodines

    SciTech Connect

    Hedrick, W.R.; Milavickas, L.R.

    1987-07-01

    The basis for the current thyroid absorbed dose estimates for radioiodines has been examined. The values for the newborn thyroid dose were found to underestimate the dose by a factor of 3. This underestimation of the dose was caused by the assumption that the biokinetic distribution of iodine is the same for the newborn and the adult. Increased thyroid uptake by the newborn requires that higher cumulated activities be incorporated into the dose determinations for the newborn.

  9. Factors Influencing Newborns' Preference for Faces with Eye Contact

    ERIC Educational Resources Information Center

    Farroni, Teresa; Menon, Enrica; Johnson, Mark H.

    2006-01-01

    We investigated newborns' sensitivity to the direction of gaze of another's face by using a preferential looking technique. This study extends earlier work on a preference for faces with direct gaze in newborns. In Experiment 1, we replicate the basic finding of Farroni and colleagues that newborns prefer to look at faces with direct gaze. In…

  10. Newborn Screening for Lysosomal Storage Disorders and Other Neuronopathic Conditions

    ERIC Educational Resources Information Center

    Matern, Dietrich; Oglesbee, Devin; Tortorelli, Silvia

    2013-01-01

    Newborn screening (NBS) is a public health program aimed at identifying treatable conditions in presymptomatic newborns to avoid premature mortality, morbidity, and disabilities. Currently, every newborn in the Unites States is screened for at least 29 conditions where evidence suggests that early detection is possible and beneficial. With new or…

  11. Differential Facial Responses to Four Basic Tastes in Newborns.

    ERIC Educational Resources Information Center

    Rosentstein, Diana; Oster, Harriet

    1988-01-01

    Investigated the distinctiveness and recognizability of taste-elicited facial expressions in 12 newborns two hours of age. Findings demonstrated that newborns differentiate sour and bitter from each other and from salty, and discriminate between sweet and nonsweet. Judges accurately identified newborns' responses to sucrose, but systematically…

  12. National Evaluation of US Newborn Screening System Components

    ERIC Educational Resources Information Center

    Therrell, Bradford L.; Hannon, W. Harry

    2006-01-01

    Newborn screening has existed as a state-based public health service since the early 1960s. Every state and most territorial jurisdictions have comprehensive newborn screening programs in place, but in the United States a national newborn screening policy does not exist. This results in different administrative infrastructures, screening…

  13. Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex.

    PubMed

    Telley, Ludovic; Govindan, Subashika; Prados, Julien; Stevant, Isabelle; Nef, Serge; Dermitzakis, Emmanouil; Dayer, Alexandre; Jabaudon, Denis

    2016-03-25

    During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high-temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mice, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence and pace of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a road map for the reverse engineering of specific classes of cortical neurons from undifferentiated cells. PMID:26940868

  14. Watershed Restoration Project

    SciTech Connect

    Julie Thompson; Betsy Macfarlan

    2007-09-27

    In 2003, the U.S. Department of Energy issued the Eastern Nevada Landscape Coalition (ENLC) funding to implement ecological restoration in Gleason Creek and Smith Valley Watersheds. This project was made possible by congressionally directed funding that was provided through the US Department of Energy, Energy Efficiency and Renewable Energy, Office of the Biomass Program. The Ely District Bureau of Land Management (Ely BLM) manages these watersheds and considers them priority areas within the Ely BLM district. These three entities collaborated to address the issues and concerns of Gleason Creek and Smith Valley and prepared a restoration plan to improve the watersheds’ ecological health and resiliency. The restoration process began with watershed-scale vegetation assessments and state and transition models to focus on restoration sites. Design and implementation of restoration treatments ensued and were completed in January 2007. This report describes the restoration process ENLC undertook from planning to implementation of two watersheds in semi-arid Eastern Nevada.

  15. Restoring the worn dentition.

    PubMed

    Ibsen, R L; Ouellet, D F

    1992-01-01

    Strong dental materials and dental porcelains are providing dentists with restorative opportunities that are more conservative because they require less destruction of healthy tooth structure and yield a more esthetic result. In cases of severe wear due to attrition, abrasion, and erosion, this process can be stopped, restoring the esthetics and function by using proper techniques and materials. The case report described in this article demonstrates the conservative restoration of severe wear due to attrition and erosion. Teeth were lengthened, wear was restored, and further wear was ceased by using a combination of bonded porcelain, a heat, light, and self-cure resin system, and a new glass-ionomer restorative material. The result was a strong, durable restoration (that required no anesthesia) with high esthetics.

  16. Iris pigment epithelial cysts in a newborn

    PubMed Central

    Zargar, Shabnam; Prendiville, Kevin John; Martinez, Eladio

    2016-01-01

    Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia. Methods: We describe a case of an abnormal red reflex seen on a newborn exam. Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2–3 mm dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months. Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia. PMID:27625966

  17. Nasogastric Tube Placement in Newborns Before Discharge.

    PubMed

    Alnemri, Abdulrahman M; Saeed, Anjum; Assiri, Asaad M

    2016-04-01

    The aim of this study was to assess the knowledge of medical staff (physicians) at different levels about insertion or placement of nasogastric tube (NGT) in a normal newborn before discharge. It was a survey-based, observational study conducted at King Khalid University Hospital. Atotal of 103 doctors were sent text message; among those 81 (78.6%) responded. Among the respondents, 27, 16, 11 and 27 were neonatologists, general physicians, obstetricians/ ENT/pediatric surgeons, and senior registrars neonatology (SRN), respectively. Majority of physicians, 57 (70.3%) rejected the idea of insertion of NGTin a normal newborn but in 24 (29.6%), answer was to insert NGTin all the newborns before discharge to check the patency of nasal cavities. Regarding the position, region of doctors and their response, majority from Center said ‘No’(not in favour of insertion) but from South, 17/18 (94.4%) said ‘Yes’(in favour of insertion). Regarding other specialties, majority of them showed rejection of this idea. In conclusion, most of the healthcare professionals, directly involved with neonatal care, rejected the idea of routine insertion of NGTin normal newborn examination before discharge; rather, some non-invasive technique could be opted.

  18. Unexpected behavioural consequences of preterm newborns' clothing

    PubMed Central

    Durier, Virginie; Henry, Séverine; Martin, Emmanuelle; Dollion, Nicolas; Hausberger, Martine; Sizun, Jacques

    2015-01-01

    Restrictions of preterm newborns' movements could have consequences ranging from stress enhancement to impairment of their motor development. Therefore, ability to freely express motor activities appears crucial for their behavioural and physiological development. Our aim was to evaluate behavioural issues of two types of clothing used in NICU. We observed 18 healthy 34–37 post-conception week-old preterm newborns, during resting periods, when they were undisturbed by any interventions. Newborns wore either light clothing (bodysuit and a light wrapping) or heavy clothing (pyjamas, cardigan and sleep-sack). The percentages of time each subject spent in different postures were compared between clothing situations. Arm and hand postures differed in relation to clothing: babies bent their arms more and held their hands nearer their heads when in bodysuits than when in sleepwear. Consequently, babies in bodysuits spent more time touching their body or their environment whereas the others generally were touching nothing. Self-touch is an important way to comfort one's self. Heavy clothing may impair self-soothing behaviours of preterm newborn babies that already lack other forms of contact. Results suggest that more attention should be paid to apparently routine and marginal decisions such as choice of clothes. PMID:25776252

  19. Perceptual Completion in Newborn Human Infants

    ERIC Educational Resources Information Center

    Valenza, Eloisa; Leo, Irene; Gava, Lucia; Simion, Francesca

    2006-01-01

    Despite decades of studies of human infants, a still open question concerns the role of visual experience in the development of the ability to perceive complete shapes over partial occlusion. Previous studies show that newborns fail to manifest this ability, either because they lack the visual experience required for perceptual completion or…

  20. Newborns' Face Recognition over Changes in Viewpoint

    ERIC Educational Resources Information Center

    Turati, Chiara; Bulf, Hermann; Simion, Francesca

    2008-01-01

    The study investigated the origins of the ability to recognize faces despite rotations in depth. Four experiments are reported that tested, using the habituation technique, whether 1-to-3-day-old infants are able to recognize the invariant aspects of a face over changes in viewpoint. Newborns failed to recognize facial perceptual invariances…

  1. Binocular Fixation in the Newborn Baby

    ERIC Educational Resources Information Center

    Slater, Alan M.; Findlay, John M.

    1975-01-01

    Three experiments are reported in which 15 babies were presented with visual stimuli which varied in shape and distance from the eye. Results indicated that the majority of subjects binocularly fixated all three stimuli and it was concluded that the newborn baby has the basic requirements for binocular vision. (Author/GO)

  2. Auditory-Oral Matching Behavior in Newborns

    ERIC Educational Resources Information Center

    Chen, Xin; Striano, Tricia; Rakoczy, Hannes

    2004-01-01

    Twenty-five newborn infants were tested for auditory-oral matching behavior when presented with the consonant sound /m/ and the vowel sound /a/--a precursor behavior to vocal imitation. Auditory-oral matching behavior by the infant was operationally defined as showing the mouth movement appropriate for producing the model sound just heard (mouth…

  3. Management of Newborn Infants with Phenylketonuria.

    ERIC Educational Resources Information Center

    Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

    The booklet covers the identification, diagnosis, and clinical treatment of newborns with Phenylketonuria (PKU), an inborn error of metabolism, which, if untreated, can lead to mental retardation. An initial section considers biochemical and genetic factors of PKU including a diagram of aromatic amino acid hydroxylation systems. Screening…

  4. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice.

    PubMed

    Coughlan, Karen S; Halang, Luise; Woods, Ina; Prehn, Jochen H M

    2016-09-01

    Transgenic transactivation response DNA-binding protein 43 (TDP-43) mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS); however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43(A315T) mice. Similar to our recent results in SOD1(G93A) mice, TDP-43(A315T) mice fed a standard pellet diet showed increased 5' adenosine monophosphate-activated protein kinase (AMPK) activation at postnatal day (P)80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43(A315T) mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC) at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43(A315T) model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS. PMID:27491077

  5. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice

    PubMed Central

    Coughlan, Karen S.; Halang, Luise; Woods, Ina

    2016-01-01

    ABSTRACT Transgenic transactivation response DNA-binding protein 43 (TDP-43) mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS); however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43A315T mice. Similar to our recent results in SOD1G93A mice, TDP-43A315T mice fed a standard pellet diet showed increased 5′ adenosine monophosphate-activated protein kinase (AMPK) activation at postnatal day (P)80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43A315T mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC) at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43A315T model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS. PMID:27491077

  6. Frequency of Spontaneous BOLD Signal Differences between Moderate and Late Preterm Newborns and Term Newborns.

    PubMed

    Wu, Xiushuang; Wei, Luqing; Wang, Nan; Hu, Zhangxue; Wang, Li; Ma, Juan; Feng, Shuai; Cai, Yue; Song, Xiaopeng; Shi, Yuan

    2016-10-01

    Little is known about the frequency features of spontaneous neural activity in the brains of moderate and late preterm (MLPT) newborns. We used resting-state functional magnetic resonance imaging (rs-fMRI) and the amplitude of low-frequency fluctuation (ALFF) method to investigate the frequency properties of spontaneous blood oxygen level-dependent (BOLD) signals in 26 MLPT and 35 term newborns. Two frequency bands, slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz), were analyzed. Our results showed widespread differences in ALFF between the two bands; differences occurred mainly in the primary sensory and motor cortices and to a lesser extent in association cortices and subcortical areas. Compared with term newborns, MLPT newborns showed significantly altered neural activity predominantly in the primary sensory and motor cortices and in the posterior cingulate gyrus/precuneus. In addition, a significant interaction between frequency bands and groups was observed in the primary somatosensory cortex. Intriguingly, these primary sensory and motor regions have been proven to be the major cortical hubs during the neonatal period. Our results revealed the frequency of spontaneous BOLD signal differences between MLPT and term newborns, which contribute to the understanding of regional development of spontaneous brain rhythms of MLPT newborns. PMID:27316633

  7. Frequency of Spontaneous BOLD Signal Differences between Moderate and Late Preterm Newborns and Term Newborns.

    PubMed

    Wu, Xiushuang; Wei, Luqing; Wang, Nan; Hu, Zhangxue; Wang, Li; Ma, Juan; Feng, Shuai; Cai, Yue; Song, Xiaopeng; Shi, Yuan

    2016-10-01

    Little is known about the frequency features of spontaneous neural activity in the brains of moderate and late preterm (MLPT) newborns. We used resting-state functional magnetic resonance imaging (rs-fMRI) and the amplitude of low-frequency fluctuation (ALFF) method to investigate the frequency properties of spontaneous blood oxygen level-dependent (BOLD) signals in 26 MLPT and 35 term newborns. Two frequency bands, slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz), were analyzed. Our results showed widespread differences in ALFF between the two bands; differences occurred mainly in the primary sensory and motor cortices and to a lesser extent in association cortices and subcortical areas. Compared with term newborns, MLPT newborns showed significantly altered neural activity predominantly in the primary sensory and motor cortices and in the posterior cingulate gyrus/precuneus. In addition, a significant interaction between frequency bands and groups was observed in the primary somatosensory cortex. Intriguingly, these primary sensory and motor regions have been proven to be the major cortical hubs during the neonatal period. Our results revealed the frequency of spontaneous BOLD signal differences between MLPT and term newborns, which contribute to the understanding of regional development of spontaneous brain rhythms of MLPT newborns.

  8. Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched environment of newborn neurons in the hippocampus.

    PubMed

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-11-01

    Hippocampal adult neurogenesis contributes to key functions of the dentate gyrus (DG), including contextual discrimination. This is due, at least in part, to the unique form of plasticity that new neurons display at a specific stage of their development when compared with the surrounding principal neurons. In addition, the contribution that newborn neurons make to dentate function can be enhanced by an increase in their numbers induced by a stimulating environment. However, signaling mechanisms that regulate these properties of newborn neurons are poorly understood. Here, we show that Ras-GRF2 (GRF2), a calcium-regulated exchange factor that can activate Ras and Rac GTPases, contributes to both of these properties of newborn neurons. Using Ras-GRF2 knockout mice and wild-type mice stereotactically injected with retrovirus containing shRNA against the exchange factor, we demonstrate that GRF2 promotes the survival of newborn neurons of the DG at approximately 1-2 weeks after their birth. GRF2 also controls the distinct form of long-term potentiation that is characteristic of new neurons of the hippocampus through its effector Erk MAP kinase. Moreover, the enhancement of neuron survival that occurs after mice are exposed to an enriched environment also involves GRF2 function. Consistent with these observations, GRF2 knockout mice display defective contextual discrimination. Overall, these findings indicate that GRF2 regulates both the basal level and environmentally induced increase of newborn neuron survival, as well as in the induction of a distinct form of synaptic plasticity of newborn neurons that contributes to distinct features of hippocampus-derived learning and memory.

  9. Restoring the smile: Inexpensive biologic restorations

    PubMed Central

    Mittal, Neeti P.

    2014-01-01

    Extensive breakdown of primary teeth to the cervical level and their loss in very young children is not uncommon. Owing to increasing concerns over self-appearance, due considerations to esthetic aspects in addition to restoring function are necessary aspects of rehabilitation of mutilated teeth to help children grow into a psychologically balanced personality. The present article describes rehabilitation of grossly decayed teeth with biologic restorations such as dentine posts, dentine post and core and biologic shell crown. This treatment modality provided a cost-effective esthetic solution. PMID:25097656

  10. Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

    PubMed

    Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

    2014-01-01

    Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

  11. Utah Paiute Tribal Restoration.

    ERIC Educational Resources Information Center

    Turner, Allen C.

    The Paiute Indian Tribe of Utah Restoration Act (1980) restored federal recognition of the tribe after a quarter century of ambiguous political status, and resulted in significant improvements of educational status of tribal members and intensification of the political presence of Southern Paiutes. Following the Paiute Indian Termination Act…

  12. Power system restoration issues

    SciTech Connect

    Adibi, M.M. ); Kafka, R.J. )

    1991-04-01

    This article describes some of the problems encountered in the three phases of power system restoration (PSR). The three phases of PSR are: Planning for restart and reintegration of the bulk power supply; Actions during system degradation for saving and retaining critical sources of power; Restoration when the power system has stabilized at some degraded level.

  13. Gill's 'History' restored

    NASA Astrophysics Data System (ADS)

    Hurn, Mark

    2009-06-01

    Note about the restoration of the copy of Sir David Gill's 'A History and Description of the Royal Observatory, Cape of Good Hope' in the Library of the Institute of Astronomy, Cambridge. The book was restored with funds provided by the SHA in thanks for facilities for meetings provided to the Institute.

  14. Sexual dimorphism in newborns and adults.

    PubMed

    Antoszewska, A; Wolański, N

    1992-01-01

    A total of 1034 newborns were used to analyze sexual dimorphism with respect to 37 somatic traits and ratios between them, describing body shape. Arithmetic means and standard deviations were calculated for both sexes. Similarly, sexual dimorphism of adults was analyzed. Sexual differences in newborns were statistically significant for most measurements but only for some body proportions (relative chest size, foot shape, relative lower extremity length, and the ratio of head to chest circumference). The highest degree of sexual dimorphism in newborns was shown by the index standardized on the mean (dsex/mean) of such traits as the thickness of subcutaneous fat tissue on the thigh, subscapular fat tissue and fat tissue on the 10th rib, body weight, hand breadth, and relative chest size (Marty index). A moderate dimorphism was found for the length of upper extremities, forearm with the hand, head with the neck, hand and trunk, the size of the nose and foot, the breadth of hips and mandible, and the upper-face height. A low dimorphism was found for body length, circumference and breadth of head, face diameter, chest circumference, foot shape, relative length of lower extremities, and proportion between head and chest circumferences. Sexual differences (dsex/mean) for all the somatic traits examined in adults were statistically significant. The dimorphism of all the traits (except hip breadth) was higher in adults than in newborns. The highest increase in sexual dimorphism was noted for chest breadth (ca 55 times), then for chest depth (ca 17 times), thickness of subcutaneous fat tissue on arm (ca. 17 times), and the length of lower extremities (ca 15 times). Sexual differences in proportions (shape) of the body were also better pronounced in adults than in newborns. Sexual dimorphism standardized for dispersion (dsex/SD) in newborns differed from that in adults with respect to the degree of its expression and the sequence of the traits showing the highest and the

  15. Transcriptome Profiling of the Newborn Mouse Lung Response to Acute Ozone Exposure

    PubMed Central

    Loader, Joan E.; White, Carl W.; Dakhama, Azzeddine

    2014-01-01

    Ozone pollution is associated with adverse effects on respiratory health in adults and children but its effects on the neonatal lung remain unknown. This study was carried out to define the effect of acute ozone exposure on the neonatal lung and to profile the transcriptome response. Newborn mice were exposed to ozone or filtered air for 3h. Total RNA was isolated from lung tissues at 6 and 24h after exposure and was subjected to microarray gene expression analysis. Compared to filtered air-exposed littermates, ozone-exposed newborn mice developed a small but significant neutrophilic airway response associated with increased CXCL1 and CXCL5 expression in the lung. Transcriptome analysis indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5-fold at 6h post-ozone exposure (t-test, p < .05). At 24h, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed, compared to filtered air-exposed, newborn mice (t-test, p < .05). After controlling for false discovery rate, 50 genes were identified as significantly down-regulated and only a few (RORC, GRP, VREB3, and CYP2B6) were up-regulated at 24h post-ozone exposure (q < .05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation were the most impacted pathways, which were negatively regulated by ozone exposure, an adverse effect that was associated with reduced bromo-deoxyuridine incorporation. These results demonstrate that acute ozone exposure alters cell proliferation in the developing neonatal lung through a global suppression of cell cycle function. PMID:24336422

  16. Retributive and restorative justice.

    PubMed

    Wenzel, Michael; Okimoto, Tyler G; Feather, Norman T; Platow, Michael J

    2008-10-01

    The emergence of restorative justice as an alternative model to Western, court-based criminal justice may have important implications for the psychology of justice. It is proposed that two different notions of justice affect responses to rule-breaking: restorative and retributive justice. Retributive justice essentially refers to the repair of justice through unilateral imposition of punishment, whereas restorative justice means the repair of justice through reaffirming a shared value-consensus in a bilateral process. Among the symbolic implications of transgressions, concerns about status and power are primarily related to retributive justice and concerns about shared values are primarily related to restorative justice. At the core of these processes, however, lies the parties' construal of their identity relation, specifically whether or not respondents perceive to share an identity with the offender. The specific case of intergroup transgressions is discussed, as are implications for future research on restoring a sense of justice after rule-breaking.

  17. [Newborn children under phototherapy: the mother's perception].

    PubMed

    Campos, Antonia do Carmo Soares; Cardoso, Maria Vera Lúcia Moreira Leitão

    2004-01-01

    Since 1958, phototherapy has been used as a method to cure jaundice, which is still an important disease in newborn children. Supported by a phenomenological and qualitative approach, this study aims to investigate the mothers' perception of the phototherapy treatment their children are submitted to. Research subjects were ten mothers of newborns under phototherapy treatment at the Neonatological Hospitalization Unit of a public maternity in Fortaleza-CE, Brazil. Data were collected between May and July 2002. We used group meetings with the mothers as suggested by Carl Rogers. Discourse was organized into categories according to Bardin, which revealed themes that were analyzed in view of Paterson's and Zderad's humanistic nursing theory, as follows: mothers' knowledge on phototherapy and concerns about the treatment. We concluded that the analyzed mothers' major concern is related to the babies' vision.

  18. Infrared and optical imaging of newborn stars

    SciTech Connect

    Heyer, M.H.; Ladd, E.F.; Myers, P.C.; Campbell, B. Harvard Univ., Cambridge, MA Harvard-Smithsonian Center for Astrophysics, Cambridge, MA New Mexico Univ., Albuquerque )

    1990-05-01

    Deep optical and near-infrared imaging observations of five low- to intermediate-luminosity pre-main-sequence stars embedded within dense cores reveal an extended emission component. Four of the five stars were previously identified as outflow sources. Nebulosity is detected with the optical and J and H bandpasses for each source. The large measured polarization values (p = 10 to 70 percent) at H and K identify the nebulosity as scattered light. At K the intensity distribution is generally less extended than at J and H, and is characterized by an additional, unresolved component. The position of this point source likely identifies the location of the newborn star within the field. For all sources, the illuminating star is redder than its associated nebula. The observed correlation of cometary reflection nebulae with newborn stars undergoing mass outflow suggests that the low-opacity paths are cavities associated with energetic stellar winds. 35 refs.

  19. Primary health care of the newborn baby.

    PubMed

    Bhakoo, O N; Kumar, R

    1990-01-01

    More than 50% of infant deaths in India occur during the neonatal period. High priority therefore needs to be given to improving the survival of newborns. A large number of neonatal deaths have their origin in the perinatal period and are mainly determined by the health and nutritional status of the mother, the quality of care during pregnancy and delivery, and the immediate care of the newborn at birth. Main causes of neonatal mortality are birth asphyxia, respiratory problems, and infections, especially tetanus. Most such deaths occur among low birthweight babies. Hypothermia, undernutrition, and mismanaged breast feeding may also indirectly contribute to neonatal mortality. Community-based studies have, however, demonstrated that most neonatal mortality can be affordably prevented through primary health care. Efforts are underway to expand the health care infrastructure, but the outreach of maternal and child health care remains unsatisfactory especially in rural areas. PMID:12319228

  20. Pain assessment scales in newborns: integrative review

    PubMed Central

    de Melo, Gleicia Martins; Lélis, Ana Luíza Paula de Aguiar; de Moura, Alline Falconieri; Cardoso, Maria Vera Lúcia Moreira Leitão; da Silva, Viviane Martins

    2014-01-01

    OBJECTIVE: To analyze studies on methods used to assess pain in newborns. DATA SOURCES: Integrative review study of articles published from 2001 to 2012, carried out in the following databases: Scopus, PubMed, CINAHL, LILACS and Cochrane. The sample consisted of 13 articles with level of evidence 5. DATA SYNTHESIS: 29 pain assessment scales in newborns, including 13 one-dimensional and 16 multidimensional, that assess acute and prolonged pain in preterm and full-term infants were available in scientific publications. CONCLUSION: Based on the characteristics of scales, one cannot choose a single one as the most appropriate scale, as this choice will depend on gestational age, type of painful stimulus and the environment in which the infant is inserted. It is suggested the use of multidimensional or one-dimensional scales; however, they must be reliable and validated. PMID:25511005

  1. [Newborn children under phototherapy: the mother's perception].

    PubMed

    Campos, Antonia do Carmo Soares; Cardoso, Maria Vera Lúcia Moreira Leitão

    2004-01-01

    Since 1958, phototherapy has been used as a method to cure jaundice, which is still an important disease in newborn children. Supported by a phenomenological and qualitative approach, this study aims to investigate the mothers' perception of the phototherapy treatment their children are submitted to. Research subjects were ten mothers of newborns under phototherapy treatment at the Neonatological Hospitalization Unit of a public maternity in Fortaleza-CE, Brazil. Data were collected between May and July 2002. We used group meetings with the mothers as suggested by Carl Rogers. Discourse was organized into categories according to Bardin, which revealed themes that were analyzed in view of Paterson's and Zderad's humanistic nursing theory, as follows: mothers' knowledge on phototherapy and concerns about the treatment. We concluded that the analyzed mothers' major concern is related to the babies' vision. PMID:15651644

  2. Instantaneous frequency based newborn EEG seizure characterisation

    NASA Astrophysics Data System (ADS)

    Mesbah, Mostefa; O'Toole, John M.; Colditz, Paul B.; Boashash, Boualem

    2012-12-01

    The electroencephalogram (EEG), used to noninvasively monitor brain activity, remains the most reliable tool in the diagnosis of neonatal seizures. Due to their nonstationary and multi-component nature, newborn EEG seizures are better represented in the joint time-frequency domain than in either the time domain or the frequency domain. Characterising newborn EEG seizure nonstationarities helps to better understand their time-varying nature and, therefore, allow developing efficient signal processing methods for both modelling and seizure detection and classification. In this article, we used the instantaneous frequency (IF) extracted from a time-frequency distribution to characterise newborn EEG seizures. We fitted four frequency modulated (FM) models to the extracted IFs, namely a linear FM, a piecewise-linear FM, a sinusoidal FM, and a hyperbolic FM. Using a database of 30-s EEG seizure epochs acquired from 35 newborns, we were able to show that, depending on EEG channel, the sinusoidal and piecewise-linear FM models best fitted 80-98% of seizure epochs. To further characterise the EEG seizures, we calculated the mean frequency and frequency span of the extracted IFs. We showed that in the majority of the cases (>95%), the mean frequency resides in the 0.6-3 Hz band with a frequency span of 0.2-1 Hz. In terms of the frequency of occurrence of the four seizure models, the statistical analysis showed that there is no significant difference( p = 0.332) between the two hemispheres. The results also indicate that there is no significant differences between the two hemispheres in terms of the mean frequency ( p = 0.186) and the frequency span ( p = 0.302).

  3. Changes in responsiveness to newborn pups in pregnant, nulliparous golden hamsters.

    PubMed

    Buntin, J D; Jaffe, S; Lisk, R D

    1984-03-01

    Virgin female hamsters were mated and tested once daily for maternal retrieving behavior beginning on days 0, 5, 9, 13, 15, of the 16 day gestation period to determine if responsiveness toward newborn pups changes as pregnancy proceeds. Upon initial exposure to 3 newborn pups, only a small percentage of early-to-mid-pregnant females exhibited maternal retrieving behavior spontaneously. In contrast, over half of the 15 day pregnant females displayed retrieving during the first test. Despite the high frequency of initial pup-directed aggression and cannibalism, maternal retrieval was induced in the majority of the females in all groups by repeated daily exposure to 3 newborn pups. However, no significant differences were observed in the number of pup exposure periods required to induce maternal retrieving in 0, 5, and 9 day pregnant females. It is concluded that the high level of maternal responsiveness observed in the parturient hamster develops somewhat abruptly during late pregnancy. In this respect, the pattern observed in the hamster differs from the more gradual increase in maternal responsiveness reported in mid-to-late-pregnant mice and rats. PMID:6540458

  4. Bearing restoration by grinding

    NASA Technical Reports Server (NTRS)

    Hanau, H.; Parker, R. J.; Zaretsky, E. V.; Chen, S. M.; Bull, H. L.

    1976-01-01

    A joint program was undertaken by the NASA Lewis Research Center and the Army Aviation Systems Command to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. No bearing failures occurred related to the restoration by grinding process. The risk and cost of a bearing restoration by grinding programs was analyzed. A microeconomic impact analysis was performed.

  5. Life cycle of Cystoisospora felis (Coccidia: Apicomplexa) in cats and mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cystoisospora felis is a ubiquitous apicomplexan protozoon of cats. The endogenous development of C. felis was studied in cats after feeding them infected mice. For this, 5 newborn cats were killed at 24, 48, 72, 96, and 120 h after having been fed mesenteric lymph nodes and spleens of mice that wer...

  6. Fracture resistance of posterior teeth restored with modern restorative materials

    PubMed Central

    Hamouda, Ibrahim M.; Shehata, Salah H.

    2011-01-01

    We studied the fracture resistance of maxillary premolars restored with recent restorative materials. Fifty maxillary premolars were divided into five groups: Group 1 were unprepared teeth; Group 2 were teeth prepared without restoration; Group 3 were teeth restored with tetric ceram HB; Group 4 were teeth restored with InTen S; and Group 5 were teeth restored with Admira. The samples were tested using a universal testing machine. Peak loads at fracture were recorded. The teeth restored with Admira had the highest fracture resistance followed by those restored with InTen-S and tetric ceram HB. Prepared, unrestored teeth were the weakest group. There was a significant difference between the fracture resistance of intact teeth and the prepared, unrestored teeth. There was also a significant difference among the tested restorative materials. Teeth restored with Admira showed no significant difference when compared with the unprepared teeth. It was concluded that the teeth restored with Admira exhibited the highest fracture resistance. PMID:23554719

  7. A Comprehensive Initiative to Prevent Falls Among Newborns.

    PubMed

    Ainsworth, Rose Mary; Summerlin-Long, Shelley; Mog, Cathy

    2016-01-01

    Our hospital experienced seven instances of newborns falling over a 7-month period. Until that time, there had been no reported newborn falls. We formed a committee to study the situation and make recommendations for change. Common factors observed were early morning hours and an exhausted parent, usually the mother, falling asleep while feeding the newborn. The committee developed a policy and procedure addressing falls among newborns, created staff education and tools, and posted signage in mothers' rooms. We also updated crib cards to include information about falls and safe sleep, and we revised newborn admission education for parents with additional information about falls. The incidence of newborns falling has decreased since we implemented these changes.

  8. Ecosystem restoration: Chapter 4

    USGS Publications Warehouse

    Cullinane Thomas, Catherine M.; Skrabis, K. E.; Gascoigne, William

    2012-01-01

    The Department of the Interior extensively supports―through its mission, policy, programs, and funding― the study, planning, implementation, and monitoring of ecosystem restoration. This commitment is reflected in the Department's FY2011-2016 Strategic Plan.

  9. Restoration of Ailing Wetlands

    PubMed Central

    Schmitz, Oswald J.

    2012-01-01

    It is widely held that humankind's destructive tendencies when exploiting natural resources leads to irreparable harm to the environment. Yet, this thinking runs counter to evidence that many ecological systems damaged by severe natural environmental disturbances (e.g., hurricanes) can restore themselves via processes of natural recovery. The emerging field of restoration ecology is capitalizing on the natural restorative tendencies of ecological systems to build a science of repairing the harm inflicted by humans on natural environment. Evidence for this, for example, comes from a new meta-analysis of 124 studies that synthesizes recovery of impacted wetlands worldwide. While it may take up to two human generations to see full recovery, there is promise, given human will, to restore many damaged wetlands worldwide. PMID:22291573

  10. ESTUARINE HABITAT RESTORATION

    SciTech Connect

    Thom, Ronald M.; Borde, Amy B.

    2015-09-01

    Restoring estuarine habitats generally means repairing damages caused by humans and natural forces. Because of the extensive human occupation, development, and use of coastal areas for centuries, the extensive estuarine habitats have been either destroyed or significantly impaired.

  11. Restoration of ailing wetlands.

    PubMed

    Schmitz, Oswald J

    2012-01-01

    It is widely held that humankind's destructive tendencies when exploiting natural resources leads to irreparable harm to the environment. Yet, this thinking runs counter to evidence that many ecological systems damaged by severe natural environmental disturbances (e.g., hurricanes) can restore themselves via processes of natural recovery. The emerging field of restoration ecology is capitalizing on the natural restorative tendencies of ecological systems to build a science of repairing the harm inflicted by humans on natural environment. Evidence for this, for example, comes from a new meta-analysis of 124 studies that synthesizes recovery of impacted wetlands worldwide. While it may take up to two human generations to see full recovery, there is promise, given human will, to restore many damaged wetlands worldwide.

  12. Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia

    PubMed Central

    Shaikh, Henna; Boudes, Elodie; Khoja, Zehra; Shevell, Michael; Wintermark, Pia

    2015-01-01

    Background Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns. Objective This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns. Design/Methods Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns. Results Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns. Conclusions These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery. PMID:25996847

  13. Restoring primary anterior teeth.

    PubMed

    Waggoner, William F

    2002-01-01

    A variety of esthetic restorative materials are available for restoring primary incisors. Knowledge of the specific strengths, weakness, and properties of each material will enhance the clinician's ability to make the best choice of selection for each individual situation. Intracoronal restorations of primary teeth may utilize resin composites, glass ionomer cements, resin-modified ionomers, or polyacid-modified resins. Each has distinct advantages and disadvantages and the clinical conditions of placement may be a strong determining factor as to which material is utilized. Full coronal restoration of primary incisors may be indicated for a number of reasons. Crowns available for restoration of primary incisors include those that are directly bonded onto the tooth, which generally are a resin material, and those crowns that are luted onto the tooth and are some type of stainless steel crown. However, due to lack of supporting clinical data, none of the crowns can be said to be superior to the others under all circumstances. Though caries in the mandibular region is rare, restorative solutions for mandibular incisors are needed. Neither stainless steel crowns nor celluloid crown forms are made specifically for mandibular incisors. Many options exist to repair carious primary incisors, but there is insufficient controlled, clinical data to suggest that one type of restoration is superior to another. This does not discount the fact that dentists have been using many of these crowns for years with much success. Operator preferences, esthetic demands by parents, the child's behavior, and moisture and hemorrhage control are all variables which affect the decision and ultimate outcome of whatever restorative treatment is chosen.

  14. Restoring primary anterior teeth.

    PubMed

    Waggoner, William F

    2002-01-01

    A variety of esthetic restorative materials are available for restoring primary incisors. Knowledge of the specific strengths, weakness, and properties of each material will enhance the clinician's ability to make the best choice of selection for each individual situation. Intracoronal restorations of primary teeth may utilize resin composites, glass ionomer cements, resin-modified ionomers, or polyacid-modified resins. Each has distinct advantages and disadvantages and the clinical conditions of placement may be a strong determining factor as to which material is utilized. Full coronal restoration of primary incisors may be indicated for a number of reasons. Crowns available for restoration of primary incisors include those that are directly bonded onto the tooth, which generally are a resin material, and those crowns that are luted onto the tooth and are some type of stainless steel crown. However, due to lack of supporting clinical data, none of the crowns can be said to be superior to the others under all circumstances. Though caries in the mandibular region is rare, restorative solutions for mandibular incisors are needed. Neither stainless steel crowns nor celluloid crown forms are made specifically for mandibular incisors. Many options exist to repair carious primary incisors, but there is insufficient controlled, clinical data to suggest that one type of restoration is superior to another. This does not discount the fact that dentists have been using many of these crowns for years with much success. Operator preferences, esthetic demands by parents, the child's behavior, and moisture and hemorrhage control are all variables which affect the decision and ultimate outcome of whatever restorative treatment is chosen. PMID:12412967

  15. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer

    PubMed Central

    Dominguez-Bello, Maria G.; De Jesus-Laboy, Kassandra M.; Shen, Nan; Cox, Laura M.; Amir, Amnon; Gonzalez, Antonio; Bokulich, Nicholas A.; Song, Se Jin; Hoashi, Marina; Rivera-Vina, Juana I.; Mendez, Keimari; Knight, Rob; Clemente, Jose C.

    2016-01-01

    Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by Cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section are exposed to maternal vaginal fluids at birth. Similar to vaginally delivered babies, the gut, oral, and skin microbiome of these newborns during the first 30 days of life was enriched in vaginal bacteria underrepresented in unexposed C-section infants, albeit similarity to vaginally-delivered infants was higher in oral and skin than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section born infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section delivered babies. PMID:26828196

  16. Pharmacology of some oral penicillins in the newborn infant.

    PubMed

    Cohen, M D; Raeburn, J A; Devine, J; Kirkwood, J; Elliott, B; Cockburn, F; Forfar, J O

    1975-03-01

    Serum and urine concentrations of ampicillin, amoxycillin, and flucloxacillin achieved after oral administration have been measured in 27 newborn infants. Compared with adults and children, newborn infants show a delay in achieving adequate blood concentrations, presumably due to delayed absorption. However most infants achieve therapeutic concentrations in the serum. Infected newborn infants should be given these antibiotics by intramuscular injection for the first dose, but thereafter oral therapy (25 mg/lg every 6 hours begun concomitantly) should be satisfactory. The better absorption of amoxycillin compared with ampicillin reported in adults has not been confirmed in the newborn infant.

  17. Emergency preparedness for newborn screening and genetic services.

    PubMed

    Pass, Kenneth A; Thoene, Jess; Watson, Michael S

    2009-06-01

    Patients identified in newborn screening programs can be among the most vulnerable during a disaster due to their need to have prompt diagnosis and medical management. Recent disasters have challenged the ability of newborn screening programs to maintain the needed continuity during emergency situations. This has significant implications for the newborn screening laboratories, the diagnostic confirmation providers, and the patients who either require diagnosis or maintenance of their therapeutic interventions. In 2007, the National Coordinating Center (NCC) for the Regional Genetics and Newborn Screening Collaboratives (RCs) sponsored a meeting involving representatives of the Regional Genetics and Newborn Screening Collaborative Groups, state newborn screening programs, providers of diagnosis and confirmation services, manufacturers of equipment, medical foods, and other treatments used in patients identified in newborn screening programs, and individuals from agencies involved in disaster response including the National Disaster Medical Service, the Centers for Disease Control and Prevention, the Emergency Management Assistance Compact, the Federal Emergency Management Agency, and others. In addition to developing contingency plans for newborn screening, we have considered other uses of genetics as it is used in DNA-based kinship identification of mass casualties. The meeting resulted in the description of a wide range of issues facing newborn screening programs, provider groups, and patients for which emergency preparedness development is needed in order that appropriate response is enabled. PMID:19444127

  18. Preventing in-hospital newborn falls: a literature review.

    PubMed

    Matteson, Tara; Henderson-Williams, Audery; Nelson, Jessica

    2013-01-01

    In-hospital newborn falls are arguably one of the most underresearched and underreported issues for organizations that care for newborn patients. From the few published statistics of in-hospital fall rates, we know that perhaps 600 to 1,600 newborn falls occur annually. Many of these falls can result in injury or even death of the newborn, legal issues for the institution, and severe emotional stress to the caregiver(s) and parents. Therefore, we searched the literature to ascertain causation and associated risks associated with in-hospital newborn falls. This is an important issue for nurses to understand because not only can the newborn be harmed due to a fall, but the actual newborn fall can also elicit strong feelings of guilt and culpability in the caregiver(s). This article reviews the literature to examine what is known about the factors associated with in-hospital newborn falls, to explore prevention measures, and to present best practices for how to adopt safe-sleep policy to prevent newborn falls. PMID:24013477

  19. Microglia engulf viable newborn cells in the epileptic dentate gyrus.

    PubMed

    Luo, Cong; Koyama, Ryuta; Ikegaya, Yuji

    2016-09-01

    Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase-negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis. GLIA 2016;64:1508-1517.

  20. Melior Via: A Better Way to Integrate and Restore Movement into Orthopedic Rehabilitation.

    PubMed

    Hetzler, Brandon; Mahaffey, Brian

    2016-01-01

    Movement develops uniformly and predictably in all normal newborns and infants. The genetic roadmap for every complex movement that will ever be performed is written intoevery infant's nervous system and develops from these basic ingredients: unlimited mobility, an undeveloped nervous system, primal reflexes, and breathing. Following an injury, surgery or trauma, restoring movement is the same as learning movement only with slightly differing parameters. The principles, however, remain the same and can be used to improve orthopedic rehabilitation. PMID:27443044

  1. A Special Extract of Bacopa monnieri (CDRI-08)-Restored Memory in CoCl2-Hypoxia Mimetic Mice Is Associated with Upregulation of Fmr-1 Gene Expression in Hippocampus

    PubMed Central

    Rani, Anupama; Prasad, S.

    2015-01-01

    Fragile X mental retardation protein (FMRP) is a neuronal translational repressor and has been implicated in learning, memory, and cognition. However, the role of Bacopa monnieri extract (CDRI-08) in enhancing cognitive abilities in hypoxia-induced memory impairment via Fmr-1 gene expression is not known. Here, we have studied effects of CDRI-08 on the expression of Fmr-1 gene in the hippocampus of well validated cobalt chloride (CoCl2)-induced hypoxia mimetic mice and analyzed the data with alterations in spatial memory. Results obtained from Morris water maze test suggest that CoCl2 treatment causes severe loss of spatial memory and CDRI-08 is capable of reversing it towards that in the normal control mice. Our semiquantitative RT-PCR, Western blot, and immunofluorescence microscopic data reveal that CoCl2-induced hypoxia significantly upregulates the expression of Hif-1α and downregulates the Fmr-1 expression in the hippocampus, respectively. Further, CDRI-08 administration reverses the memory loss and this is correlated with significant downregulation of Hif-1α and upregulation of Fmr-1 expression. Our data are novel and may provide mechanisms of hypoxia-induced impairments in the spatial memory and action of CDRI-08 in the recovery of hypoxia led memory impairment involving Fmr-1 gene encoded protein called FMRP. PMID:26413121

  2. Newborn screening in the Asia Pacific region.

    PubMed

    Padilla, Carmencita D; Therrell, Bradford L

    2007-08-01

    The success of blood spot newborn screening in the USA led to early screening efforts in parts of the Asia Pacific Region in the mid-1960s. While there were early screening leaders in the region, many of the countries with depressed and developing economies are only now beginning organized screening efforts. Four periods of screening growth in the Asia Pacific region were identified. Beginning in the 1960s, blood spot screening began in New Zealand and Australia, followed by Japan and a cord blood screening programme for G6PD deficiency in Singapore. In the 1980s, established programmes added congenital hypothyroidism and new programmes developed in Taiwan, Hong Kong, China (Shanghai), India and Malaysia. Programmes developing in the 1990s built on the experience of others developing more rapidly in Korea, Thailand and the Philippines. In the 2000s, with limited funding support from the International Atomic Energy Agency, there has been screening programme development around detection of congenital hypothyroidism in Indonesia, Mongolia, Sri Lanka, Myanmar and Pakistan. Palau has recently contracted with the Philippine newborn screening programme. There is little information available on newborn screening activities in Nepal, Cambodia, Laos and the other Pacific Island nations, with no organized screening efforts apparent. Since approximately half of the births in the world occur in the Asia Pacific Region, it is important to continue the ongoing implementation and expansion efforts so that these children can attain the same health status as children in more developed parts of the world and their full potential can be realized.

  3. [Recommendations for respiratory support in the newborn].

    PubMed

    2012-10-01

    The recommendations included in this document will be part a series of updated reviews of the literature on respiratory support in the newborn infant. These recommendations are structured into twelve modules, with modules 4, 5, and 6 presented here. Each module is the result of a consensus process of all members of the Surfactant and Respiratory Group of the Spanish Society of Neonatology. They represent a summary of the published papers on each specific topic, and of the clinical experience of each one of the members of the group. Each module includes a summary of the scientific evidence available, graded into 4 levels of recommendations.

  4. Retroperitoneal pulmonary choristoma in a newborn calf.

    PubMed

    Bassi, Patrizia; Gentile, Arcangelo; Militerno, Gianfranco

    2010-11-01

    A newborn male Romagnola calf, who had died a few hours after birth, was submitted for postmortem examination. Necropsy revealed a 23 cm × 22 cm × 5 cm, pale pink, lobulated, elastic, partially fluctuant mass that protruded from the dorsal retroperitoneal space into the abdominal cavity, extending from the diaphragm to the left kidney. The mass consisted of mature pulmonary tissue and was consistent with a pulmonary choristoma. The gross and microscopic appearance of this rare tumor-like congenital lesion and the possible pathogenesis are discussed.

  5. Photochemical approaches to vision restoration

    PubMed Central

    Van Gelder, Russell N.

    2015-01-01

    Photoswitches are traditional pharmacologic agonists, antagonists, or channel blockers that are covalently modified with an azobenzene derivative. Azobenzene undergoes wavelength-dependent isomerization between cis and trans conformation. For some photoswitches, only one of these configurations is biologically active, resulting in light-dependent activation or inhibition of function. Photoswitches that feature a quaternary ammonium coupled to the azobenzene moiety cause light-dependent neuronal depolarization due to blockage of voltage-gated potassium channels. Two photoswitch strategies have been pursued. In the one-component strategy, the photoswitch is applied to native receptors; in the two-component strategy, the photoswitch is combined with virally-mediated expression of a genetically modified receptor, to which the photoswitch may covalently bind. The former approach is simpler but the latter allows precise anatomic targeting of photoswitch activity. Acrylamide-azobenzene-quaternary ammonium (AAQ) is the prototypical first-generation one-component photoswitch. When applied to retinas with outer retinal degeneration, ganglion cell firing occurs in response to blue light, and is abrogated by green light. In vivo, AAQ restored pupillary light responses and behavioral light responses in blind animals. DENAQ is a prototypical second generation one-component photoswitch. It features spontaneous thermal relaxation so cell firing ceases in dark, and features a red-shifted activation spectrum. Interestingly, DENAQ only photoswitches in retinas with outer retinal degeneration. MAG is a photoswitched glutamate analog which covalently binds to a modified ionotropic glutamate receptor, LiGluR. When applied together, MAG and LiGluR also rescue physiologic and behavioral light responses in blind mice. Together, photoswitch compounds offer a potentially useful approach to restoration of vision in outer retinal degeneration. PMID:25680758

  6. Transient bacteremia following endotracheal suctioning in ventilated newborns.

    PubMed

    Storm, W

    1980-03-01

    Endotracheal suctioning is a routine procedure in ventilated newborns. A study of ten neonates demonstrates the association of transient bacteremia with endotracheal suctioning. This complication in ventilated newborns, with colonization of the respiratory tract by the same organism, must be considered in the pathogenesis of systemic infection.

  7. Newborns' Orientation toward Sound: Possible Implications for Cortical Development.

    ERIC Educational Resources Information Center

    Clifton, Rachel K.; And Others

    1981-01-01

    Newborns were presented with a tape-recorded rattle sound through a single loudspeaker, through two loudspeakers with one onset leading the other by seven msecs., and through two loudspeakers simultaneously. Newborns turned toward the single source sound, but not toward either of the dual source sounds. (Author/RH)

  8. Newborn Screening Information Supports Public Health More than Informed Choice

    ERIC Educational Resources Information Center

    Hargreaves, Katrina; Stewart, Ruth; Oliver, Sandy

    2005-01-01

    Objective: To appraise information resources on newborn blood spot screening currently available for parents and health professionals internationally. Method: Health information on newborn blood spot screening was sourced internationally through the internet and, in the United Kingdom, through health service providers and support organisations. An…

  9. [2 newborn infants with severe arrhythmia caused by hyperkalemia].

    PubMed

    Maclaine Pont, J; Hack, W W; Sobotka-Plojhar, M; Ekkelkamp, S

    1987-02-01

    Two newborn infants with ventricular arrhythmias secondary to hyperkalaemia are presented. One child also showed a decreased serum calcium concentration. There is scanty literature concerning the often life threatening cardiac arrhythmias due to hyperkalaemia in the newborn infants. Treatment of the cardiac arrhythmias require intravenous calcium gluconat and sodium bicarbonate infusion beside lowering the serum potassium level in the usual way.

  10. Newborn Screening To Prevent Mental Retardation. The Arc Q & A.

    ERIC Educational Resources Information Center

    Arc, Arlington, TX.

    This information fact sheet on screening newborns to prevent mental retardation defines newborn screening and outlines how screening is performed. It discusses the six most common disorders resulting in mental retardation for which states most commonly screen. These include phenylketonuria, congenital hypothyroidism, galactosemia, maple syrup…

  11. Universal Newborn Screening and Adverse Medical Outcomes: A Historical Note

    ERIC Educational Resources Information Center

    Brosco, Jeffrey P.; Seider, Michael I.; Dunn, Angela C.

    2006-01-01

    Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and…

  12. Nosocomial Outbreak of Parechovirus 3 Infection among Newborns, Austria, 2014.

    PubMed

    Strenger, Volker; Diedrich, Sabine; Boettcher, Sindy; Richter, Susanne; Maritschnegg, Peter; Gangl, Dietmar; Fuchs, Simone; Grangl, Gernot; Resch, Bernhard; Urlesberger, Berndt

    2016-09-01

    In 2014, sepsis-like illness affected 9 full-term newborns in 1 hospital in Austria. Although results of initial microbiological testing were negative, electron microscopy identified picornavirus. Archived serum samples and feces obtained after discharge were positive by PCR for human parechovirus 3. This infection should be included in differential diagnoses of sepsis-like illness in newborns. PMID:27532333

  13. The Effects of Sound Duration on Newborns' Head Orientation.

    ERIC Educational Resources Information Center

    Clarkson, Marsha G.; And Others

    1985-01-01

    Two experiments assessed the importance of sound duration for eliciting head orientation responses from newborn infants. Results suggest that newborns' head orientation response may reflect a motor program that is initiated by auditory input and then executed in a similar fashion regardless of further stimulation. (Author/AS)

  14. Nosocomial Outbreak of Parechovirus 3 Infection among Newborns, Austria, 2014

    PubMed Central

    Diedrich, Sabine; Boettcher, Sindy; Richter, Susanne; Maritschnegg, Peter; Gangl, Dietmar; Fuchs, Simone; Grangl, Gernot; Resch, Bernhard; Urlesberger, Berndt

    2016-01-01

    In 2014, sepsis-like illness affected 9 full-term newborns in 1 hospital in Austria. Although results of initial microbiological testing were negative, electron microscopy identified picornavirus. Archived serum samples and feces obtained after discharge were positive by PCR for human parechovirus 3. This infection should be included in differential diagnoses of sepsis-like illness in newborns. PMID:27532333

  15. Newborns' Face Recognition: Role of Inner and Outer Facial Features

    ERIC Educational Resources Information Center

    Turati, Chiara; Macchi Cassia, Viola; Simion, Francesca; Leo, Irene

    2006-01-01

    Existing data indicate that newborns are able to recognize individual faces, but little is known about what perceptual cues drive this ability. The current study showed that either the inner or outer features of the face can act as sufficient cues for newborns' face recognition (Experiment 1), but the outer part of the face enjoys an advantage…

  16. Posture as a Determinant of Visual Behavior in Newborns

    ERIC Educational Resources Information Center

    Fredrickson, W. Timm; Brown, Josephine V.

    1975-01-01

    The effects of posture on the visual behavior of 15 3-day-old healthy, black, newborn infants were assessed. Findings suggest that the vestibular, proprioceptive, and contact stimulation provided by the on-shoulder position affects the newborn's ability to follow and process visual stimuli. (Author/CS)

  17. Auditory Brainstem Evoked Responses in Newborns with Down Syndrome

    ERIC Educational Resources Information Center

    Kittler, Phyllis M.; Phan, Ha T. T.; Gardner, Judith M.; Miroshnichenko, Inna; Gordon, Anne; Karmel, Bernard Z.

    2009-01-01

    Auditory brainstem evoked responses (ABRs) were compared in 15 newborns with Down syndrome and 15 sex-, age-, and weight-matched control newborns. Participants had normal ABRs based upon values specific to 32- to 42-weeks postconceptional age. Although Wave III and Wave V component latencies and the Wave I-III interpeak latency (IPL) were shorter…

  18. Conference on Newborn Hearing Screening; Proceedings Summary and Recommendations.

    ERIC Educational Resources Information Center

    Alexander Graham Bell Association for the Deaf, Inc., Washington, DC.

    Presented in the conference proceedings are schedule and list of participants, seven major papers, and the newborn hearing screening recommendations of the interdisciplinary conference on newborn hearing and early identification of hearing impairment. Neonatal auditory testing is reviewed by Sanford E. Gerber, and Sheldon B. Korones gives a…

  19. Bilateral ovarian cysts in a newborn: a case report.

    PubMed

    Lim, C T; Wong, K K; Yap, Y F; Sivanesaratnam, V

    1992-03-01

    Large ovarian cysts in the fetus are uncommon. Ultrasonography has helped in the detection of these cysts antenatally and in the newborn female infant. A case of bilateral ovarian cysts in a newborn is presented. The choice of management between conservative measures and surgical approaches remains controversial.

  20. Creating esthetic composite restorations.

    PubMed

    Grin, D

    2000-05-01

    The purpose of this article is to describe a fabrication technique to assist dental technicians creating esthetic indirect composite restorations. After the teeth have been prepared and the models completed, the technician can begin the fabrication process. Translucent dentin is selected to reduce opacity and enhance the blend with the remaining dentition. High chroma modifiers can then be placed into the fossa area to replicate dentin seen in natural dentition. Different incisal materials can then be layered into the build-up to regulate the value of the restoration. Special effects such as hypocalcification are placed internally to mimic naturally occurring esthetics. Realistic anatomy is created using a small-tipped instrument directly into the final layer of uncured enamel material. Fissure characterization is placed in the restoration to match existing dentition. Fit and margins are verified on separate dies to minimize discrepancies. Path of insertion and proximal contacts are established on a solid model to minimize chairside adjustments.

  1. Restoring the prairie

    SciTech Connect

    Mlot, C.

    1990-12-01

    The US DOE at the Fermi National Accelerator Laboratory in Batavia, Illinois, prairie restoration is taking place in order to conserve the rich topsoil. This is the largest of many prairie restoration experiments. Big bluestem grass (Andropogon gerardi), blue grama (Bouteloua gracilis), and buffalo grass (Buchloe dactyloides) are the main initial grasses grown. After their growth reaches enough biomass to sustain a fire, other prairie plants such as purple prairie clover and dropseed grass appear. The goal of this is to provide a generous refuge for disappearing native plants and animals, a site for scientific research, and a storehouse of genes adapted to a region that produces much of the worlds food. Plans for restoring the marsh and oak savanna, also native to the Fermilab site are also in the works.

  2. A Small Molecule Swertisin from Enicostemma littorale Differentiates NIH3T3 Cells into Islet-Like Clusters and Restores Normoglycemia upon Transplantation in Diabetic Balb/c Mice.

    PubMed

    Dadheech, Nidheesh; Soni, Sanket; Srivastava, Abhay; Dadheech, Sucheta; Gupta, Shivika; Gopurappilly, Renjitha; Bhonde, Ramesh R; Gupta, Sarita

    2013-01-01

    Aim. Stem cell therapy is one of the upcoming therapies for the treatment of diabetes. Discovery of potent differentiating agents is a prerequisite for increasing islet mass. The present study is an attempt to screen the potential of novel small biomolecules for their differentiating property into pancreatic islet cells using NIH3T3, as representative of extra pancreatic stem cells/progenitors. Methods. To identify new agents that stimulate islet differentiation, we screened various compounds isolated from Enicostemma littorale using NIH3T3 cells and morphological changes were observed. Characterization was performed by semiquantitative RT-PCR, Q-PCR, immunocytochemistry, immunoblotting, and insulin secretion assay for functional response in newly generated islet-like cell clusters (ILCC). Reversal of hyperglycemia was monitored after transplanting ILCC in STZ-induced diabetic mice. Results. Among various compounds tested, swertisin, an isolated flavonoid, was the most effective in differentiating NIH3T3 into endocrine cells. Swertisin efficiently changed the morphology of NIH3T3 cells from fibroblastic to round aggregate cell cluster in huge numbers. Dithizone (DTZ) stain primarily confirmed differentiation and gene expression studies signified rapid onset of differentiation signaling cascade in swertisin-induced ILCC. Molecular imaging and immunoblotting further confirmed presence of islet specific proteins. Moreover, glucose induced insulin release (in vitro) and decreased fasting blood glucose (FBG) (in vivo) in transplanted diabetic BALB/c mice depicted functional maturity of ILCC. Insulin and glucagon expression in excised islet grafts illustrated survival and functional integrity. Conclusions. Rapid induction for islet differentiation by swertisin, a novel herbal biomolecule, provides low cost and readily available differentiating agent that can be translated as a therapeutic tool for effective treatment in diabetes. PMID:23662125

  3. Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice.

    PubMed

    Bernstein, Lori R; Mackenzie, Amelia C L; Lee, Se-Jin; Chaffin, Charles L; Merchenthaler, István

    2016-03-01

    Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women. PMID:26713784

  4. Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice.

    PubMed

    Bernstein, Lori R; Mackenzie, Amelia C L; Lee, Se-Jin; Chaffin, Charles L; Merchenthaler, István

    2016-03-01

    Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women.

  5. Restoration of Shoulder Function.

    PubMed

    Boe, Chelsea C; Elhassan, Bassem T

    2016-08-01

    Restoration of shoulder function in patients with brachial plexus injury can be challenging. Initial reported efforts were focused on stabilizing the shoulder, improving inferior subluxation and restoring abduction and flexion of the joint. Recent advancements and improved understanding of coordinated shoulder motion and the biomechanical properties of the muscles around the shoulder applicable to tendon transfer have expanded available surgical options to improve shoulder function, specifically external rotation. Despite the advances in reconstructive options, brachial plexus injury remains a serious problem that requires complex surgical solutions, prolonged recovery, and acceptance of functional loss. PMID:27387074

  6. Newborn screening for congenital infectious diseases.

    PubMed

    Neto, Eurico Camargo; Rubin, Rosélia; Schulte, Jacqueline; Giugliani, Roberto

    2004-06-01

    To estimate the prevalence of congenital toxoplasmosis, Chagas disease, cytomegalovirus, and rubella, blood samples on dried blood spot (DBS) from neonates (day 3-20 of life) were screened for immunoglobulin (Ig) M against Toxoplasma gondii, cytomegalovirus, rubella virus, and IgG against Trypanosoma cruzi by methods used for serum and adapted for use with DBS. Positive samples were further analyzed for IgM and IgG in serum from neonates and mothers. DBS samples from 364,130 neonates were tested for Toxoplasma gondii-specific IgM, and 15,873 neonates were also tested for IgM against cytomegalovirus and rubella virus and for Trypanosoma cruzi-specific IgG. A total of 195 were diagnosed with congenital toxoplasmosis, 16 with cytomegalovirus, and 11 with congenital rubella. One newborn had a confirmed result for Chagas disease, and 21 mothers had positive serum antibodies. These results suggest that infectious diseases should be considered for future inclusion in programs for newborn screening of metabolic diseases in disease-endemic areas. PMID:15207059

  7. Newborn infant skin: physiology, development, and care.

    PubMed

    Visscher, Marty O; Adam, Ralf; Brink, Susanna; Odio, Mauricio

    2015-01-01

    Infant skin is critical to the newborn child's transition from the womb environment to the journey to self-sufficiency. This review provides an integrative perspective on the skin development in full term and premature infants. There is a particular focus on the role of vernix caseosa and on the implications of skin development for epidermal penetration of exogenous compounds. Healthy full-term newborn skin is well-developed and functional at birth, with a thick epidermis and well-formed stratum corneum (SC) layers. Transepidermal water loss is very low at birth, equal to, or lower than adults, indicating a highly effective skin barrier. Vernix facilitates SC development in full-term infants through a variety of mechanisms including physical protection from amniotic fluid and enzymes, antimicrobial effects, skin surface pH lowering, provision of lipids, and hydration. Premature infants, particularly those of very low birth weight, have a poor skin barrier with few cornified layers and deficient dermal proteins. They are at increased risk for skin damage, increased permeability to exogenous agents and infection. The SC barrier develops rapidly after birth but complete maturation requires weeks to months. The best methods for caring for infant skin, particularly in the diaper region, are described and related to these developmental changes. PMID:25889127

  8. Surfactant secretion and clearance in the newborn

    SciTech Connect

    Stevens, P.A.; Wright, J.R.; Clements, J.A. )

    1989-10-01

    Pregnant rabbits (30 days) were injected intravenously with (3H)choline 8 h before delivery. The fetuses were delivered, and lung lavage and lamellar body phospholipids (PL) were analyzed. Some newborns also received radioactively labeled surfactant intratracheally on delivery and were permitted to breathe. With time, intratracheal label decreased in lavage and appeared in the lamellar body fraction, and intravenous label accumulated in both pools. Using a tracer analysis for non-steady state, we calculated surfactant secretion and clearance rates for the newborn period. Before birth, both rates rose slightly from 1.8 micrograms PL.g body wt-1.h-1 at 6 h before birth to 7.3 at birth. Immediately after birth, secretion rate rose to 37.7 micrograms PL.g body wt-1.h-1. Between 1.5 and 2 h after birth it fell to a minimum of 1.8 micrograms PL.g body wt-1.h-1 and then rose slowly to 6.0 at 12 h. After birth, clearance rate increased less than secretion rate (maximum 24.7 micrograms PL.g body wt-1.h-1 shortly after birth) then followed the same pattern but did not balance secretion rate in the 1st day.

  9. Newborn infant skin: physiology, development, and care.

    PubMed

    Visscher, Marty O; Adam, Ralf; Brink, Susanna; Odio, Mauricio

    2015-01-01

    Infant skin is critical to the newborn child's transition from the womb environment to the journey to self-sufficiency. This review provides an integrative perspective on the skin development in full term and premature infants. There is a particular focus on the role of vernix caseosa and on the implications of skin development for epidermal penetration of exogenous compounds. Healthy full-term newborn skin is well-developed and functional at birth, with a thick epidermis and well-formed stratum corneum (SC) layers. Transepidermal water loss is very low at birth, equal to, or lower than adults, indicating a highly effective skin barrier. Vernix facilitates SC development in full-term infants through a variety of mechanisms including physical protection from amniotic fluid and enzymes, antimicrobial effects, skin surface pH lowering, provision of lipids, and hydration. Premature infants, particularly those of very low birth weight, have a poor skin barrier with few cornified layers and deficient dermal proteins. They are at increased risk for skin damage, increased permeability to exogenous agents and infection. The SC barrier develops rapidly after birth but complete maturation requires weeks to months. The best methods for caring for infant skin, particularly in the diaper region, are described and related to these developmental changes.

  10. Red blood cell transfusion in newborn infants.

    PubMed

    Whyte, Robin K; Jefferies, Ann L

    2014-04-01

    Red blood cell transfusion is an important and frequent component of neonatal intensive care. The present position statement addresses the methods and indications for red blood cell transfusion of the newborn, based on a review of the current literature. The most frequent indications for blood transfusion in the newborn are the acute treatment of perinatal hemorrhagic shock and the recurrent correction of anemia of prematurity. Perinatal hemorrhagic shock requires immediate treatment with large quantities of red blood cells; the effects of massive transfusion on other blood components must be considered. Some guidelines are now available from clinical trials investigating transfusion in anemia of prematurity; however, considerable uncertainty remains. There is weak evidence that cognitive impairment may be more severe at follow-up in extremely low birth weight infants transfused at lower hemoglobin thresholds; therefore, these thresholds should be maintained by transfusion therapy. Although the risks of transfusion have declined considerably in recent years, they can be minimized further by carefully restricting neonatal blood sampling. PMID:24855419

  11. [Pharmacology for the fetus and the newborn].

    PubMed

    Juárez-Olguín, Hugo; Buendía-Soto, Erick; Lares-Asseff, Ismael

    2015-01-01

    During intrauterine life, the fetus can be exposed to a series of substances ingested by the mother, some of which are necessary for her health but detrimental to fetus. The noxious effects of such exposure could present immediately after exposure in the fetus or be manifested at the time of delivery and sometimes weeks after birth. The passage of drugs or nutrients across the placenta depends on some physicochemicals that have the ability to cross the placenta barrier, and thus get in contact with the fetus and produce harmful effects. Considering the physicochemical properties of the substances, the possibility of such compounds to cross the placenta barrier and thence to the fetus can be predicted. Equally, it is important to consider the characteristics of the newborn as an immature being, different from adults, when carrying out pharmacokinetic and pharmacodynamic processes. Based on the latter, it is important to know the behavior or characteristics of the fetus and the newborn in the face of drug management and above all consider the advantages and disadvantages of the use of such drugs for the care of a being yet in development, as is described in this work.

  12. Non-invasive distress evaluation in preterm newborn infants.

    PubMed

    Manfredi, C; Bocchi, L; Orlandi, S; Calisti, M; Spaccaterra, L; Donzelli, G P

    2008-01-01

    With the increased survival of very preterm infants, there is a growing concern for their developmental outcomes. Infant cry characteristics reflect the development and possibly the integrity of the central nervous system. In this paper, relationships between fundamental frequency (F(0)) and vocal tract resonance frequencies (F(1)-F(3)) are investigated for a set of preterm newborns, by means of a multi-purpose voice analysis tool (BioVoice), characterised by high-resolution and tracking capabilities. Also, first results about possible distress occurring during cry in preterm newborn infants, as related to the decrease of central blood oxygenation, are presented. To this aim, a recording system (Newborn Recorder) has been developed, that allows synchronised, non-invasive monitoring of blood oxygenation and audio recordings of newborn infant's cry. The method has been applied to preterm newborns at the Intensive Care Unit, A.Meyer Children Hospital, Firenze, Italy.

  13. Newborn screening progress in developing countries--overcoming internal barriers.

    PubMed

    Padilla, Carmencita D; Krotoski, Danuta; Therrell, Bradford L

    2010-04-01

    Newborn screening is an important public health measure aimed at early identification and management of affected newborns thereby lowering infant morbidity and mortality. It is a comprehensive system of education, screening, follow-up, diagnosis, treatment/management, and evaluation that must be institutionalized and sustained within public health systems often challenged by economic, political, and cultural considerations. As a result, developing countries face unique challenges in implementing and expanding newborn screening that can be grouped into the following categories: (1) planning, (2) leadership, (3) medical support, (4) technical support, (5) logistical support, (6) education, (7) protocol and policy development, (8) administration, (9) evaluation, and (10) sustainability. We review some of the experiences in overcoming implementation challenges in developing newborn screening programs, and discuss recent efforts to encourage increased newborn screening through support networking and information exchange activities in 2 regions-the Asia Pacific and the Middle East/North Africa. PMID:20207264

  14. Carotid chemoreceptor development in mice.

    PubMed

    Shirahata, Machiko; Kostuk, Eric W; Pichard, Luis E

    2013-01-01

    Mice are the most suitable species for understanding genetic aspects of postnatal developments of the carotid body due to the availability of many inbred strains and knockout mice. Our study has shown that the carotid body grows differentially in different mouse strains, indicating the involvement of genes. However, the small size hampers investigating functional development of the carotid body. Hypoxic and/or hyperoxic ventilatory responses have been investigated in newborn mice, but these responses are indirect assessment of the carotid body function. Therefore, we need to develop techniques of measuring carotid chemoreceptor neural activity from young mice. Many studies have taken advantage of the knockout mice to understand chemoreceptor function of the carotid body, but they are not always suitable for addressing postnatal development of the carotid body due to lethality during perinatal periods. Various inbred strains with well-designed experiments will provide useful information regarding genetic mechanisms of the postnatal carotid chemoreceptor development. Also, targeted gene deletion is a critical approach.

  15. Restoring Fossil Creek

    ERIC Educational Resources Information Center

    Flaccus, Kathleen; Vlieg, Julie; Marks, Jane C.; LeRoy, Carri J.

    2004-01-01

    Fossil Creek had been dammed for the past 90 years, and plans were underway to restore the stream. The creek runs through Central Arizona and flows from the high plateaus to the desert, cutting through the same formations that form the Grand Canyon. This article discusses the Fossil Creek monitoring project. In this project, students and teachers…

  16. Model for Coastal Restoration

    SciTech Connect

    Thom, Ronald M.; Judd, Chaeli

    2007-07-27

    Successful restoration of wetland habitats depends on both our understanding of our system and our ability to characterize it. By developing a conceptual model, looking at different spatial scales and integrating diverse data streams: GIS datasets and NASA products, we were able to develop a dynamic model for site prioritization based on both qualitative and quantitative relationships found in the coastal environment.

  17. Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice

    PubMed Central

    Praag, Henriette van; Shubert, Tiffany; Zhao, Chunmei; Gage, Fred H.

    2005-01-01

    Aging causes changes in the hippocampus that may lead to cognitive decline in older adults. In young animals, exercise increases hippocampal neurogenesis and improves learning. We investigated whether voluntary wheel running would benefit mice that were sedentary until 19 months of age. Specifically, young and aged mice were housed with or without a running wheel and injected with bromodeoxyuridine or retrovirus to label newborn cells. After 1 month, learning was tested in the Morris water maze. Aged runners showed faster acquisition and better retention of the maze than age-matched controls. The decline in neurogenesis in aged mice was reversed to 50% of young control levels by running. Moreover, fine morphology of new neurons did not differ between young and aged runners, indicating that the initial maturation of newborn neurons was not affected by aging. Thus, voluntary exercise ameliorates some of the deleterious morphological and behavioral consequences of aging. PMID:16177036

  18. 14. EAST ELEVATION, COTTAGE. EXTERIOR NEARLY RESTORED. INTERIOR UNDERGOING RESTORATION. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. EAST ELEVATION, COTTAGE. EXTERIOR NEARLY RESTORED. INTERIOR UNDERGOING RESTORATION. EUCALYPTUS TREE PLANTED BY GERTRUDE KEIL PLANNED FOR REMOVAL. - Gold Ridge Farm, 7777 Bodega Avenue, Sebastopol, Sonoma County, CA

  19. [Influence of implant restoration on traditional restoration idea].

    PubMed

    Liu, H C

    2016-01-01

    Implant restoration affected the traditional restoration idea. Artificial implant restoration has a profound influence on the design of dental restoration. Implant supported prostheses have not only changed the method of oral rehabilitation, but also integrated revolutionary concept with the traditional treatment protocol. By using implants, posterior missing molars can be effectively restored and thus eliminating the disadvantages of traditional removable partial denture for Kennedy classification Ⅰ, Ⅱ partically edentulous dentition. Full edentulous arch can also be restored with implant fixed denture which provide much better oral health related quality of life compared with the traditional complete denture. It is useful to master the theory and skills of artificial implant restoration, and to provide a reference for the restoration of oral physiological function.

  20. Thermal protection of the newborn in resource-limited environments.

    PubMed

    Lunze, K; Hamer, D H

    2012-05-01

    Appropriate thermal protection of the newborn prevents hypothermia and its associated burden of morbidity and mortality. Yet, current global birth practices tend to not adequately address this challenge. Here, we discuss the pathophysiology of hypothermia in the newborn, its prevention and therapeutic options with particular attention to resource-limited environments. Newborns are equipped with sophisticated mechanisms of body temperature regulation. Neonatal thermoregulation is a critical function for newborn survival, regulated in the hypothalamus and mediated by endocrine pathways. Hypothermia activates cellular metabolism through shivering and non-shivering thermogenesis. In newborns, optimal temperature ranges are narrow and thermoregulatory mechanisms easily overwhelmed, particularly in premature and low-birth weight infants. Hyperthermia most commonly is associated with dehydration and potentially sepsis. The lack of thermal protection promptly leads to hypothermia, which is associated with detrimental metabolic and other pathophysiological processes. Simple thermal protection strategies are feasible at community and institutional levels in resource-limited environments. Appropriate interventions include skin-to-skin care, breastfeeding and protective clothing or devices. Due to poor provider training and limited awareness of the problem, appropriate thermal care of the newborn is often neglected in many settings. Education and appropriate devices might foster improved hypothermia management through mothers, birth attendants and health care workers. Integration of relatively simple thermal protection interventions into existing mother and child health programs can effectively prevent newborn hypothermia even in resource-limited environments. PMID:22382859

  1. Does intrauterine tobacco exposure increase the pain perception of newborns?

    PubMed Central

    Tekin, Mustafa; Yıldırım, Şule; Aylanç, Hakan; Kaymaz, Nazan; Battal, Fatih; Topaloğlu, Naci; Başer, Esra; Binnetoğlu, Fatih Köksal

    2016-01-01

    Background This study aimed to assess whether there was a difference in the pain-perception levels of newborns born to mothers who smoked during pregnancy and newborns born to mothers who were not exposed to active or passive smoking during pregnancy. Materials and methods A total of 60 newborns born by normal spontaneous vaginal birth between June 2013 and June 2014 were included in the study: 30 born to mothers who smoked during pregnancy, and 30 born to mothers not exposed to smoking. Mothers or newborns who had taken analgesics or sedative medications in the previous 24 hours, newborns not born at term, and sick newborns were not included in the study. During the routine hepatitis B-vaccination injection given at postnatal 48 hours, the newborns’ behavior was monitored and recorded by video camera. The data obtained from the recordings were evaluated according to the Neonatal Pain, Agitation, and Sedation Scale and analyzed with SPSS 20. Results The median pain score of the group exposed to tobacco smoke in utero was 8.5, while the median pain score of the unexposed group was 6 (P<0.001). Conclusion Exposure to tobacco smoke in utero may increase the pain-perception levels of newborns. PMID:27330324

  2. Impact of Conditional Cash Transfers on Maternal and Newborn Health

    PubMed Central

    Duran, Denizhan; Fleisher, Lisa; Singer, Daniel; Sturke, Rachel; Angeles, Gustavo; Charles, Jodi; Emrey, Bob; Gleason, Joanne; Mwebsa, Winnie; Saldana, Kelly; Yarrow, Kristina; Koblinsky, Marge

    2013-01-01

    Maternal and newborn health (MNH) is a high priority for global health and is included among the Millennium Development Goals (MDGs). However, the slow decline in maternal and newborn mortality jeopardizes achievements of the targets of MDGs. According to UNICEF, 60 million women give birth outside of health facilities, and family planning needs are satisfied for only 50%. Further, skilled birth attendance and the use of antenatal care are most inequitably distributed in maternal and newborn health interventions in low- and middle-income countries. Conditional cash transfer (CCT) programmes have been shown to increase health service utilization among the poorest but little is written on the effects of such programmes on maternal and newborn health. We carried out a systematic review of studies on CCT that report maternal and newborn health outcomes, including studies from 8 countries. The CCT programmes have increased antenatal visits, skilled attendance at birth, delivery at a health facility, and tetanus toxoid vaccination for mothers and reduced the incidence of low birthweight. The programmes have not had a significant impact on fertility while the impact on maternal and newborn mortality has not been well-documented thus far. Given these positive effects, we make the case for further investment in CCT programmes for maternal and newborn health, noting gaps in knowledge and providing recommendations for better design and evaluation of such programmes. We recommend more rigorous impact evaluations that document impact pathways and take factors, such as cost-effectiveness, into account.

  3. Necrotizing enterocolitis in premature infants and newborns.

    PubMed

    Mϋller, M J; Paul, T; Seeliger, S

    2016-09-16

    Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract (GIT) in premature infants and newborns. It is defined as an ulcerative inflammation of the intestinal wall. The clinical signs of incipient NEC are often very discrete, and range from localized intestinal symptoms to generalized signs of sepsis. NEC is classified depending on its severity into disease states according to the modified Bell's Classification. Treatment of NEC ranges, depending on its severity, from a conservative therapeutic approach to surgery with resection of the affected parts of the intestine. Mortality is considerably high in extremely small preterm infants reaching up to 42% of the affected children. Measures such as breastfeeding or alternatively nutrition with pasteurized human donor milk from a milk bank, administration of probiotics, avoidance of histamine type II receptor antagonists, and restrictive antibiotic treatment should be considered early on for prevention of NEC. PMID:27589549

  4. Direct magnification radiography of the newborn infant

    SciTech Connect

    Brasch, R.C.; Gould, R.G.

    1982-03-01

    Recent advances in technology have made direct radiographic magnification of the newborn infant clinically feasible. A microfocus radiographic tube and a rare-earth, high-speed recording system were combined to obtain more than 2,000 radiographs at magnifications of 2 to 2.5. Special positioning devices permitted imaging of even those infants confined to incubators and connected to life-supporting systems. When quantitatively compared with three conventional contact radiographic systems with respect to resolution, contrast, and noise, magnification radiography showed overall superiority of image characteristics. Definition of subtle abnormalities and anatomically small structures permitted diagnoses which could not be made from conventional images. Furthermore, infant radiation exposure was markedly less (15 mR (3.9 mC/kg) maximum skin exposure) as compared with conventional contact radiographic systems (24 mR(6.1 mC/kg) to 45 mR (11.6 mC/kg)).

  5. Direct magnification radiography of the newborn infant

    SciTech Connect

    Brasch, R.C.; Gould, R.G.

    1982-03-01

    Recent advances in technology have made direct radiographic magnification of the newborn infant clinically feasible. A microfocus radiographic tube and a rare-earth, high-speed recording system were combined to obtain more than 2,000 radiographs at magnifications of 2-2.5. Special positioning devices permitted imaging of even those infants confined to incubators and connected to life-supporting systems. When quantitatively compared with three conventional contact radiographic systems with respect to resolution, contrast, and noise, magnification radiography showed overall superiority of image characteristics. Definition of subtle abnormalities and anatomically small structures permitted diagnoses which could not be made from conventional images. Furthermore, infant radiation exposure was markedly less (15 mR (3.9 mC/kg) maximum skin exposure) as compared with conventional contact radiographic systems (24 mR (6.1 mC/kg) to 45 mR (11.6 mC/kg)).

  6. Newborn infants detect the beat in music.

    PubMed

    Winkler, István; Háden, Gábor P; Ladinig, Olivia; Sziller, István; Honing, Henkjan

    2009-02-17

    To shed light on how humans can learn to understand music, we need to discover what the perceptual capabilities with which infants are born. Beat induction, the detection of a regular pulse in an auditory signal, is considered a fundamental human trait that, arguably, played a decisive role in the origin of music. Theorists are divided on the issue whether this ability is innate or learned. We show that newborn infants develop expectation for the onset of rhythmic cycles (the downbeat), even when it is not marked by stress or other distinguishing spectral features. Omitting the downbeat elicits brain activity associated with violating sensory expectations. Thus, our results strongly support the view that beat perception is innate.

  7. Hypoglycaemia of the newborn: a review.

    PubMed Central

    Williams, A. F.

    1997-01-01

    It is almost a century since hypoglycaemia (a reduction in the glucose concentration of circulating blood) was first described in children, and over 50 years since the condition was first recognized in infants. Nevertheless, controversy still surrounds the definition, significance, and management of neonatal hypoglycaemia. Technological developments such as bedside glucose monitoring have, paradoxically, exacerbated rather than eased the situation. This article reviews the literature on hypoglycaemia of the newborn, and covers the following: historical aspects; glucose homeostasis and metabolic adaptation at birth; the effect of low blood glucose levels on the central nervous system; the definition of hypoglycaemia; screening; prevention; treatment; research needs; and concludes with recommendations for prevention and management. PMID:9277014

  8. Why do we treat the newborn differently?

    PubMed

    Bellieni, Carlo V; Tei, Monica; Coccina, Francesca; Buonocore, Giuseppe

    2012-04-01

    End-of-life decisions are often taken in neonatology, based on widely accepted guidelines, to avoiding futile therapies. Usually, the criteria upon which these guidelines rely are different from those used for older patients, even when patients require a guardian to decide on their behalf. Main differences are the weight of parental interests and the probabilistic base of the choice. A careful analysis of the literature found three main reasons of this difference: the obsolescence of the guidelines criteria, the difficulty to distinguish between parents' and babies' interests and the neonatologist's responsibility to prolong a life with the prospective of severe disability. In conclusion, the future guidelines for newborn end-of-life decisions should follow at least the same moral criteria used for older patients. PMID:22324397

  9. Determinants of heat production in newborn lambs

    NASA Astrophysics Data System (ADS)

    Eales, F. A.; Small, J.

    1980-06-01

    Measurement of summit metabolism (the maximum rate of heat production) in lambs aged 1 or 4h revealed considerable between animal variation. Summit metabolism per unit body weight decreased as body weight increased whereas summit metabolism per unit body surface area was independent of body weight. Severe pre-partum hypoxia was apparently associated with a low summit metabolism at 1 or 4h of age which made such lambs very susceptible to hypothermia. This deficiency in heat production capacity did not appear to be a permanent featuresince most lambs so affected recovered full thermoregulatory ability by 12h of age. Feeding of colostrum conferred an immediate 18% increase in summit metabolism. The significance of these findings to the prevention of hypothermia in the newborn lamb is discussed.

  10. Immunization of newborns with bacterial conjugate vaccines.

    PubMed

    van den Biggelaar, Anita H J; Pomat, William S

    2013-05-17

    Bacterial conjugate vaccines are based on the principle of coupling immunogenic bacterial capsular polysaccharides to a carrier protein to facilitate the induction of memory T-cell responses. Following the success of Haemophilus influenzae type b conjugate vaccines in the 1980s, conjugate vaccines for Streptococcus pneumoniae and Neisseria meningitidis infections were developed and proven to be effective in protecting children against invasive disease. In this review, the use of conjugate vaccines in human newborns is discussed. Neonatal Haemophilus influenzae type b and pneumococcal conjugate vaccination schedules have been trialed and proven to be safe, with the majority of studies demonstrating no evidence for the induction of immune tolerance. Whether their neonatal administration also results in an earlier induction of clinical protection in the first 2-3 critical months of life is still to be demonstrated. PMID:22728221

  11. Ecosystem Restoration Research at GWERD

    EPA Science Inventory

    Ground Water and Ecosystems Restoration Division, Ada, OK Mission: Conduct research and technical assistance to provide the scientific basis to support the development of strategies and technologies to protect and restore ground water, surface water, and ecosystems impacted b...

  12. Tissue carnitine reserves of newborn infants.

    PubMed

    Shenai, J P; Borum, P R

    1984-07-01

    This study assessed the tissue reserves of carnitine at birth in a group of neonates (n = 22) of varying gestational age dying within 24 h of birth, prior to possible changes in carnitine status induced by postnatal intervention. Tissue carnitine concentration was highest in the muscle in each infant. The mean (+/- SD) muscle carnitine concentration of 8.4 +/- 3.6 nmol/mg noncollagen protein (NCP) in very immature infants (less than or equal to 1000 g birth weight) was significantly lower than the corresponding mean (+/- SD) values of 14.0 +/- 3.2 nmol/mg NCP in larger preterm infants (1001-2500 g; P less than 0.01) and 19.4 +/- 2.6 nmol/mg NCP in term infants (greater than or equal to 2501 g; P less than 0.001). Muscle carnitine concentration correlated positively with gestational age (r = 0.832; P less than 0.001) and with body dimensions. Liver and heart carnitine concentrations did not correlate significantly with gestation or body dimensions. The mean (+/- SD) liver carnitine concentration for all the neonates as a group was 4.1 +/- 1.5 nmol/mg NCP. The mean (+/- SD) heart carnitine concentration was 4.7 +/- 1.3 nmol/mg NCP. In comparison to adult controls, tissue carnitine concentrations were markedly lower in neonates, particularly in immature newborns. These data suggest that newborn infants, especially premature babies, are born with limited tissue reserves of carnitine and are therefore at an increased risk for developing carnitine deficiency and its adverse effects in the postnatal period, particularly if maintained on carnitine-free intravenous nutrition for prolonged periods of time.

  13. Buen Comienzo, Buen Futuro: Su Recien Nacido. (Healthy Start, Grow Smart: Your Newborn).

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This booklet offers guidance to parents in caring for their newborn babies. Advice is given on the following topics: (1) newborn health screening; (2) what a healthy newborn looks like; (3) newborn reflexes; (4) baby checkups; (5) fathers' role; (6) the baby blues; (7) sleeping position; (8) breast milk; (9) breast feeding; (10) bottle feeding;…

  14. Behavioral Organization in Newborns and Its Relation to Adrenocortical and Cardiac Activity.

    ERIC Educational Resources Information Center

    Spangler, Gottfried; Scheubeck, Roswitha

    1993-01-01

    Twice during the neonatal period, the behavioral organization of 42 newborns was assessed by the Neonatal Behavioral Assessment Scale (NBAS), and the newborns' cortisol response to the NBAS procedure was determined. Newborns with low orientation showed a higher increase in cortisol during the NABS than newborns with high orientation. (MDM)

  15. Comparison of aesthetic posterior restorations.

    PubMed

    Trushkowsky, R D

    1991-09-01

    In the past decade there has been an increased desire by the profession and the public for an aesthetic restoration that will restore a posterior tooth to its original form and function. The currently available aesthetic posterior restoration materials and techniques are porcelain, cast ceramic, direct composite, direct-indirect composite, indirect composite, and CAD-CAM fabrications. The indications and contraindications of these restorative materials and proper diagnosis and case selection are described.

  16. Family-centered Care for Sick Newborns: A Thumbnail View

    PubMed Central

    Maria, Arti; Dasgupta, Rajib

    2016-01-01

    Family-centered care (FCC) for sick newborns is emerging as a paradigmatic shift in the practice of facility-based newborn care. It seeks to transforming a provider-centered model into a client-centered one and thus build a new therapeutic alliance. FCC is the cornerstone of continuum of care, imparting caregiving competencies to parents/caregivers both within institutions as well as after the discharge. This has potential gains for the newborn, family members, and facility-level staff. The initial model piloted in tertiary-care settings is now undergoing translation at five sites across the country; the outcomes are keenly awaited. PMID:26917867

  17. Family-centered Care for Sick Newborns: A Thumbnail View.

    PubMed

    Maria, Arti; Dasgupta, Rajib

    2016-01-01

    Family-centered care (FCC) for sick newborns is emerging as a paradigmatic shift in the practice of facility-based newborn care. It seeks to transforming a provider-centered model into a client-centered one and thus build a new therapeutic alliance. FCC is the cornerstone of continuum of care, imparting caregiving competencies to parents/caregivers both within institutions as well as after the discharge. This has potential gains for the newborn, family members, and facility-level staff. The initial model piloted in tertiary-care settings is now undergoing translation at five sites across the country; the outcomes are keenly awaited. PMID:26917867

  18. Combined amalgam and composite restorations.

    PubMed

    Abu-Hanna, Amer A; Mjör, Ivar A

    2004-01-01

    All indirect restorative techniques involving cast metals, ceramics or resin-based materials are expensive compared to directly placed restorations. A restorative technique is presented that combines the esthetic properties of directly bonded resin-based composite material and the wide range of indications for dental amalgam in stress-bearing areas.

  19. Volume restoration and facial aesthetics.

    PubMed

    Glasgold, Mark J; Glasgold, Robert A; Lam, Samuel M

    2008-11-01

    This article discusses the rationale for the use of volume restoration to restore natural, youthful contours to an aging face. Topics discussed include the discrepancy that can exist between patients' stated wishes and optimal results and the concepts of framing the eye, creating highlights, and restoring facial shape and volume.

  20. Engineering approaches to ecosystem restoration

    SciTech Connect

    Hayes, D.F.

    1998-07-01

    This proceedings CD ROM contains 127 papers on developing and evaluating engineering approaches to wetlands and river restoration. The latest engineering developments are discussed, providing valuable insights to successful approaches for river restoration, wetlands restoration, watershed management, and constructed wetlands for stormwater and wastewater treatment. Potential solutions to a wide variety of ecosystem concerns in urban, suburban, and coastal environments are presented.

  1. Prairie Restoration for Wisconsin Schools.

    ERIC Educational Resources Information Center

    Murray, Molly Fifield; Greenler, Robin McC.

    This packet is composed of several resources for teachers interested in prairie ecology and restoration. "A Guide to Restoration from Site Analysis to Management" focuses on the Prairie/Oak Savanna communities of Wisconsin and takes teachers through the planning and design process for a restoration project on school grounds including site…

  2. Adaptive wiener image restoration kernel

    DOEpatents

    Yuan, Ding

    2007-06-05

    A method and device for restoration of electro-optical image data using an adaptive Wiener filter begins with constructing imaging system Optical Transfer Function, and the Fourier Transformations of the noise and the image. A spatial representation of the imaged object is restored by spatial convolution of the image using a Wiener restoration kernel.

  3. Relativistic Linear Restoring Force

    ERIC Educational Resources Information Center

    Clark, D.; Franklin, J.; Mann, N.

    2012-01-01

    We consider two different forms for a relativistic version of a linear restoring force. The pair comes from taking Hooke's law to be the force appearing on the right-hand side of the relativistic expressions: d"p"/d"t" or d"p"/d["tau"]. Either formulation recovers Hooke's law in the non-relativistic limit. In addition to these two forces, we…

  4. Restoration of Elbow Flexion.

    PubMed

    Loeffler, Bryan J; Lewis, Daniel R

    2016-08-01

    Active elbow flexion is required to position the hand in space, and loss of this function is debilitating. Nerve transfers or nerve grafts to restore elbow flexion may be options when the target muscle is viable, but in delayed reconstruction when the biceps and brachialis are atrophied or damaged, muscle transfer options should be considered. Muscle transfer options are discussed with attention to the advantages and disadvantages of each transfer option. PMID:27387075

  5. No tumour-initiating risk associated with scAAV transduction in newborn rat liver.

    PubMed

    Gauttier, V; Pichard, V; Aubert, D; Kaeppel, C; Schmidt, M; Ferry, N; Conchon, S

    2013-07-01

    Delivery of recombinant adeno-associated virus (rAAV) vectors to the newborn liver is followed by a rapid loss of episomal vector copies because of hepatocyte proliferation. In selected hepatocytes, integration of rAAV genomes can lead to a sustained expression of the transgene. The safety of in vivo gene therapy with single-stranded AAV vectors has been questioned in a study reporting a high incidence of hepatocellular carcinoma, associated with provirus integration events in mice that receive an single-stranded AAV injection at birth. To investigate the tumour-initiating potential of the newly established self-complementary AAV (scAAV) vectors in the liver, groups of newborn rats received intravenous injection of a scAAV vector encoding the green fluorescent protein (GFP), or were injected with phosphate-buffered saline (PBS) or diethylnitrosamine (DEN), a well-known liver tumour initiator. The rats were fed on a diet containing 2-acetylaminofluorene, a potent liver tumour-promoting agent to accelerate the carcinogenic process. After 2 months, the animals were killed and their livers analysed. Preneoplastic nodules were identified by glutathion S-transferase-p (GSTp) staining, and GFP expression was detected by immunohistochemistry. Vector genome integration events were analysed. The numbers of GSTp-positive foci were comparable in the PBS and the scAAV-GFP groups and significantly higher in the DEN group. The proportion of GSTp-positive foci that also expressed GFP was low and in the range expected for random occurrence. No specific integration hot spots were detected by linear amplification-mediated-PCR in transduced liver. In conclusion, scAAV transduction of newborn rat liver does not trigger preneoplastic lesions suggesting an absence of liver tumourigenesis.

  6. Global Maternal, Newborn, and Child Health: Successes, Challenges, and Opportunities.

    PubMed

    Shetty, Avinash K

    2016-02-01

    Considerable progress has been made towards reducing under-5 childhood mortality in the Millennium Development Goals era. Reduction in newborn mortality has lagged behind maternal and child mortality. Effective implementation of innovative, evidence-based, and cost-effective interventions can reduce maternal and newborn mortality. Interventions aimed at the most vulnerable group results in maximal impact on mortality. Intervention coverage and scale-up remains low, inequitable and uneven in low-income countries due to numerous health-systems bottle-necks. Innovative service delivery strategies, increased integration and linkages across the maternal, newborn, child health continuum of care are vital to accelerate progress towards ending preventable maternal and newborn deaths. PMID:26613686

  7. Newborn falls in-hospital: time to address the issue.

    PubMed

    Paul, Siba Prosad; Goodman, Alexander; Remorino, Rowena; Bolger, Sarah

    2011-04-01

    Newborn falls in-hospital are considered rare and mostly accidental. Few studies are available explaining such accidents. The number of cases may be under reported by parents because of the inevitable sense of guilt they experience. Although deaths have been rarely reported, such accidents may be associated with serious outcomes. An urgent assessment by both the midwifery and paediatric teams should be undertaken following the reporting of such accidents. This paper explains what is meant by newborn falls, presents some relevant literature and uses a case study involving a newborn in hospital to form the basis of a discussion. Importantly it is felt that there is a need to raise awareness of the potential of these accidents amongst health professionals. We hope this paper goes some way towards highlighting some key issues and, moreover, increases awareness of newborn falls in hospital. PMID:21560948

  8. Pregnancy Flu Shot Protects Newborn for 8 Weeks: Study

    MedlinePlus

    ... html Pregnancy Flu Shot Protects Newborn for 8 Weeks: Study Effectiveness drops dramatically after that To use ... protection is likely limited to the first eight weeks of life, said Marta Nunes, of the University ...

  9. Screening Newborns | NIH MedlinePlus the Magazine

    MedlinePlus

    ... today. 1999 NIDCD research explores intervention strategies for children with hearing loss. 1999 President Clinton signs the Newborn and Infant Hearing Screening and Intervention Act , authorizing support for statewide screening programs. 1998 NIDCD research demonstrates the need for both ...

  10. Improvement of maternal and newborn health through midwifery.

    PubMed

    ten Hoope-Bender, Petra; de Bernis, Luc; Campbell, James; Downe, Soo; Fauveau, Vincent; Fogstad, Helga; Homer, Caroline S E; Kennedy, Holly Powell; Matthews, Zoe; McFadden, Alison; Renfrew, Mary J; Van Lerberghe, Wim

    2014-09-27

    In the concluding paper of this Series about midwifery, we look at the policy implications from the framework for quality maternal and newborn care, the potential effect of life-saving interventions that fall within the scope of practice of midwives, and the historic sequence of health system changes that made a reduction in maternal mortality possible in countries that have expanded their midwifery workforce. Achievement of better health outcomes for women and newborn infants is possible, but needs improvements in the quality of reproductive, maternal, and newborn care, alongside necessary increases in universal coverage. In this report, we propose three priority research areas and outline how national investment in midwives and in their work environment, education, regulation, and management can improve quality of care. Midwifery and midwives are crucial to the achievement of national and international goals and targets in reproductive, maternal, newborn, and child health; now and beyond 2015.

  11. Zika May Have Caused Death of Texas Newborn

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160325.html Zika May Have Caused Death of Texas Newborn Baby ... birth defect linked to fetal exposure to the Zika virus, state health officials say. According to a ...

  12. Can Conditioned Responses be Established in the Newborn Infant: 1971?

    ERIC Educational Resources Information Center

    Sameroff, Arnold J.

    1971-01-01

    Evidence indicates that the newborn infant must first develop cognitive systems, through his experience with various stimuli, to differentiate each modality separately before he can integrate any two modalities in classical conditioning. (Author/NH)

  13. [Newborn screening : the point of view of the paediatrician].

    PubMed

    De Laet, C; Laeremans, H; Ferster, A; Gulbis, B; Mansbach, A-L; Jonniaux, E; Regal, L; Goyens, P

    2015-09-01

    Newborn screening is a public health effort that has changed the prognosis of some congenital diseases. Newborn screening programmes differ between countries in which it is organized. Demographic, epidemiological or economic factors play a role in the choice of the screening panel. In the French Community of Belgium, the programme focuses on 13 metabolic and endocrine diseases, hearing loss and hemoglobinopathies (Brussels and Liege). Newborn screening is a complex process that requires the involvement of all stakeholders : parent information, blood sampling or testing, lab analysis, follow-up of the results, initiate adequate care in case of positive test and genetic counselling. Newborn screening programmes will evolve in the next years. New therapeutic and diagnostic methods will make other genetic diseases candidates for screening. Whole genome sequencing may be the next expansion; it will create new opportunities but will pose new ethical dilemmas. We must all prepare now for future challenges. PMID:26591303

  14. What Disorders Are Newborns Screened for in the United States?

    MedlinePlus

    ... the most appropriate application of universal newborn screening tests, technologies, policies, guidelines, and standards. A complete list of the conditions screened for in each state can be found at Baby's First Test . What are some examples of the benefits of ...

  15. A Valuable and Promising Method for Recording Brain Activity in Behaving Newborn Rodents

    PubMed Central

    Sokoloff, Greta; Tiriac, Alexandre; Del Rio-Bermudez, Carlos

    2015-01-01

    Neurophysiological recording of brain activity has been critically important to the field of neuroscience, but has contributed little to the field of developmental psychobiology. The reasons for this can be traced largely to methodological difficulties associated with recording neural activity in behaving newborn rats and mice. Over the last decade, however, the evolution of methods for recording from head-fixed newborns has heralded a new era in developmental neurophysiology. Here, we review these recent developments and provide a step-by-step primer for those interested in applying the head-fix method to their own research questions. Until now, this method has been used primarily to investigate spontaneous brain activity across sleep and wakefulness, the contributions of the sensory periphery to brain activity, or intrinsic network activity. Now, with some ingenuity, the uses of the head-fix method can be expanded to other domains to benefit our understanding of brain-behavior relations under normal and pathophysiological conditions across early development. PMID:25864710

  16. Hereditary hemochromatosis restores the virulence of plague vaccine strains.

    PubMed

    Quenee, Lauriane E; Hermanas, Timothy M; Ciletti, Nancy; Louvel, Helene; Miller, Nathan C; Elli, Derek; Blaylock, Bill; Mitchell, Anthony; Schroeder, Jay; Krausz, Thomas; Kanabrocki, Joseph; Schneewind, Olaf

    2012-10-01

    Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.

  17. [Screening project of identification of hearing deficits in newborns].

    PubMed

    Møller, Troels Reinholdt; Jensen, Frank Kjeldsen; Ekmann, Anita; Wetke, Randi; Ovesen, Terese

    2007-03-01

    A screening project of identification of hearing deficits in newborns has been implemented in the County of Arhus, Denmark in January and February 2005 and is still ongoing. The purpose of the screening is to diagnose the hearing deficits during the first month postpartum and institute treatment of the handicap. During the first year of screening, 6154 children have been tested and 12 newborns with hearing deficits have been identified. PMID:17359732

  18. Incontinentia Pigmenti presenting as a newborn eruption: two case presentations.

    PubMed

    Xu, Michelle; Flamm, Alexandra; Shagalov, Devorah; Hsu, Emily; Glick, Sharon A

    2016-01-01

    Linear vesicles or papules in a newborn can be a presenting sign of incontinentia pigmenti (IP). In this report, we present two cases of neonates with cutaneous manifestations of incontinentia pigmenti. In one case, mild peripheral eosinophilia was noted. No extra-cutaneous manifestations were noted otherwise in both cases after complete ophthalmological and neurological evaluations. These cases serve as a reminder for clinicians to consider IP in newborns presenting with linear vesicles or papules. PMID:27617597

  19. Congenital giant epulis obstructing oral cavity: newborn emergency.

    PubMed

    Gnassingbe, Komla; Mihluedo-Agbolan, Komlan A; Bissa, Harefetéguéna; Amegbor, Koffi; Noumedem, Nguefack Blanchard; Egbohou, Pilakimwe; Mama, Wakatou; Akakpo-Numado, Gamedzi K; Tekou, Hubert

    2014-01-01

    The congenital epulis is a benign congenital granular cell tumor arising most often of the alveolar ridge of the jawbone. When giant, it is source of digestive discomfort disabling feeding. We report the case of a newborn female, vaginal delivery, presented with a giant intraoral tumor. Tumor obstructing the mouth of the newborn and prevent the attachment and feeding. The treatment consisted of excision of the tumor under general anesthesia. The histology of the tumor was revealed that it was an epulis.

  20. Nurses' Attitudes and Knowledge of Their Roles in Newborn Abandonment

    PubMed Central

    Cesario, Sandra K.

    2003-01-01

    The practice of abandoning newborns shortly after birth has always existed. Occurring in primitive and contemporary societies, the motivations for newborn abandonment are varied and dependent upon the social norms of a specific geographic region at a given point in time. Because the desire to abandon an infant has had no support system in American society, such unwanted infants have been abandoned in a manner leading to their deaths. In response, many states have passed safe-haven legislation to save the lives of unwanted newborns. The laws typically specify a mother's ability to “abandon” her child to a medical service provider. However, judgmental attitudes and a lack of accurate information may impede a health care provider's ability to carry out a safe-haven law. The study described here examines a sample of nurses in a state with a safe-haven law. The study revealed no significant correlation between a nurse's knowledge, attitude, and self-perception of preparedness to manage a newborn abandonment event. owever, the outcomes highlight the negative attitudes and lack of knowledge many nurses possess regarding newborn abandonment and the women who commit this act. Educational programs for all health care providers and the community are essential to the efficacy of the legislation that currently exists. Continued multidisciplinary strategizing and general awareness are needed to serve as catalysts to build supports for unwanted newborns and their safe assimilation into the community. PMID:17273338

  1. Newborn Screening: What Does the Emergency Physician Need to Know?

    PubMed

    Lavin, Lindsay Roofe; Higby, Nicholas; Abramo, Thomas

    2015-09-01

    Newborn screening programs were established in the United States in the early 1960s. Newborn screening programs were then developed by states and have continued to be the responsibility of the state. All states require a newborn screening, but what is required of these programs and screening panels has differed greatly by state. Historically, the most commonly screened disorders are the following: congenital hypothyroidism, congenital adrenal hyperplasia, sickle cell disease and associated hemoglobinopathies, biotinidase deficiency, galactosemia, cystic fibrosis and phenylketonuria, maple syrup urine disease, and homocystinuria. However, under new guidelines in 2006 and with new advances in technology, the scope of newborn screening programs has expanded to include at a minimum 9 organic acidurias, 5 fatty acid oxidation disorders, 3 hemoglobinopathies, and 6 other conditions. This CME article reviews the logistics of newborn screening and explores the effect of new technology and recent policy on state screens and what that means for providers. This article also highlights several of the disorders most relevant to emergency room physicians and discusses future considerations of newborn screening. PMID:26335232

  2. Retroviral induction of GSK-3β expression blocks the stimulatory action of physical exercise on the maturation of newborn neurons.

    PubMed

    Llorens-Martín, María; Teixeira, Catia M; Jurado-Arjona, Jerónimo; Rakwal, Randeep; Shibato, Junko; Soya, Hideaki; Ávila, Jesús

    2016-09-01

    Adult hippocampal neurogenesis (AHN) is a key process for certain types of hippocampal-dependent learning. Alzheimer's disease (AD) is accompanied by memory deficits related to alterations in AHN. Given that the increased activity of GSK-3β has been related to alterations in the population of hippocampal granule neurons in AD patients, we designed a novel methodology by which to induce selective GSK-3β overexpression exclusively in newborn granule neurons. To this end, we injected an rtTA-IRES-EGFP-expressing retrovirus into the hippocampus of tTO-GSK-3β mice. Using this novel retroviral strategy, we found that GSK-3β caused a cell-autonomous impairment of the morphological and synaptic maturation of newborn neurons. In addition, we examined whether GSK-3β overexpression in newborn neurons limits the effects of physical activity. While physical exercise increased the number of dendritic spines, the percentage of mushroom spines, and the head diameter of the same in tet-OFF cells, these effects were not triggered in tet-ON cells. This observation suggests that GSK-3β blocks the stimulatory actions of exercise. Given that the activity of GSK-3β is increased in the brains of individuals with AD, these data may be relevant for non-pharmacological therapies for AD. PMID:27010990

  3. Percutaneous left ventricular restoration.

    PubMed

    Ige, Mobolaji; Al-Kindi, Sadeer G; Attizzani, Guilherme; Costa, Marco; Oliveira, Guilherme H

    2015-04-01

    The ventricular partitioning device known as Parachute is the first and only percutaneously implantable device aimed at restoration of normal left ventricular geometry in humans. Since its conception, this technology has undergone extensive animal and human testing, with proved feasibility and safety, and is currently being studied in a pivotal randomized clinical trial. This article discusses ventricular remodeling and therapies attempted in the past, details the components of the ventricular partitioning device, describes the implanting technique, and reviews the most current experience of this device in humans.

  4. Percutaneous left ventricular restoration.

    PubMed

    Ige, Mobolaji; Al-Kindi, Sadeer G; Attizzani, Guilherme; Costa, Marco; Oliveira, Guilherme H

    2015-04-01

    The ventricular partitioning device known as Parachute is the first and only percutaneously implantable device aimed at restoration of normal left ventricular geometry in humans. Since its conception, this technology has undergone extensive animal and human testing, with proved feasibility and safety, and is currently being studied in a pivotal randomized clinical trial. This article discusses ventricular remodeling and therapies attempted in the past, details the components of the ventricular partitioning device, describes the implanting technique, and reviews the most current experience of this device in humans. PMID:25834974

  5. Robotic hair restoration.

    PubMed

    Rose, Paul T; Nusbaum, Bernard

    2014-01-01

    The latest innovation to hair restoration surgery has been the introduction of a robotic system for harvesting grafts. This system uses the follicular unit extraction/follicular isolation technique method for harvesting follicular units, which is particularly well suited to the abilities of a robotic technology. The ARTAS system analyzes images of the donor area and then a dual-chamber needle and blunt dissecting punch are used to harvest the follicular units. The robotic technology is now being used in various locations around the world. This article discusses the use of the robotic system, its capabilities, and the advantages and disadvantages of the system. PMID:24267426

  6. Absence of TNF-α enhances inflammatory response in the newborn lung undergoing mechanical ventilation.

    PubMed

    Ehrhardt, Harald; Pritzke, Tina; Oak, Prajakta; Kossert, Melina; Biebach, Luisa; Förster, Kai; Koschlig, Markus; Alvira, Cristina M; Hilgendorff, Anne

    2016-05-15

    Bronchopulmonary dysplasia (BPD), characterized by impaired alveolarization and vascularization in association with lung inflammation and apoptosis, often occurs after mechanical ventilation with oxygen-rich gas (MV-O2). As heightened expression of the proinflammatory cytokine TNF-α has been described in infants with BPD, we hypothesized that absence of TNF-α would reduce pulmonary inflammation, and attenuate structural changes in newborn mice undergoing MV-O2 Neonatal TNF-α null (TNF-α(-/-)) and wild type (TNF-α(+/+)) mice received MV-O2 for 8 h; controls spontaneously breathed 40% O2 Histologic, mRNA, and protein analysis in vivo were complemented by in vitro studies subjecting primary pulmonary myofibroblasts to mechanical stretch. Finally, TNF-α level in tracheal aspirates from preterm infants were determined by ELISA. Although MV-O2 induced larger and fewer alveoli in both, TNF-α(-/-) and TNF-α(+/+) mice, it caused enhanced lung apoptosis (TUNEL, caspase-3/-6/-8), infiltration of macrophages and neutrophils, and proinflammatory mediator expression (IL-1β, CXCL-1, MCP-1) in TNF-α(-/-) mice. These differences were associated with increased pulmonary transforming growth factor-β (TGF-β) signaling, decreased TGF-β inhibitor SMAD-7 expression, and reduced pulmonary NF-κB activity in ventilated TNF-α(-/-) mice. Preterm infants who went on to develop BPD showed significantly lower TNF-α levels at birth. Our results suggest a critical balance between TNF-α and TGF-β signaling in the developing lung, and underscore the critical importance of these key pathways in the pathogenesis of BPD. Future treatment strategies need to weigh the potential benefits of inhibiting pathologic cytokine expression against the potential of altering key developmental pathways. PMID:27016588

  7. Does monitoring newborn weight discourage breast feeding?

    PubMed Central

    McKie, A; Young, D

    2006-01-01

    Background A policy of regular neonatal weight monitoring was introduced to a geographically defined population in 2000. This was combined with targeted breast feeding support for infants reaching specified intervention thresholds. Aims To look for evidence of compromise in breast feeding rates as a result of this policy change. Methods Breast feeding rates at 10 days and 6 weeks were compared for this intervention population and two local non‐intervention groups for the years 1999 and 2001. The data were analysed using Poisson regression analysis and the Z‐test. Results There was a 3.1% (95% CI 0.8% to 5.5%) rise in the deprivation corrected breast feeding rate at 6 weeks for the intervention population compared to an increase of 0.8% (95% CI –0.8% to 2.3%) for the combined control groups. Multivariate analysis showed that breast feeding rates were adversely influenced by deprivation, but were not significantly influenced by the intervention. Conclusion No evidence was found to support claims that regular monitoring of newborn weight adversely affects breast feeding rates. PMID:16239247

  8. Persistent pulmonary hypertension of the newborn.

    PubMed

    Sharma, Vinay; Berkelhamer, Sara; Lakshminrusimha, Satyan

    2015-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is characterized by elevated pulmonary vascular resistance resulting in right-to-left shunting of blood and hypoxemia. PPHN is often secondary to parenchymal lung disease (such as meconium aspiration syndrome, pneumonia or respiratory distress syndrome) or lung hypoplasia (with congenital diaphragmatic hernia or oligohydramnios) but can also be idiopathic. The diagnosis of PPHN is based on clinical evidence of labile hypoxemia often associated with differential cyanosis. The diagnosis is confirmed by the echocardiographic demonstration of - (a) right-to-left or bidirectional shunt at the ductus or foramen ovale and/or, (b) flattening or leftward deviation of the interventricular septum and/or, (c) tricuspid regurgitation, and finally (d) absence of structural heart disease. Management strategies include optimal oxygenation, avoiding respiratory and metabolic acidosis, blood pressure stabilization, sedation and pulmonary vasodilator therapy. Failure of these measures would lead to consideration of extracorporeal membrane oxygenation (ECMO); however decreased need for this rescue therapy has been documented with advances in medical management. While trends also note improved survival, long-term neurodevelopmental disabilities such as deafness and learning disabilities remain a concern in many infants with severe PPHN. Funded by: 1R01HD072929-0 (SL). PMID:27057331

  9. Newborn Screening for Lysosomal Storage Diseases

    PubMed Central

    Gelb, Michael H.; Scott, C. Ronald; Turecek, Frantisek

    2015-01-01

    BACKGROUND There is worldwide interest in newborn screening for lysosomal storage diseases because of the development of treatment options that give better results when carried out early in life. Screens with high differentiation between affected and nonaffected individuals are critical because of the large number of potential false positives. CONTENT This review summarizes 3 screening methods: (a) direct assay of enzymatic activities using tandem mass spectrometry or fluorometry, (b) immunocapture-based measurement of lysosomal enzyme abundance, and (c) measurement of biomarkers. Assay performance is compared on the basis of small-scale studies as well as on large-scale pilot studies of mass spectrometric and fluorometric screens. SUMMARY Tandem mass spectrometry and fluorometry techniques for direct assay of lysosomal enzymatic activity in dried blood spots have emerged as the most studied approaches. Comparative mass spectrometry vs fluorometry studies show that the former better differentiates between nonaffected vs affected individuals. This in turn leads to a manageable number of screen positives that can be further evaluated with second-tier methods. PMID:25477536

  10. [Acute adrenal insufficiency in the newborn].

    PubMed

    Limal, J-M; Bouhours-Nouet, N; Rouleau, S; Gatelais, F; Coutant, R

    2006-10-01

    Neonatal acute adrenal insufficiency is a rare condition. Congenital adrenal hyperplasia with 21-hydroxylase defect appears to be the most frequent cause, but the neonatal screening has improved its potential severe outcome. The other causes and the various clinical presentations have been exposed, with a special reference to the salt-wasting syndrome. Among them, the severity of X-linked adrenal hypoplasia congenita (AHC) deserves special attention. Two other causes of adrenal hypoplasia have been recently discovered, i.e. a mutation of the SF-1 gene and the syndrome IMAGe. Adrenal insufficiency secondary to ACTH deficiency is often unrecognised despite the risk of severe seizures and hypoglycaemia with brain damage. Finally, the hormonal diagnostic testing and the main therapeutic approach by corticosteroids have been indicated. The aim of this work is to focus the attention of paediatricians who examine a newborn because the risk of delayed diagnosis and fatal outcome may be limited if the clinical symptoms are soon recognized. PMID:16962294

  11. Serum and Urinary NGAL in Septic Newborns

    PubMed Central

    Suchojad, Anna; Majcherczyk, Malgorzata; Jadamus-Niebroj, Danuta; Owsianka-Podlesny, Teresa; Brzozowska, Aniceta

    2014-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a potentially new and highly specific/sensitive marker of acute kidney injury (AKI). The aim of this study was to assess the impact of inflammation on serum and urine NGAL in newborns that were treated due to infection. We determined serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe sepsis) admitted to the Intensive Care Unit in the first month of life, for three consecutive days during the course of treatment for infection. 29 neonates without infection served as the control group. Septic patients, in particular, severe sepsis patients, had increased serum and urinary NGAL levels in the three subsequent days of observation. Five septic patients who developed AKI had elevated serum and urinary NGAL values to a similar extent as septic neonates without AKI. A strong correlation was found between the concentration of serum and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum and urinary NGAL levels were also significantly associated with NTISS (neonatal therapeutic intervention scoring system) values. We conclude that increased serum and urinary NGAL values are not solely a marker of AKI, and more accurately reflect the severity of inflammatory status. PMID:24579085

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

    SciTech Connect

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

    2013-11-15

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

  13. Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke.

    PubMed

    Zhang, Wenting; Wang, Hailian; Zhang, Hui; Leak, Rehana K; Shi, Yejie; Hu, Xiaoming; Gao, Yanqin; Chen, Jun

    2015-10-01

    Stroke is a devastating neurological disease with no satisfactory therapies to preserve long-term neurological function, perhaps due to the sole emphasis on neuronal survival in most preclinical studies. Recent studies have revealed the importance of protecting multiple cell types in the injured brain, such as oligodendrocytes and components of the neurovascular unit, before long-lasting recovery of function can be achieved. For example, revascularization in the ischemic penumbra is critical to provide various neurotrophic factors that enhance the survival and activity of neurons and other progenitor cells, such as oligodendrocyte precursor cells. In the present study, we hypothesized that chronic dietary supplementation with fish oil promotes post-stroke angiogenesis, neurogenesis, and oligodendrogenesis, thereby leading to long-term functional improvements. Mice received dietary supplementation with n-3 PUFA-enriched fish oil for three months before and up to one month after stroke. As expected, dietary n-3 PUFAs significantly increased levels of n-3 PUFAs in the brain and improved long-term behavioral outcomes after cerebral ischemia. n-3 PUFAs also robustly improved revascularization and angiogenesis and boosted the survival of NeuN/BrdU labeled newborn neurons up to 35days after stroke injury. Furthermore, these pro-neurogenic effects were accompanied by robust oligodendrogenesis. Thus, this is the first study to demonstrate that chronic dietary intake of n-3 PUFAs is an effective prophylactic measure not only to protect against ischemic injury for the long term but also to actively promote neurovascular restorative dynamics and brain repair. PMID:25771800

  14. Metabolomic Research on Newborn Infants With Intrauterine Growth Restriction

    PubMed Central

    Liu, Jing; Chen, Xin-Xin; Li, Xiang-Wen; Fu, Wei; Zhang, Wan-Qiao

    2016-01-01

    Abstract To compare differences in metabolites between newborns with intrauterine growth restriction (IUGR) and those who are appropriate for gestational age (AGA) in order to understand the changes in metabolites of newborns with IUGR and to explore the possible metabolic mechanism of tissue and organ damages in patients with IUGR, with the ultimate goal of providing the basis for clinical intervention. A total of 60 newborns with IUGR and 60 AGA newborns who were hospitalized in the neonatal intensive care unit of our hospital between January 2011 and December 2015 and who underwent metabolic disease screening were enrolled in this study. The differences in 21 amino acids and 55 carnitines in peripheral blood, as well as changes in the ratios of free carnitine and acylcarnitine to total carnitine, were compared. Metabolites, particularly alanine, homocysteine, leucine, methionine, ornithine, serine, tyrosine, isovaleryl carnitine, and eicosenoyl carnitine, differed according to newborns’ birth weight (<3rd percentile, 3rd–5th percentiles, 5th–10th percentiles, and 10th–90th percentiles), with those with lower birth weight showing the greater difference (P < 0.05). Metabolites also differed by gestational age, and the differences observed were mainly as follows: preterm and full-term newborns showed differences in metabolites, mainly in alanine, proline, cerotoyl carnitine, and tetradecanedioyl carnitine (P < 0.05); preterm and full-term AGA newborns showed differences in metabolites, mainly in alanine, glutamine, homocysteine, pipecolic acid, proline, heptanoyl carnitine, and sebacoyl carnitine (P < 0.05); and preterm and full-term newborns with IUGR showed differences in metabolites, mainly in arginine, glutamic acid, homocysteine, histidine, leucine, isoleucine, ornithine, serine, threonine, tryptophan, valine, heptanoyl carnitine, decanoyl carnitine, linoleyl carnitine, methylmalonyl carnitine, glutarylcarnitine, sebacoyl carnitine

  15. Overlapping left ventricular restoration.

    PubMed

    Matsui, Yoshiro

    2009-06-01

    Cardiac transplantation, a final option of treatment for refractory heart failure, has not been a standard procedure in Japan especially, mainly because of the shortage of donors. However, surgical methods to restore native heart function, such as surgical ventricular restoration (SVR), are often effective for these cases. The Dor procedure has been used for ischemic cardiomyopathy cases presenting with broad akinetic segments. This is a fine method to exclude the scarred septum and to reduce the intraventricular cavity by encircling purse-string suture, but it may produce a postoperative spherical ventricular shape as a result of endoventricular patch repair. Also, partial left ventriculectomy is not recommended for non-ischemic dilated cardiomyopathy cases for now. A modification of these SVR and surgical approaches to functional mitral regurgitation has been named "overlapping ventriculoplasty" without endoventricular patch and resection of viable cardiac muscle, and "mitral complex reconstruction", which consists of mitral annuloplasty, papillary muscle approximation, and suspension. Although the long-term prognosis of these procedures is undetermined, they could be an important option, at least as an alternative bridge to transplantation. This review will describe the concepts and some technical aspects of these procedures for the end-stage heart. PMID:19474505

  16. Reparative dentistry or restorative dentistry?

    PubMed

    Small, Bruce W

    2008-01-01

    The real definition of restorative dentistry is found in the heart and hands of each individual restorative dentist. His or her training, continuing dental education, mentors, needs (financial and emotional), and style of practice all help to develop a philosophy of dental practice that affects daily restorative decisions. Depending on the factors described above, the decision to repair a tooth or change the environment and restore the tooth to a different shape, size, or color also may change. In recent years, patients' esthetic desires have become more of a factor than they were in previous decades. There are no exact written-tn-stone definitions of restorative dentistry, since the answers are operator-dependent and can vary. This column is meant to be food for thought and perhaps inspire discussion when dentists assemble for meetings or study clubs with the goal of delivering longer-lasting dentistry through a restorative dental practice. PMID:18348367

  17. A Tool to Investigate Symmetry Properties of Newborns Brain: The Newborns' Symmetric Brain Atlas

    PubMed Central

    Noorizadeh, Negar; Kazemi, Kamran; Grebe, Reinhard; Helfroush, Mohammad Sadegh; Mahmoudzadeh, Mahdi; Wallois, Fabrice

    2013-01-01

    It is well established that the two hemispheres of the human brain exhibit a certain degree of asymmetry. Postmortem studies of developing brains of pre- and postpartum infants have shown that already in this early stage of development Heschl gyrus, planum temporale and superior temporal sulcus (STS) exhibit pronounced asymmetry. Advances in acquisition and computational evaluation of high-resolution magnetic resonance images provide enhanced tools for noninvasive studies of brain asymmetry in newborns. Until now most atlases used for image processing contain themselves asymmetry and may thus introduce and/or increase asymmetry already contained in the original data of brain structural or functional images. So, it is preferable to avoid the application of these asymmetric atlases. Thus, in this paper we present our framework to create a symmetric brain atlas from a group of newborns aged between 39 and 42 weeks after gestation. The resulting atlas demonstrates no difference between its original and its flipped version as should be the case for an asymmetric atlas. Consequently, the resulting symmetric atlas can be used for applications such as analysis of development of brain asymmetry in the context of language development. PMID:24967308

  18. Whole-Genome Screening of Newborns? The Constitutional Boundaries of State Newborn Screening Programs

    PubMed Central

    King, Jaime S.; Smith, Monica E.

    2016-01-01

    State newborn screening (NBS) programs routinely screen nearly all of the 4 million newborns in the United States each year for ~30 primary conditions and a number of secondary conditions. NBS could be on the cusp of an unprecedented expansion as a result of advances in whole-genome sequencing (WGS). As WGS becomes cheaper and easier and as our knowledge and understanding of human genetics expand, the question of whether WGS has a role to play in state NBS programs becomes increasingly relevant and complex. As geneticists and state public health officials begin to contemplate the technical and procedural details of whether WGS could benefit existing NBS programs, this is an opportune time to revisit the legal framework of state NBS programs. In this article, we examine the constitutional underpinnings of state-mandated NBS and explore the range of current state statutes and regulations that govern the programs. We consider the legal refinements that will be needed to keep state NBS programs within constitutional bounds, focusing on 2 areas of concern: consent procedures and the criteria used to select new conditions for NBS panels. We conclude by providing options for states to consider when contemplating the use of WGS for NBS. PMID:26729704

  19. Restoration of rivers and streams

    SciTech Connect

    Gore, J.A.

    1985-01-01

    All of the major topics which must be addressed when considering reclamation of a river ecosystem are detailed. Specific chapters deal with hydrologic considerations, including the estimation of meander patterns as well as geomorphic considerations of runoff patterns. Also covered are the preservation and restoration of water quality, as well as biological techniques for restoration of riparian vegetation, habitat enhancement for benthic invertebrates and fisheries, and methods for determining successful biotic restoration.

  20. Maternal attitudes to newborn screening for fragile X syndrome.

    PubMed

    Christie, Louise; Wotton, Tiffany; Bennetts, Bruce; Wiley, Veronica; Wilcken, Bridget; Rogers, Carolyn; Boyle, Jackie; Turner, Catherine; Hansen, Jessica; Hunter, Matthew; Goel, Himanshu; Field, Michael

    2013-02-01

    Although fragile X syndrome (FXS) is the commonest cause of inherited intellectual disability the mean age of diagnosis in Australia is 5.5 years. Newborn screening for FXS can provide an early diagnosis, preventing the "diagnostic odyssey", allowing access to early interventions, and providing reproductive information for parents. Parents of affected children support newborn screening, but few clinical studies have evaluated community attitudes. A pilot study in 2009-2010 was performed in a tertiary hospital to explore feasibility and maternal attitudes. FXS testing of male and female newborns was offered to mothers in addition to routine newborn screening. Mothers were provided with information about FXS, inheritance pattern, carrier status, and associated adult-onset disorders. One thousand nine hundred seventy-one of 2,094 mothers (94%) consented to testing of 2,000 newborns. 86% completed the attitudinal survey and 10% provided written comments. Almost all parents (99%) elected to be informed of both premutation and full mutation status and there was little concern about identification of carrier status or associated adult-onset disorders. Most mothers (96%) were comfortable being approached in the postnatal period and supported testing because no extra blood test was required. Mothers considered an early diagnosis beneficial to help prepare for a child with additional needs (93%) and for reproductive planning (64%). Some were anxious about the potential test results (10%) and others felt their feelings towards their newborn may change if diagnosed with FXS (16%). High participation rates and maternal attitudes indicate a high level of maternal acceptance and voluntary support for newborn screening for FXS.

  1. Early Weight Loss Nomograms for Exclusively Breastfed Newborns

    PubMed Central

    Schaefer, Eric W.; Kuzniewicz, Michael W.; Li, Sherian X.; Walsh, Eileen M.; Paul, Ian M.

    2015-01-01

    BACKGROUND: The majority of newborns are exclusively breastfed during the birth hospitalization, and weight loss is nearly universal for these neonates. The amount of weight lost varies substantially among newborns with higher amounts of weight loss increasing risk for morbidity. No hour-by-hour newborn weight loss nomogram exists to assist in early identification of those on a trajectory for adverse outcomes. METHODS: For 161 471 term, singleton neonates born at ≥36 weeks’ gestation at Northern California Kaiser Permanente hospitals in 2009–2013, data were extracted from the birth hospitalization regarding delivery mode, race/ethnicity, feeding type, and weights from electronic records. Quantile regression was used to create nomograms stratified by delivery mode that estimated percentiles of weight loss as a function of time among exclusively breastfed neonates. Weights measured subsequent to any nonbreastmilk feeding were excluded. RESULTS: Among this sample, 108 907 newborns had weights recorded while exclusively breastfeeding with 83 433 delivered vaginally and 25 474 delivered by cesarean. Differential weight loss by delivery mode was evident 6 hours after delivery and persisted over time. Almost 5% of vaginally delivered newborns and >10% of those delivered by cesarean had lost ≥10% of their birth weight 48 hours after delivery. By 72 hours, >25% of newborns delivered by cesarean had lost ≥10% of their birth weight. CONCLUSIONS: These newborn weight loss nomograms demonstrate percentiles for weight loss by delivery mode for those who are exclusively breastfed. The nomograms can be used for early identification of neonates on a trajectory for greater weight loss and related morbidities. PMID:25554815

  2. Longevity of Posterior Composite Restorations

    PubMed Central

    Opdam, N.J.M.; van de Sande, F.H.; Bronkhorst, E.; Cenci, M.S.; Bottenberg, P.; Pallesen, U.; Gaengler, P.; Lindberg, A.; Huysmans, M.C.D.N.J.M.; van Dijken, J.W.

    2014-01-01

    The aim of this meta-analysis, based on individual participant data from several studies, was to investigate the influence of patient-, materials-, and tooth-related variables on the survival of posterior resin composite restorations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a search resulting in 12 longitudinal studies of direct posterior resin composite restorations with at least 5 years’ follow-up. Original datasets were still available, including placement/failure/censoring of restorations, restored surfaces, materials used, reasons for clinical failure, and caries-risk status. A database including all restorations was constructed, and a multivariate Cox regression method was used to analyze variables of interest [patient (age; gender; caries-risk status), jaw (upper; lower), number of restored surfaces, resin composite and adhesive materials, and use of glass-ionomer cement as base/liner (present or absent)]. The hazard ratios with respective 95% confidence intervals were determined, and annual failure rates were calculated for subgroups. Of all restorations, 2,816 (2,585 Class II and 231 Class I) were included in the analysis, of which 569 failed during the observation period. Main reasons for failure were caries and fracture. The regression analyses showed a significantly higher risk of failure for restorations in high-caries-risk individuals and those with a higher number of restored surfaces. PMID:25048250

  3. Magnesium is a cerebrovasodilator in newborn piglets.

    PubMed

    Kim, C R; Oh, W; Stonestreet, B S

    1997-01-01

    We tested the hypothesis that, in newborn piglets, magnesium results in a dose-dependent prostanoid-mediated cerebrovasodilation. Pial arterioles (50-200 microns in diameter) were serially measured, and cortical subarachnoid cerebrospinal fluid (CSF) was collected for radioimmunoassay of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, hydrolysis product of prostacyclin) and thromboxane B2 (TxB2, metabolite of thromboxane A2) before and after CSF containing 1.2, 2.4, 4.8, and 9.6 mM MgCl2 was suffused over the parietal cortex under a closed cranial window in twelve 2- to 4-day-old piglets. Magnesium suffusion resulted (P < 0.05) in a dose-dependent pial arteriolar vasodilation. The increase in vessel diameter was greater (P < 0.001) with 2.4, 4.8, and 9.6 mM than with 1.2 mM concentration of magnesium. The increase in vessel diameter with 9.6 mM was also greater (P < 0.001) than with the 2.4 mM concentration of magnesium. Magnesium suffusion did not result in changes in cortical CSF prostanoid concentrations. The effect of intravenous indomethacin (5 mg/kg) on cyclooxygenase inhibition in the pial arterioles was confirmed by a 24 +/- 3% decrease in vessel diameter at the baseline (1.2 mM) magnesium concentration. In contrast, cyclooxygenase inhibition with intravenous indomethacin did not attenuate the magnesium-induced cerebrovasodilation. We conclude that in new born piglets magnesium suffusion over the parietal cortex results in a dose-dependent cerebrovasodilation that is most likely not mediated by prostanoids.

  4. Metabolism of threonine in newborn infants.

    PubMed

    Parimi, Prabhu S; Gruca, Lourdes L; Kalhan, Satish C

    2005-12-01

    Threonine kinetics, threonine oxidative pathway, and the relationship between threonine and whole body protein turnover were quantified in 10 healthy term infants during the first 48 h after birth. The kinetic data were obtained 6 h after the last feed (fasting) and in response to formula feeding, using [U-(13)C(4),(15)N]threonine, [(2)H(5)]phenylalanine, and [(15)N]glycine tracers. The rate of carbon dioxide production (Vco(2)) and (13)C enrichment of the expired CO(2) were measured to quantify the rate of oxidation of threonine. The rate of appearance (R(a)) of threonine (136 +/- 37 micromol.kg(-1).h(-1)) was higher in newborn infants than that reported in adults. Formula feeding resulted in a significant decrease in threonine R(a) (P < 0.05). A significant positive correlation was seen between phenylalanine R(a) and threonine R(a), both during fasting and after formula feeding (r(2) = 0.65). In contrast to a 1:1 ratio of threonine and phenylalanine in mixed muscle protein, threonine R(a) relative to phenylalanine R(a) was 2.2 +/- 0.4. The fractional rate of threonine flux oxidized was 20% during fasting and 26% (P < 0.05) in response to nutrient administration. There was a significant correlation between plasma threonine concentration and threonine oxidation (r(2) = 0.75). No measurable incorporation of threonine in plasma glycine was seen. These data suggest that threonine is exclusively degraded by the glycine-independent serine/threonine dehydratase pathway. A higher flux of threonine relative to phenylalanine indicates higher turnover of threonine enriched proteins.

  5. Fatal Melioidosis in a Newborn from Hainan, China.

    PubMed

    Fang, Yao; Chen, Hai; Zhu, Xiong; Mao, Xuhu

    2016-08-01

    Herein, we report a case of fatal melioidosis in a newborn. The newborn died of serious melioidosis with respiratory and multiorgan failure at 16 days of age despite extensive treatment with antibiotics and methylprednisolone. Burkholderia pseudomallei was isolated from the infant's blood and cerebrospinal fluid and identified as a novel sequence type (ST-1341). His father had cough and fever when the newborn was born, and a localized patchy infiltration on the right upper lung was seen in chest radiography, but B. pseudomallei was not isolated. Two years later, the father developed cough and fever again, and the same novel sequence type of B. pseudomallei was isolated from the blood of the father. It is postulated that transmission of B. pseudomallei from the father to the newborn might have occurred during close contact in the first couple of days after birth. Given the high mortality of neonatal melioidosis, particular attention must be paid when the caretakers of the newborn develop fever of unknown origin in a melioidosis-endemic region. PMID:27162267

  6. Newborns' cry melody is shaped by their native language.

    PubMed

    Mampe, Birgit; Friederici, Angela D; Christophe, Anne; Wermke, Kathleen

    2009-12-15

    Human fetuses are able to memorize auditory stimuli from the external world by the last trimester of pregnancy, with a particular sensitivity to melody contour in both music and language. Newborns prefer their mother's voice over other voices and perceive the emotional content of messages conveyed via intonation contours in maternal speech ("motherese"). Their perceptual preference for the surrounding language and their ability to distinguish between prosodically different languages and pitch changes are based on prosodic information, primarily melody. Adult-like processing of pitch intervals allows newborns to appreciate musical melodies and emotional and linguistic prosody. Although prenatal exposure to native-language prosody influences newborns' perception, the surrounding language affects sound production apparently much later. Here, we analyzed the crying patterns of 30 French and 30 German newborns with respect to their melody and intensity contours. The French group preferentially produced cries with a rising melody contour, whereas the German group preferentially produced falling contours. The data show an influence of the surrounding speech prosody on newborns' cry melody, possibly via vocal learning based on biological predispositions.

  7. Hemoglobinopathies in newborns from Salvador, Bahia, Northeast Brazil.

    PubMed

    Adorno, Elisângela Vitória; Couto, Fábio David; Moura Neto, José Pereira de; Menezes, Joelma Figueiredo; Rêgo, Marco; Reis, Mitermayer Galvão dos; Gonçalves, Marilda Souza

    2005-01-01

    Hemoglobinopathies are hereditary disorders of the hemoglobin molecule with a high prevalence worldwide. Brazil has a prevalence of 0.1 to 0.3% of newborns with sickle cell anemia and 20.0 to 25.0% of heterozygous alpha2 thalassemia among African Brazilians. In the present study, we investigated the presence of variant hemoglobins and alpha2(3.7 Kb) and alpha2 (4.2 Kb) thalassemia in newborns from Salvador, Bahia, Brazil. Samples of umbilical cord blood from a total of 590 newborns were analyzed, of which 57 (9.8%) were FAS; 36 (6.5%) FAC; one (0.2%) SF; and five (0.9%) FSC. One hundred fourteen (22.2%) newborns had alpha2(3.7 Kb) thalassemia, of whom 101 (19.7%) were heterozygous and 13 (2.5%) homozygous, showing statistical significance for hematological data between newborns with normal alpha genes and alpha2(3.7 Kb) thalassemia carriers. The alpha2(4.2 Kb) thalassemia was not found. Frequencies found in the present study confirm that hemoglobinopathies are a public health problem in Brazil, emphasizing the need for neonatal screening and genetic counseling programs.

  8. 15 CFR 990.56 - Restoration selection-use of a Regional Restoration Plan or existing restoration project.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Restoration selection-use of a..., DEPARTMENT OF COMMERCE OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.56 Restoration selection—use of a Regional Restoration Plan or existing restoration...

  9. 15 CFR 990.56 - Restoration selection-use of a Regional Restoration Plan or existing restoration project.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Restoration selection-use of a..., DEPARTMENT OF COMMERCE OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.56 Restoration selection—use of a Regional Restoration Plan or existing restoration...

  10. 15 CFR 990.56 - Restoration selection-use of a Regional Restoration Plan or existing restoration project.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Restoration selection-use of a..., DEPARTMENT OF COMMERCE OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Planning Phase § 990.56 Restoration selection—use of a Regional Restoration Plan or existing restoration...

  11. Restorative Nurse Assistant. Instructor Guide.

    ERIC Educational Resources Information Center

    Missouri Univ., Columbia. Instructional Materials Lab.

    This curriculum material covers the basic orientation and necessary skills which would enable the practicing Certified Nurse Assistant to be trained as a Restorative Nurse Assistant. The shift in emphasis from maintenance care to restorative care in the long-term care setting has created a need for trained paraprofessionals who are competent in…

  12. Restorative Justice in School Communities.

    ERIC Educational Resources Information Center

    Karp, David R.; Breslin, Beau

    2001-01-01

    Explores the recent implementation of restorative justice practices in Minnesota, Colorado, and Pennsylvania school communities, examining how their approaches can address substance abuse problems and offer alternatives to zero-tolerance policies. The three programs are committed to the idea that restoration is a more appropriate educational tool…

  13. Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal changes accompanying aging are associated with both increased risk of fractures and impaired fracture healing, which, in turn, is due to compromised bone regeneration potential. These changes are associated with increased serum levels of selected proinflammatory cytokines, e.g., tumor necro...

  14. Restorative biological processes and health

    PubMed Central

    Robles, Theodore F.; Carroll, Judith E.

    2011-01-01

    Research on psychological influences on physiology primarily focuses on biological responses during stressful challenges, and how those responses can become dysregulated with prolonged or repeated exposure to stressful circumstances. At the same time, humans spend considerable time recovering from those challenges, and a host of biological processes involved in restoration and repair take place during normal, non-stressed activities. We review restorative biological processes and evidence for links between psychosocial factors and several restorative processes including sleep, wound healing, antioxidant production, DNA repair, and telomerase function. Across these biological processes, a growing body of evidence suggests that experiencing negative emotional states, including acute and chronic stress, depressive symptoms, and individual differences in negative affectivity and hostility, can influence these restorative processes. This review calls attention to restorative processes as fruitful mechanisms and outcomes for future biobehavioral research. PMID:21927619

  15. Universal newborn hearing screening coming soon: "hear's" why.

    PubMed

    Knott, C

    2001-12-01

    Screening the hearing of all newborns, both NICU and well nursery, is rapidly becoming the standard of care. The impetus for universal newborn hearing screening (UNHS) has come from outside the domain of nursing and the newborn nursery. Because nursing will be involved in nearly all aspects of UNHS, nurses need a thorough knowledge base about permanent childhood hearing loss (PCHL) and UNHS. Technology exisits today that can objectively and physiologically screen for this condition at a cost comparable to metabolic screening. PCHL occurs more than twice as often as all the hemoglobinopathies and inborn errors of metabolism combined. Undiagnosed hearing loss often leads to permanent developmental delays. The ultimate goal of early diagnosis and intervention for a congenital hearing loss is to enable the child to develop language and communication skills that correspond to his chronological age and innate cognitive abilities.

  16. Papaverine intoxication in a newborn: an unusual case report.

    PubMed

    Kahramaner, Zelal; Erdemir, Aydın; Türkoğlu, Ebru; Coşar, Hese; Sütçüoğlu, Sümer; Özer, Esra Arun

    2014-01-01

    Herbal agents are increasingly used for medicinal purposes, but there is a lack of knowledge about the content of these agents. Indiscriminate use of herbal agents may cause severe side effects and also death. We report a newborn who developed convulsions and respiratory arrest after oral intake of an opium poppy preparation containing papaverine for its antitussive effect. The infant experienced a good outcome with supportive treatment. To the best of our knowledge, this is the first time a newborn with papaverine intoxication has been described. Parents should avoid self-medication of their children, and the possibility of exposure to foreign products should be kept in mind in any seizure of a newborn with unexplained origin.

  17. Anaphylactic shock due to hepatitis B immunoglobulin in a newborn.

    PubMed

    Bulbul, Ali; Karadag, Ahmet; Köklü, Esad; Pamuk, Utku; Sarici, Serdar Umit

    2010-10-01

    Hepatitis B immunoglobulin (HBIG) is administered for the passive immunisation of all infants born to HBsAg-positive mothers within 12 h of birth. Adverse effects of HBIG are very rare. In this study, we report a newborn (a female, 33 weeks' gestation and 2030 g birth weight) developing anaphylaxis after HBIG administration. The mother was a Hepatitis B virus (HBV) carrier. Hypotension and erythematous rash developed 7 min after HBIG administration. Reporting the first anaphylaxis case in newborns due to HBIG in literature, we suggest the condition be taken into account, and requisite precautions should be taken against this probable complication in the newborn. PMID:20210693

  18. Newborns' face recognition: role of inner and outer facial features.

    PubMed

    Turati, Chiara; Macchi Cassia, Viola; Simion, Francesca; Leo, Irene

    2006-01-01

    Existing data indicate that newborns are able to recognize individual faces, but little is known about what perceptual cues drive this ability. The current study showed that either the inner or outer features of the face can act as sufficient cues for newborns' face recognition (Experiment 1), but the outer part of the face enjoys an advantage over the inner part (Experiment 2). Inversion of the face stimuli disrupted recognition when only the inner portion of the face was shown, but not when the whole face was fully visible or only the outer features were presented (Experiment 3). The results enhance our picture of what information newborns actually process and encode when they discriminate, learn, and recognize faces.

  19. Crying of a newborn child: alarm signal or protocommunication?

    PubMed

    Clarici, A; Travan, L; Accardo, A; De Vonderweid, U; Bava, A

    2002-12-01

    The purpose of the study was to explore whether the new-born cry is a simple alarm signal or differentiated cries with different meanings. 12 digital audio taped recordings of 6 full-term healthy babies were analysed. Cries of 6 newborns in this preliminary study were recorded in a pain condition after a prick for the hematic check-up the third day after delivery and then while crying spontaneously in the cradle. The sounds were sampled at 44100 Hz with a 16-bit resolution and converted to the .wav format. All the analyses were performed with a software written in the MAT-LAB environment. The most important result was that these new-born children modulated the supralaryngeal tract considerably more in cries following the painful stimulus than in "spontaneous" ones, as would be expected by the hypothesis of crying as "protolanguage."

  20. [Tracheal phospholipid composition and respiratory distress syndrome of the newborn].

    PubMed

    Obladen, M

    1979-03-01

    Tracheal or pharyngeal aspirates were collected in 50 newborn infants with and without respiratory distress syndrome (RDS). After lipid extraction the phospholipids were analyzed with 2-dimensional thin layer chromatography. Surface-active are lecithin (PC), phosphatidylglycerol (PG), and phosphatidylinositol (PI). Newborn infants with RDS always have a complete lack of PG, which makes up to 11% of phospholipid-phosphors in mature newborns. In all infants with and without RDS, a sharp increase of PC occurs in the lung effluent after birth. The recovery from RDS is characterized by marked changes of PI: this phospholipid rises up to twice its initial value if the infants survive. The PI-increase parallels the clinical improvement and reaches its maximum usually on the 5th day of life. At the time of the PI-peak, the infants' surfactant function is sufficient to maintain alveolar stability with spontaneous breathing. In infants dying from RDS the PI-increase was not observed.