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Sample records for newborn mice restore

  1. Safety study of Ciprofloxacin in newborn mice.

    PubMed

    Bourgeois, Thomas; Delezoide, Anne-Lise; Zhao, Wei; Guimiot, Fabien; Adle-Biassette, Homa; Durand, Estelle; Ringot, Maud; Gallego, Jorge; Storme, Thomas; Le Guellec, Chantal; Kassaï, Behrouz; Turner, Mark A; Jacqz-Aigrain, Evelyne; Matrot, Boris

    2016-02-01

    Ciprofloxacin, a broad-spectrum antimicrobial agent belonging to the fluoroquinolone family, is prescribed off-label in infants less than one year of age. Ciprofloxacin is included in the European Medicines Agency priority list of off-patent medicinal products requiring evaluation in neonates. This evaluation is undergoing within the TINN (Treat Infections in Neonates) FP7 EU project. As part of the TINN project, the present preclinical study was designed to assess the potential adverse effects of Ciprofloxacin on neurodevelopment, liver and joints in mice. Newborn mice received subcutaneous Ciprofloxacin at 10, 30 and 100 mg/kg/day from 2 to 12 postnatal days. Peak plasma levels of Ciprofloxacin were in the range of levels measured in human neonates. We examined vital functions in vivo, including cardiorespiratory parameters and temperature, psychomotor development, exploratory behavior, arthro-, nephro- and hepato-toxic effects. We found no effect of Ciprofloxacin at 10 and 30 mg/kg/day. In contrast, administration at 100 mg/kg/day delayed weight gain, impaired cardiorespiratory and psychomotor development, caused inflammatory infiltrates in the connective tissues surrounding the knee joint, and moderately increased extramedullary hematopoiesis. The present study pleads for careful watching of cardiorespiratory and motor development in neonates treated with Ciprofloxacin, in addition to the standard surveillance of arthrotoxicity.

  2. Hyperoxia exposure alters hepatic eicosanoid metabolism in newborn mice.

    PubMed

    Rogers, Lynette K; Tipple, Trent E; Britt, Rodney D; Welty, Stephen E

    2010-02-01

    Prematurely born infants are often treated with supraphysiologic amounts of oxygen, which is associated with lung injury and the development of diseases such as bronchopulmonary dysplasia. Complimentary responses between the lung and liver during the course of hyperoxic lung injury have been studied in adult animals, but little is known about this relationship in neonates. These studies tested the hypothesis that oxidant stress occurs in the livers of newborn mice in response to continuous hyperoxia exposure. Greater levels of glutathione disulfide and nitrotyrosine were detected in lung tissues but not liver tissues from newborn mice exposed to hyperoxia than in room air-exposed controls. However, early increases in 5-lipoxygenase and cyclooxygenases-2 protein levels and increases in total hydroxyeicosatetraenoic acid and prostaglandin levels were observed in the liver tissues of hyperoxia-exposed pups. These studies indicate that free radical oxidation occurs in the lungs of newborn pups exposed to hyperoxia, and alterations in lipid metabolism could be a primary response in the liver tissues. The findings of this study identify possible new mechanisms associated with hyperoxic lung injury in a newborn model of bronchopulmonary dysplasia and thus open opportunities for research.

  3. Cold stimulates the behavioral response to hypoxia in newborn mice.

    PubMed

    Bollen, Bieke; Bouslama, Myriam; Matrot, Boris; Rotrou, Yann; Vardon, Guy; Lofaso, Frédéric; Van den Bergh, Omer; D'Hooge, Rudi; Gallego, Jorge

    2009-05-01

    In newborns, hypoxia elicits increased ventilation, arousal followed by defensive movements, and cries. Cold is known to affect the ventilatory response to hypoxia, but whether it affects the arousal response remains unknown. The aim of the present study was to assess the effects of cold on the ventilatory and arousal responses to hypoxia in newborn mice. We designed an original platform measuring noninvasively and simultaneously the breathing pattern by whole body plethysmography, body temperature by infrared thermography, as well as motor and ultrasonic vocal (USV) responses. Six-day-old mice were exposed twice to 10% O(2) for 3 min at either cold temperature (26 degrees C) or thermoneutrality (33 degrees C). At 33 degrees C, hypoxia elicited a marked increase in ventilation followed by a small ventilatory decline, small motor response, and almost no USVs. Body temperature was not influenced by hypoxia, and oxygen consumption (Vo(2)) displayed minimal changes. At 26 degrees C, hypoxia elicited a slight increase in ventilation with a large ventilatory decline and a large drop of Vo(2). This response was accompanied by marked USV and motor responses. Hypoxia elicited a small decrease in temperature after the return to normoxia, thus precluding any causal influence on the motor and USV responses to hypoxia. In conclusion, cold stimulated arousal and stress responses to hypoxia, while depressing hypoxic hyperpnea. Arousal is an important defense mechanism against sleep-disordered breathing. The dissociation between ventilatory and behavioral responses to hypoxia suggests that deficits in the arousal response associated with sleep breathing disorders cannot be attributed to a depressed hypoxic response.

  4. 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.

  5. Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy.

    PubMed

    Mendonça, Fabricio N; Santos, Luiz E C; Rodrigues, Antônio M; Gomes da Silva, Sérgio; Arida, Ricardo M; da Silveira, Gilcélio A; Scorza, Fulvio A; Almeida, Antônio-Carlos G

    2017-01-01

    Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group. Notably, a larger number of newborn granule cells exhibiting morphological characteristics indicative of correct targeting into the hippocampal circuitry and the absence of basal dendrite projections was also observed in the epileptic animals subjected to physical exercise compared to the epileptic animals. The results described here could represent a positive interference of the physical exercise on the neurogenesis process in subjects with chronic epilepsy. The results may also help to reinterpret the benefits of the physical exercise in alleviating symptoms of depression and cognitive dysfunction.

  6. Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy

    PubMed Central

    Mendonça, Fabricio N.; Santos, Luiz E. C.; Rodrigues, Antônio M.; Gomes da Silva, Sérgio; Arida, Ricardo M.; da Silveira, Gilcélio A.; Scorza, Fulvio A.; Almeida, Antônio-Carlos G.

    2017-01-01

    Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group. Notably, a larger number of newborn granule cells exhibiting morphological characteristics indicative of correct targeting into the hippocampal circuitry and the absence of basal dendrite projections was also observed in the epileptic animals subjected to physical exercise compared to the epileptic animals. The results described here could represent a positive interference of the physical exercise on the neurogenesis process in subjects with chronic epilepsy. The results may also help to reinterpret the benefits of the physical exercise in alleviating symptoms of depression and cognitive dysfunction. PMID:28298884

  7. 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.

  8. 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

  9. 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.

  10. Arsenic speciation transported through the placenta from mother mice to their newborn pups.

    PubMed

    Jin, Yaping; Xi, Shuhua; Li, Xin; Lu, Chunwei; Li, Gexin; Xu, Yuanyuan; Qu, Chunqing; Niu, Yuhong; Sun, Guifan

    2006-07-01

    The primary goal of the present study was to confirm the arsenic species that can be transferred from the mother to the bodies of newborn pups through the placenta and the speciated arsenic distribution in the liver and brain of newborn mice after gestational maternal exposure to inorganic arsenic (iAs). Mother mice were exposed to iAsIII and iAsV in drinking water during gestation. The livers and brains of the mother mice and their newborn pups were taken. Contents of iAs, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic (TMA) compound were detected using the HG-AAS method. Contents of iAs, MMA, and DMA in the liver of mother mice increased with the concentration of arsenite or arsenate in their drinking water. However, only DMA increased with the concentration of arsenate or arsenite in the drinking water in the brain of mother mice. On the other hand, contents of both iAs and DMA in the liver and brain of newborn mice increased with the concentration of arsenate or arsenite administered to their mother orally. Contents of arsenic species in the liver and brain of both mother mice and their newborn pups were significantly lower in the 10 ppm iAsV group than in the 10 ppm iAsIII group. Ratios of iAs or DMA levels between the brain and the liver of newborn mice were larger than 1, whereas those in mother mice were much smaller than 1. iAs taken from drinking water was distributed and metabolized mainly in the liver of mother mice. iAsIII in low levels may be taken up and metabolized easily in the liver compared to iAsV. Both iAs and DMA are transferred from the mother through the placenta and cross the immature blood-brain barrier (BBB) easily. Compared to that in the liver of newborn mice, DMA as an organic metabolite is prevalent in brain, a lipidic organ, if the BBB is not matured enough to prevent it from entering the brain.

  11. EFFECT OF HYPOXIA ON THE RATE OF OXYGEN CONSUMPTION OF NEWBORN, YOUNG, AND ADULT MICE AT VARIOUS ENVIRONMENTAL TEMPERATURES,

    DTIC Science & Technology

    Critical Po2 that is, Po2 below the point at which oxygen consumption is reduced - was measured in newborn, 5-day-old, and adult mice. At...thermoneutral environmental temperatures, the critical Po2 of newborn was 85 mm. Hg; that of 5-day-old mice was 100 mm. Hg; and that of adults was 70 mm. Hg

  12. 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.

  13. 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.

  14. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice.

    PubMed

    Garcia, Stéphanie; Dirat, Béatrice; Tognacci, Thomas; Rochet, Nathalie; Mouska, Xavier; Bonnafous, Stéphanie; Patouraux, Stéphanie; Tran, Albert; Gual, Philippe; Le Marchand-Brustel, Yannick; Gennero, Isabelle; Gouze, Elvire

    2013-09-18

    Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3(ach/+) mice-the mouse model of achondroplasia-twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3(ach/+) mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.

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

    PubMed

    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; Bland, Richard

    2015-03-01

    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.

  16. Photochemical restoration of visual responses in blind mice.

    PubMed

    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

    2012-07-26

    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 behavior in mice lacking retinal photoreceptors, indicating reconstitution of light signaling to brain circuits. AAQ and related photoswitch molecules present a potential drug strategy for restoring retinal function in degenerative blinding diseases.

  17. 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

  18. Carcinogenic Activity of Some Benz(a)Anthracene Derivatives in Newborn Mice

    PubMed Central

    Roe, F. J. C.; Dipple, A.; Mitchley, B. C. V.

    1972-01-01

    Equimolar doses of 7-methylbenz(a)anthracene and 3 of its derivatives were given to newborn male and female Swiss mice. All 4 substances tested increased the risk of tumour development compared with that seen in control mice given the vehicle, arachis oil, only. 7-Methylbenz(a)anthracene itself was the most actively tumorigenic of the compounds studied, giving rise to subcutaneous sarcomata at the site of injection, and multiple lung tumours and liver tumours. 7-Bromomethyl-12-methylbenz(a)-anthracene was similarly active in the lung and liver but evoked fewer subcutaneous sarcomata. 7-Bromomethylbenz(a)anthracene was seemingly slightly less active than either 7-methylbenz(a)anthracene or 7-bromomethyl-12-methylbenz(a)anthracene. 4-Chloro-7-bromomethylbenz(a)anthracene exhibited only marginal activity in that it slightly increased the risk of liver tumour development in male mice. PMID:4647396

  19. Tmc gene therapy restores auditory function in deaf mice.

    PubMed

    Askew, Charles; Rochat, Cylia; Pan, Bifeng; Asai, Yukako; Ahmed, Hena; Child, Erin; Schneider, Bernard L; Aebischer, Patrick; Holt, Jeffrey R

    2015-07-08

    Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken β-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations.

  20. Pathology of Murine Cytomegalovirus Infection in Newborn Mice. Muscle, Heart and Brown Fat Lesions

    PubMed Central

    Lussier, G.

    1974-01-01

    Newborn mice were inoculated intracerebrally with murine cytomegalovirus and studies were made of the pathological changes in the striate and cardiac muscle and brown fat. Widespread necrosis was seen in muscle and brown fat in the early stages of the infection. Necrotic lesions became calcified. By 56 days lesions were not resolved in the heart and brown fat but were completely resolved in skeletal muscle. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.Fig. 9. PMID:4363374

  1. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice

    PubMed Central

    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. PMID:26272953

  2. VARA attenuates hyperoxia-induced impaired alveolar development and lung function in newborn mice

    PubMed Central

    James, Masheika L.; Ross, A. Catharine; Nicola, Teodora; Steele, Chad

    2013-01-01

    We have recently shown that a combination of vitamin A (VA) and retinoic acid (RA) in a 10:1 molar ratio (VARA) synergistically increases lung retinoid content in newborn rodents, more than either VA or RA alone in equimolar amounts. We hypothesized that the increase in lung retinoids would reduce oxidative stress and proinflammatory cytokines, resulting in attenuation of alveolar simplification and abnormal lung function in hyperoxia-exposed newborn mice. Newborn C57BL/6 mice were exposed to 85% O2 (hyperoxia) or air (normoxia) for 7 or 14 days from birth and given vehicle or VARA every other day. Lung retinol content was measured by HPLC, function was assessed by flexiVent, and development was evaluated by radial alveolar counts, mean linear intercept, and secondary septal crest density. Mediators of oxidative stress, inflammation, and alveolar development were evaluated in lung homogenates. We observed that VARA increased lung retinol stores and attenuated hyperoxia-induced alveolar simplification while increasing lung compliance and lowering resistance. VARA attenuated hyperoxia-induced increases in DNA damage and protein oxidation accompanied with a reduction in nuclear factor (erythroid-derived 2)-like 2 protein but did not alter malondialdehyde adducts, nitrotyrosine, or myeloperoxidase concentrations. Interferon-γ and macrophage inflammatory protein-2α mRNA and protein increased with hyperoxia, and this increase was attenuated by VARA. Our study suggests that the VARA combination may be a potential therapeutic strategy in conditions characterized by VA deficiency and hyperoxia-induced lung injury during lung development, such as bronchopulmonary dysplasia in preterm infants. PMID:23585226

  3. Experimental Zika virus infection induces spinal cord injury and encephalitis in newborn Swiss mice.

    PubMed

    Fernandes, Natália C C A; Nogueira, Juliana S; Réssio, Rodrigo A; Cirqueira, Cinthya S; Kimura, Lidia M; Fernandes, Karolina R; Cunha, Mariana S; Souza, Renato P; Guerra, Juliana M

    2017-02-01

    A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America, with neurological symptons including meningoencephalitis and Guillain-Barré syndrome in adults, besides an apparent increased incidence of microcephaly in infants born to infected mothers. It is becoming a necessity to have a trustworthy animal model to better understand ZIKV infection. In this study we used newborn white Swiss mice as a model to investigate the ZIKV strain recently isolated in Brazil. ZIKV was inoculated via intracerebral and subcutaneous routes and analysed through gross histopathology and immunohistochemistry. Here we demonstrated first that the intracerebral group (ICG) displayed severe cerebral lesions, with neuronal death, presence of apoptotic bodies, white matter degeneration and neutrophil perivascular cuffing. In the subcutaneous group (SCG), we observed moderate cerebral lesions, morphologically similar to that found in ICG and additional myelopathy, with architectural loss, marked by neuronal death and apoptotic bodies. Interestingly, we found an intense astrogliosis in brain of both groups, with increased immunoexpression of GFAP (glial fibrillary acidic protein) and presence of hypertrophic astrocytes. The spinal cord of subcutaneous group (SCG) exhibited reduction of astrocytes, but those positive for GFAP were hypertrophic and presented prolonged cellular processes. Finally significant lesions in the central nervous system (CNS) were present in newborn mice inoculated by both routes, but SCG method led to an important neurological manifestations (including myelopathy), during a longer period of time and appears for us to be a better model for ZIKV infection.

  4. Hyperoxia-induced immature brain injury through the TLR4 signaling pathway in newborn mice.

    PubMed

    Liu, Yang; Jiang, Pu; Du, Min; Chen, Kun; Chen, Amber; Wang, Yang; Cao, Fei; Deng, Shixiong; Xu, Ying

    2015-06-12

    hyperoxia-induced immune responses in the immature brain and 2) the loss of TLR4 activation may abrogate the neuronal apoptosis and cognitive deficits following hyperoxia exposure in newborn mice.

  5. Restoration of Regenerative Osteoblastogenesis in Aged Mice: Modulation of TNF

    PubMed Central

    Wahl, Elizabeth C; Aronson, James; Liu, Lichu; Fowlkes, John L; Thrailkill, Kathryn M; Bunn, Robert C; Skinner, Robert A; Miller, Mike J; Cockrell, Gael E; Clark, Lindsey M; Ou, Yang; Isales, Carlos M; Badger, Thomas M; Ronis, Martin J; Sims, John; Lumpkin, Charles K

    2010-01-01

    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 necrosis factor α (TNF-α). We have used a unique model of bone regeneration to demonstrate (1) that aged-related deficits in direct bone formation can be restored to young mice by treatment with TNF blockers and (2) that the cyclin-dependent kinase inhibitor p21 is a candidate for mediation of the osteoinhibitory effects of TNF. It has been hypothesized recently that TNF antagonists may represent novel anabolic agents, and we believe that the data presented here represent a successful test of this hypothesis. © 2010 American Society for Bone and Mineral Research PMID:19580462

  6. GABA Regulates Corticotropin Releasing Hormone Levels in the Paraventricular Nucleus of the Hypothalamus in Newborn Mice

    PubMed Central

    Stratton, Matthew S.; Searcy, Brian T.; Tobet, Stuart A.

    2011-01-01

    The paraventricular nucleus of the hypothalamus (PVN) is a major regulator of stress responses via release of Corticotropin Releasing Hormone (CRH) to the pituitary gland. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is characteristic of individuals with Major Depressive Disorder (MDD). Postmortem data from individuals diagnosed with MDD show increased levels of CRH mRNA and CRH immunoreactive neurons in the PVN. In the current study, an immunohistochemical (IHC) analysis revealed increased levels of CRH in the PVN of newborn mice lacking functional GABAB receptors. There was no difference in the total number of CRH immunoreactive cells. By contrast, there was a significant increase in the amount of CRH immunoreactivity per cell. Interestingly, this increase in CRH levels in the GABAB receptor R1 subunit knockout was limited to the rostral PVN. While GABAergic regulation of the HPA axis has been previously reported in adult animals, this study provides evidence of region-specific GABA modulation of immunoreactive CRH in newborns. PMID:21236282

  7. A simple method for short-term controlled anesthesia in newborn mice.

    PubMed

    Drobac, Estelle; Durand, Estelle; Laudenbach, Vincent; Mantz, Jean; Gallego, Jorge

    2004-09-15

    In this study, we describe a simple and inexpensive method for inducing short-term anesthesia and rapid recovery in newborn mice. Litters of Swiss mice pups were randomly allocated to testing on postnatal days 2, 5, and 8. Anesthesia was induced by placing the pup in a syringe and adding a volume of isoflurane-saturated gas that produced an estimated level of 32% isoflurane. Exposure to isoflurane lasted 30 s. All the pups survived the anesthesia. At all study ages, this method abolished the nociceptive response to tail clamp without inducing mortality, thus showing effective anesthesia. Recovery from anesthesia was assessed immediately after isoflurane exposure, based on two nonnoxious behavioral tests: the defensive response to a drop of water (10 tests, 1 min apart) and 10 min later the righting reflex, i.e., the time to recovery of the prone position (five tests, 10 min apart). The water drop test scores increased during the recovery phase toward the control values in all age groups. Treatment and time had no significant effect on righting reflex scores. The initial volume in the syringe, the volume of added isoflurane-saturated gas, and the duration of exposure may be adjusted according to postnatal age and specific strains or species (e.g., rats). This method is well suited to behavioral or physiological phenotype studies in developing mice, in which noxious procedures must precede functional testing, making rapid recovery from anesthesia a key requirement.

  8. 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.

  9. 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.

  10. Glucocortiocoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development

    PubMed Central

    Kosmac, Kate; Bantug, Glenn R.; Pugel, Ester P.; Cekinovic, Djurdjica; Jonjic, Stipan; Britt, William J.

    2013-01-01

    Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV. PMID:23505367

  11. 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.

  12. Restoration of cardiopulmonary function with 21% versus 100% oxygen after hypoxaemia in newborn pigs

    PubMed Central

    Fugelseth, D; Borke, W; Lenes, K; Matthews, I; Saugstad, O; Thaulow, E

    2005-01-01

    Objective: To assess the consequences of hypoxaemia and resuscitation with room air versus 100% O2 on cardiac troponin I (cTnI), cardiac output (CO), and pulmonary artery pressure (PAP) in newborn pigs. Design: Twenty anaesthetised pigs (12–36 hours; 1.7–2.7 kg) were subjected to hypoxaemia by ventilation with 8% O2. When mean arterial blood pressure fell to 15 mm Hg, or arterial base excess was ⩽ –20 mmol/l, resuscitation was performed with 21% (n = 10) or 100% (n = 10) O2 for 30 minutes, then ventilation with 21% O2 for 120 minutes. Blood was analysed for cTnI. Ultrasound examinations of CO and PAP (estimated from tricuspid regurgitation velocity (TR-Vmax)) were performed at baseline, during hypoxia, and at the start of and during reoxygenation. Results: cTnI increased from baseline to the end point (p<0.001), confirming a serious myocardial injury, with no differences between the 21% and 100% O2 group (p = 0.12). TR-Vmax increased during the insult and returned towards baseline values during reoxygenation, with no differences between the groups (p = 0.11) or between cTnI concentrations (p = 0.31). An inverse relation was found between increasing age and TR-Vmax during hypoxaemia (p = 0.034). CO per kg body weight increased during the early phase of hypoxaemia (p<0.001), then decreased. Changes in CO per kg were mainly due to changes in heart rate, with no differences between the groups during reoxygenation (p = 0.298). Conclusion: Hypoxaemia affects the myocardium and PAP. During this limited period of observation, reoxygenation with 100% O2 showed no benefits compared with 21% O2 in normalising myocardial function and PAP. The important issue may be resuscitation and reoxygenation without hyperoxygenation. PMID:15846013

  13. 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.

  14. Fluorescent Labeling of Newborn Dentate Granule Cells in GAD67-GFP Transgenic Mice: A Genetic Tool for the Study of Adult Neurogenesis

    PubMed Central

    Zhao, Shengli; Zhou, Yang; Gross, Jimmy; Miao, Pei; Qiu, Li; Wang, Dongqing; Chen, Qian; Feng, Guoping

    2010-01-01

    Neurogenesis in the adult hippocampus is an important form of structural plasticity in the brain. Here we report a line of BAC transgenic mice (GAD67-GFP mice) that selectively and transitorily express GFP in newborn dentate granule cells of the adult hippocampus. These GFP+ cells show a high degree of colocalization with BrdU-labeled nuclei one week after BrdU injection and express the newborn neuron marker doublecortin and PSA-NCAM. Compared to mature dentate granule cells, these newborn neurons show immature morphological features: dendritic beading, fewer dendritic branches and spines. These GFP+ newborn neurons also show immature electrophysiological properties: higher input resistance, more depolarized resting membrane potentials, small and non-typical action potentials. The bright labeling of newborn neurons with GFP makes it possible to visualize the details of dendrites, which reach the outer edge of the molecular layer, and their axon (mossy fiber) terminals, which project to the CA3 region where they form synaptic boutons. GFP expression covers the whole developmental stage of newborn neurons, beginning within the first week of cell division and disappearing as newborn neurons mature, about 4 weeks postmitotic. Thus, the GAD67-GFP transgenic mice provide a useful genetic tool for studying the development and regulation of newborn dentate granule cells. PMID:20824075

  15. 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

  16. Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

    PubMed Central

    Ghislin, Stéphanie; Ouzren-Zarhloul, Nassima; Kaminski, Sandra; Frippiat, Jean-Pol

    2015-01-01

    During spaceflight, organisms are subjected to mechanical force changes (gravity (G) changes) that affect the immune system. However, gravitational effects on lymphopoiesis have rarely been studied. Consequently, we investigated whether the TCRβ repertoire, created by V(D)J recombination during T lymphopoiesis, is affected by hypergravity exposure during murine development. To address this question, C57BL/6j mice were mated in a centrifuge so that embryonic development, birth and TCRβ rearrangements occurred at 2G. Pups were sacrificed at birth, and their thymus used to quantify transcripts coding for factors required for V(D)J recombination and T lymphopoiesis. We also created cDNA mini-libraries of TCRβ transcripts to study the impact of hypergravity on TCRβ diversity. Our data show that hypergravity exposure increases the transcription of TCRβ chains, and of genes whose products are involved in TCR signaling, and affects the V(D)J recombination process. We also observed that ~85% of the TCRβ repertoire is different between hypergravity and control pups. These data indicate that changing a mechanical force (the gravity) during ontogeny will likely affect host immunity because properties of loops constituting TCR antigen-binding sites are modified in hypergravity newborns. The spectrum of peptides recognized by TCR will therefore likely be different. PMID:25792033

  17. 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

  18. Clone-forming activity of embryonal stem hemopoietic cells after transplantation to newborn or adult sublethally irradiated mice.

    PubMed

    Drize, N I; Chertkov, I L

    2000-07-01

    Hemopoietic activity of stem hemopoietic cells from the liver of embryos was studied at different terms of intrauterine development. The fate of individual clones of hemopoietic cells marked by human adenosine deaminase gene was followed up in sublethally irradiated or newborn recipients. The efficiency of marker gene incorporation in primitive stem hemopoietic cells from the liver of 12-, 13-, and 17-day embryos was not high. Gene transfer was performed without cell prestimulation to division, and hence, these data show that primitive stem cells proliferate even in 17-day embryos. Cells from embryonal liver in all terms maintain hemopoiesis both in newborn and adult microenvironment, hemopoiesis being realized according to the clonal succession model, i. e. in the some way after transplantation of the bone marrow from adult mice.

  19. Maternal docosahexaenoic acid supplementation decreases lung inflammation in hyperoxia-exposed newborn mice.

    PubMed

    Rogers, Lynette K; Valentine, Christina J; Pennell, Michael; Velten, Markus; Britt, Rodney D; Dingess, Kelly; Zhao, Xuilan; Welty, Stephen E; Tipple, Trent E

    2011-02-01

    DHA is a long-chain fatty acid that has potent antiinflammatory properties. Whereas maternal DHA dietary supplementation has been shown to improve cognitive development in infants fed DHA-supplemented milk, the antiinflammatory effects of maternal DHA supplementation on the developing fetus and neonate have not been extensively explored. Pregnant C3H/HeN dams were fed purified control or DHA-supplemented diets (~0.25% of total fat) at embryonic d 16 and consumed these diets throughout the study. At birth, the nursing mouse pups were placed in room air (RA; 21% O(2)) or >95% O(2) (hyperoxia) for up to 7 d. These studies tested the hypothesis that maternal DHA supplementation would decrease inflammation and improve alveolarization in the lungs of newborn mouse pups exposed to hyperoxia. Survival, inflammatory responses, and lung growth were compared among control diet/RA, DHA/RA, control/O(2), and DHA/O(2) pups. There were fewer neutrophils and macrophages in lung tissues from pups nursed by DHA-supplemented dams than in those nursed by dams fed the control diet at 7 d of hyperoxia exposure (P < 0.015). Although differences due to hyperoxia exposure were observed, maternal diet did not affect keratinocyte-derived chemokine, macrophage inflammatory protein-2, IL-1β, or TNFα mRNA levels in pup tissues. Hyperoxia also induced NF-κB activity, but maternal diet did not affect NF-κB or PPARγ activities. In mice, DHA supplementation decreases leukocyte infiltration in the offspring exposed to hyperoxia, suggesting a potential role for DHA supplementation as a therapy to reduce inflammation in preterm infants.

  20. Transient restoration of gene rearrangement at multiple T cell receptor loci in gamma-irradiated scid mice

    PubMed Central

    1996-01-01

    The developmental arrest of thymocytes from scid mice, deficient in variable, (diversity), and joining, or V(D)J recombination, can be overcome by sublethal gamma-irradiation. Since previous studies focused on restoration of rearrangement of the T cell receptor (TCR) beta locus, productive rearrangement of which is selected for, we sought to examine to what extent locus specificity and cellular selection contributed to the observed effects. We report here that irradiation of newborn scid mice induces normal V-D-J rearrangements of the TCR delta locus, which like TCR beta, is also actively rearranged in CD(4-)CD(8-) (double negative) thymocytes. In contrast, no complete V-J alpha rearrangements were detected. Instead, we detected substantial levels of hairpin-terminated coding ends at the 5' end of the J alpha locus, demonstrating that TCR alpha rearrangements manifest the effects of the scid mutation. Irradiation, therefore, transiently compensates for the effects of the scid mutation in a locus-nonspecific manner in thymocytes, resulting in a burst of normal TCR beta and delta rearrangements. Irradiation also allows the development of cells that can initiate but fail to complete V(D)J recombination events at the TCR alpha locus, which is normally inaccessible in scid thymocytes. PMID:8760795

  1. 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.

  2. 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.

  3. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice

    PubMed Central

    Tamarat, Radia; Silvestre, Jean-Sébastien; Huijberts, Maya; Benessiano, Joelle; Ebrahimian, Teni G.; Duriez, Micheline; Wautier, Marie-Paule; Wautier, Jean Luc; Lévy, Bernard I.

    2003-01-01

    We hypothesized that formation of advanced glycation end products (AGEs) associated with diabetes reduces matrix degradation by metalloproteinases (MMPs) and contributes to the impairment of ischemia-induced angiogenesis. Mice were treated or not with streptozotocin (40 mg/kg) and streptozotocin plus aminoguanidine (AGEs formation blocker, 50 mg/kg). After 8 weeks of treatment, hindlimb ischemia was induced by right femoral artery ligature. Plasma AGE levels were strongly elevated in diabetic mice when compared with control mice (579 ± 21 versus 47 ± 4 pmol/ml, respectively; P < 0.01). Treatment with aminoguanidine reduced AGE plasma levels when compared with untreated diabetic mice (P < 0.001). After 28 days of ischemia, ischemic/nonischemic leg angiographic score, capillary density, and laser Doppler skin-perfusion ratios were 1.4-, 1.5-, and 1.4-fold decreased in diabetic mice in reference to controls (P < 0.01). Treatment with aminoguanidine completely normalized ischemia-induced angiogenesis in diabetic mice. We next analyzed the role of proteolysis in AGE formation-induced hampered neovascularization process. After 3 days of ischemia, MMP-2 activity and MMP-3 and MMP-13 protein levels were increased in untreated and aminoguanidine-treated diabetic mice when compared with controls (P < 0.05). Despite this activation of the MMP pathway, collagenolysis was decreased in untreated diabetic mice. Conversely, treatment of diabetic mice with aminoguanidine restored collagenolysis toward levels found in control mice. In conclusion, blockade of AGE formation by aminoguanidine normalizes impaired ischemia-induced angiogenesis in diabetic mice. This effect is probably mediated by restoration of matrix degradation processes that are disturbed as a result of AGE accumulation. PMID:12805564

  4. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice.

    PubMed

    Tamarat, Radia; Silvestre, Jean-Sébastien; Huijberts, Maya; Benessiano, Joelle; Ebrahimian, Teni G; Duriez, Micheline; Wautier, Marie-Paule; Wautier, Jean Luc; Lévy, Bernard I

    2003-07-08

    We hypothesized that formation of advanced glycation end products (AGEs) associated with diabetes reduces matrix degradation by metalloproteinases (MMPs) and contributes to the impairment of ischemia-induced angiogenesis. Mice were treated or not with streptozotocin (40 mg/kg) and streptozotocin plus aminoguanidine (AGEs formation blocker, 50 mg/kg). After 8 weeks of treatment, hindlimb ischemia was induced by right femoral artery ligature. Plasma AGE levels were strongly elevated in diabetic mice when compared with control mice (579 +/- 21 versus 47 +/- 4 pmol/ml, respectively; P < 0.01). Treatment with aminoguanidine reduced AGE plasma levels when compared with untreated diabetic mice (P < 0.001). After 28 days of ischemia, ischemic/nonischemic leg angiographic score, capillary density, and laser Doppler skin-perfusion ratios were 1.4-, 1.5-, and 1.4-fold decreased in diabetic mice in reference to controls (P < 0.01). Treatment with aminoguanidine completely normalized ischemia-induced angiogenesis in diabetic mice. We next analyzed the role of proteolysis in AGE formation-induced hampered neovascularization process. After 3 days of ischemia, MMP-2 activity and MMP-3 and MMP-13 protein levels were increased in untreated and aminoguanidine-treated diabetic mice when compared with controls (P < 0.05). Despite this activation of the MMP pathway, collagenolysis was decreased in untreated diabetic mice. Conversely, treatment of diabetic mice with aminoguanidine restored collagenolysis toward levels found in control mice. In conclusion, blockade of AGE formation by aminoguanidine normalizes impaired ischemia-induced angiogenesis in diabetic mice. This effect is probably mediated by restoration of matrix degradation processes that are disturbed as a result of AGE accumulation.

  5. Voltage-activated Ca2+ channels and their role in the endocrine function of the pituitary gland in newborn and adult mice

    PubMed Central

    Sedej, Simon; Tsujimoto, Tetsuhiro; Zorec, Robert; Rupnik, Marjan

    2004-01-01

    We have prepared fresh pituitary gland slices from adult and, for the first time, from newborn mice to assess modulation of secretory activity via voltage-activated Ca2+ channels (VACCs). Currents through VACCs and membrane capacitance have been measured with the whole-cell patch-clamp technique. Melanotrophs in newborns were significantly larger than in adults. In both newborn and adult melanotrophs activation of VACCs triggered exocytosis. All pharmacologically isolated VACC types contributed equally to the secretory activity. However, the relative proportion of VACCs differed between newborns and adults. In newborn cells L-type channels dominated and, in addition, an exclusive expression of a toxin-resistant R-type-like current was found. The expression of L-type VACCs was up-regulated by the increased oestrogen levels observed in females, and was even more emphasized in the cells of pregnant females and oestrogen-treated adult male mice. We suggest a general mechanism modulating endocrine secretion in the presence of oestrogen and particularly higher sensitivity to treatments with L-type channel blockers during high oestrogen physiological states. PMID:14724188

  6. Prophylactic versus Therapeutic Fingolimod: Restoration of Presynaptic Defects in Mice Suffering from Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Merega, Elisa; Di Prisco, Silvia; Padolecchia, Cristina; Grilli, Massimo; Milanese, Marco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Bonanno, Giambattista; Marchi, Mario

    2017-01-01

    Fingolimod, the first oral, disease-modifying therapy for MS, has been recently proposed to modulate glutamate transmission in the central nervous system (CNS) of mice suffering from Experimental Autoimmune Encephalomyelitis (EAE) and in MS patients. Our study aims at investigating whether oral fingolimod recovers presynaptic defects that occur at different stages of disease in the CNS of EAE mice. In vivo prophylactic (0.3 mg/kg for 14 days, from the 7th day post immunization, d.p.i, the drug dissolved in the drinking water) fingolimod significantly reduced the clinical symptoms and the anxiety-related behaviour in EAE mice. Spinal cord inflammation, demyelination and glial cell activation are markers of EAE progression. These signs were ameliorated following oral fingolimod administration. Glutamate exocytosis was shown to be impaired in cortical and spinal cord terminals isolated from EAE mice at 21 ± 1 d.p.i., while GABA alteration emerged only at the spinal cord level. Prophylactic fingolimod recovered these presynaptic defects, restoring altered glutamate and GABA release efficiency. The beneficial effect occurred in a dose-dependent, region-specific manner, since lower (0.1–0.03 mg/kg) doses restored, although to a different extent, synaptic defects in cortical but not spinal cord terminals. A delayed reduction of glutamate, but not of GABA, exocytosis was observed in hippocampal terminals of EAE mice at 35 d.p.i. Therapeutic (0.3 mg/kg, from 21 d.p.i. for 14 days) fingolimod restored glutamate exocytosis in the cortex and in the hippocampus of EAE mice at 35 ± 1 d.p.i. but not in the spinal cord, where also GABAergic defects remained unmodified. These results improve our knowledge of the molecular events accounting for the beneficial effects elicited by fingolimod in demyelinating disorders. PMID:28125677

  7. 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

  8. Normalization of Patient-Identified Plasma Biomarkers in SMNΔ7 Mice following Postnatal SMN Restoration

    PubMed Central

    Arnold, W. David; Duque, Sandra; Iyer, Chitra C.; Zaworski, Phillip; McGovern, Vicki L.; Taylor, Shannon J.; von Herrmann, Katharine M.; Kobayashi, Dione T.; Chen, Karen S.; Kolb, Stephen J.; Paushkin, Sergey V.; Burghes, Arthur H. M.

    2016-01-01

    Introduction and Objective Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function. The goal was to determine whether levels of plasma markers were altered in the SMNΔ7 mouse model of SMA and whether postnatal SMN restoration resulted in normalization of the biomarkers. Methods SMNΔ7 and control mice were treated with antisense oligonucleotides (ASO) targeting ISS-N1 to increase SMN protein from SMN2 or scramble ASO (sham treatment) via intracerebroventricular injection on postnatal day 1 (P1). Brain, spinal cord, quadriceps muscle, and liver were analyzed for SMN protein levels at P12 and P90. Ten plasma biomarkers (a subset of biomarkers in the SMA-MAP panel available for analysis in mice) were analyzed in plasma obtained at P12, P30, and P90. Results Of the eight plasma biomarkers assessed, 5 were significantly changed in sham treated SMNΔ7 mice compared to control mice and were normalized in SMNΔ7 mice treated with ASO. Conclusion This study defines a subset of the SMA-MAP plasma biomarker panel that is abnormal in the most commonly used mouse model of SMA. Furthermore, some of these markers are responsive to postnatal SMN restoration. These findings support continued clinical development of these potential prognostic and pharmacodynamic biomarkers. PMID:27907033

  9. Prophylactic versus Therapeutic Fingolimod: Restoration of Presynaptic Defects in Mice Suffering from Experimental Autoimmune Encephalomyelitis.

    PubMed

    Bonfiglio, Tommaso; Olivero, Guendalina; Merega, Elisa; Di Prisco, Silvia; Padolecchia, Cristina; Grilli, Massimo; Milanese, Marco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Bonanno, Giambattista; Marchi, Mario; Pittaluga, Anna

    2017-01-01

    Fingolimod, the first oral, disease-modifying therapy for MS, has been recently proposed to modulate glutamate transmission in the central nervous system (CNS) of mice suffering from Experimental Autoimmune Encephalomyelitis (EAE) and in MS patients. Our study aims at investigating whether oral fingolimod recovers presynaptic defects that occur at different stages of disease in the CNS of EAE mice. In vivo prophylactic (0.3 mg/kg for 14 days, from the 7th day post immunization, d.p.i, the drug dissolved in the drinking water) fingolimod significantly reduced the clinical symptoms and the anxiety-related behaviour in EAE mice. Spinal cord inflammation, demyelination and glial cell activation are markers of EAE progression. These signs were ameliorated following oral fingolimod administration. Glutamate exocytosis was shown to be impaired in cortical and spinal cord terminals isolated from EAE mice at 21 ± 1 d.p.i., while GABA alteration emerged only at the spinal cord level. Prophylactic fingolimod recovered these presynaptic defects, restoring altered glutamate and GABA release efficiency. The beneficial effect occurred in a dose-dependent, region-specific manner, since lower (0.1-0.03 mg/kg) doses restored, although to a different extent, synaptic defects in cortical but not spinal cord terminals. A delayed reduction of glutamate, but not of GABA, exocytosis was observed in hippocampal terminals of EAE mice at 35 d.p.i. Therapeutic (0.3 mg/kg, from 21 d.p.i. for 14 days) fingolimod restored glutamate exocytosis in the cortex and in the hippocampus of EAE mice at 35 ± 1 d.p.i. but not in the spinal cord, where also GABAergic defects remained unmodified. These results improve our knowledge of the molecular events accounting for the beneficial effects elicited by fingolimod in demyelinating disorders.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Ajoene restored behavioral patterns and liver glutathione level in morphine treated C57BL6 mice.

    PubMed

    Yun, Jaesuk; Oliynyk, Sergiy; Lee, Yeonju; Kim, Jieun; Yun, Kyunghwa; Jeon, Raok; Ryu, Jae-Ha; Oh, Seikwan

    2017-01-01

    Oxidative stress exacerbates drug dependence induced by administration of opiate analgesics such as morphine-induced tolerance and physical dependence associated with the reduction in hepatic glutathione (GSH) level. Ajoene obtained from garlic (Allium sativum L.) has been reported for anti-tumorigenic, anti-oxidative and neuroprotective properties, however, little is known about its effect on morphine-induced dependence. Therefore, this study aimed at the effect of ajoene on physical and/or psychological dependence and liver GSH content in morphine-treated mice. Conditioned place preference (CPP) test and measurement of morphine withdrawal syndrome were performed in C57BL6 mice for behavioral experiments. Thereafter, mice were sacrificed for measurement of serum and liver GSH levels. Ajoene restored CPP and naloxone-precipitated jumping behavior in mice exposed to morphine. Moreover, the reduced level of liver GSH content in morphine treated mice was back to normal after ajoene administration. Taken together, ajoene improved behavioral patterns in mice exposed to morphine suggesting its potential therapeutic benefit against morphine-induced dependence.

  15. PD-1 deletion restores susceptibility to experimental autoimmune encephalomyelitis in miR-155-deficient mice.

    PubMed

    Zhang, Jinyu; Braun, Michel Y

    2014-07-01

    MiR-155 (-/-) mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), while Pdcd1 (-/-) mice develop a more severe form of the disease. To determine the conflicting roles of these two molecules in the disease, we generated miR-155 (-/-) Pdcd1 (-/-) double knockout (DKO) mice. We found that ablation of programmed cell death protein 1 (PD-1) expression in miR-155-deficient mice restored the susceptibility to EAE. The increased severity of the disease in DKO mice was accompanied by an enhanced T-cell infiltration into the brain as well as an increased production of pro-inflammatory cytokines IFN-γ and IL-17. Furthermore, the major contribution of the DKO to EAE was T-cell intrinsic since adoptive transfer of CD4(+) T cells from DKO donors promoted the disease in lymphopenic recipients. These results define PD-1 deficiency in miR-155 (-/-) mice as a promoting factor of autoimmune inflammation by increasing antigen-driven T-cell expansion and infiltration.

  16. 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.

  17. Tumor-promoting activities of hydroquinone and 1,1-dimethylhydrazine after initiation of newborn mice with 1-methyl-1-nitrosourea.

    PubMed

    Tamura, T; Shibutani, M; Toyoda, K; Shoda, T; Takada, K; Uneyama, C; Takahashi, M; Hirose, M

    1999-08-23

    To clarify the suitability of a newborn-mouse carcinogenesis assay to detect tumor-promoting activities of carcinogens, the non-genotoxic hydroquinone (HQ) and genotoxic 1,1-dimethylhydrazine (UDMH) were administered to mice during the promotion stage after treatment with 1-methyl-1-nitrosourea (MNU) (20 mg/kg body wt, single intraperitoneal injection) at day 9 after birth. Initiated males and females thus received either HQ at 0.8% in basal diet, or UDMH, at 20 mg/kg body wt once weekly by subcutaneous injection, from day 14 until the end of the experiment at 30 weeks of age. Uninitiated newborn mice, given an injection of the vehicle (0.01 M citrate buffer (pH 5.5), 20 mg/kg body wt), also received HQ or UDMH in the same way. Histopathologically, focal proliferative lesions were found in the livers of male mice and in the lungs of both male and female mice in the MNU-treated groups. HQ significantly increased the incidence and multiplicity of altered hepatocellular foci, the combined incidence of hepatocellular adenomas and carcinomas in males and the incidence and multiplicity of lung adenomas and the combined incidence of lung adenomas and carcinomas in female mice. In addition, four out of eleven MNU + HQ-treated male mice developed lung carcinomas, showing a significant elevation in multiplicity. UDMH also exhibited a tendency to increase the incidence and multiplicity of lung adenomas in female mice. Thus tumor-promoting effects of HQ or UDMH were apparently exerted in the target organs and the MNU-initiated two-stage newborn-mouse carcinogenesis assay may be useful for detection of genotoxic or non-genotoxic carcinogenicity.

  18. Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF

    PubMed Central

    Racki, Waldemar J.; Leif, Jean; Burzenski, Lisa; Hosur, Vishnu; Wetmore, Amber; Gott, Bruce; Herlihy, Mary; Ignotz, Ronald; Dunn, Raymond; Shultz, Leonard D.; Greiner, Dale L.

    2012-01-01

    Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγnull (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45+ cell chimerism were observed after transplantation of cord blood–derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development. PMID:22246028

  19. Modafinil improves methamphetamine-induced object recognition deficits and restores prefrontal cortex ERK signaling in mice

    PubMed Central

    Gonzalez, Betina; Raineri, Mariana; Cadet, Jean Lud; García-Rill, Edgar; Urbano, Francisco J.; Bisagno, Veronica

    2016-01-01

    Chronic use of methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans and in animal models. Modafinil is a wake-promoting compound approved for the treatment of sleeping disorders. It is also prescribed off label to treat METH dependence. In the present study, we investigated whether modafinil could improve cognitive deficits induced by sub-chronic METH treatment in mice by measuring visual retention in a Novel Object Recognition (NOR) task. After sub-chronic METH treatment (1 mg/Kg, once a day for 7 days), mice performed the NOR task, which consisted of habituation to the object recognition arena (5 min a day, 3 consecutive days), training session (2 equal objects, 10 min, day 4), and a retention session (1 novel object, 5 min, day 5). One hour before the training session, mice were given a single dose of modafinil (30 or 90 mg/Kg). METH-treated mice showed impairments in visual memory retention, evidenced by equal preference of familiar and novel objects during the retention session. The lower dose of modafinil (30 mg/Kg) had no effect on visual retention scores in METH-treated mice, while the higher dose (90 mg/Kg) rescued visual memory retention to control values. We also measured ERK phosphorylation in medial prefrontal cortex (mPFC), hippocampus, and nucleus accumbens (NAc) of METH- and vehicle-treated mice that received modafinil 1 hr before exposure to novel objects in the training session, compared to mice placed in the arena without objects. Elevated Extracellular signal-regulated kinase (ERK) phosphorylation was found in the mPFC of vehicle-treated mice, but not in METH-treated mice, exposed to objects (p<0.05). The lower dose of modafinil had no effect on ERK phosphorylation in METH-treated mice, while 90 mg/Kg modafinil treatment restored the ERK phosphorylation induced by novelty in METH-treated mice to values comparable to controls (p<0.05). We found neither a novelty nor treatment effect on ERK phosphorylation in hippocampus or

  20. Modafinil improves methamphetamine-induced object recognition deficits and restores prefrontal cortex ERK signaling in mice.

    PubMed

    González, Betina; Raineri, Mariana; Cadet, Jean Lud; García-Rill, Edgar; Urbano, Francisco J; Bisagno, Veronica

    2014-12-01

    Chronic use of methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans and in animal models. Modafinil is a wake-promoting compound approved for the treatment of sleeping disorders. It is also prescribed off label to treat METH dependence. In the present study, we investigated whether modafinil could improve cognitive deficits induced by sub-chronic METH treatment in mice by measuring visual retention in a Novel Object Recognition (NOR) task. After sub-chronic METH treatment (1 mg/kg, once a day for 7 days), mice performed the NOR task, which consisted of habituation to the object recognition arena (5 min a day, 3 consecutive days), training session (2 equal objects, 10 min, day 4), and a retention session (1 novel object, 5 min, day 5). One hour before the training session, mice were given a single dose of modafinil (30 or 90 mg/kg). METH-treated mice showed impairments in visual memory retention, evidenced by equal preference of familiar and novel objects during the retention session. The lower dose of modafinil (30 mg/kg) had no effect on visual retention scores in METH-treated mice, while the higher dose (90 mg/kg) rescued visual memory retention to control values. We also measured extracellular signal-regulated kinase (ERK) phosphorylation in medial prefrontal cortex (mPFC), hippocampus, and nucleus accumbens (NAc) of METH- and vehicle-treated mice that received modafinil 1 h before exposure to novel objects in the training session, compared to mice placed in the arena without objects. Elevated ERK phosphorylation was found in the mPFC of vehicle-treated mice, but not in METH-treated mice, exposed to objects. The lower dose of modafinil had no effect on ERK phosphorylation in METH-treated mice, while 90 mg/kg modafinil treatment restored the ERK phosphorylation induced by novelty in METH-treated mice to values comparable to controls. We found neither a novelty nor treatment effect on ERK phosphorylation in hippocampus or NAc of vehicle

  1. 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

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

    PubMed

    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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Neurodevelopmental Consequences of Sub-Clinical Carbon Monoxide Exposure in Newborn Mice

    PubMed Central

    Cheng, Ying; Thomas, Adia; Mardini, Feras; Bianchi, Shannon L.; Tang, Junxia X.; Peng, Jun; Wei, Huafeng; Eckenhoff, Maryellen F.; Eckenhoff, Roderic G.; Levy, Richard J.

    2012-01-01

    Carbon monoxide (CO) exposure at high concentrations results in overt neurotoxicity. Exposure to low CO concentrations occurs commonly yet is usually sub-clinical. Infants are uniquely vulnerable to a variety of toxins, however, the effects of postnatal sub-clinical CO exposure on the developing brain are unknown. Apoptosis occurs normally within the brain during development and is critical for synaptogenesis. Here we demonstrate that brief, postnatal sub-clinical CO exposure inhibits developmental neuroapoptosis resulting in impaired learning, memory, and social behavior. Three hour exposure to 5 ppm or 100 ppm CO impaired cytochrome c release, caspase-3 activation, and apoptosis in neocortex and hippocampus of 10 day old CD-1 mice. CO increased NeuN protein, neuronal numbers, and resulted in megalencephaly. CO-exposed mice demonstrated impaired memory and learning and reduced socialization following exposure. Thus, CO-mediated inhibition of neuroapoptosis might represent an important etiology of acquired neurocognitive impairment and behavioral disorders in children. PMID:22348142

  8. Newborn Screening

    MedlinePlus

    ... Activities Importance of Newborn Screening Newborn Screening and Molecular Biology Branch Pulse Oximetry Screening for CCHDs Sickle Cell Disease Laboratory SCID Quality Assurance Training and Resources ...

  9. 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

  10. Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy.

    PubMed

    Sokolowska, P; Passemard, S; Mok, A; Schwendimann, L; Gozes, I; Gressens, P

    2011-01-26

    Activity-dependent neuroprotective protein (ADNP) was shown to be essential for embryogenesis and brain development while NAP, an active motif of ADNP, is neuroprotective in a broad range of neurodegenerative disorders. In the present study, we examined the protective potential of ADNP/NAP in a mouse model of excitotoxic brain lesion mimicking brain damage associated with cerebral palsy. We demonstrated that NAP had a potent neuroprotective effect against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice, and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP appears not to be involved in the response to excitotoxic challenge in the studied model. Our findings further show that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented ibotenate-induced loss of pre-oligodendrocytes without affecting the number of astrocytes or activated microglia around the site of injection. These findings indicate that protective actions of NAP are mediated by triggering transduction pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP might be a promising therapeutic agent for treating developing brain damage.

  11. 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

  12. Morphological restoration of gonadotrope population by thymulin gene therapy in nude mice

    PubMed Central

    Reggiani, Paula; Martines, Eliana; Ferese, Celia; Goya, Rodolfo; Cónsole, Gloria

    2009-01-01

    Summary The integrity of the thymus during the first week of life is necessary for a proper maturation of the pituitary-gonadal axis as revealed by the significantly reduced levels of circulating gonadotropins in congenitally athymic (nude) mice. In the present work we studied the impact of athymia and the effect of neonatal thymulin gene therapy on the pituitaries of adult nude mice. Also circulating thymulin and gonadotropin levels were evaluated. We used an adenoviral vector expressing a synthetic gene for the thymic peptide thymulin (metFTS) termed RAd-FTS. On postnatal day 1, each experimental heterozygous (nu/+) and homozygous (nu/nu) pup of both sexes received a single bilateral i.m. injection of RAd-FTS or RAd-GFP/TK, a control vector expressing green fluorescent protein. On postnatal days 51-52, mice were bled and sacrificed, their pituitaries were immediately dissected, fixed and immunostained. Morphometry was performed by means of an image analysis system. The following parameters were calculated: volume density (VD: cell area/reference area), cell density (CD: number of cells/reference area), and cell size (expressed in μm2). Serum thymulin levels were measured by a bioassay and gonadotropin levels were assayed by RIA. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels. The histometrical analysis revealed that the treatment prevented the reduction in gonadotrope CD and the VD in athymic mice. Our data suggest that thymulin gene therapy may be an effective strategy to approach reproductive deficits associated with endocrine thymus dysfunction. PMID:19337971

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

    PubMed Central

    Persson, Karin; Rekling, Jens C

    2011-01-01

    Abstract 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-8 AM 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

  14. 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.

  15. Developmental cell death in the liver and newborn lethality of Ku86 deficient mice suppressed by antioxidant N-acetyl-cysteine.

    PubMed

    Reliene, Ramune; Goad, Marry E P; Schiestl, Robert H

    2006-11-08

    Repair of DNA double-strand breaks (DSBs) is essential for genome integrity and cell survival. Ku86 is involved in the repair of DNA DSBs by non-homologous end joining (NHEJ). Mice deficient in Ku86 show growth retardation, dwarfism, premature aging, and immunodeficiency. In this study, we observed severely compromised survival of Ku86(-/-) mice, such that most Ku86(-/-) mice died within the first postnatal weeks and only 1.5% of the expected 25% from heterozygous crosses survived for 1 month. Since post-mortem analysis was not possible due to parental cannibalism, histopathological examination was performed on Ku86(-/-) fetuses to assess possible causes of newborn death. Eighty percent and 75% of Ku86(-/-) fetuses exhibited apoptosis and necrosis in the liver, while only 20% and 10% of Ku86(+/+) littermates had apoptosis and necrosis, respectively. In addition, the severity of liver damage was significantly higher in Ku86(-/-) fetuses. Developmental liver damage may have led to postnatal lethality because the fetal liver with pre-existing injury may not be able to undergo transformation from a lymphohematopoietic to an indispensable metabolic organ. Free radicals can cause chromosomal breaks and lead to cell death. We postulated that endogenous oxidative stress might be involved in the resulting liver damage and animal lethality in Ku86(-/-) mice deficient in DNA DSB repair. This hypothesis was tested by treating Ku86(-/-) mice with the well known free radical scavenger, thiol antioxidant N-acetyl-cysteine (NAC), during embryonic development. We found that a significantly higher percentage, 7.7% of NAC treated Ku86(-/-) offspring versus 1.5% untreated Ku86(-/-) mice were alive at 1 month of age. In addition, the incidence of liver necrosis decreased by 21% and the severity of necrosis significantly reduced. Thus, Ku86 deficiency results in severe developmental liver damage and newborn lethality associated with oxidative stress.

  16. 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

  17. Relationship between age of allogeneic thymus donor and immunological restoration of athymic ('nude") mice.

    PubMed

    Radov, L A; Sussdorf, D H; McCann, R L

    1975-12-01

    In nude mice back-crossed a minimum of five times to BALB/c, solid thymus grafts from C57Bl donors 3 days of age or younger restored both the humoral immune response against sheep erythrocytes and cellular immunity as tested by rejection of CBA skin grafts. Donor thymus placed under the renal capsule at a dose of 0-5 mg/g of recipient resulted in normal humoral immunity, while a minimum dose of 1-5 mg/g was required to reconstitute cellular competence. None of the various amounts of allogeneic thymus tissue transplanted affected the immunological status of nude recipients when grafts were obtained from donors 4 days of age or older. Histological findings correlated with the humoral and cellular responses observed. In nudes grafted with neonatal tissue, the thymus implant proliferated and developed normal architecture. The density of lymphocytes in thymus-dependent regions of peripheral lymphoid organs was near normal. On the other hand, most grafts from older (3-week-old) donors were resorbed by 90 days after implantation. In a number of cases, however, Russell bodies and numerous blast and plasma cells were seen in the graft site. Our observations suggest a possible cytotoxic rejection of implants from older allogeneic donors, while the survival and restorative capacity of transplants from 3-day-old or younger donors may have been due to a tolerogenic effect of the graft on the nude recipient.

  18. Partial Restoration of CFTR Function in cftr-Null Mice following Targeted Cell Replacement Therapy.

    PubMed

    Duchesneau, Pascal; Besla, Rickvinder; Derouet, Mathieu F; Guo, Li; Karoubi, Golnaz; Silberberg, Amanda; Wong, Amy P; Waddell, Thomas K

    2017-03-01

    Cystic fibrosis (CF) is a fatal recessive genetic disorder caused by a mutation in the gene encoding CF transmembrane conductance regulator (CFTR) protein. Alteration in CFTR leads to thick airway mucus and bacterial infection. Cell therapy has been proposed for CFTR restoration, but efficacy has been limited by low engraftment levels. In our previous studies, we have shown that using a pre-conditioning regimen in combination with optimization of cell number and time of delivery, we could obtain greater bone marrow cell (BMC) retention in the lung. Here, we found that optimized delivery of wild-type (WT) BMC contributed to apical CFTR expression in airway epithelium and restoration of select ceramide species and fatty acids in CFTR(-/-) mice. Importantly, WT BMC delivery delayed Pseudomonas aeruginosa lung infection and increased survival of CFTR(-/-) recipients. Only WT BMCs had a beneficial effect beyond 6 months, suggesting a dual mechanism of BMC benefit: a non-specific effect early after cell delivery, possibly due to the recruitment of macrophages and neutrophils, and a late beneficial effect dependent on long-term CFTR expression. Taken together, our results suggest that BMC can improve overall lung function and may have potential therapeutic benefit for the treatment of CF.

  19. 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.

  20. CRISPR-mediated Genome Editing Restores Dystrophin Expression and Function in mdx Mice.

    PubMed

    Xu, Li; Park, Ki Ho; Zhao, Lixia; Xu, Jing; El Refaey, Mona; Gao, Yandi; Zhu, Hua; Ma, Jianjie; Han, Renzhi

    2016-03-01

    Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by genetic mutations that lead to the disruption of dystrophin in muscle fibers. There is no curative treatment for this devastating disease. Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) has emerged as a powerful tool for genetic manipulation and potential therapy. Here we demonstrate that CRIPSR-mediated genome editing efficiently excised a 23-kb genomic region on the X-chromosome covering the mutant exon 23 in a mouse model of DMD, and restored dystrophin expression and the dystrophin-glycoprotein complex at the sarcolemma of skeletal muscles in live mdx mice. Electroporation-mediated transfection of the Cas9/gRNA constructs in the skeletal muscles of mdx mice normalized the calcium sparks in response to osmotic shock. Adenovirus-mediated transduction of Cas9/gRNA greatly reduced the Evans blue dye uptake of skeletal muscles at rest and after downhill treadmill running. This study provides proof evidence for permanent gene correction in DMD.

  1. Dietary Nitrite Restores NO Homeostasis and is Cardioprotective in eNOS Deficient Mice

    PubMed Central

    Bryan, Nathan S.; Calvert, John W.; Gundewar, Susheel; Lefer, David J.

    2008-01-01

    Endothelial production of nitric oxide (NO) is critical for vascular homeostasis. Nitrite and nitrate are formed endogenously by the step wise oxidation of NO and have for years been regarded as inactive degradation products. As a result both anions are routinely used as surrogate markers of NO production with nitrite as a more sensitive marker. However, both nitrite and nitrate are derived from dietary sources. We sought to determine how exogenous nitrite affects steady state concentrations of NO metabolites thought to originate from NOS derived NO as well as blood pressure and myocardial ischemia-reperfusion (I/R) injury. Mice deficient in endothelial nitric oxide synthase (eNOS−/−) demonstrated decreased blood and tissue nitrite, nitrate and nitroso which were further reduced by low nitrite (NOx) diet for 1 week. Nitrite supplementation (50mg/L) in the drinking water for 1 week restored NO homeostasis in eNOS−/− mice and protected against I/R injury. Nitrite failed to alter heart rate or mean arterial blood pressure at the protective dose. These data demonstrate the significant influence of dietary nitrite intake on the maintenance of steady-state NO levels. Dietary nitrite and nitrate may serve as essentials nutrient for optimal cardiovascular health and may provide a novel prevention/treatment modality for disease associated with NO insufficiency. PMID:18501719

  2. REPLACEMENT WITH GABAERGIC STEROID PRECURSORS RESTORES THE ACUTE ETHANOL WITHDRAWAL PROFILE IN ADX/GDX MICE

    PubMed Central

    Kaufman, KR; Tanchuck, MA; Strong, MN; Finn, DA

    2010-01-01

    The neurosteroid allopregnanolone (ALLO) is a progesterone metabolite that is one of a family of neuroactive steroids (NAS) that are potent positive allosteric modulators of γ-aminobutyric acidA (GABAA) receptors. These GABAergic NAS are produced peripherally (in the adrenals and gonads) and centrally in the brain. Peripherally produced NAS modulate some effects of ethanol intoxication (e.g., anxiolytic, antidepressant, and anticonvulsant effects) in rodents. We have found that NAS also may be involved in the rebound neural hyperexcitability following a high ethanol dose. Removal of the adrenals and gonads (ADX/GDX) increased withdrawal severity following 4 g/kg ethanol, as measured by handling-induced convulsions (HICs) in male and female DBA/2J mice. NAS are produced through the metabolism of progesterone (PROG), deoxycorticosterone (DOC), or testosterone, which can be blocked with the administration of finasteride (FIN), a 5α-reductase enzyme inhibitor. The current investigation was undertaken to clarify the step(s) in the biosynthetic NAS pathway that were sufficient to restore the acute ethanol withdrawal profile in ADX/GDX mice to that seen in intact animals. Male and female DBA/2J mice underwent ADX/GDX or SHAM surgery. After recovery, separate groups of animals were administered PROG, DOC, PROG+FIN, DOC+FIN, FIN, ALLO, ganaxalone (a synthetic ALLO derivative), corticosterone, or vehicle. Animals were then administered a 4 g/kg ethanol dose and allowed to undergo withdrawal. HICs were measured for 12 hours and again at 24 hours. The results indicate that replacement with PROG and DOC restored the withdrawal profile in ADX/GDX animals to SHAM levels, and that this effect was blocked with co-administration of FIN. Administration of FIN alone increased the withdrawal profile in both SHAM and ADX/GDX males. These findings indicate that the increase in acute withdrawal severity after ADX/GDX may be due to the loss of GABAergic NAS, providing insight into the

  3. 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

  4. Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism.

    PubMed Central

    Barker, P M; Nguyen, M S; Gatzy, J T; Grubb, B; Norman, H; Hummler, E; Rossier, B; Boucher, R C; Koller, B

    1998-01-01

    Genetic evidence supports a critical role for the epithelial sodium channel (ENaC) in both clearance of fetal lung liquid at birth and total body electrolyte homeostasis. Evidence from heterologous expression systems suggests that expression of the alphaENaC subunit is essential for channel function, whereas residual channel function can be measured in the absence of beta or gamma subunits. We generated mice without gammaENaC (gammaENaC -/-) to test the role of this subunit in neonatal lung liquid clearance and total body electrolyte balance. Relative to controls, gammaENaC (-/-) pups showed low urinary [K+] and high urinary [Na+] and died between 24 and 36 h, probably from hyperkalemia (gammaENaC -/- 18.3 mEq/l, control littermates 9.7 mEq/l). Newborn gammaENaC (-/-) mice cleared lung liquid more slowly than control littermates, but lung water at 12 h (wet/dry = 5.5) was nearly normal (wet/dry = 5.3). This study suggests that gammaENaC facilitates neonatal lung liquid clearance and is critical for renal Na+ and K+ transport, and that low level Na+ transport may be sufficient for perinatal lung liquid absorption but insufficient to maintain electrolyte balance by the distal nephron. The gammaENaC (-/-) newborn exhibits a phenotype that resembles the clinical manifestations of human neonatal PHA1. PMID:9788978

  5. 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.

  6. Carnitine deficiency in OCTN2-/- newborn mice leads to a severe gut and immune phenotype with widespread atrophy, apoptosis and a pro-inflammatory response.

    PubMed

    Sonne, Srinivas; Shekhawat, Prem S; Matern, Dietrich; Ganapathy, Vadivel; Ignatowicz, Leszek

    2012-01-01

    We have investigated the gross, microscopic and molecular effects of carnitine deficiency in the neonatal gut using a mouse model with a loss-of-function mutation in the OCTN2 (SLC22A5) carnitine transporter. The tissue carnitine content of neonatal homozygous (OCTN2(-/-)) mouse small intestine was markedly reduced; the intestine displayed signs of stunted villous growth, early signs of inflammation, lymphocytic and macrophage infiltration and villous structure breakdown. Mitochondrial β-oxidation was active throughout the GI tract in wild type newborn mice as seen by expression of 6 key enzymes involved in β-oxidation of fatty acids and genes for these 6 enzymes were up-regulated in OCTN2(-/-) mice. There was increased apoptosis in gut samples from OCTN2(-/-) mice. OCTN2(-/-) mice developed a severe immune phenotype, where the thymus, spleen and lymph nodes became atrophied secondary to increased apoptosis. Carnitine deficiency led to increased expression of CD45-B220(+) lymphocytes with increased production of basal and anti-CD3-stimulated pro-inflammatory cytokines in immune cells. Real-time PCR array analysis in OCTN2(-/-) mouse gut epithelium demonstrated down-regulation of TGF-β/BMP pathway genes. We conclude that carnitine plays a major role in neonatal OCTN2(-/-) mouse gut development and differentiation, and that severe carnitine deficiency leads to increased apoptosis of enterocytes, villous atrophy, inflammation and gut injury.

  7. 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

  8. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

    PubMed

    Ohlmann, Andreas; Scholz, Michael; Goldwich, Andreas; Chauhan, Bharesh K; Hudl, Kristiane; Ohlmann, Anne V; Zrenner, Eberhart; Berger, Wolfgang; Cvekl, Ales; Seeliger, Mathias W; Tamm, Ernst R

    2005-02-16

    Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

  9. 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.

  10. NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems in brain - Restoration by chronic amitriptyline.

    PubMed

    Aonurm-Helm, Anu; Anier, Kaili; Zharkovsky, Tamara; Castrén, Eero; Rantamäki, Tomi; Stepanov, Vladimir; Järv, Jaak; Zharkovsky, Alexander

    2015-12-01

    Mood disorders are associated with alterations in serotonergic system, deficient BDNF (brain-derived neurotrophic factor) signaling and abnormal synaptic plasticity. Increased degradation and reduced functions of NCAM (neural cell adhesion molecule) have recently been associated with depression and NCAM deficient mice show depression-related behavior and impaired learning. The aim of the present study was to investigate potential changes in serotonergic and BDNF systems in NCAM knock-out mice. Serotonergic nerve fiber density and SERT (serotonin transporter) protein levels were robustly reduced in the hippocampus, prefrontal cortex and basolateral amygdala of adult NCAM(-)(/-) mice. This SERT reduction was already evident during early postnatal development. [(3)H]MADAM binding experiments further demonstrated reduced availability of SERT in cell membranes of NCAM(-)(/-) mice. Moreover, the levels of serotonin and its major metabolite 5-HIAA were down regulated in the brains of NCAM(-)(/-) mice. NCAM(-)(/-) mice also showed a dramatic reduction in the BDNF protein levels in the hippocampus and prefrontal cortex. This BDNF deficiency was associated with reduced phosphorylation of its receptor TrkB. Importantly, chronic administration of antidepressant amitriptyline partially or completely restored these changes in serotonergic and BDNF systems, respectively. In conclusion, NCAM deficiency lead to prominent and persistent abnormalities in brain serotonergic and BDNF systems, which likely contributes to the behavioral and neurobiological phenotype of NCAM(-/-) mice.

  11. 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

  12. Pharmacological concentrations of rFVIIa restore hemostasis independent of tissue factor in antibody-induced hemophilia mice

    PubMed Central

    KESHAVA, S.; SUNDARAM, J.; RAJULAPATI, A.; PENDURTHI, U.R.; RAO, L.V.M.

    2016-01-01

    Summary Background Recombinant factor VIIa (rFVIIa) has been used widely for treating hemophilia patients with inhibitory autoantibodies against factor VIII or IX. Its mechanism of action is not entirely known. A majority of in vitro studies suggested that pharmacological concentrations of rFVIIa restore hemostasis in hemophilia in a phospholipid-dependent mechanism, independent of tissue factor (TF). However, a few studies suggested that a TF-dependent mechanism plays a primary role in rFVIIa correction of bleeding in hemophilia patients. Here, we investigated the potential contribution of TF in rFVIIa-induced hemostasis in hemophilia employing a model system of FVIII antibody-induced hemophilia in TF transgenic mice. Methods Mice expressing low levels of human TF (LTF mice), relatively high levels of human TF (HTF mice) or wild-type mice (WT mice) were administered with neutralizing anti-FVIII antibodies to induce hemophilia in these mice. The mice were then treated with varying concentrations of rFVIIa. rFVIIa-induced hemostasis was evaluated with the saphenous vein bleeding model. Results Administration of FVIII inhibitory antibodies induced the hemophilic bleeding phenotype in all three genotypes. rFVIIa administration rescued the bleeding phenotype in all three genotypes. No significant differences were observed in rFVIIa-induced correction in the bleeding of LTF and HTF mice administered with FVIII antibodies. Conclusions Our results provide strong evidence supporting that the hemostatic effect of pharmacological doses of rFVIIa stems from a TF-independent mechanism. PMID:26727350

  13. 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.

  14. Human invariant chain isoform p35 restores thymic selection and antigen presentation in CD74-deficient mice.

    PubMed

    Genève, Laetitia; Chemali, Magali; Desjardins, Michel; Labrecque, Nathalie; Thibodeau, Jacques

    2012-10-01

    The invariant chain (Ii) has pleiotropic functions and is a key factor in antigen presentation. Ii associates with major histocompatibility complex class II molecules in the endoplasmic reticulum (ER) and targets the complex in the endocytic pathway to allow antigenic peptide loading. The human Iip35 isoform includes a cytoplasmic extension containing a di-arginine motif causing ER retention. This minor isoform does not exist in mice and its function in humans has not been thoroughly investigated. We have recently generated transgenic mice expressing Iip35 and these were crossed with Ii-deficient mice to generate animals (Tgp35/mIiKO) expressing exclusively the human isoform. In these mice, we show that Iip35 is expressed in antigen presenting cells and is inducible by interferon gamma (IFN-γ). Despite the low constitutive expression of the protein and some minor differences in the Vβ repertoire of Tgp35/mIiKO mice, Iip35 restored thymic selection of CD4(+) T cells and of invariant natural killer T cells. In vitro functional assays using purified primary macrophages treated with IFN-γ showed that Iip35 allows presentation of an Ii-dependent ovalbumin T-cell epitope. Altogether, our results suggest that Iip35 is functional and does not require co-expression of other isoforms for antigen presentation.

  15. The p35 human invariant chain in transgenic mice restores mature B cells in the absence of endogenous CD74.

    PubMed

    Genève, Laetitia; Ménard, Catherine; Labrecque, Nathalie; Thibodeau, Jacques

    2012-10-01

    The invariant chain (Ii; CD74) has pleiotropic functions and Ii-deficient mice show defects in MHC class II (MHC II) transport and B cell maturation. In humans, but not in mice, a minor Iip35 isoform of unknown function includes an endoplasmic reticulum-retention motif that is masked upon binding of MHC II molecules. To gain further insight into the roles of Ii in B cell homeostasis, we generated Iip35 transgenic mice (Tgp35) and bred these with mice deficient for Ii (Tgp35/mIiKO). Iip35 was shown to compete with mIi for the binding to I-A(b) . In addition, classical endosomal degradation products (p20/p10) and the class II-associated invariant chain peptide (CLIP) fragment were detected. Moreover, Iip35 favored the formation of compact peptide-MHC II complexes in the Tgp35/mIiKO mice. I-A(b) levels were restored at the plasma membrane of mature B cells but Iip35 affected the fine conformation of MHC II molecules as judged by the increased reactivity of the AF6-120.1 antibody in permeabilized cells. However, the human Iip35 cannot fully replace the endogenous Ii. Indeed, most immature B cells in the bone marrow and spleen of transgenic mice had reduced surface expression of MHC II molecules, demonstrating a dominant-negative effect of Iip35 in Tgp35 mice. Interestingly, while maturation to follicular B cells was normal, Iip35 expression appeared to reduce the proportions of marginal zone B cells. These results emphasize the importance of Ii in B cell homeostasis and suggest that Iip35 could have regulatory functions.

  16. Immune function in cyclophosphamide-treated mice is restored by the T-cell-tropic isoxazole derivative R-13.

    PubMed

    Zimecki, Michał; Artym, Jolanta; Kocięba, Maja; Obmińska-Mrukowicz, Bożena; Mączyński, Marcin; Ryng, Stanisław

    2015-01-01

    Reconstitution of the immune function in chemotherapy patients will lead to decreases in post-operative complications. A preliminary investigation showed that an isoxazole derivative R-13 (3,5-dimethyl-isoxazole[5,4-e]8H-triazepin-4-one) hydrochloride, given in a single oral dose to normal mice, induced significant increases in the content of CD4(+) cells in the spleens and lymph nodes. That observation prompted the authors to assess the immune reconstituting effects of R-13 in mice pre-treated with cyclophosphamide (CP). Mice were given intraperitoneally (IP) a sublethal dose of CP (200 mg/kg) and then R-13 (as 20 µg IP doses, every 3 days post-CP treatment). Control mice, not treated with CP, received R-13 or the vehicle (DMSO in appropriate dilution). Blood leukocyte and splenocyte numbers, blood cell type levels, splenocyte spontaneous and ConA-induced proliferation, and delayed-type hypersensitivity (DTH) to ovalbumin (OVA) were investigated on day 15 post-CP treatment and five R-13 doses. The humoral immune response (antibody-forming cell development to sheep erythrocytes) was measured 30 days post-CP treatment and 10 R-13 doses. In CP-treated mice, five dosings with R-13 led to increases in numbers of splenocytes and blood leukocytes, as well as in spontaneous and ConA-induced splenocyte proliferation, relative to levels in mice that received only CP 15 days earlier. Blood analysis revealed decreases in neutrophil and eosinophil contents and an increased appearance of lymphocyte immature forms in all mice that received the R-13. Both cell-mediated responses to OVA and humoral immune response to sheep erythrocytes in CP-treated hosts were restored. Based on the data here, it is concluded that R-13 may be of potential value for reconstitution of the immune function of chemotherapy patients.

  17. Epigallocatechin-3-gallate Prevents Triptolide-Induced Hepatic Injury by Restoring the Th17/Treg Balance in Mice.

    PubMed

    Yu, Shu-Jing; Jiang, Rong; Mazzu, Ying Z; Wei, Cai-Bing; Sun, Zong-Liang; Zhang, Yu-Zhen; Zhou, Lian-Di; Zhang, Qi-Hui

    2016-01-01

    Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment. The hepatic histology analysis further proved that EGCG protected mice from TP-induced liver injury. The imbalance of Th17/Treg was induced by TP treatment, as shown by the upregulation of TLR4 and downregulation of Tim3 expression. EGCG pretreatment can maintain the expression of TLR4 and Tim3 at normal levels to restore the Th17/Treg imbalance. In addition, EGCG can block the TP-induced expression of the downstream targets of TLR4, including MyD88, NF[Formula: see text]B, and retinoid related orphan receptor (ROR-[Formula: see text]t), while EGCG can restore the TP inhibition of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) that is the downstream target of Tim3. Consequently, EGCG pretreatment can effectively inhibit the Th17-related pro-inflammatory cytokine (e.g. IL-17 and IL-6) upregulation induced by TP treatment. However, TP inhibition of Treg-related anti-inflammatory cytokine IL-10 production was restored by EGCG pretreatment. Taken together, these results suggest that EGCG possesses significant protective properties against TP-induced hepatic inflammatory injury, and that these properties are carried out via the restoration of the Th17/Treg imbalance by the inhibition of the TLR4 signaling pathway and the enhanced activation of the Tim3 signaling pathway.

  18. 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.

  19. 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

  20. Developmental restoration of LTP deficits in heterozygous CaMKIIα KO mice.

    PubMed

    Goodell, Dayton J; Benke, Tim A; Bayer, K Ulrich

    2016-11-01

    The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. The heterozygous CaMKIIα isoform KO (CaMKIIα(+/-)) mice have a schizophrenia-related phenotype, including impaired working memory. Here, we examined synaptic strength and plasticity in two brain areas implicated in working memory, hippocampus CA1 and medial prefrontal cortex (mPFC). Young CaMKIIα(+/-) mice (postnatal days 12-16; corresponding to a developmental stage well before schizophrenia manifestation in humans) showed impaired hippocampal CA1 LTP. However, this LTP impairment normalized over development and was no longer detected in older CaMKIIα(+/-) mice (postnatal weeks 9-11; corresponding to young adults). By contrast, the CaMKIIα(+/-) mice failed to show the developmental increase of basal synaptic transmission in the CA1 seen in wild-type (WT) mice, resulting in impaired basal synaptic transmission in the older CaMKIIα(+/-) mice. Other electrophysiological parameters were normal, including mPFC basal transmission, LTP, and paired-pulse facilitation, as well as CA1 LTD, depotentiation, and paired-pulse facilitation at either age tested. Hippocampal CaMKIIα levels were ∼60% of WT in both the older CaMKIIα(+/-) mice and in the younger WT mice, resulting in ∼30% of adult WT expression in the younger CaMKIIα(+/-) mice; levels in frontal cortex were the same as in hippocampus. Thus, in young mice, ∼30% of adult CaMKIIα expression is sufficient for normal LTD and depotentiation, while normal LTP requires higher levels, with ∼60% of CaMKIIα expression sufficient for normal LTP in adult mice.

  1. FNDC5 Alleviates Hepatosteatosis by Restoring AMPK/mTOR-Mediated Autophagy, Fatty Acid Oxidation, and Lipogenesis in Mice.

    PubMed

    Liu, Tong-Yan; Xiong, Xiao-Qing; Ren, Xing-Sheng; Zhao, Ming-Xia; Shi, Chang-Xiang; Wang, Jue-Jin; Zhou, Ye-Bo; Zhang, Feng; Han, Ying; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-11-01

    Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat and mediates the beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with hepatic steatosis, autophagy, fatty acid oxidation (FAO), and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy, and lipid metabolism. Fasted FNDC5(-/-) mice exhibited severe steatosis, reduced autophagy, and FAO, and enhanced lipogenesis in the liver compared with wild-type mice. Energy deprivation-induced autophagy, FAO, and AMPK activity were attenuated in FNDC5(-/-) hepatocytes, which were restored by activating AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Inhibition of mammalian target of rapamycin (mTOR) complex 1 with rapamycin enhanced autophagy and FAO and attenuated lipogenesis and steatosis in FNDC5(-/-) livers. FNDC5 deficiency exacerbated hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. Exogenous FNDC5 stimulated autophagy and FAO gene expression in hepatocytes and repaired the attenuated autophagy and palmitate-induced steatosis in FNDC5(-/-) hepatocytes. FNDC5 overexpression prevented hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. These results indicate that FNDC5 deficiency impairs autophagy and FAO and enhances lipogenesis via the AMPK/mTOR pathway. FNDC5 deficiency aggravates whereas FNDC5 overexpression prevents the HFD-induced hyperlipemia, hepatic lipid accumulation, and impaired FAO and autophagy in the liver.

  2. Targeted Restoration of the Intestinal Microbiota with a Simple, Defined Bacteriotherapy Resolves Relapsing Clostridium difficile Disease in Mice

    PubMed Central

    Lawley, Trevor D.; Stares, Mark D.; Connor, Thomas R.; Raisen, Claire; Goulding, David; Rad, Roland; Schreiber, Fernanda; Brandt, Cordelia; Deakin, Laura J.; Pickard, Derek J.; Duncan, Sylvia H.; Flint, Harry J.; Clark, Taane G.; Parkhill, Julian; Dougan, Gordon

    2012-01-01

    Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis. PMID:23133377

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

    PubMed

    Yu, Q; Wang, Y; Chang, Q; Wang, J; Gong, S; Li, H; Lin, X

    2014-01-01

    Mutations in GJB2, which codes for the gap junction (GJ) protein connexin26 (Cx26), are the most common causes of human nonsyndromic hereditary deafness. We inoculated modified adeno-associated viral (AAV) vectors into the scala media of early postnatal conditional Gjb2 knockout mice to drive exogenous Cx26 expression. We found extensive virally expressed Cx26 in cells lining the scala media, and intercellular GJ network was re-established in the organ of Corti of mutant mouse cochlea. Widespread ectopic Cx26 expression neither formed ectopic GJs nor affected normal hearing thresholds in wild-type (WT) mice, suggesting that autonomous cellular mechanisms regulate proper membrane trafficking of exogenously expressed Cx26 and govern the functional manifestation of them. Functional recovery of GJ-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 GJ 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.

  4. Restoring expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation.

    PubMed

    Wang, Yongxing; Suh, Young-Ah; Fuller, Maren Y; Jackson, James G; Xiong, Shunbin; Terzian, Tamara; Quintás-Cardama, Alfonso; Bankson, James A; El-Naggar, Adel K; Lozano, Guillermina

    2011-03-01

    The transcription factor p53 is a tumor suppressor. As such, the P53 gene is frequently altered in human cancers. However, over 80% of the P53 mutations found in human cancers are missense mutations that lead to expression of mutant proteins that not only lack p53 transcriptional activity but exhibit new functions as well. Recent studies show that restoration of p53 expression leads to tumor regression in mice carrying p53 deletions. However, the therapeutic efficacy of restoring p53 expression in tumors containing p53 missense mutations has not been evaluated. Here we demonstrate that restoring wild-type p53 expression halted tumor growth in mice inheriting a p53(R172H) missense mutation that is equivalent to a P53 missense mutation detected in approximately 6% of human cancers. However, it did not lead to tumor regression, as was observed in mice lacking p53. We further showed that the dominant-negative effect of the mutant p53 encoded by p53(R172H) dampened the activity of the restored wild-type p53. We therefore conclude that in a mutant p53 background, p53 restoration has the therapeutic potential to suppress tumor progression. Our findings support using p53 restoration as a strategy to treat human cancers with P53 missense mutations and provide direction for optimizing p53 restoration in cancer therapy.

  5. Restoring expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation

    PubMed Central

    Wang, Yongxing; Suh, Young-Ah; Fuller, Maren Y.; Jackson, James G.; Xiong, Shunbin; Terzian, Tamara; Quintás-Cardama, Alfonso; Bankson, James A.; El-Naggar, Adel K.; Lozano, Guillermina

    2011-01-01

    The transcription factor p53 is a tumor suppressor. As such, the P53 gene is frequently altered in human cancers. However, over 80% of the P53 mutations found in human cancers are missense mutations that lead to expression of mutant proteins that not only lack p53 transcriptional activity but exhibit new functions as well. Recent studies show that restoration of p53 expression leads to tumor regression in mice carrying p53 deletions. However, the therapeutic efficacy of restoring p53 expression in tumors containing p53 missense mutations has not been evaluated. Here we demonstrate that restoring wild-type p53 expression halted tumor growth in mice inheriting a p53R172H missense mutation that is equivalent to a P53 missense mutation detected in approximately 6% of human cancers. However, it did not lead to tumor regression, as was observed in mice lacking p53. We further showed that the dominant-negative effect of the mutant p53 encoded by p53R172H dampened the activity of the restored wild-type p53. We therefore conclude that in a mutant p53 background, p53 restoration has the therapeutic potential to suppress tumor progression. Our findings support using p53 restoration as a strategy to treat human cancers with P53 missense mutations and provide direction for optimizing p53 restoration in cancer therapy. PMID:21285512

  6. 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.

  7. 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

  8. Thrush in newborns

    MedlinePlus

    Candidiasis - oral - newborn; Oral thrush - newborn; Fungal infection - mouth - newborn; Candida - oral - newborn ... yeast called Candida albicans grows in a baby's mouth. Germs called bacteria and fungi naturally grow in ...

  9. Anemia in the Newborn

    MedlinePlus

    ... Cancer Caregivers Help Themselves 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 ...

  10. 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.

  11. 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

  12. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice

    PubMed Central

    Takiishi, Tatiana; Korf, Hannelie; Van Belle, Tom L.; Robert, Sofie; Grieco, Fabio A.; Caluwaerts, Silvia; Galleri, Letizia; Spagnuolo, Isabella; Steidler, Lothar; Van Huynegem, Karolien; Demetter, Pieter; Wasserfall, Clive; Atkinson, Mark A.; Dotta, Francesco; Rottiers, Pieter; Gysemans, Conny; Mathieu, Chantal

    2012-01-01

    Current interventions for arresting autoimmune diabetes have yet to strike the balance between sufficient efficacy, minimal side effects, and lack of generalized immunosuppression. Introduction of antigen via the gut represents an appealing method for induction of antigen-specific tolerance. Here, we developed a strategy for tolerance restoration using mucosal delivery in mice of biologically contained Lactococcus lactis genetically modified to secrete the whole proinsulin autoantigen along with the immunomodulatory cytokine IL-10. We show that combination therapy with low-dose systemic anti-CD3 stably reverted diabetes in NOD mice and increased frequencies of local Tregs, which not only accumulated in the pancreatic islets, but also suppressed immune response in an autoantigen-specific way. Cured mice remained responsive to disease-unrelated antigens, which argues against excessive immunosuppression. Application of this therapeutic tool achieved gut mucosal delivery of a diabetes-relevant autoantigen and a biologically active immunomodulatory cytokine, IL-10, and, when combined with a low dose of systemic anti-CD3, was well tolerated and induced autoantigen-specific long-term tolerance, allowing reversal of established autoimmune diabetes. Therefore, we believe this method could be an effective treatment strategy for type 1 diabetes in humans. PMID:22484814

  13. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice.

    PubMed

    Takiishi, Tatiana; Korf, Hannelie; Van Belle, Tom L; Robert, Sofie; Grieco, Fabio A; Caluwaerts, Silvia; Galleri, Letizia; Spagnuolo, Isabella; Steidler, Lothar; Van Huynegem, Karolien; Demetter, Pieter; Wasserfall, Clive; Atkinson, Mark A; Dotta, Francesco; Rottiers, Pieter; Gysemans, Conny; Mathieu, Chantal

    2012-05-01

    Current interventions for arresting autoimmune diabetes have yet to strike the balance between sufficient efficacy, minimal side effects, and lack of generalized immunosuppression. Introduction of antigen via the gut represents an appealing method for induction of antigen-specific tolerance. Here, we developed a strategy for tolerance restoration using mucosal delivery in mice of biologically contained Lactococcus lactis genetically modified to secrete the whole proinsulin autoantigen along with the immunomodulatory cytokine IL-10. We show that combination therapy with low-dose systemic anti-CD3 stably reverted diabetes in NOD mice and increased frequencies of local Tregs, which not only accumulated in the pancreatic islets, but also suppressed immune response in an autoantigen-specific way. Cured mice remained responsive to disease-unrelated antigens, which argues against excessive immunosuppression. Application of this therapeutic tool achieved gut mucosal delivery of a diabetes-relevant autoantigen and a biologically active immunomodulatory cytokine, IL-10, and, when combined with a low dose of systemic anti-CD3, was well tolerated and induced autoantigen-specific long-term tolerance, allowing reversal of established autoimmune diabetes. Therefore, we believe this method could be an effective treatment strategy for type 1 diabetes in humans.

  14. Newborn jaundice

    MedlinePlus

    ... be very tired and feed poorly. Exams and Tests Health care providers will watch for signs of jaundice at the hospital. After the newborn goes home, family members will usually spot the ... with a blood test. Many hospitals check total bilirubin levels on all ...

  15. Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice.

    PubMed

    Seleme, Maria C; Kosmac, Kate; Jonjic, Stipan; Britt, William J

    2017-04-15

    Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing antibodies decreased the frequency of CD45(+) Ly6C(hi) CD11b(+) CCR2(+) activated myeloid mononuclear cells (MMCs) and the levels of proinflammatory cytokines in the blood and the brains of murine CMV-infected mice. This treatment also normalized neurodevelopment in infected mice without significantly impacting the level of virus replication. These results indicate that TNF-α is a major component of the inflammatory response associated with altered neurodevelopment that follows murine CMV infection of the developing brain and that a subset of peripheral blood myeloid mononuclear cells represent a key effector cell population in this model of virus-induced inflammatory disease of the developing brain.IMPORTANCE Congenital human cytomegalovirus (HCMV) infection is the most common viral infection of the developing human fetus and can result in neurodevelopmental sequelae. Mechanisms of disease leading to neurodevelopmental deficits in infected infants remain undefined, but postulated pathways include loss of neuronal progenitor cells, damage to the developing vascular system of the brain, and altered cellular positioning. Direct virus-mediated cytopathic effects cannot explain the phenotypes of brain damage in most infected infants. Using a

  16. Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration

    PubMed Central

    Bi, Anding; Cui, Jinjuan; Ma, Yu-Ping; Olshevskaya, Elena; Pu, Mingliang; Dizhoor, Alexander M.; Pan, Zhuo-Hua

    2006-01-01

    Summary The death of photoreceptor cells caused by retinal degenerative diseases often results in a complete loss of retinal responses to light. We explore the feasibility of converting inner retinal neurons to photosensitive cells as a possible strategy for imparting light sensitivity to retinas lacking rods and cones. Using delivery by an adeno-associated viral vector, here, we show that long-term expression of a microbial-type rhodopsin, channelrhodopsin-2 (ChR2), can be achieved in rodent inner retinal neurons in vivo. Furthermore, we demonstrate that expression of ChR2 in surviving inner retinal neurons of a mouse with photoreceptor degeneration can restore the ability of the retina to encode light signals and transmit the light signals to the visual cortex. Thus, expression of microbial-type channelrhodopsins, such as ChR2, in surviving inner retinal neurons is a potential strategy for the restoration of vision after rod and cone degeneration. PMID:16600853

  17. 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.

  18. Post-Training Reward Partially Restores Chronic Stress Induced Effects in Mice

    PubMed Central

    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. PMID:22745700

  19. Characterization of Minaçu virus (Reoviridae: Orbivirus) and pathological changes in experimentally infected newborn mice

    PubMed Central

    Martins, Lívia C; Diniz, José A P; Silva, Eliana V P; Barros, Vera L R S; Monteiro, Hamilton A O; Azevedo, Raimunda S S; Quaresma, Juarez A S; Vasconcelos, Pedro F C

    2007-01-01

    Minaçu virus was isolated from Ochlerotatus scapularis (Diptera: Culicidae) in Minaçu, Goiás State, Brazil, in 1996. In attempting characterization of virus serological (hemagluttination inhibition, HI; indirect immunofluorescence assay, IFA), physicochemical [test for deoxycholate acid (DCA) sensitivity; polyacrylamide gel electrophoresis (PAGE)] tests and ultrastructural studies were made. Virus was also assayed in suckling mice after intracerebral inoculation of 0.02 ml and in VERO and C6/36 cells with 0.1 ml of viral suspension containing 105 LD50/ml. Inoculated and control systems were observed daily. Every 24 h, one control and two inoculated animals were killed for tissue testing, including histopathological changes by haematoxylin and eosin (HE)-stained sections, which were semi-quantified. Research into viral antigen in the tissues of mice [central nervous system (CNS), liver, heart, lungs, spleen and kidneys] was carried out by the immunohistochemical technique using the peroxidase system. The virus only replicated in VERO cells, with antigen positive by IFA. Positive complement fixation tests were only obtained using antiserum of Minaçu virus. Minaçu virus is DCA resistant; haemagglutinating activity was negative. By electronic microscopy non-enveloped virus particles were 75 nm in diameter. PAGE analysis showed Minaçu virus genome profile with 10 RNA segments. Infected, non-killed animals died 7 days after inoculation. Tissue lesions were observed in all organs, except the lungs. Intense lesions were observed in the CNS and the heart, where neurone and cardiocyte necroses, respectively, were noted. The liver, spleen and kidneys had moderate tissue changes. Viral antigens were more abundant in the CNS and the heart, and absent in the lungs. In conclusion, Minaçu virus belongs to the family Reoviridae, genus Orbivirus. PMID:17244340

  20. Attenuated methamphetamine-induced locomotor sensitization in serotonin transporter knockout mice is restored by serotonin 1B receptor antagonist treatment.

    PubMed

    Igari, Moe; Shen, Hao-Wei; Hagino, Yoko; Fukushima, Setsu; Kasahara, Yoshiyuki; Lesch, Klaus-Peter; Murphy, Dennis L; Hall, Frank Scott; Uhl, George R; Ikeda, Kazutaka; Yaegashi, Nobuo; Sora, Ichiro

    2015-02-01

    Repeated administration of methamphetamine (METH) enhances acute locomotor responses to METH administered in the same context, a phenomenon termed as 'locomotor sensitization'. Although many of the acute effects of METH are mediated by its influences on the compartmentalization of dopamine, serotonin systems have also been suggested to influence the behavioral effects of METH in ways that are not fully understood. The present experiments examined serotonergic roles in METH-induced locomotor sensitization by assessing: (a) the effect of serotonin transporter (SERT; Slc6A4) knockout (KO) on METH-induced locomotor sensitization; (b) extracellular monoamine levels in METH-treated animals as determined by in-vivo microdialysis; and (c) effects of serotonin (5-HT) receptor antagonists on METH-induced behavioral sensitization, with focus on effects of the 5-HT1B receptor antagonist SB 216641 and a comparison with the 5-HT2 receptor antagonist ketanserin. Repeated METH administration failed to induce behavioral sensitization in homozygous SERT KO (SERT-/-) mice under conditions that produced substantial sensitization in wild-type or heterozygous SERT KO (SERT+/-) mice. The selective 5-HT1B antagonist receptor SB 216641 restored METH-induced locomotor sensitization in SERT-/- mice, whereas ketanserin was ineffective. METH-induced increases in extracellular 5-HT (5-HTex) levels were substantially reduced in SERT-/- mice, although SERT genotype had no effect on METH-induced increases in extracellular dopamine. These experiments demonstrate that 5-HT actions, including those at 5-HT1B receptors, contribute to METH-induced locomotor sensitization. Modulation of 5-HT1B receptors might aid therapeutic approaches to the sequelae of chronic METH use.

  1. Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice

    PubMed Central

    Di Pardo, Alba; Maglione, Vittorio; Alpaugh, Melanie; Horkey, Melanie; Atwal, Randy S.; Sassone, Jenny; Ciammola, Andrea; Steffan, Joan S.; Fouad, Karim; Truant, Ray; Sipione, Simonetta

    2012-01-01

    Huntington disease (HD) is a progressive neurodegenerative monogenic disorder caused by expansion of a polyglutamine stretch in the huntingtin (Htt) protein. Mutant huntingtin triggers neural dysfunction and death, mainly in the corpus striatum and cerebral cortex, resulting in pathognomonic motor symptoms, as well as cognitive and psychiatric decline. Currently, there is no effective treatment for HD. We report that intraventricular infusion of ganglioside GM1 induces phosphorylation of mutant huntingtin at specific serine amino acid residues that attenuate huntingtin toxicity, and restores normal motor function in already symptomatic HD mice. Thus, our studies have identified a potential therapy for HD that targets a posttranslational modification of mutant huntingtin with critical effects on disease pathogenesis. PMID:22331905

  2. 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.

  3. Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.

    PubMed

    Won, Hyejung; Lee, Hye-Ryeon; Gee, Heon Yung; Mah, Won; Kim, Jae-Ick; Lee, Jiseok; Ha, Seungmin; Chung, Changuk; Jung, Eun Suk; Cho, Yi Sul; Park, Sae-Geun; Lee, Jung-Soo; Lee, Kyungmin; Kim, Daesoo; Bae, Yong Chul; Kaang, Bong-Kiun; Lee, Min Goo; Kim, Eunjoon

    2012-06-13

    Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

  4. 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.

  5. Treatment with Salvianolic Acid B restores endothelial function in angiotensin II-induced hypertensive mice.

    PubMed

    Ling, Wei Chih; Liu, Jian; Lau, Chi Wai; Murugan, Dharmani Devi; Mustafa, Mohd Rais; Huang, Yu

    2017-04-07

    Salvianolic acid B (Sal B) is one of the most abundant phenolic acids derived from the root of Danshen with potent anti-oxidative properties. The present study examined the vasoprotective effect of Sal B in hypertensive mice induced by angiotensin II (Ang II). Sal B (25 mg/kg/day) was administered via oral gavage for 11 days to Ang II (1.2 mg/kg/day)-infused C57BL/6J mice (8-10 weeks old). The vascular reactivity (both endothelium-dependent relaxations and contractions) in mouse arteries was examined by wire myography. The production of reactive oxygen species (ROS), protein level and localization of angiotensin AT1 receptors and the proteins involved in ROS formation were evaluated using dihydroethidium (DHE) fluorescence, lucigenin-enhanced chemiluminescence, immunohistochemistry and Western blotting, respectively. The changes of ROS generating proteins were also assessed in vitro in human umbilical vein endothelial cells (HUVECs) exposed to Ang II with and without co-treatment with Sal B (0.1 - 10 nM). Oral administration of Sal B reversed the Ang II-induced elevation of arterial systolic blood pressure in mice, augmented the impaired endothelium-dependent relaxations and attenuated the exaggerated endothelium-dependent contractions in both aortas and renal arteries of Ang II-infused mice. In addition, Sal B treatment normalized the elevated levels of AT1 receptors, NADPH oxidase subunits (NOx-2 and NOx-4) and nitrotyrosine in arteries of Ang II-infused mice or in Ang II-treated HUVECs. In summary, the present study provided additional evidence demonstrating that Sal B treatment for 11 days reverses the impaired endothelial function and with a marked inhibition of AT1 receptor-dependent vascular oxidative stress. This vasoprotective and anti-oxidative action of Sal B most likely contributes to the anti-hypertensive action of the plant-derived compound.

  6. 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.

  7. 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

  8. 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

  9. Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice

    PubMed Central

    Mosca, Barbara; Delbono, Osvaldo; Messi, Maria Laura; Bergamelli, Leda; Wang, Zhong-Min; Vukcevic, Mirko; Lopez, Ruben; Treves, Susan; Nishi, Miyuki; Takeshima, Hiroshi; Paolini, Cecilia; Martini, Marta; Rispoli, Giorgio; Protasi, Feliciano; Zorzato, Francesco

    2016-01-01

    Muscle strength declines with age in part due to a decline of Ca2+ release from sarcoplasmic reticulum calcium stores. Skeletal muscle dihydropyridine receptors (Cav1.1) initiate muscle contraction by activating ryanodine receptors in the sarcoplasmic reticulum. Cav1.1 channel activity is enhanced by a retrograde stimulatory signal delivered by the ryanodine receptor. JP45 is a membrane protein interacting with Cav1.1 and the sarcoplasmic reticulum Ca2+ storage protein calsequestrin (CASQ1). Here we show that JP45 and CASQ1 strengthen skeletal muscle contraction by modulating Cav1.1 channel activity. Using muscle fibres from JP45 and CASQ1 double knockout mice, we demonstrate that Ca2+ transients evoked by tetanic stimulation are the result of massive Ca2+ influx due to enhanced Cav1.1 channel activity, which restores muscle strength in JP45/CASQ1 double knockout mice. We envision that JP45 and CASQ1 may be candidate targets for the development of new therapeutic strategies against decay of skeletal muscle strength caused by a decrease in sarcoplasmic reticulum Ca2+ content. PMID:23443569

  10. Restoration of virulence of escape mutants of H5 and H9 influenza viruses by their readaptation to mice.

    PubMed

    Rudneva, Irina A; Ilyushina, Natalia A; Timofeeva, Tatiana A; Webster, Robert G; Kaverin, Nikolai V

    2005-10-01

    Antigenic mapping of the haemagglutinin (HA) molecule of H5 and H9 influenza viruses by selecting escape mutants with monoclonal anti-HA antibodies and subjecting the selected viruses to immunological analysis and sequencing has previously been performed. The viruses used as wild-type strains were mouse-adapted variants of the original H5 and H9 isolates. Phenotypic characterization of the escape mutants revealed that the amino acid change in HA that conferred resistance to a monoclonal antibody was sometimes associated with additional effects, including decreased virulence for mice. In the present study, the low-virulence H5 and H9 escape mutants were readapted to mice. Analysis of the readapted variants revealed that the reacquisition of virulence was not necessarily achieved by reacquisition of the wild-type HA gene sequence, but was also associated either with the removal of a glycosylation site (the one acquired previously by the escape mutant) without the exact restoration of the initial wild-type amino acid sequence, or, for an H5 escape mutant that had no newly acquired glycosylation sites, with an additional amino acid change in a remote part of the HA molecule. The data suggest that such 'compensating' mutations, removing the damaging effects of antibody-selected amino acid changes, may be important in the course of influenza virus evolution.

  11. 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

  12. Sleep and Newborns

    MedlinePlus

    ... 12-Month-Old Bed-Sharing All About Sleep Sleep and Your 1- to 2-Year-Old Communication and Your Newborn Medical Care and Your Newborn Your Newborn's Growth Choosing Safe Baby Products: Cribs Flat Head Syndrome ( ...

  13. Restoration of Declined Immune Responses and Hyperlipidemia by Rubus occidenalis in Diet-Induced Obese Mice

    PubMed Central

    Lee, Youngjoo; Kim, Jiyeon; An, Jinho; Lee, Sungwon; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Choi, Hye Ran; Kwon, Ji-Wung; Shin, Daekeun; Lee, Chong-Kil; Kim, Kyungjae

    2017-01-01

    Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline. PMID:27737523

  14. Killer Treg restore immune homeostasis and suppress autoimmune diabetes in prediabetic NOD mice.

    PubMed

    Kaminitz, Ayelet; Yolcu, Esma S; Stein, Jerry; Yaniv, Isaac; Shirwan, Haval; Askenasy, Nadir

    2011-08-01

    We hypothesized that regulatory T cells (Treg) effectively target diabetogenic cells, and reinforcing their killing capacity will attenuate the course of disease. For proof of concept, Fas-ligand (FasL) protein was conjugated to CD25(+) Treg (killer Treg) to simulate the physiological mechanism of activation-induced cell death. Cytotoxic and suppressive activity of killer Treg was superior to naïve Treg in vitro. Administration of 3-4 × 10(6) Treg prevented hyperglycemia in 65% prediabetic NOD females, however only killer Treg postponed disease onset by 14 weeks. CD25(+) Treg homed to the pancreas and regional lymph nodes of prediabetic NOD females, proliferated and ectopic FasL protein induced apoptosis in CD25(-) T cells in situ. This mechanism of pathogenic cell debulking is specific to killer Treg, as FasL-coated splenocytes have no immunomodulatory effect, and only killer Treg prevent the disease in 80% of NOD.SCID recipients of effector:suppressor T cells (10:1 ratio). All immunomodulated mice displayed increased fractional expression of FoxP3 in the pancreas and draining lymph nodes, which was accompanied by CD25 only in recipients of killer Treg. A therapeutic intervention that uses the affinity of Treg to reduce the pathogenic load has long-term consequences: arrest of destructive insulitis in mice with established disease prior to β-cell extinction.

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

    PubMed Central

    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 LD100, 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. PMID:19553386

  16. 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

  17. Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo(-/-) mice.

    PubMed

    Campbell, Elizabeth J; Vissers, Margreet C M; Bozonet, Stephanie; Dyer, Arron; Robinson, Bridget A; Dachs, Gabi U

    2015-02-01

    Hypoxia-inducible factor-1 (HIF-1) governs cellular adaption to the hypoxic microenvironment and is associated with a proliferative, metastatic, and treatment-resistant tumor phenotype. HIF-1 levels and transcriptional activity are regulated by proline and asparagine hydroxylases, which require ascorbate as cofactor. Ascorbate supplementation reduced HIF-1 activation in vitro, but only limited data are available in relevant animal models. There is no information of the effect of physiological levels of ascorbate on HIF activity and tumor growth, which was measured in this study. C57BL/6 Gulo(-/-) mice (a model of the human ascorbate dependency condition) were supplemented with 3300 mg/L, 330 mg/L, or 33 mg/L of ascorbate in their drinking water before and during subcutaneous tumor growth of B16-F10 melanoma or Lewis lung carcinoma (LL/2). Ascorbate levels in tumors increased significantly with elevated ascorbate intake and restoration of wild-type ascorbate levels led to a reduction in growth of B16-F10 (log phase P < 0.001) and LL/2 tumors (lag growth P < 0.001, log phase P < 0.05). Levels of HIF-1α protein in tumors decreased as dietary ascorbate supplementation increased for both tumor models (P < 0.001). Similarly, tumor ascorbate was inversely correlated with levels of the HIF-1 target proteins CA-IX, GLUT-1, and VEGF in both B16-F10 and LL/2 tumors (P < 0.05). The extent of necrosis was similar between ascorbate groups but varied between models (30% for B16-F10 and 21% for LL/2), indicating that ascorbate did not affect tumor hypoxia. Our data support the hypothesis that restoration of optimal intracellular ascorbate levels reduces tumor growth via moderation of HIF-1 pathway activity.

  18. 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

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

    2010-08-23

    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-gamma-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.

  19. 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

  20. Broadly impaired NK cell function in non-obese diabetic mice is partially restored by NK cell activation in vivo and by IL-12/IL-18 in vitro.

    PubMed

    Johansson, Sofia E; Hall, Håkan; Björklund, Jens; Höglund, Petter

    2004-01-01

    NK cells represent a link between innate and adaptive immunity, and may play a role in regulating autoimmune disorders. We have characterized the NK cell population in non-obese diabetic (NOD) mice. The percentage and absolute numbers of NK cells were similar in NOD and control MHC-matched B6.g7 mice. However, the capacity of NOD NK cells to mediate natural cytotoxicity as well as FcR- and Ly49D-mediated killing was compromised in vitro, suggesting a defect affecting multiple activation pathways. The defect was neither linked to the NK gene complex nor to the MHC, as determined by comparison with mice congenic for these regions. Introducing the beta(2)-microglobulin mutation on the NOD background further impaired NK cell function, showing that the compromised cytotoxic capacity in these two strains arises from two independent mechanisms. In vivo rejection responses against tumor cells and against MHC class I-deficient spleen cells were decreased in naive NOD recipients, but restored in mice pre-activated with tilorone, a potent activator of NK cells. In addition, killing of some tumor targets was restored in vitro after activation of NK cells with IL-12 plus IL-18 or with IFN-alpha/beta, but not with IL-2. Interestingly, natural killing of RMA-S targets by NOD NK cells could not be restored in vitro, indicating that restoration of killing capacity was only partial. Our data suggest a severe, but partially restorable, killing defect in NOD NK cells, affecting activation through several pathways.

  1. Nicotinamide restores cognition in AD transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau

    PubMed Central

    Green, Kim N.; Steffan, Joan S.; Martinez-Coria, Hilda; Sun, Xuemin; Schreiber, Steven S.; Thompson, Leslie Michels; LaFerla, Frank M.

    2008-01-01

    Memory loss is the signature feature of Alzheimer’s disease and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated-α-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of mono-ubiquitin-conjugated tau, suggesting that this post-translationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared to wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability. PMID:18987186

  2. 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.

  3. Rescue of motor coordination by Purkinje cell-targeted restoration of Kv3.3 channels in Kcnc3-null mice requires Kcnc1.

    PubMed

    Hurlock, Edward C; Bose, Mitali; Pierce, Ganon; Joho, Rolf H

    2009-12-16

    The role of cerebellar Kv3.1 and Kv3.3 channels in motor coordination was examined with an emphasis on the deep cerebellar nuclei (DCN). Kv3 channel subunits encoded by Kcnc genes are distinguished by rapid activation and deactivation kinetics that support high-frequency, narrow action potential firing. Previously we reported that increased lateral deviation while ambulating and slips while traversing a narrow beam of ataxic Kcnc3-null mice were corrected by restoration of Kv3.3 channels specifically to Purkinje cells, whereas Kcnc3-mutant mice additionally lacking one Kcnc1 allele were partially rescued. Here, we report mice lacking all Kcnc1 and Kcnc3 alleles exhibit no such rescue. For Purkinje cell output to reach the rest of the brain it must be conveyed by neurons of the DCN or vestibular nuclei. As Kcnc1, but not Kcnc3, alleles are lost, mutant mice exhibit increasing gait ataxia accompanied by spike broadening and deceleration in DCN neurons, suggesting the facet of coordination rescued by Purkinje-cell-restricted Kv3.3 restoration in mice lacking just Kcnc3 is hypermetria, while gait ataxia emerges when additionally Kcnc1 alleles are lost. Thus, fast repolarization in Purkinje cells appears important for normal movement velocity, whereas DCN neurons are a prime candidate locus where fast repolarization is necessary for normal gait patterning.

  4. Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV Restores ON and OFF visual responses in blind mice.

    PubMed

    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.

  5. BACE1 RNAi Restores the Composition of Phosphatidylethanolamine-Derivates Related to Memory Improvement in Aged 3xTg-AD Mice

    PubMed Central

    Villamil-Ortiz, Javier G.; Barrera-Ocampo, Alvaro; Piedrahita, Diego; Velásquez-Rodríguez, Claudia M.; Arias-Londoño, Julian D.; Cardona-Gómez, Gloria P.

    2016-01-01

    β-amyloid (Aβ) is produced by the β-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer’s disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism. The objective of this study was to determine the effect of RNA interference against BACE1 (shBACEmiR) on the phospholipid profile in hippocampal CA1 area in aged 3xTg-AD mice after 6 and 12 months of treatment compared to aged PS1KI mice. The shBACEmiR treatment induced cognitive function recovery and restored mainly the fatty acid composition of lysophosphatidylethanolamine and etherphosphatidylethanolamine, reduced the cPLA2’s phosphorylation, down-regulated the levels of arachidonic acid and COX2 in the hippocampi of 3xTg-AD mice. Together, our findings suggest, for the first time, that BACE1 silencing restores phospholipids composition which could favor the recovery of cellular homeostasis and cognitive function in the hippocampus of triple transgenic AD mice. PMID:27891075

  6. 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.

  7. 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

  8. Interleukin 3 perfusion in W/Wv mice allows the development of macroscopic hematopoietic spleen colonies and restores cutaneous mast cell number

    SciTech Connect

    Ody, C.; Kindler, V.; Vassalli, P. )

    1990-07-01

    The genetically anemic W/Wv mice are characterized by the inability of their bone marrow cells to form macroscopic pluripotent hematopoietic colonies in the spleen of irradiated recipients upon transfer (colony-forming units). Furthermore, they almost totally lack mast cells, notably in the skin. In the present study, we have tested the effect of recombinant murine interleukin 3 (rmIL-3) on W/Wv mice hematopoiesis. Transfer of W/Wv bone marrow cells into lethally irradiated recipients perfused with rmIL-3 is followed by the appearance of macroscopic spleen colonies. Moreover, perfusion of rmIL-3 in W/Wv mice: (a) restores almost normal total numbers of hematopoietic precursors (colony-forming cells), but without modification of anemia; and (b) leads to the appearance of a normal number of mastocytes in the skin.

  9. Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduces Aβ level and microglia activation in the brains of 3xTg-AD mice.

    PubMed

    Chen, Yanxing; Zhao, Yang; Dai, Chun-Ling; Liang, Zhihou; Run, Xiaoqin; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2014-11-01

    Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced Aβ40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD.

  10. Hormonal effects in newborns

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb babies ...

  11. Senses and Your Newborn

    MedlinePlus

    ... the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to ... Other Senses: 1 Month Your Newborn's Growth Your Child's Development: Newborn Contact Us Print Resources Send to a ...

  12. Communication and Your Newborn

    MedlinePlus

    ... the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to ... Sleep and Newborns Jaundice in Healthy Newborns Your Child’s Development: 3-5 Days Contact Us Print Resources Send ...

  13. 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, ...

  14. Your Child's Development: Newborn

    MedlinePlus

    ... Your 1- to 2-Year-Old Your Child's Development: Newborn KidsHealth > For Parents > Your Child's Development: Newborn ... changed; or goes to sleep ) Movement and Physical Development moves in response to sights and sounds rooting ...

  15. Low blood sugar - newborns

    MedlinePlus

    ... medlineplus.gov/ency/article/007306.htm Low blood sugar - newborns To use the sharing features on this page, please enable JavaScript. A low blood sugar level in newborn babies is also called neonatal ...

  16. Newborn screening tests

    MedlinePlus

    Newborn screening tests look for developmental, genetic, and metabolic disorders in the newborn baby. This allows steps to be taken before symptoms develop. Most of these illnesses are very rare, but can be treated if caught ...

  17. 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 ...

  18. Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice

    PubMed Central

    Braudeau, J; Delatour, B; Duchon, A; Pereira, P Lopes; Dauphinot, L; de Chaumont, F; Olivo-Marin, J-C; Dodd, RH; Hérault, Y; Potier, M-C

    2011-01-01

    An imbalance between inhibitory and excitatory neurotransmission has been proposed to contribute to altered brain function in individuals with Down syndrome (DS). Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and accordingly treatment with GABA-A antagonists can efficiently restore cognitive functions of Ts65Dn mice, a genetic model for DS. However, GABA-A antagonists are also convulsant which preclude their use for therapeutic intervention in DS individuals. Here, we have evaluated safer strategies to release GABAergic inhibition using a GABA-A-benzodiazepine receptor inverse agonist selective for the α5-subtype (α5IA). We demonstrate that α5IA restores learning and memory functions of Ts65Dn mice in the novel-object recognition and in the Morris water maze tasks. Furthermore, we show that following behavioural stimulation, α5IA enhances learning-evoked immediate early gene products in specific brain regions involved in cognition. Importantly, acute and chronic treatments with α5IA do not induce any convulsant or anxiogenic effects that are associated with GABA-A antagonists or non-selective inverse agonists of the GABA-A-benzodiazepine receptors. Finally, chronic treatment with α5IA did not induce histological alterations in the brain, liver and kidney of mice. Our results suggest that non-convulsant α5-selective GABA-A inverse agonists could improve learning and memory deficits in DS individuals. PMID:21693554

  19. 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.

  20. Restoration of Dlk1 and Rtl1 is necessary but insufficient to rescue lethality in intergenic differentially methylated region (IG-DMR)-deficient mice.

    PubMed

    Takahashi, Nozomi; Kobayashi, Ryota; Kono, Tomohiro

    2010-08-20

    In the Dlk1-Dio3 imprinted domain, an intergenic differentially methylated region (IG-DMR) regulates the parental allele-specific expression of imprinted genes. The maternally inherited deletion of IG-DMR (IG-DMR((-/+))) results in perinatal lethality because of the overexpression of paternally expressed genes and repression of maternally expressed noncoding RNAs (ncRNAs), including Gtl2. To better understand the possible contribution of paternally expressed genes to the lethality, we attempted to rescue the lethality of IG-DMR((-/+)) mutants by restoring the paternally expressed genes. Because the paternally inherited Gtl2 deletion (Gtl2((+/-))) induced a decrease in the expression of paternally expressed genes, we crossed female IG-DMR heterozygous mice and male Gtl2 heterozygous mutant mice. The resultant IG-DMR((-/+))/Gtl2((+/-)) double mutant mice had normal expression levels of paternally expressed genes, and none of them showed perinatal lethality; however, most mice showed postnatal lethality with decreased expression of the maternally expressed ncRNAs. Thus, we inferred that paternally expressed genes are necessary for perinatal survivability and that maternally expressed ncRNAs are involved in postnatal lethality.

  1. Prebiotic inulin supplementation modulates the immune response and restores gut morphology in Giardia duodenalis-infected malnourished mice.

    PubMed

    Shukla, Geeta; Bhatia, Ruchika; Sharma, Anuj

    2016-11-01

    Malnutrition induces a state of growth retardation and immunologic depression, enhancing the host susceptibility to various infections. In the present study, it was observed that prebiotic supplementation either prior or simultaneously with Giardia infection in malnourished mice significantly reduced the severity of giardiasis and increased the body and small intestine mass, along with increased lactobacilli counts in faeces compared with malnourished-Giardia-infected mice. More specifically, prebiotic supplementation significantly increased the levels of anti-giardial IgG and IgA antibodies and anti-inflammatory cytokines IL-6 and IL-10 and reduced the pro-inflammatory cytokine TNF-α, along with increased levels of nitric oxide in both the serum and intestinal fluid of malnourished-prebiotic-Giardia-infected mice compared with malnourished-Giardia-infected mice. Histopathology and scanning electron microscopy of the small intestine also revealed less cellular and mucosal damage in the microvilli of prebiotic-supplemented malnourished-Giardia-infected mice compared with severely damaged mummified and blunted villi of malnourished-Giardia-infected mice. This is the first study to report that prebiotic supplementation modulated the gut morphology and improved the immune status even in malnourished-Giardia-infected mice.

  2. 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.

  3. 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

  4. 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.

  5. 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

    2016-02-04

    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.

  6. Newborn jaundice - discharge

    MedlinePlus

    ... Jaundice of the newborn - discharge; Neonatal hyperbilirubinemia - discharge; Breastfeeding jaundice - discharge; Physiologic jaundice - discharge Images Exchange transfusion - series Infant jaundice References Kaplan M, ...

  7. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice.

    PubMed

    Rodríguez, Amaia; Moreno, Natalia R; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M; Frühbeck, Gema

    2015-07-10

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity.

  8. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice

    PubMed Central

    Rodríguez, Amaia; Moreno, Natalia R.; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M.; Frühbeck, Gema

    2015-01-01

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity. PMID:26159457

  9. 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

  10. Communication and Your Newborn

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Communication and Your Newborn KidsHealth > For Parents > Communication and Your Newborn A A A What's in ... first smile — a welcome addition to your baby's communication skills! continue What Should I Do? As soon ...

  11. Your Child's Development: Newborn

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Your Child's Development: Newborn KidsHealth > For Parents > Your Child's Development: Newborn Print A A A en español El ... the sole of the foot Social and Emotional Development soothed by a parent's ... When to Talk to Your Doctor Every child develops at his or her own pace, but ...

  12. Amebiasis in the newborn.

    PubMed

    Güven, Ayla

    2003-05-01

    Infestation with Entamoeba histolytica is especially common in areas with low socioeconomic status. Extra intestinal invasive involvement is more frequent in young children with significant mortality. This disease is rarely reported in the newborns. This 19-day-old newborn who was infected with orally given surgar solution is presented. He was successfully treated with omidazole.

  13. Delineation of biochemical, molecular, and physiological changes accompanying bile acid pool size restoration in Cyp7a1(-/-) mice fed low levels of cholic acid.

    PubMed

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

    2012-07-15

    Cholesterol 7α-hydroxylase (CYP7A1) is the initiating and rate-limiting enzyme in the neutral pathway that converts 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.

  14. 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

  15. 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.

  16. 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

  17. The γ-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice.

    PubMed

    Balducci, Claudia; Mehdawy, Bisan; Mare, Lydia; Giuliani, Alessandro; Lorenzini, Luca; Sivilia, Sandra; Giardino, Luciana; Calzà, Laura; Lanzillotta, Annamaria; Sarnico, Ilenia; Pizzi, Marina; Usiello, Alessandro; Viscomi, Arturo R; Ottonello, Simone; Villetti, Gino; Imbimbo, Bruno P; Nisticò, Giuseppe; Forloni, Gianluigi; Nisticò, Robert

    2011-01-01

    Abnormal amyloid-β (Aβ) production and deposition is believed to represent one of the main causes of Alzheimer's disease (AD). γ-Secretase is the enzymatic complex responsible for Aβ generation from its precursor protein. Inhibition or modulation of γ-secretase represents an attractive therapeutic approach. CHF5074 is a new γ-secretase modulator that has been shown to inhibit brain plaque deposition and to attenuate memory deficit in adult AD transgenic mice after chronic treatment. To date, it is not known whether the positive behavioral effects of this compound also occur in young transgenic mice without plaque deposition. Here, we evaluated the effects of acute and subchronic treatment with CHF5074 on contextual and recognition memory and on hippocampal synaptic plasticity in plaque-free Tg2576 mice. We found that at 5 months of age, contextual memory impairment was significantly attenuated after acute subcutaneous administration of 30 mg/kg CHF5074. At 6 months of age, recognition memory impairment was fully reversed after a 4-week oral treatment in the diet (≈60 mg/kg/day). These cognitive effects were associated with a reversal of long-term potentiation (LTP) impairment in the hippocampus. A significant reduction in brain intraneuronal AβPP/Aβ levels and hyperphosphorylated tau, but no change in soluble or oligomeric Aβ levels was detected in Tg2576 mice showing functional recovery following CHF5074 treatment. We conclude that the beneficial effects of CHF5074 treatment in young transgenic mice occurred at a stage that precedes plaque formation and were associated with a reduction in intraneuronal AβPP/Aβ and hyperphosphorylated tau.

  18. 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

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

    PubMed

    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

    2015-07-01

    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.

  20. 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

  1. 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.

  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. ABLATION OF THE UPR–MEDIATOR CHOP RESTORES MOTOR FUNCTION AND REDUCES DEMYELINATION IN CHARCOT MARIE TOOTH 1B MICE

    PubMed Central

    Pennuto, Maria; Tinelli, Elisa; Malaguti, MariaChiara; Del Carro, Ubaldo; D'Antonio, Maurizio; Ron, David; Quattrini, Angelo; Feltri, M. Laura; Wrabetz, Lawrence

    2008-01-01

    SUMMARY Deletion of serine 63 from P0 glycoprotein (P0S63del) causes Charcot-Marie-Tooth 1B neuropathy in humans, and P0S63del produces a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum and fails to be incorporated into myelin. Here we report that P0S63del is globally misfolded and Schwann cells mount a consequential canonical unfolded protein response (UPR), that includes expression of the transcription factor CHOP, previously associated with apoptosis in ER-stressed cells. UPR activation and CHOP expression respond dynamically to P0S63del levels and are reversible, but are associated with only limited apoptosis of Schwann cells. Nonetheless, Chop ablation in S63del mice completely rescues their motor deficit and reduces active demyelination two-fold. This is the first indication that signaling through the CHOP arm of the UPR provokes demyelination in inherited neuropathy. In addition, S63del mice provide a unique opportunity to explore how cells can dysfunction yet survive in prolonged ER stress—important for neurodegeneration related to misfolded proteins. PMID:18255032

  4. 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

  5. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease

    PubMed Central

    Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. PMID:23801246

  6. 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

  7. Gene dysregulation is restored in the Parkinson's disease MPTP neurotoxic mice model upon treatment of the therapeutic drug Cu(II)(atsm).

    PubMed

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

    2016-03-01

    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 Cu(II)(atsm) rescues nigral cell loss and improves dopamine metabolism in the MPTP model. The mechanism of action of Cu(II)(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 Cu(II)(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 Cu(II)(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.

  8. 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

  9. Melanin nanoparticles (MNPs) provide protection against whole-body ɣ-irradiation in mice via restoration of hematopoietic tissues.

    PubMed

    Rageh, Monira M; El-Gebaly, Reem H; Abou-Shady, H; Amin, Doaa G

    2015-01-01

    During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attack various cellular components. The hematopoietic system is easily recognized to be radiosensitive and its damage may be severe. Melanin nanoparticles (MNPs) act as free radical scavengers prepared by polymerization of dopamine. In this study, a total of 110 male BALB/C mice were divided into five equal groups. Each group contained 22 mice. Mice of group A did not receive MNPs or irradiation (control group), group B was injected intraperitoneally (i.p.) with 50 mg/kg MNPs. Mice of group C and D were exposed to a dose of 7 Gy ɣ-irradiation and injected with the same dose of MNPs as in group B either 30 min pre- or post-irradiation, and group E was exposed to a dose of 7 Gy ɣ-irradiation only. The impact of MNPs on peripheral blood, spleen, and DNA damage induced by irradiation was evaluated by blood count, histopathology of the spleen, and comet assay for the DNA in the bone marrow at 1, 4, 8, and 12 days post-irradiation. Results of group E compared with control group (A) showed a significant depression in complete blood count. Additionally, histopathological observation showed the absence of megakaryocytes with delayed time post-irradiation, deposition of eosinophilic protein of their spleen appeared, as well as a remarkable decrease in spleen size was observed. Moreover, ɣ-irradiation-induced DNA damage as can be inferred from a significant increase by about 5-10 folds in all comet parameters (% of DNA, tail length, tail moment, and olive moment) in the DNA of the bone marrow. In contrast, pre-post treatment with MNPs protected hematopoietic tissues against radiation damage, and therefore, enhanced the survival of mice with 40 % in groups (C&D) compared with 10 % to group (E) till 30 days post-irradiation. In conclusion, these results demonstrated that synthetic MNPs provide significant radioprotection to the hematopoietic tissues.

  10. 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.

  11. 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

  12. Immunization of Newborn Mice Accelerates the Architectural Maturation of Lymph Nodes, But AID-Dependent IgG Responses Are Still Delayed Compared to the Adult

    PubMed Central

    Munguía-Fuentes, Rosario; Yam-Puc, Juan Carlos; Silva-Sánchez, Aarón; Marcial-Juárez, Edith; Gallegos-Hernández, Isis Amara; Calderón-Amador, Juana; Randall, Troy D.; Flores-Romo, Leopoldo

    2017-01-01

    Lymph nodes (LNs) have evolved to maximize antigen (Ag) collection and presentation as well as lymphocyte proliferation and differentiation—processes that are spatially regulated by stromal cell subsets, including fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs). Here, we showed that naïve neonatal mice have poorly organized LNs with few B and T cells and undetectable FDCs, whereas adult LNs have numerous B cells and large FDC networks. Interestingly, immunization on the day of birth accelerated B cell accumulation and T cell recruitment into follicles as well as FDC maturation and FRC organization in neonatal LNs. However, compared to adults, the formation of germinal centers was both delayed and reduced following immunization of neonatal mice. Although immunized neonates poorly expressed activation-induced cytidine deaminase (AID), they were able to produce Ag-specific IgGs, but with lower titers than adults. Interestingly, the Ag-specific IgM response in neonates was similar to that in adults. These results suggest that despite an accelerated structural maturation of LNs in neonates following vaccination, the B cell response is still delayed and reduced in its ability to isotype switch most likely due to poor AID expression. Of note, naïve pups born to Ag-immunized mothers had high titers of Ag-specific IgGs from day 0 (at birth). These transferred antibodies confirm a mother-derived coverage to neonates for Ags to which mothers (and most likely neonates) are exposed, thus protecting the neonates while they produce their own antibodies. Finally, the type of Ag used in this study and the results obtained also indicate that T cell help would be operating at this stage of life. Thus, neonatal immune system might not be intrinsically immature but rather evolutionary adapted to cope with Ags at birth. PMID:28154564

  13. Newborn Screening Tests

    MedlinePlus

    ... difference between lifelong impairment and healthy development. Which Tests Are Offered? Newborn screening varies by state and is subject to change, especially given advancements in technology. However, the disorders listed here are those usually ...

  14. Growth and Your Newborn

    MedlinePlus

    ... dimpled thighs was many people's picture of a healthy newborn. But a baby born much larger than average may have special medical problems that need attention. Some exceptionally large babies — especially those born to ...

  15. 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 ...

  16. Growth and Your Newborn

    MedlinePlus

    ... the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to ... Your Child's Growth Breastfeeding vs. Formula Feeding Your Child's Development: Newborn Contact Us Print Resources Send to a ...

  17. Jaundice in Healthy Newborns

    MedlinePlus

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... common condition in newborns, refers to the yellow color of the skin and whites of the eyes ...

  18. Newborn Screening Tests Approved

    MedlinePlus

    ... The screens are used to detect four rare metabolic disorders To use the sharing features on this page, ... of screening tests designed to detect four rare metabolic disorders in newborns has been approved by the U.S. ...

  19. Jaundice in Healthy Newborns

    MedlinePlus

    ... eyes that happens when there is too much bilirubin in the blood. Bilirubin (bill-uh-ROO-bin) is produced by the ... liquid that helps with digestion). Jaundice happens when bilirubin builds up faster than a newborn's liver can ...

  20. 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 ...

  1. 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

  2. Central anatomy of individual rapidly adapting low-threshold mechanoreceptors innervating the "hairy" skin of newborn mice: early maturation of hair follicle afferents.

    PubMed

    Woodbury, C J; Ritter, A M; Koerber, H R

    2001-07-30

    Adult skin sensory neurons exhibit characteristic projection patterns in the dorsal horn of the spinal gray matter that are tightly correlated with modality. However, little is known about how these patterns come about during the ontogeny of the distinct subclasses of skin sensory neurons. To this end, we have developed an intact ex vivo somatosensory system preparation in neonatal mice, allowing single, physiologically identified cutaneous afferents to be iontophoretically injected with Neurobiotin for subsequent histological analyses. The present report, centered on rapidly adapting mechanoreceptors, represents the first study of the central projections of identified skin sensory neurons in neonatal animals. Cutaneous afferents exhibiting rapidly adapting responses to sustained natural stimuli were encountered as early as recordings were made. Well-stained representatives of coarse (tylotrich and guard) and fine-diameter (down) hair follicle afferents, along with a putative Pacinian corpuscle afferent, were recovered from 2-7-day-old neonates. All were characterized by narrow, uninflected somal action potentials and generally low mechanical thresholds, and many could be activated via deflection of recently erupted hairs. The central collaterals of hair follicle afferents formed recurrent, flame-shaped arbors that were essentially miniaturized replicas of their adult counterparts, with identical laminar terminations. The terminal arbors of down hair afferents, previously undescribed in rodents, were distinct and consistently occupied a more superficial position than tylotrich and guard hair afferents. Nevertheless, the former extended no higher than the middle of the incipient substantia gelatinosa, leaving a clear gap more dorsally. In all major respects, therefore, hair follicle afferents display the same laminar specificity in neonates as they do in adults. The widely held misperception that their collaterals extend exuberant projections into pain

  3. Pharmacological activation of PPARbeta/delta stimulates utrophin A expression in skeletal muscle fibers and restores sarcolemmal integrity in mature mdx mice.

    PubMed

    Miura, Pedro; Chakkalakal, Joe V; Boudreault, Louise; Bélanger, Guy; Hébert, Richard L; Renaud, Jean-Marc; Jasmin, Bernard J

    2009-12-01

    A therapeutic strategy to treat Duchenne muscular dystrophy (DMD) involves identifying compounds that can elevate utrophin A expression in muscle fibers of affected patients. The dystrophin homologue utrophin A can functionally substitute for dystrophin when its levels are enhanced in the mdx mouse model of DMD. Utrophin A expression in skeletal muscle is regulated by mechanisms that promote the slow myofiber program. Since activation of peroxisome proliferator-activated receptor (PPAR) beta/delta promotes the slow oxidative phenotype in skeletal muscle, we initiated studies to determine whether pharmacological activation of PPARbeta/delta provides functional benefits to the mdx mouse. GW501516, a PPARbeta/delta agonist, was found to stimulate utrophin A mRNA levels in C2C12 muscle cells through an element in the utrophin A promoter. Expression of PPARbeta/delta was greater in skeletal muscles of mdx versus wild-type mice. We treated 5-7-week-old mdx mice with GW501516 for 4 weeks. This treatment increased the percentage of muscle fibers expressing slower myosin heavy chain isoforms and stimulated utrophin A mRNA levels leading to its increased expression at the sarcolemma. Expression of alpha1-syntrophin and beta-dystroglycan was restored to the sarcolemma. Improvement of mdx sarcolemmal integrity was evidenced by decreased intracellular IgM staining and decreased in vivo Evans blue dye (EBD) uptake. GW501516 treatment also conferred protection against eccentric contraction (ECC)-induced damage of mdx skeletal muscles, as shown by a decreased contraction-induced force drop and reduction of dye uptake during ECC. These results demonstrate that pharmacological activation of PPARbeta/delta might provide functional benefits to DMD patients through enhancement of utrophin A expression.

  4. Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells.

    PubMed

    Lien, Chun-Yang; Chih-Yuan Ho, Kevin; Lee, Oscar K; Blunn, Gordon W; Su, Yeu

    2009-05-01

    Transplantation of gene-modified mesenchymal stem cells (MSCs) in animals for bone regeneration therapy has been evaluated extensively in recent years. However, increased endosteal bone formation by intravenous injection of MSCs ectopically expressing a foreign gene has not yet been shown. Aside from the clearance by lung and other tissues, the surface compositions of MSCs may not favor their bone marrow (BM) migration and engraftment. To overcome these hurdles, a gene encoding the chemokine receptor largely responsible for stromal-derived factor-1 (SDF-1)-mediated BM homing and engraftment of hematopoietic stem cells (HSCs), CXCR4, was transduced into mouse C3H10T1/2 cells by adenovirus infection. A dose-dependent increase of CXCR4 surface expression with a parallel enhanced chemotaxis toward SDF-1 in these cells after virus infection was clearly observed. Higher BM retention and homing of CXCR4-expressing MSCs were also found after they were transplanted by intramedullary and tail vein injections, respectively, into immunocompetent C3H/HeN mice. Interestingly, a full recovery of bone mass and a partial restoration of bone formation in glucocorticoid-induced osteoporotic mice were observed 4 wk after a single intravenous infusion of one million CXCR4-expressing C3H10T1/2 cells. In the meantime, complete recovery of bone stiffness and strength in these animals was consistently detected only after a systemic transplantation of CXCR4 and Cbfa-1 co-transduced MSCs. To our knowledge, this is the first report to show unequivocally the feasibility of ameliorating glucocorticoid-induced osteoporosis by systemic transplantation of genetically manipulated MSCs.

  5. 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

  6. 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.

  7. 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

  8. Melatonin restores hippocampal neural precursor cell proliferation and prevents cognitive deficits induced by jet lag simulation in adult mice.

    PubMed

    Iggena, Deetje; Winter, York; Steiner, Barbara

    2017-05-01

    Frequent flyers and shift workers undergo circadian dysrhythmia with adverse impact on body and mind. The circadian rhythm disorder "jet lag" disturbs hippocampal neurogenesis and spatial cognition, which represent morphological and functional adult brain plasticity. This raises the question if pro-neurogenic stimuli might prevent those consequences. However, suitable measures to mitigate jet lag-induced adverse effects on brain plasticity have been neglected so far. Here, we used adult C57Bl6 mice to investigate the pro-neurogenic stimuli melatonin (8 mg/kg i.p.) as well as environmental enrichment as potential measures. We applied photoperiod alterations to simulate "jet lag" by shortening the dark period every third day by 6 hours for 3 weeks. We found that "jet lag" simulation reduced hippocampal neural precursor cell proliferation by 24% and impaired spatial memory performance in the water maze indicated by a prolonged swim path to the target (~23%). While melatonin prevented both the cellular (~1%) as well as the cognitive deficits (~5%), environmental enrichment only preserved precursor cell proliferation (~12%). Our results indicate that lifestyle interventions are insufficient to completely compensate jet lag-induced consequences. Instead, melatonin is required to prevent cognitive impairment caused by the same environmental factors to which frequent flyers and shift workers are typically exposed to.

  9. Gene therapy for newborns.

    PubMed

    Kohn, D B; Parkman, R

    1997-07-01

    Application of gene therapy to treat genetic and infectious diseases may have several advantages if performed in newborns. Because of the minimal adverse effect of the underlying disease on cells of the newborn, the relatively small size of infants, and the large amount of future growth, gene therapy may be more successful in newborns than in older children or adults. The presence of umbilical cord blood from newborns provides a unique and susceptible target for the genetic modification of hematopoietic stem cells. In our first trial of gene therapy in newborns, we inserted a normal adenosine deaminase gene into umbilical cord blood cells of three neonates with a congenital immune deficiency. The trial demonstrated the successful transduction and engraftment of stem cells, which continue to contribute to leukocyte production more than 3 years later. A similar approach may be taken to insert genes that inhibit replication of HIV-1 into umbilical cord blood cells of HIV-1-infected neonates. Many other metabolic and infectious disorders could be treated by gene therapy during the neonatal period if prenatal diagnoses are made and the appropriate technical and regulatory requirements have been met.

  10. Clostridium butyricum Combined with Bifidobacterium infantis Probiotic Mixture Restores Fecal Microbiota and Attenuates Systemic Inflammation in Mice with Antibiotic-Associated Diarrhea

    PubMed Central

    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. PMID:25802855

  11. Minocycline restores sAPPα levels and reduces the late histopathological consequences of traumatic brain injury in mice.

    PubMed

    Siopi, Eleni; Cho, Angelo H; Homsi, Shadi; Croci, Nicole; Plotkine, Michel; Marchand-Leroux, Catherine; Jafarian-Tehrani, Mehrnaz

    2011-10-01

    Traumatic brain injury (TBI) induces both focal and diffuse lesions that are concurrently responsible for the ensuing morbidity and mortality and for which no established treatment is available. It has been recently reported that an endogenous neuroprotector, the soluble form α of the amyloid precursor protein (sAPPα), exerts neuroprotective effects following TBI. However, the emergent post-traumatic neuroinflammatory environment compromises sAPPα production and may promote neuronal degeneration and consequent brain atrophy. Hence, the aim of this study was to examine the effects of the anti-inflammatory drug minocycline on sAPPα levels, as well as on long-term histological consequences post-TBI. The weight-drop model was used to induce TBI in mice. Minocycline or its vehicle were administered three times: at 5 min (90 mg/kg, i.p.) and at 3 and 9 h (45 mg/kg, i.p.) post-TBI. The levels of sAPPα, the extent of brain atrophy, and reactive gliosis were evaluated by ELISA, cresyl violet, and immunolabeling of GFAP and CD11b, respectively. Our results revealed a post-TBI sAPPα decrease that was significantly attenuated by minocycline. Additionally, corpus callosum and striatal atrophy, ventriculomegaly, astrogliosis, and microglial activation were observed at 3 months post-TBI. All the above consequences were significantly reduced by minocycline. In conclusion, inhibition of the acute phase of post-TBI neuroinflammation was associated with the sparing of sAPPα and the protection of brain tissue in the long-term, emphasizing the potential role of minocycline as an effective treatment for TBI.

  12. Assessment of Risk in Newborns.

    ERIC Educational Resources Information Center

    Umansky, Warren; Seaton, Jane B.

    1979-01-01

    To assess risk status of newborns, data were collected on 776 newborns using a high risk register. Analysis of high risk characteristics revealed 261 primary risk incidents in the sample and 292 secondary risk factors. (Author/PHR)

  13. Jaundice in the newborn.

    PubMed

    Agrawal, R; Aggarwal, R; Deorari, A K; Paul, V K

    2001-10-01

    Hyperbilirubinemia is the commonest morbidity in the neonatal period and 5-10% of all newborns require intervention for pathological jaundice. Neonates on exclusive breast-feeding have a different pattern of physiological jaundice as compared to artificially fed babies. Guidelines from American Academy of Pediatrics (AAP) for management of jaundice in a normal term newborn have been included in the protocol. Separate guidelines have been provided for the management of jaundice in sick term babies, preterm and low birth weight babies, for jaundice secondary to hemolysis and for prolonged hyperbilirubinemia. Although hour specific bilirubin charts are available, these have to be validated in Indian infants before they are accepted for widespread use.

  14. 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…

  15. Analysis of Spine Motility of Newborn Granule Cells in Acute Brain Slices.

    PubMed

    Tashiro, Ayumu; Zhao, Chunmei; Suh, Hoonkyo; Gage, Fred H

    2015-10-01

    In this protocol, acute brain slices are prepared from mice in which newborn granule cells have been labeled using retroviral vector technology. Using a live-cell imaging stage and confocal microscopy coupled to imaging software, dendritic spines are analyzed.

  16. 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…

  17. Nail care for newborns

    MedlinePlus

    ... MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Nail care for newborns URL of this page: //medlineplus.gov/ ...

  18. Naturally occurring antibodies for the group B streptococcal surface immunogenic protein (Sip) in pregnant women and newborn babies.

    PubMed

    Manning, Shannon D; Wood, Stephen; Kasha, Katherine; Martin, Denis; Rioux, Stéphane; Brodeur, Bernard; Davies, H Dele

    2006-11-17

    Sip is a surface-exposed protein of GBS, which causes severe neonatal disease. Because Sip elicits a protective immune response in mice, we assessed whether pregnant women and newborns have Sip antibodies. Sera were collected from 644 pregnant women and 176 of their healthy newborns, and 10 newborns with GBS disease and their mothers. Using ELISA, most (99%) women and newborns (97%) had serum Sip antibodies, as did most newborns followed through 6 months. This suggests that naturally occurring Sip antibodies cross the placenta and persist into infancy, which underscores the need to study Sip further as a potential vaccine candidate.

  19. 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

  20. Advancing newborn health: The Saving Newborn Lives initiative

    PubMed Central

    Tinker, A.; Parker, R.; Lord, D.; Grear, K.

    2009-01-01

    Until recently, newborn health was virtually absent from the global health agenda. Now, assistance agencies, national governments and non-governmental organisations are increasingly addressing this previously neglected issue of close to four million newborns dying every year. The experience of the Saving Newborn Lives initiative documents some of the progress that has been made and the challenges and opportunities that lie ahead. Since the start of the initiative in 2000, targeted research, focused on overcoming the key barriers to improved newborn survival, has demonstrated low-cost, community-based interventions and strategies that can significantly reduce newborn mortality. Building on what has been learned from this and other efforts to date, the challenge now is to reach the millions of newborns still at risk. PMID:19851911

  1. 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

  2. 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.

  3. Newborn screening in India.

    PubMed

    Rama Devi, A Radha; Naushad, S M

    2004-02-01

    Expanded newborn screening (NBS) is aimed for early detection and intervention of treatable inborn errors of metabolism and also to establish incidence of these disorders in this part of the globe. The first expanded NBS programme initiated in the capital city of Andhra Pradesh to screen all the newborns born in four major Government Maternity Hospitals in Hyderabad by heel prick capillary blood collected on S&S 903 filter paper. Chromatographic (TLC and HPLC), electrophoretic (cellulose acetate and agarose) and ELISA based assays have been employed for screening of common inborn errors of metabolism. This study has shown a high prevalence of treatable Inborn errors of metabolism. Congenital hypothyroidsm is the most common disorder (1 in 1700) followed by congenital Adrenal Hyperplasia (1 in 2575) and Hyperhomocystenemia (1 in 100). Interestingly, a very high prevalence of inborn errors of metabolism to the extent of 1 in every thousand newborns was observed. The study reveals the importance of screening in India, necessitating nation wide large-scale screening.

  4. T cells from baxalpha transgenic mice show accelerated apoptosis in response to stimuli but do not show restored DNA damage-induced cell death in the absence of p53.

    PubMed Central

    Brady, H J; Salomons, G S; Bobeldijk, R C; Berns, A J

    1996-01-01

    Baxalpha was isolated due to its interaction with Bcl-2. Baxalpha overexpression in an interleukin (IL)-3 dependent cell line accelerates apoptosis upon removal of the cytokine. The ratio of Baxalpha to Bcl-2 appears to be crucial for the effect. To study the action of the bax gene product in vivo, we have generated transgenic mice overexpressing Baxalpha specifically in T cells. Such T cells show accelerated apoptosis in response to gamma-radiation, dexamethasone and etoposide. By crossing baxalpha mice with bcl-2 transgenics we show that the critical nature of the Baxalpha:Bcl-2 ratio holds in primary T cells and that it can be manipulated to elicit a strong response to previously resisted stimuli. p53 has a role in the regulation of apoptosis in response to DNA-damaging agents. p53 directly activates transcription of the bax gene. The presence of the baxalpha transgene accelerated apoptosis in thymocytes from both p53-l- and p53+l- mice in response to dexamethasone. Thymocytes from p53-l- mice with the baxalpha transgene showed similar resistance to apoptosis by DNA-damaging agents as did p53-l- mice without the transgene. Baxalpha overexpression alone cannot restore the DNA damage apoptosis pathway, suggesting that p53 is required to induce or activate other factor(s) to reconstitute the response fully. Images PMID:8635454

  5. 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.

  6. [Bednar's aphthae in newborn].

    PubMed

    Fariñas Salto, Mercedes; Menéndez Hernando, Cristina; Martín Molina, Raquel; Galán Gómez, Víctor; García de Pedro, Fernando J

    2017-02-01

    The description of the Bednar's ulcer is uncommon in the current literature. It has been associated with the traumatic effect of the bottle's nipple and/or no orthodontic soothers while breastfeeding. We present a newborn of 20 days of life attended at the emergency room for irritability, with the only finding on physical examination of two oral ulcers. We describe the clinical presentation, evolution and treatment. The normality of the diagnostic test, clinical characteristics and evolution lead to the diagnosis of Bednar´s ulcer.

  7. Management of the depressed newborn.

    PubMed

    Welch, K A; Philips, J B

    1984-03-01

    The experienced obstetrician knows that depressed neonates do not always herald their coming, and that the potential liability for failure to intervene promptly is great. It is imperative that all personnel involved in the delivery and care of newborns be familiar with these principles of newborn resuscitation.

  8. Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice.

    PubMed

    Renko, Kostja; Werner, Margarethe; Renner-Müller, Ingrid; Cooper, Trevor G; Yeung, Ching Hei; Hollenbach, Birgit; Scharpf, Marcus; Köhrle, Josef; Schomburg, Lutz; Schweizer, Ulrich

    2008-02-01

    SePP (selenoprotein P) is central for selenium transport and distribution. Targeted inactivation of the Sepp gene in mice leads to reduced selenium content in plasma, kidney, testis and brain. Accordingly, activities of selenoenzymes are reduced in Sepp(-/-) organs. Male Sepp(-/-) mice are infertile. Unlike selenium deficiency, Sepp deficiency leads to neurological impairment with ataxia and seizures. Hepatocyte-specific inactivation of selenoprotein biosynthesis reduces plasma and kidney selenium levels similarly to Sepp(-/-) mice, but does not result in neurological impairment, suggesting a physiological role of locally expressed SePP in the brain. In an attempt to define the role of liver-derived circulating SePP in contrast with locally expressed SePP, we generated Sepp(-/-) mice with transgenic expression of human SePP under control of a hepatocyte-specific transthyretin promoter. Secreted human SePP was immunologically detectable in serum from SEPP1-transgenic mice. Selenium content and selenoenzyme activities in serum, kidney, testis and brain of Sepp(-/-;SEPP1) (SEPP1-transgenic Sepp(-/-)) mice were increased compared with Sepp(-/-) controls. When a selenium-adequate diet (0.16-0.2 mg/kg of body weight) was fed to the mice, liver-specific expression of SEPP1 rescued the neurological defects of Sepp(-/-) mice and rendered Sepp(-/-) males fertile. When fed on a low-selenium diet (0.06 mg/kg of body weight), Sepp(-/-;SEPP1) mice survived 4 weeks longer than Sepp(-/-) mice, but ultimately developed the neurodegenerative phenotype. These results indicate that plasma SePP derived from hepatocytes is the main transport form of selenium supporting the kidney, testis and brain. Nevertheless, local Sepp expression is required to maintain selenium content in selenium-privileged tissues such as brain and testis during dietary selenium restriction.

  9. 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.

  10. 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

  11. 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;…

  12. Antifungal Immunological Defenses in Newborns

    PubMed Central

    Michalski, Christina; Kan, Bernard; Lavoie, Pascal M.

    2017-01-01

    Newborns are prone to fungal infections, largely due to Candida species. The immunological basis for this vulnerability is not yet fully understood. However, useful insights can be gained from the knowledge of the maturation of immune pathways during ontogeny, particularly when placed in context with how rare genetic mutations in humans predispose to fungal diseases. In this article, we review these most current data on immune functions in human newborns, highlighting pathways most relevant to the response to Candida. While discussing these data, we propose a framework of why deficiencies in these pathways make newborns particularly vulnerable to this opportunistic pathogen. PMID:28360910

  13. Conjunctivitis (Pink Eye) in Newborns

    MedlinePlus

    ... Get Smart: Know When Antibiotics Work Adenovirus Non-Polio Enterovirus Parent Portal Conjunctivitis (Pink Eye) in Newborns ... Get Smart: Know When Antibiotics Work Adenovirus Non-Polio Enterovirus Parent Portal Language: English Español (Spanish) File ...

  14. Medical Care and Your Newborn

    MedlinePlus

    ... Weight, length, and head circumference will be measured. Temperature will be taken, and your baby's breathing and ... an eye infection. Fever in a newborn (rectal temperature above 100.4°F or 38°C) should ...

  15. Learning, Play, and Your Newborn

    MedlinePlus

    ... their backs to reduce the risk of SIDS (sudden infant death syndrome) . Talk to your baby. Keep in mind ... For Kids For Parents MORE ON THIS TOPIC Sudden Infant Death Syndrome (SIDS) Movement, Coordination, and Your Newborn Your ...

  16. Learning, Play, and Your Newborn

    MedlinePlus

    ... the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to ... Month-Old About the Play & Learn Center Your Child's Development: Newborn Your Child’s Development: 3-5 Days Contact ...

  17. 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

  18. A novel cognitive enhancer, ZSET1446/ST101, promotes hippocampal neurogenesis and ameliorates depressive behavior in olfactory bulbectomized mice.

    PubMed

    Shioda, Norifumi; Yamamoto, Yui; Han, Feng; Moriguchi, Shigeki; Yamaguchi, Yoshimasa; Hino, Masataka; Fukunaga, Kohji

    2010-04-01

    In the adult brain, neurogenesis persistently occurs in the subgranular zone of the hippocampal dentate gyrus (DG), and impaired neurogenesis is implicated in depressive behaviors and poor learning memory. Here, we investigated the effects of oral administration of spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101), a novel cognitive enhancer stimulating acetylcholine release, on adult neurogenesis in olfactory bulbectomized (OBX) mice. OBX mice showed significant decreases in the number of newborn cells in the DG by immunohistochemical analysis of 5-bromo-2-deoxyuridine incorporation. Impaired neurogenesis observed in OBX mice was significantly improved by chronic administration with ZSET1446. We confirmed that administration with mecamylamine, a nicotinic acetylcholine receptor antagonist, inhibits ZSET1446-enhanced neurogenesis in the DG. ZSET1446 administration also restored decreased phosphorylation of Akt and extracellular signal-regulated kinase in the DG of OBX mice. Consistent with restored neurogenesis, chronic but not single ZSET1446 administration promoted significant decreases in immobility in tail suspension tests and improved cognitive behaviors in OBX mice. Taken together, chronic ZSET1446 administration antagonized impaired neurogenesis seen in OBX mice, an effect closely associated with improvement of depressive behavior.

  19. History and Current Status of Newborn Screening for Severe Combined Immunodeficiency

    PubMed Central

    Kwan, Antonia; Puck, Jennifer M.

    2015-01-01

    The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T cell lymphopenia in newborns. Diagnosis of severe combined immunodeficiency (SCID) in affected infants in the neonatal period while asymptomatic permits early treatment and restoration of a functional immune system. SCID was the first immunodeficiency disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions. PMID:25937517

  20. History and current status of newborn screening for severe combined immunodeficiency.

    PubMed

    Kwan, Antonia; Puck, Jennifer M

    2015-04-01

    The development of a T-cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T-cell lymphopenia in newborns. Diagnosis of severe combined immunodeficiency (SCID) in affected infants in the neonatal period, while asymptomatic, permits early treatment and restoration of a functional immune system. SCID was the first immunodeficiency disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and it is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions.

  1. 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

  2. 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.

  3. 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.

  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.

  5. Selective restoration of male fertility in mice lacking angiotensin-converting enzymes by sperm-specific expression of the testicular isozyme.

    PubMed Central

    Ramaraj, P; Kessler, S P; Colmenares, C; Sen, G C

    1998-01-01

    Although angiotensin-converting enzyme (ACE) has been studied primarily in the context of its role in blood pressure regulation, this widely distributed enzyme has many other physiological functions. The ACE gene encodes two isozymes. The somatic isozyme is expressed in many tissues, including vascular endothelial cells, renal epithelial cells, and testicular Leydig cells, whereas the testicular or germinal angiotensin-converting enzyme is expressed only in sperm. The ACE gene knockout mice lack both isozymes and they exhibit low blood pressure, kidney dysfunctions, and male infertility. Here, we report the use of a sperm-specific promoter and interbreeding of transgenic and gene knockout mice for generating a mouse strain that expressed ACE only in sperm. The experimental mice maintained the kidney defects of ACE-/- mice, but unlike the knockout strain, the males were fertile. Thus, we established that the role of ACE in male fertility is completely dependent on its exclusive expression in sperm. Our study clearly demonstrated how transgenic and knockout techniques can be combined for ascribing a specific physiological function to the expression of a multifunctional protein in a given tissue. PMID:9664078

  6. Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

    PubMed Central

    Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

  7. Restoration of on-time embryo implantation corrects the timing of parturition in cytosolic phospholipase A2 group IVA deficient mice.

    PubMed

    Brown, Naoko; Morrow, Jason D; Slaughter, James C; Paria, Bibhash C; Reese, Jeff

    2009-12-01

    Cytosolic phospholipase A2 (cPLA2, PLA2G4A) catalyzes the release of arachidonic acid for prostaglandin synthesis by cyclooxygenase 1 (PTGS1) and cyclooxygenase 2 (PTGS2). Mice with Pla2g4a deficiency have parturition delay and other reproductive deficits, including deferred onset of implantation, crowding of implantation sites, and small litters. In this study, we examined the contribution of PLA2G4A to parturition in mice. Pla2g4a mRNA and protein expression were discretely localized in the term and preterm uterine luminal epithelium and colocalized with Ptgs1, but not Ptgs2, expression. The levels of PGE2, PGF2alpha, 6-keto-PGF1alpha, and TxB2 were significantly decreased in Pla2g4a-null uterine tissues, similar to Ptgs1-null uteri, consistent with predominance of PLA2G4A-PTGS1-mediated prostaglandin synthesis in preparation for murine parturition. Litter size was strongly associated with the timing of parturition in Pla2g4a-null mice but could not fully account for the parturition delay. Pla2g4a-null females that received PGE2 + carbaprostacyclin at the time of implantation delivered earlier (20.5 +/- 0.2 days vs. 21.6 +/- 0.2 days, P < 0.01), although litter size was not improved (4.6 vs. 4.4 pups per litter, P = 0.6). After correction for small litter size, multivariate analysis indicated that Pla2g4a-null mice given prostaglandin treatment to improve implantation timing had gestational length that was similar to wild-type and Pla2g4a heterozygous mice. These results indicate that, despite specific Pla2g4a expression and function in term gestation uteri, the delayed parturition phenotype in Pla2g4a-null mice is primarily due to deferral of implantation. The role of PLA2G4A in timely parturition appears to be critically related to its actions in early pregnancy.

  8. Total glucosides of paeony inhibit the inflammatory responses of mice with allergic contact dermatitis by restoring the balanced secretion of pro-/anti-inflammatory cytokines.

    PubMed

    Wang, Chun; Yuan, Jun; Wu, Hua-Xun; Chang, Yan; Wang, Qing-Tong; Wu, Yu-Jing; Zhou, Peng; Yang, Xiao-Dan; Yu, Jun; Wei, Wei

    2015-02-01

    The present study aimed to investigate the regulation exerted by the total glucosides of paeony (TGP) on the production of interleukin-2 (IL-2), IL-4, IL-10 and IL-17 in the serum and lymphocytes of mice with allergic contact dermatitis (ACD). ACD in mice was induced by the repeated application of 2,4-dinitrochlorobenzene (DNCB) to their skins. The mice were orally administered TGP (35, 70, and 140mg/kg/d) and prednisone (Pre, 5mg/kg/d) from day 1 to day 7 after immunization. The inflammatory responses were evaluated by ear swelling and histological examination. Thymocyte proliferation was assayed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide assay. The cytokine production in the serum and lymphocytes supernatant was measured by enzyme-linked immunosorbent assay. The results indicated that the topical application of DNCB to the skin provoked obvious inflammatory responses. The oral administration of TGP (70 and 140mg/kg/d) and Pre (5mg/kg/d) significantly inhibited skin inflammation, decreased the thymus and spleen indices, and inhibited thymocyte proliferation in mice treated with DNCB. Further study indicated that TGP increased IL-4 and IL-10 production but decreased the production of IL-2 and IL-17 in the serum and lymphocyte supernatant. The correlation analysis suggested significantly positive correlations between IL-2 and IL-17 production and the severity of skin inflammation, whereas negative correlations were obtained for IL-4 and IL-10 production and skin inflammation. In summary, these results suggest that the therapeutic effects of TGP on ACD may result from its regulation of the imbalanced secretion of IL-2/IL-4 and IL-10/IL-17.

  9. Single administration of recombinant IL‐6 restores the gene expression of lipogenic enzymes in liver of fasting IL‐6‐deficient mice

    PubMed Central

    Gavito, AL; Cabello, R; Suarez, J; Serrano, A; Pavón, F J; Vida, M; Romero, M; Pardo, V; Bautista, D; Arrabal, S; Decara, J; Cuesta, AL; Valverde, A M; Rodríguez de Fonseca, F

    2016-01-01

    Background and Purpose Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL‐6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL‐6 in mediating fasting/re‐feeding changes in the expression of hepatic lipogenic enzymes. Experimental Approach Gene and protein expression of lipogenic enzymes were examined in livers of wild‐type (WT) and IL‐6‐deficient (IL‐6−/−) mice during fasting and re‐feeding conditions. Effects of exogenous IL‐6 administration on gene expression of these enzymes were evaluated in vivo. The involvement of STAT3 in mediating these IL‐6 responses was investigated by using siRNA in human HepG2 cells. Key Results During feeding, the up‐regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL‐6−/− mice. During fasting, expression of lipogenic genes decreased gradually over time in both strains, although the initial drop was more marked in IL‐6−/− mice. Protein levels of hepatic lipogenic enzymes were lower in IL‐6−/− than in WT mice at the end of the fasting period. In WT, circulating IL‐6 levels paralleled gene expression of hepatic lipogenic enzymes. IL‐6 administration in vivo and in vitro showed that IL‐6‐mediated signalling was associated with the up‐regulation of hepatic lipogenic enzyme genes. Moreover, silencing STAT3 in HepG2 cells attenuated IL‐6 mediated up‐regulation of lipogenic gene transcription levels. Conclusions and Implications IL‐6 sustains levels of hepatic lipogenic enzymes during fasting through activation of STAT3. Our findings indicate that clinical use of STAT3‐associated signalling cytokines, particularly against steatosis, should be undertaken with caution. PMID:26750868

  10. 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.

  11. 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.

  12. 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

  13. Group B streptococcal septicemia of the newborn

    MedlinePlus

    ... septicemia is a severe bacterial infection that affects newborn infants . Causes Septicemia is an infection in the bloodstream ... in which it may be passed to a newborn baby: The infant can become infected as the baby passes through ...

  14. Newborn Screening: MedlinePlus Health Topic

    MedlinePlus

    ... away. NIH: National Institute of Child Health and Human Development Start Here How Are Newborn Screening Tests Done? (National Institute of Child Health and Human Development) Also in Spanish Newborn Screening (Centers for Disease ...

  15. 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'…

  16. 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.

  17. 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

  18. 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…

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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…

  5. 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.

  6. PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells

    PubMed Central

    Azzi, Jamil; Thueson, Lindsay; Moore, Robert; Abdoli, Rozita; Reijonen, Helena; Abdi, Reza

    2017-01-01

    With a steady increase in its incidence and lack of curative treatment, type 1 diabetes (T1D) has emerged as a major health problem worldwide. To design novel effective therapies, there is a pressing need to identify regulatory targets controlling the balance of autoreactive to regulatory-T-cells (Tregs). We previously showed that the inhibition of the γ-subunit of the Phosphoinositide-3-kinase (PI3K), significantly suppress autoimmune-diabetes. To further delineate the mechanisms and the selectivity of specific immune modulation by PI3Kγ-inhibition, we developed a new NOD mouse model of T1D lacking the γ-subunit of PI3K. Strikingly, the loss of PI3Kγ protected 92% of the NOD-mice from developing spontaneous diabetes. The NOD.PI3Kγ-/- mice are protected from insulitis secondary to a defect in CD4 and CD8 autoreactive-T-cells activation and survival. In addition, PI3Kγ-deficiency promoted Treg generation in-vitro and in-vivo. Furthermore, PI3Kγ-inhibitor (AS605240) inhibited proliferation and cytokine production of a human CD4+ T-cell clone specific for GAD555-567 peptide that was isolated from a patient with T1D. These studies demonstrate the key role of the PI3Kγ pathway in regulating autoimmune-diabetes and provide rationales for future devise of anti- PI3Kγ therapy in T1D. PMID:28081180

  7. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients.

    PubMed

    Lagresle-Peyrou, Chantal; Benjelloun, Fatine; Hue, Christophe; Andre-Schmutz, Isabelle; Bonhomme, Delphine; Forveille, Monique; Beldjord, Kheira; Hacein-Bey-Abina, Salima; De Villartay, Jean-Pierre; Charneau, Pierre; Durandy, Anne; Fischer, Alain; Cavazzana-Calvo, Marina

    2008-02-01

    Severe combined immunodeficiency (SCID) caused by mutation of the recombination-activating gene 1 (RAG1) or Artemis gene lead to the absence of B- and T-cell differentiation. The only curative treatment is allogeneic bone marrow (BM) transplantation, which displays a high survival rate when an HLA compatible donor is available but has a poorer prognosis when the donor is partially compatible. Consequently, gene therapy may be a promising alternative strategy for these diseases. Here, we report that lentiviral gene-corrected BM CD34(+) cells (isolated from Artemis- or RAG1-deficient patients) sustain human B-cell differentiation following injection into non-obese diabetic/SCID (NOD-SCID) mice previously infused with anti-interleukin-2 receptor beta chain monoclonal antibody. In most of the mice BM, engrafted with Artemis-transduced cells, human B-cell differentiation occurred until the mature stage. The B cells were functional as human immunoglobulin M (IgM) was present in the serum. Following injection with RAG1-transduced cells, human engraftment occurred in vivo but B-cell differentiation until the mature stage was less frequent. However, when it occurred, it was always associated with human IgM production. This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation.

  8. Kluyvera meningitis in a newborn.

    PubMed

    Rosso, Marisa; Rojas, Pilar; Garcia, Elisa; Marquez, Javier; Losada, Antonio; Muñoz, Miguel

    2007-11-01

    Kluyvera is described infrequently in association with clinically significant infections in humans. It can produce a wide range of clinically significant manifestations. We describe a newborn with ventriculoperitoneal shunt, who was successfully treated for Kluyvera meningitis. We believe that this is the first case of Kluyvera central nervous system infection reported in a child.

  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. Medical Care and Your Newborn

    MedlinePlus

    ... Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to 3-Month-Old Feeding Your 4- to 7-Month-Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old ... > For Parents > Medical Care and Your Newborn Print A A ...

  11. Orthopaedic conditions in the newborn.

    PubMed

    Sankar, Wudbhav N; Weiss, Jennifer; Skaggs, David L

    2009-02-01

    The occasional consultation on a neonate can be unfamiliar territory for many orthopaedic surgeons. Just as children are not little adults, newborns are not just little children; rather, they have a unique physiology that affects the presentation of their orthopaedic concerns. Careful physical examination with appropriate understanding of neonatal development is essential to making the proper diagnosis. A flail extremity in the newborn is most commonly attributed to fracture or brachial plexus palsy; however, infection must also be considered and ruled out to prevent long-term morbidity. Metatarsus adductus is the most common foot abnormality, but clubfoot, calcaneovalgus deformity, and congenital vertical talus may also be encountered. Joint contractures that spontaneously improve are normal in the newborn, but it is important to identify and institute proper treatment for early developmental dysplasia of the hip, congenital knee dislocation, and torticollis. Clavicular pseudarthrosis and periosteal reactions may be discovered on radiographic examination. A basic understanding of the relevant conditions will help the orthopaedist with the initial diagnosis and management of orthopaedic issues in the newborn.

  12. 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.

  13. 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)

  14. 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.…

  15. The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function.

    PubMed

    Sitapara, Ravikumar A; Antoine, Daniel J; Sharma, Lokesh; Patel, Vivek S; Ashby, Charles R; Gorasiya, Samir; Yang, Huan; Zur, Michelle; Mantell, Lin L

    2014-06-19

    Mechanical ventilation with supraphysiological concentrations of oxygen (hyperoxia) is routinely used to treat patients with respiratory distress. However, prolonged exposure to hyperoxia compromises the ability of the macrophage to phagocytose and clear bacteria. Previously, we showed that the exposure of mice to hyperoxia elicits the release of the nuclear protein high mobility group box-1 (HMGB1) into the airways. Extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected with Pseudomonas aeruginosa (PA). The aim of this study was to determine whether GTS-21 [3-(2,4 dimethoxybenzylidene)-anabaseine dihydrochloride], an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could inhibit hyperoxia-induced HMGB1 release into the airways, enhance macrophage function and improve bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia. GTS-21 (0.04, 0.4 and 4 mg/kg) or saline was systemically administered via intraperitoneal injection to mice that were exposed to hyperoxia (≥99% O2) and subsequently challenged with PA. We found that systemic administration of 4 mg/kg GTS-21 significantly increased bacterial clearance, decreased acute lung injury and decreased accumulation of airway HMGB1. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophagelike cell line, were incubated with different concentrations of GTS-21 in the presence of 95% O2. The phagocytic activity of macrophages was significantly increased by GTS-21 in a dose-dependent manner. In addition, hyperoxia-induced hyperacetylation of HMGB1 was significantly reduced in macrophages incubated with GTS-21. Furthermore, GTS-21 significantly inhibited the cytoplasmic translocation and release of HMGB1 from these macrophages. Our results indicate that GTS-21 is effective in improving bacterial clearance and reducing acute lung injury by enhancing macrophage function via inhibiting the release of nuclear HMGB1

  16. 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

  17. Precondition of right frontal region with anodal tDCS can restore the fear memory impairment induced by ACPA in male mice

    PubMed Central

    Manteghi, Fariborz; Nasehi, Mohammad; Zarrindast, Mohammad-Reza

    2017-01-01

    Fear memory and learning cause behavioural patterns such as fight or flight responses, which increase survival probability, but unfit processing of fear memory and learning can lead to maladaptive behaviours and maladies such as phobias, Post-Traumatic Stress Disorder (PTSD) and anxiety disorders. The growing prevalence of these maladies shows the need to quest novel methods for their treatment. We used anodal transcranial direct current stimulation (tDCS) on the right frontal region as a precondition neuromodulator and arachidonylcyclopropylamide (ACPA), a selective CB1 cannabinoid receptor agonist, as a fear memory impairing agent to assess their effects on contextual and auditory fear conditioning (reliable model for fear studies). Right frontal anodal tDCS (0.2 mA for. 20 minutes) 24 hours before the train did not alter contextual and auditory learning and memory in short-term (24 hrs after the training phase). Moreover, intraperitoneal pre-train injection of ACPA (0.1 mg/kg) alone, decreased both contextual and auditory learning and memory in short- but not long-term. Right frontal anodal tDCS improved short-term contextual fear memory in subthreshold doses of ACPA. On the other hand, right frontal anodal tDCS in long-term improved (lower doses of ACPA) and restored (higher doses of ACPA) both fear memories. These findings showed that, aforementioned approach could cause durable learning and memory improvements. Also this combined modality could be useful for fear extinction training and maladies which inflict amnesia. PMID:28337114

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

    PubMed

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

    2016-04-01

    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.

  19. 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.

  20. Endothelial nitric oxide synthase activation through obacunone-dependent arginase inhibition restored impaired endothelial function in ApoE-null mice.

    PubMed

    Yoon, Jeongyeon; Park, Minjin; Lee, Jeong hyung; Min, Byung Sun; Ryoo, Sungwoo

    2014-03-01

    Endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion and reduces nitric oxide bioavailability. During the screening course of arginase inhibitor, we found obacunone as an arginase inhibitor. We tested the hypothesis that obacunone regulates vascular endothelial NO production. Obacunone incubation inhibited arginase I and II activities in liver and kidney lysates, respectively, in dose-dependent manner. Obacunone reciprocally increased nitrite/nitrate (NOx) production in HUVECs. In isolated aortic rings, obacunone increased intracellular l-arginine concentration and enhanced eNOS coupling, leading to increased NO and decreased superoxide production, with no changes in protein expression. Vasoconstriction response to U46619 was attenuated in obacunone-treated aortic vessels compared to that in untreated vessels. Endothelium-dependent vasorelaxant response to acetylcholine was significantly increased in obacunone-treated vessels and was modulated by the NO-dependent signaling cascade. The dose-dependent vasorelaxant response to Ach was reduced in the aortic vessels of ApoE-/- mice fed a high-cholesterol diet. Obacunone incubation increased vasorelaxation to the level of a WT mouse, although the endothelium-independent response to sodium nitroprusside was identical among the groups. Therefore, obacunone may help treat cardiovascular diseases derived from endothelial dysfunction and may be useful for designing pharmaceutical compounds.

  1. [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.

  2. [Congenital ranula in a newborn].

    PubMed

    Bernhard, M K; Hückel, D; Hamala, D

    2007-05-01

    Ranulas are cystic lesions in the floor of the mouth. They are either retention cysts of the excretory duct of the sublingual gland or pseudocysts formed by excretory duct rupture followed by extravasation and accumulation of mucus in the surrounding tissue. We report the case of a premature newborn with a congenital ranula in the floor of mouth. The ranula caused no discomfort or complications, so that immediate intervention was not necessary. The cyst resolved completely by the age of 4 months. Complications in newborns especially include airway obstruction and feeding difficulties. Surgical treatment options are needle aspiration, excision of the ranula, marsupialization, cryosurgery, and--in addition to excision of the cyst--removal of the ipsilateral sublingual gland. Sclerotherapy has shown good results as well. As many congenital cysts resolve or rupture spontaneously, they should be observed for potential resolution for several months in uncomplicated cases.

  3. Newborn healthcare in urban India

    PubMed Central

    Sharma, J; Osrin, D; Patil, B; Neogi, S B; Chauhan, M; Khanna, R; Kumar, R; Paul, V K; Zodpey, S

    2016-01-01

    The rapid population growth in urban India has outpaced the municipal capacity to build essential infrastructures that make life in cities safe and healthy. Local and national governments alike are grappling with the challenges of urbanization with thousands migrating from villages to cities. Thus, urbanization in India has been accompanied by a concentration of poverty and urban public healthcare has emerged as one of the most pressing priorities facing our country. Newborn mortality rates in urban settings are lower than rural areas, early neonatal deaths account for greater proportion than late neonatal deaths. The available evidence suggests that socio-economic inequalities and poor environment pose major challenges for newborn health. Moreover, fragmented and weak public health system, multiplicity of actors and limited capacity of public health planning further constrain the delivery of quality and affordable health care service. Though healthcare is concentrated in urban areas, delay in deciding to seek health care, reaching a source of it and receiving appropriate care affects the health outcomes disproportionately. However, a few city initiatives and innovations piloted in different states and cities have brought forth the evidences of effectiveness of different strategies. Recently launched National Urban Health Mission (NUHM) provides an opportunity for strategic thinking and actions to improve newborn health outcomes in India. There is also an opportunity for coalescence of activities around National Health Mission (NHM) and Reproductive, Maternal, Newborn and Child Health+Adolescent (RMNCH+A) strategy to develop feasible and workable models in different urban settings. Concomitant operational research needs to be carried out so that the obstacles, approaches and response to the program can be understood. PMID:27924107

  4. Newborn healthcare in urban India.

    PubMed

    Sharma, J; Osrin, D; Patil, B; Neogi, S B; Chauhan, M; Khanna, R; Kumar, R; Paul, V K; Zodpey, S

    2016-12-01

    The rapid population growth in urban India has outpaced the municipal capacity to build essential infrastructures that make life in cities safe and healthy. Local and national governments alike are grappling with the challenges of urbanization with thousands migrating from villages to cities. Thus, urbanization in India has been accompanied by a concentration of poverty and urban public healthcare has emerged as one of the most pressing priorities facing our country. Newborn mortality rates in urban settings are lower than rural areas, early neonatal deaths account for greater proportion than late neonatal deaths. The available evidence suggests that socio-economic inequalities and poor environment pose major challenges for newborn health. Moreover, fragmented and weak public health system, multiplicity of actors and limited capacity of public health planning further constrain the delivery of quality and affordable health care service. Though healthcare is concentrated in urban areas, delay in deciding to seek health care, reaching a source of it and receiving appropriate care affects the health outcomes disproportionately. However, a few city initiatives and innovations piloted in different states and cities have brought forth the evidences of effectiveness of different strategies. Recently launched National Urban Health Mission (NUHM) provides an opportunity for strategic thinking and actions to improve newborn health outcomes in India. There is also an opportunity for coalescence of activities around National Health Mission (NHM) and Reproductive, Maternal, Newborn and Child Health+Adolescent (RMNCH+A) strategy to develop feasible and workable models in different urban settings. Concomitant operational research needs to be carried out so that the obstacles, approaches and response to the program can be understood.

  5. 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.

  6. 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

  7. Newborn Screening for Biliary Atresia.

    PubMed

    Wang, Kasper S

    2015-12-01

    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.

  8. 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.

  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. 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…

  11. Modeling normal and malignant human hematopoiesis in vivo through newborn NSG xenotransplantation.

    PubMed

    Ishikawa, Fumihiko

    2013-12-01

    Various strains of immune-compromised mice have been developed to investigate human normal and malignant stem cells in vivo. NOD/SCID mice harboring complete null mutation of Il2rg (NSG mice) lack T cells, B cells, and NK cells, and support high levels of engraftment by human cord blood hematopoietic stem cells (CB HSCs) and acute myeloid leukemia stem cells (AML LSCs). In addition to achieving high levels of human hematopoietic cell engraftment, use of newborn NSG mice as recipients has enabled the investigation into how human CB HSCs generate mature immune subsets in vivo. Moreover, through establishing an in vivo model of human primary AML by xenotransplantation of human LSCs into newborn NSG mice, functional properties of human AML such as cell cycle, location, and self-renewal capacity can be examined in vivo. Newborn NSG xenogeneic transplantation model may facilitate the understanding of human normal and malignant hematopoiesis and contribute to the development of novel therapies against hematologic diseases.

  12. 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

  13. Newborn piglet model for campylobacteriosis.

    PubMed Central

    Babakhani, F K; Bradley, G A; Joens, L A

    1993-01-01

    An in vivo model system for human campylobacteriosis has been developed in which colostrum-deprived newborn piglets are orally challenged with an invasive strain of Campylobacter jejuni. Piglets developed clinical symptoms and histopathological lesions similar to those observed in humans infected with C. jejuni. Gross lesion examination at autopsy revealed the presence of edema, hyperemia, and mucus. Histopathologic examinations by light and transmission electron microscopy demonstrated damage to surface epithelial cells with the presence of intracellular bacteria, mainly in the large intestine. Similar lesions were not demonstrated in control piglets. Images PMID:8335377

  14. Flooring choices for newborn ICUs.

    PubMed

    White, R D

    2007-12-01

    Floors are a major element of newborn intensive care unit (NICU) construction. They provide visual cues, sound control, and with certain materials, some degree of physical comfort for workers. Flooring materials may entail a significant cost for installation and upkeep and can have substantial ecological impact, both in the choice of the flooring itself, as well as the substances used to clean it. In this article the important aspects to consider for each factor are explored and recommendations are offered for appropriate choices in various NICU areas.

  15. Newborn infants perceive abstract numbers.

    PubMed

    Izard, Véronique; Sann, Coralie; Spelke, Elizabeth S; Streri, Arlette

    2009-06-23

    Although infants and animals respond to the approximate number of elements in visual, auditory, and tactile arrays, only human children and adults have been shown to possess abstract numerical representations that apply to entities of all kinds (e.g., 7 samurai, seas, or sins). Do abstract numerical concepts depend on language or culture, or do they form a part of humans' innate, core knowledge? Here we show that newborn infants spontaneously associate stationary, visual-spatial arrays of 4-18 objects with auditory sequences of events on the basis of number. Their performance provides evidence for abstract numerical representations at the start of postnatal experience.

  16. Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning.

    PubMed

    Veyrac, Alexandra; Gros, Alexandra; Bruel-Jungerman, Elodie; Rochefort, Christelle; Kleine Borgmann, Felix B; Jessberger, Sebastian; Laroche, Serge

    2013-04-23

    New neurons are continuously added to the dentate gyrus of the adult mammalian brain. During the critical period of a few weeks after birth when newborn neurons progressively mature, a restricted fraction is competitively selected to survive in an experience-dependent manner, a condition for their contribution to memory processes. The mechanisms that control critical stages of experience-dependent functional incorporation of adult newborn neurons remain largely unknown. Here, we identify a unique transcriptional regulator of the functional integration of newborn neurons, the inducible immediate early gene zif268/egr1. We show that newborn neurons in zif268-KO mice undergo accelerated death during the critical period of 2-3 wk around their birth and exhibit deficient neurochemical and morphological maturation, including reduced GluR1 expression, increased NKCC1/KCC2b chloride cotransporter ratio, altered dendritic development, and marked spine growth defect. Investigating responsiveness of newborn neurons to activity-dependent expression of zif268 in learning, we demonstrate that in the absence of zif268, training in a spatial learning task during this critical period fails to recruit newborn neurons and promote their survival, leading to impaired long-term memory. This study reveals a previously unknown mechanism for the control of the selection, functional maturation, and experience-dependent recruitment of dentate gyrus newborn neurons that depends on the inducible immediate early gene zif268, processes that are critical for their contribution to hippocampal-dependent long-term memory.

  17. Caring for a critically ill Amish newborn.

    PubMed

    Gibson, Elizabeth A

    2008-10-01

    This article describes a neonatal nurse's personal experience in working with a critically ill newborn and his Amish family in a newborn intensive care unit in Montana. The description includes a cultural experience with an Amish family with application to Madeleine Leininger's theory of culture care diversity and universality.

  18. Liver Abscess: Increasing Occurrence in Premature Newborns

    PubMed Central

    Bosnalı, Oktav; Moralıoğlu, Serdar; Pektaş, Osman

    2013-01-01

    Neonatal liver abscess is a very rare condition associated with high morbidity and mortality rates. There seems to be an increasing trend of this rare condition amongst the newborns admitted to neonatal intensive care units. We report a case of liver abscess in a premature newborn and briefly review the literature and discuss its management. PMID:26023443

  19. 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…

  20. Group B Strep Infection in Newborns

    MedlinePlus

    ... Core surveillance (ABCs) CDC Streptococcus Laboratory Sepsis Group B Strep Infection in Newborns Language: English Español (Spanish) ... the difference between early- and late-onset group B strep diseases in newborns… How it Spreads and ...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  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. [Recent advances in newborn MRI].

    PubMed

    Morel, B; Hornoy, P; Husson, B; Bloch, I; Adamsbaum, C

    2014-07-01

    The accurate morphological exploration of the brain is a major challenge in neonatology that advances in magnetic resonance imaging (MRI) can now provide. MRI is the gold standard if an hypoxic ischemic pathology is suspected in a full term neonate. In prematures, the specific role of MRI remains to be defined, secondary to US in any case. We present a state of the art of hardware and software technical developments in MRI. The increase in magnetic field strength (3 tesla) and the emergence of new MRI sequences provide access to new information. They both have positive and negative consequences on the daily clinical data acquisition use. The semiology of brain imaging in full term newborns and prematures is more extensive and complex and thereby more difficult to interpret. The segmentation of different brain structures in the newborn, even very premature, is now available. It is now possible to dissociate the cortex and basal ganglia from the cerebral white matter, to calculate the volume of anatomical structures, which improves the morphometric quantification and the understanding of the normal and abnormal brain development. MRI is a powerful tool to analyze the neonatal brain. The relevance of the diagnostic contribution requires an adaptation of the parameters of the sequences to acquire and of the image processing methods.

  8. Arrhythmias in newborn thoroughbred foals.

    PubMed

    Yamamoto, K; Yasuda, J; Too, K

    1992-05-01

    Foetal electrocardiograms (ECG) were obtained from 39 of 50 Thoroughbred foaling mares close to delivery. The 50 newborn foals were studied electrocardiographically during their adaptive period, immediately after birth. In 48 foals there were paroxysmal arrhythmias or mixed arrhythmias. The most common arrhythmias were sinus arrhythmias including wandering pacemaker (32/50) and atrial premature contraction (30/50). The others observed were atrial fibrillation (15/50), ventricular premature contraction (10/50), partial atrioventricular block (7/50), ventricular tachycardia (4/50), atrial tachycardia (3/50) and idioventricular rhythm (1/50). The duration of the arrhythmias was approximately 5 min, and in all cases the arrhythmia disappeared within 15 min of birth. From foetal ECG recordings, no indication of the likelihood of neonatal arrhythmias was detected. With the exception of 2 cases, all foals have continued to grow and develop normally. These arrhythmias are considered normal physiological processes in newborn Thoroughbred foals during the adaptive period to extra-uterine life. High vagal tone and hypoxaemia at birth are probably the main contributing factors.

  9. Radial localization of odors by human newborns.

    PubMed

    Rieser, J; Yonas, A; Wikner, K

    1976-09-01

    To study sensitivity to radial location of an odor source, 20 human newborns, ranging from 16 to 130 hours of age, were presented with a small amount of ammonium hydroxide. The odor source was placed near the nose slightly to the left or right of midline, with its position randomized over repeated trails. Direction of headturn with respect to the odor location and diffuse motor activity were scored from the videotape recordings of the newborns' behavior. It was found that as a group, the newborns turned away from the odor source more frequently than they turned toward it. The tendency to turn away from the odor was stronger in infants who displayed less motor activity after the response. Newborns also exhibited a right bias in the direction of the head movements. It is concluded that a spatially appropriate avoidance response is present in the neonate and that the newborn is innately sensitive to the radial location of an odor.

  10. The roots of bilingualism in newborns.

    PubMed

    Byers-Heinlein, Krista; Burns, Tracey C; Werker, Janet F

    2010-03-01

    The first steps toward bilingual language acquisition have already begun at birth. When tested on their preference for English versus Tagalog, newborns whose mothers spoke only English during pregnancy showed a robust preference for English. In contrast, newborns whose mothers spoke both English and Tagalog regularly during pregnancy showed equal preference for both languages. A group of newborns whose mothers had spoken both Chinese and English showed an intermediate pattern of preference for Tagalog over English. Preference for two languages does not suggest confusion between them, however. Study 2 showed that both English monolingual newborns and Tagalog-English bilingual newborns could discriminate English from Tagalog. The same perceptual and learning mechanisms that support acquisition in a monolingual environment thus also naturally support bilingual acquisition.

  11. Lubricin restoration in a mouse model of congenital deficiency

    PubMed Central

    Hill, Adele; Waller, Kimberly A.; Cui, Yajun; Allen, Justin M.; Smits, Patrick; Zhang, Ling X.; Ayturk, Ugur M.; Hann, Steven; Lessard, Samantha G.; Zurakowski, David; Warman, Matthew L.; Jay, Gregory D.

    2015-01-01

    Objective Congenital deficiency of the principal boundary lubricant in cartilage (lubricin, encoded by the gene PRG4) increases joint friction and causes progressive joint failure. This study was undertaken to determine whether restoring lubricin expression would prevent, delay, or reverse the disease process caused by congenital deficiency. Methods Using genetically engineered lubricin deficient mice, we restored gene function before conception or at 3 weeks, 2 months, or 6 months after birth. We evaluated the effect of restoring gene function (i.e., expressing lubricin) on the tibial-femoral-patellar joints of mice, histologically and by ex vivo biomechanical testing. Results Restoring gene function prior to conception prevented disease. Restoring gene function at 3 weeks of age improved, but did not normalize, joint histology and whole joint friction; cyclic loading produced fewer activated caspase-3 containing chondrocytes when lubricin expression was restored at three weeks of age compared to non-restored littermates. Restoring lubricin expression in 2-month-old or 6-month-old mice had no beneficial effect on histology, whole joint friction, or activation of caspase-3 compared to non-restored littermates. Conclusions When boundary lubrication is congenitally deficient and cartilage becomes damaged, the window of opportunity for restoring lubrication and slowing disease progression is limited. PMID:26216721

  12. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.

    PubMed

    Jaskelioff, Mariela; Muller, Florian L; Paik, Ji-Hye; Thomas, Emily; Jiang, Shan; Adams, Andrew C; Sahin, Ergun; Kost-Alimova, Maria; Protopopov, Alexei; Cadiñanos, Juan; Horner, James W; Maratos-Flier, Eleftheria; Depinho, Ronald A

    2011-01-06

    An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes. Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signalling activation in vivo. Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired tissue injury responses. Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase-oestrogen receptor (TERT-ER) under transcriptional control of the endogenous TERT promoter. Homozygous TERT-ER mice have short dysfunctional telomeres and sustain increased DNA damage signalling and classical degenerative phenotypes upon successive generational matings and advancing age. Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Notably, somatic telomerase reactivation reversed neurodegeneration with restoration of proliferating Sox2(+) neural progenitors, Dcx(+) newborn neurons, and Olig2(+) oligodendrocyte populations. Consistent with the integral role of subventricular zone neural progenitors in generation and maintenance of olfactory bulb interneurons, this wave of telomerase

  13. 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.

  14. 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.

  15. 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.

  16. Postnatal hypoglycaemia and gluconeogenesis in the newborn rat. Delayed onset of gluconeogenesis in prematurely delivered newborns.

    PubMed Central

    Fernández, E; Valcarce, C; Cuezva, J M; Medina, J M

    1983-01-01

    The concentrations of glucose and lactate in the blood and of liver glycogen, and the phosphoenolpyruvate carboxykinase activity in liver and kidney of term and preterm newborn rats, were studied during the first 6 h post partum. Rates of lactate turnover and gluconeogenesis in vivo from [U-14C]lactate at 3 h and 6 h post partum were also quantified. The development of the prolonged postnatal hypoglycaemia observed after birth in the premature newborn rat is associated with lower rates of glucose production through glycogenolysis and gluconeogenesis; liver glycogenolysis was the main contributing factor to the glucose available during the neonatal period studied in both groups. Delayed induction of liver phosphoenolpyruvate carboxykinase activity was observed in premature newborn rats. Renal phosphoenolpyruvate carboxykinase activity increased 72% from birth in preterm newborns, but only a 25% increase was found in term newborns during the same experimental period. The gluconeogenesis in vivo from [U-14C]lactate paralleled the appearance of cytosolic phosphoenolpyruvate carboxykinase activity in the liver of both groups of newborns. Blood lactate concentrations remained higher in preterm than in term newborns. The postnatal utilization of lactate via the gluconeogenic pathway in either group of newborns was always less than 20% of the total lactate used. The results presented are discussed in relation to the development of postnatal hypoglycaemia and gluconeogenesis in the premature newborn rat. PMID:6615479

  17. How Are Newborn Screening Tests Done?

    MedlinePlus

    ... researchers Health Education Programs Safe to Sleep, Media-Smart Youth, Maternal/Child Health Education Program NICHD Publications ... First, hospital staff fill out a newborn screening card with the infant’s vital information—name, sex, weight, ...

  18. 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 develops shortly ... Control and Prevention. Notes from the field: late vitamin K deficiency bleeding in infants whose parents declined vitamin K ...

  19. How Are My Newborn's Screening Results Used?

    MedlinePlus

    ... newborn screening device Selected NICHD Research Advances of 2016 All related news Home Contact Accessibility Web Policies and Notices FOIA Facebook Twitter Pinterest YouTube RSS NIH...Turning Discovery Into Health ® Printed from the NICHD Web Site

  20. Changes in the newborn at birth

    MedlinePlus

    ... within about 10 seconds after delivery. This breath sounds like a gasp, as the newborn's central nervous system reacts to the sudden change in temperature and environment. Once the baby takes the first ...

  1. 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.

  2. 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)

  3. 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 ...

  4. Auto safety. Pregnancy and the newborn.

    PubMed

    Krozy, R E; McColgan, J J

    1985-01-01

    An overview of the principles, risks, and benefits, and proper usage of restraints is presented in reference to both the pregnant woman and the newborn. Also, the types and advantages of each restraint are reviewed. Finally, aspects of the nurse's role in the education of new parents during the pre- and postnatal periods are discussed. In this discussion, specific suggestions are given to meet the overall goal of safer auto travel for the pregnant woman and newborn.

  5. 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

  6. Breuner Marsh Restoration Project

    EPA Pesticide Factsheets

    Information about the San Francisco Bay Water Quality Project (SFBWQP) Breuner Marsh Restoration Project, part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources.

  7. Quartermaster Reach Restoration Project

    EPA Pesticide Factsheets

    Information about the SFBWQP Quartermaster Reach Restoration Project, part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources.

  8. 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

  9. 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.

  10. 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

  11. Restorative dentistry for children.

    PubMed

    Donly, Kevin J

    2013-01-01

    This article discusses contemporary pediatric restorative dentistry. Indications and contraindications for the choice of different restorative materials in different clinical situations, including the risk assessment of the patient, are presented. The specific use of glass ionomer cement or resin-modified glass ionomer cement, resin-based composite, and stainless steel crowns is discussed so that preparation design and restoration placement is understood.

  12. 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…

  13. Age-related decline in oligodendrogenesis retards white matter repair in mice

    PubMed Central

    Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Magnain, Caroline; Ayata, Cenk; Kim, Kyu-Won; Boas, David; Lo, Eng H.; Arai, Ken

    2013-01-01

    Background/Purpose Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask if compared to young brains, white matter regions in older brains may be more vulnerable in part due to decreased rates of compensatory oligodendrogenesis after injury. Methods A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells (OPCs) to sub-lethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Results Baseline myelin density in the corpus callosum was similar in 2-month and 8-month old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in CREB signaling may be involved because activating CREB with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of OPCs, alleviated myelin loss and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of OPCs. Conclusions An age-related decline in CREB-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate CREB signaling provide a potential therapeutic approach for treating white matter injury in aging brains. PMID:23881957

  14. 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

  15. Resuscitation of the Newborn: Simulating for Confidence

    PubMed Central

    Woodman, Anna; McCay, Wendy; Bates, Sarah E

    2016-01-01

    Introduction Non-pediatric trainees working in pediatrics in the UK are expected to attend newborn deliveries and provide initial newborn life support if needed. In Swindon, new junior doctors receive a 90-minute teaching session at the start of their pediatrics rotation, but the content has not previously been standardized, and it may be several weeks before a doctor attends a newborn delivery. Thus, the confidence and competence in newborn resuscitation of doctors attending deliveries can vastly vary. Methods A standardized teaching package was developed as part of the pediatrics induction program. This includes an interactive lecture on the physiology of the newborn, skills stations, and mini-simulations to consolidate skills. This is accompanied by a program of regular neonatal mini-simulations as part of the departmental morning teaching program. These sessions allow junior doctors to practice their skills in a safe, simulated environment and reinforce the newborn life support pathway. Results Qualitative and quantitative feedback was sought following delivery of the induction training session. Junior doctors were asked to rate their confidence before and after the induction session using Likert scales from 1 (least confident) to 5 (most confident). Median confidence in attending term deliveries increased from 2 (range 1 - 4) to 4 (2 - 5), P=0.008. There was evidence that confidence was maintained at one month following induction. Conclusions A simulation program has been successful at improving confidence among junior doctors in attending newborn deliveries. This has the potential to improve patient care and trainees’ experiences of their pediatrics placement. PMID:27774358

  16. Power system restoration planning

    SciTech Connect

    Adibi, M.M. ); Fink, L.H.

    1994-02-01

    System restoration, as an extraordinary mode of system operation, requires careful planning and operator training. The generic tasks of restoration include determination of system and equipment status, preparation of plants and network for systematic restoration, reenergization of the network, and system rebuilding. The procedures for developing an effective restoration plan include formation of a qualified planning team, review of relevant system characteristics, formulation of assumptions regarding blackout scenarios, agreement on restoration goals, development of strategy and tactics, validation of the plan, training, and documentation.

  17. Restoring the incisal edge.

    PubMed

    Terry, Douglas A

    2005-01-01

    Restorative dentistry evolves with each development of new material and innovative technique. Selection of improved restorative materials that simulate the physical properties and other characteristics of natural teeth, in combination with restorative techniques such as the proximal adaptation and incremental layering, provide the framework that ensures the optimal development of an esthetic restoration. These advanced placement techniques offer benefits such as enhanced chromatic integration, polychromatism, ideal anatomical form and function, optimal proximal contact, improved marginal integrity and longer lasting directly placed composite restorations. The purpose of this article is to give the reader a better understanding of the complex restorative challenge in achieving true harmonization of the primary parameters in esthetics (that is, color, shape and texture) represented by the replacement of a single anterior tooth. The case presented demonstrates the restoration of a Class IV fracture integrating basic adhesive principles with these placement techniques and a recently developed nanoparticle hybrid composite resin system (Premise, Kerr/Sybron, Orange, CA). The clinical presentation describes preoperative considerations, tooth preparation, development of the body layer, internal characterization with tints, development of the artificial enamel layer, shaping and contouring, and polishing of a Class IV composite restoration. The clinical significance is that anterior tooth fractures can be predictably restored using contemporary small particle hybrid composite resin systems with the aforementioned restorative techniques. These placement techniques when used with proper attention to preparation design, adhesive protocol and finishing and polishing procedures, allow the clinician to successfully restore form, function and esthetics to the single anterior tooth replacement.

  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. Newborn Analgesia Mediated by Oxytocin during Delivery.

    PubMed

    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.

  20. [Maternal anaemia: effect on the newborn].

    PubMed

    Toure-Fall, A O; Gadji, M; Diop, S; Dieye, T; Thiam, D; Diakhate, L

    2004-01-01

    Pregnancy increases considerably iron needs in mother and her foetus. The purpose of our study is to measure the effect of maternal anaemia on the foetus and the effect of iron supplementation on the maternal and foetal reserves. Therefore, we conducted a three-month cross sectional study at the gynaecological and obstetrics clinics of Aristide Le Dantec Hospital. Ninety-five women aged 16 to 43 years old and having an haemoglobin rate < 11 g/dl were recruited. Most of them were primipares. Among them 69 had a low ferritinemia (< 50 ng/ml), 36, a ferritinemia collapsed (< 30 ng/ml) and 13 virtually non-existent reserves (< 12 ng/ml). All newborns were born in terms with an apgar score >/= in 93 of them. Among them 24 had anemia (rate of haemoglobin < 14 g/dl) and 54.7% a low ferritinemia. There is no relationship between the maternal and foetal rates of haemoglobin; 74% of newborn had a normal rate of haemoglobin. Among 36 women with low ferritinemia only two gave birth to a newborn without iron reserves. In our study, among 68 women who received iron regularly, 41 had normal reserves and 43 gave birth to a newborn with high ferritinemia. There is significant difference between the women having received iron during their pregnancy and those not supplemented as regards the effect on newborn (p = 0.00001). The prevention of iron deficiency and anaemia can be done by the iron systematic and premat supplementation.

  1. Tachycardia in a newborn with enterovirus infection.

    PubMed

    Banjac, Lidija; Nikcević, Drasko; Vujosević, Danijela; Raonić, Janja; Banjac, Goran

    2014-03-01

    Enterovirus infections are common in the neonatal period. Newborns are at a higher risk of severe disease including meningoencephalitis, sepsis syndrome, cardiovascular collapse, or hepatitis. The mechanism of heart failure in patients with enterovirus infection remains unknown. Early diagnosis may help clinicians predict complications in those infants initially presenting with severe disease. An 11-day-old male newborn was admitted to our neonatal intensive care unit because of tachycardia and crises of cyanosis. His elder brother had febrile illness. The newborn was cyanotic, in respiratory distress, with tachycardia, low blood pressure and prolonged capillary refilling time. Limb pulse oximeter was around 85%. During the first day of hospitalization, the newborn had one febrile episode. Laboratory data: elevated transaminases, markers of inflammation negative, all bacterial cultures negative. Enterovirus RNA was detected in blood sample. Other blood findings were without significant abnormalities. Electrocardiogram showed tachycardia, with narrow QRS complexes (atrial tachycardia) and heart rate up to 280/min. In order to convert the rhythm, the patient was administered adenosine and amiodarone. In the further course of hospitalization, the patient was in good general condition, eucardiac and eupneic. Newborns with tachycardia and a family history of febrile illness should be suspected to have enterovirus infection. Enterovirus infection is a highly contagious and potentially life-threatening infection if not detected early. The use of sensitive molecular-based amplification methods offers potential benefits for early diagnosis and timely treatment.

  2. 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.

  3. Immunological mechanisms of hepatitis B virus persistence in newborns.

    PubMed

    Trehanpati, Nirupma; Hissar, Syed; Shrivastav, Shikha; Sarin, Shiv K

    2013-11-01

    Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about a half million people die every year. India represents the second largest pool of chronic HBV infection worldwide with an estimated 40 million infected people. The prevalence of chronic HBV infection in pregnant women is shown to be 0.82 per cent with the risk of mother-to-child vertical transmission. Hepatitis B e antigen (HBeAg) positivity indicates replicative form of HBV which may play a role in immunotolerance in utero by crossing the placenta. In case of HBeAg positivity and high viral load of mother, HBV immunoglobulin is preferably given along with HBV vaccination. Antiviral therapy is recommended for use in the third trimester of pregnancy to reduce the perinatal transmission of HBV, however, use of antiviral therapy should be individualized during pregnancy. Chronic HBV infection in neonates is linked with strong presence of Tregs (T regulatory cells) and defective CD8 T cells pool to produce interferon (IFN)-γ. T cell receptor (TCRζ) chain defects were also associated with decreased CD8 T cell dysfunction. Decreased TCRζ expression could be due to persistent intrauterine exposure of the viral antigens early in embryonic development leading to immune tolerance to HBV antigens in the newborns positive for hepatitis B surface antigen (HBsAg+ve). Therefore, due to HBV infection, T cell tolerance to HBV-antigen may probably leave the newborn as a chronic carrier. However, HBV vaccination may have benefits in restoring acquired immunity and better production of HBV specific antibodies.

  4. 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

  5. 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.

  6. Respiratory distress of the term newborn infant.

    PubMed

    Edwards, Martin O; Kotecha, Sarah J; Kotecha, Sailesh

    2013-03-01

    Respiratory distress is recognised as any signs of breathing difficulties in neonates. In the early neonatal period respiratory distress is common, occurring in up to 7% of newborn infants, resulting in significant numbers of term-born infants being admitted to neonatal units. Many risk factors are involved; the increasing number of term infants delivered by elective caesarean section has also increased the incidence. Additionally the risk decreases with each advancing week of gestation. At 37 weeks, the chances are three times greater than at 39-40 weeks gestation. Multiple conditions can present with features of respiratory distress. Common causes in term newborn infants include transient tachypnoea of the newborn, respiratory distress syndrome, pneumonia, meconium aspiration syndrome, persistent pulmonary hypertension of the neonate and pneumothorax. Early recognition of respiratory distress and initiation of appropriate treatment is important to ensure optimal outcomes. This review will discuss these common causes of respiratory distress in term-born infants.

  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. Screening Newborns | NIH MedlinePlus the Magazine

    MedlinePlus

    ... began in 1999, when President Clinton signed the Newborn and Infant Hearing Screening and Intervention Act, authorizing the coordination and funding of statewide newborn and infant hearing screening programs. In December 2010, President Obama ...

  9. Modulation of in utero total body irradiation induced newborn mouse growth retardation by maternal manganese superoxide dismutase-plasmid liposome (MnSOD-PL) gene therapy.

    PubMed

    Epperly, M W; Smith, T; Zhang, X; Goff, J P; Franicola, D; Greenberger, B; Komanduri, P; Wang, H; Greenberger, J S

    2011-06-01

    To determine the effects of manganese superoxide dismutase (MnSOD) plasmid liposome (PL) maternal radioprotection on fetal mice, timed pregnant female mice (E14 gestation) were irradiated to 3.0 Gy total body irradiation (TBI) dose, and the number, weight and growth and development over 6 months after birth of newborn mice was quantitated compared with irradiated controls. Maternal MnSOD-PL treatment at E13 improved pup survival at birth (5.4±0.9 per litter) compared with non-irradiated 3.0 Gy controls 4.9±1.1. There was no statistically significant difference in newborn abnormalities, male to female ratio in newborn litters, or other evidence of teratogenesis in surviving newborn mice from MnSOD-PL treated compared with irradiated controls. However, E14 3 Gy irradiated pups from gene therapy-treated mothers showed a significant increase in both growth and overall survival over 6 months after birth (P=0.0022). To determine if transgene product crossed the placenta pregnant E13 mice were injected intravenously with hemagglutinin-epitope-tagged MnSOD (100 μg plasmid in 100 μl liposomes), then after 24 h, fetal mice, placentas and maternal tissues were removed and tested by both immunohistochemistry and reverse transcriptase-PCR for transgene and product. There was no evidence of transgene or product in placenta or any fetal tissue while maternal liver was positive by both assays. The data provide evidence for fetal radioprotection by maternal MnSOD-PL gene therapy before irradiation, which is mediated by an indirect bystander effect and is associated with a significant improvement in both survival at birth and growth and development of newborn mice.

  10. [Hearing screening of newborns. Preliminary results].

    PubMed

    Courtmans, I; Mancilla, V; Ligny, C; Belhadi, B; Damis, E; Mahillon, P

    2005-02-01

    Since 1976, an hearing screening is organized at the Clinic Edith Cavell. The testing was based on a behavioral technique of Veit-Bizaguet and, since 2001, the otoacoustic emissions are realised. The National Institutes of Health (1993) recommends universal newborn hearing screening of all newborns before 3 months of age and identification and treatment before 6 months of age. Indeed, detection of hearing loss and early intervention allow a better access to the language and consequently an easier schooling and social integration. This article shows the results of the screening from february at the end of December 2002. These data are compared with those of the literature.

  11. Candida infections in newborns: a review.

    PubMed

    Khoory, B J; Vino, L; Dall'Agnola, A; Fanos, V

    1999-10-01

    Despite adequate treatment, nosocomial fungal infections have become an increasingly important cause of morbidity, extended hospitalization, and mortality in critically ill newborn babies. Furthermore, the high incidence of central nervous system involvement in septic newborns frequently results in serious neurological damage and psychomotorial sequelae. The prevention of fungal colonization in the population at risk, together with prompt diagnosis and treatment, are an efficient combination which lead to a better outcome of neonatal fungal infections. New drugs characterized by great efficacy and tolerance have recently been employed in clinical practice. This article summarizes certain aspects of Candida spp. infections in the neonatal period with regard to multisystemic presentation and involvement.

  12. A newborn with antenatal testis tortion

    PubMed Central

    Çelik, Fatma Çakmak; Aygün, Canan; Ayçiçek, Tuğba; Aykanat, Mustafa Alper; Ayyıldız, Suat

    2014-01-01

    Testis tortion in the newborn (especially antenatal testis tortion) is observed very rarely and constitutes 10-12% of childhood testis tortions. In testis tortion, firm and painless testicular tissue is palpated on physical examination. Doppler ultrasonography is a sensitive method in the diagnosis. In cases of neonatal testis tortion, the testis can be saved with appropriate surgical exploration in only 0–5% of the cases. Here, a newborn with antenatal testis tortion who underwent orchiectomy in the first day of life was presented. PMID:26078672

  13. What to do with an obstructed newborn.

    PubMed

    Bravo Bravo, M C; García-Herrera Taillefer, P

    2016-05-01

    Bowel obstruction is the most common abdominal emergency in newborns. Managing bowel obstruction is a challenge for both clinicians and radiologists. The clinical presentation is nonspecific, and both the diagnosis and subsequent management are based on imaging studies. The traditional approach to studying obstructed newborns consists of plain-film abdominal X-rays and contrast-based studies of the gastrointestinal tract. Ultrasonography has proven useful in bowel obstruction, thus avoiding the use of ionizing radiation in certain cases, so diagnostic strategies should include it as a first-line technique. Using an appropriate combination of these techniques, it is possible to reach an accurate diagnosis quickly, orienting treatment and decreasing complications.

  14. 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.

  15. The influence of dexamethasone administered prenatally on cartilage of newborn spiny mouse (Acomys cahirinus) offspring.

    PubMed

    Iwaniak, P; Dobrowolski, P; Tomaszewska, E; Hułas-Stasiak, M; Tomczyk, A; Gawron, A

    2015-11-17

    Considering the negative effects of glucocorticoid treatment, especially during fetal development it is important to investigate effectors decreasing such disadvantages. The aim of this study was to investigate the effect of prenatally administered dexamethasone (Dex), a synthetic glucocorticoid, on the histomorphometry of the femur in the offspring of spiny mice. The study was performed on 24 pregnant spiny mice. The time of the experiment included the prenatal period between the 20th day of gestation until birth (pregnancy lasts on average of 36-38 days). The mice from the experimental group received dexamethasone per os in a dose of 125 mg/kg birth weight daily. At the end, the newborns from the experimental and control group were weighted and euthanized. Maternal Dex treatment resulted in a 17% decrease in birth weight in newborns. Dex administration significantly reduced the thickness of the hypertrophy zone of the growth plate by 34% and total thickness by 8,7%. In addition, Dex decreased the number of cells in the articular cartilage by 27% and significantly decreased their diameter by 5%. Dex also affected the structure and spatial distribution of thick and thin collagen fibers, lowering the proportion of thin fibers compared with the control group. Moreover, Dex treatment considerably lowered the amount of proteoglycans in articular and growth cartilages. Exposure to glucocorticoids in pregnant spiny mice affects cartilage development by accelerating maturity of collagen fibers and growth plate, presumably along with further disruption of longitudinal growth of long bones.

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  20. Neonatal Thymulin Gene Therapy Prevents Ovarian Dysgenesis and Attenuates Reproductive Derangements in Nude Female Mice

    PubMed Central

    Reggiani, Paula C.; Barbeito, Claudio G.; Zuccolilli, Gustavo O.; Cónsole, Gloria M.; Flamini, Alicia M.; Dardenne, Mireille

    2012-01-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70–71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

  1. Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice.

    PubMed

    Reggiani, Paula C; Barbeito, Claudio G; Zuccolilli, Gustavo O; Cónsole, Gloria M; Flamini, Alicia M; Dardenne, Mireille; Goya, Rodolfo G

    2012-08-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis.

  2. 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

  3. 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.

  4. 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…

  5. [Cerebral Doppler ultrasonography in newborn infants].

    PubMed

    Luciano, R; Velardi, F

    1995-01-01

    Following the first study of Bada et al. (1979), Doppler assessment of cerebral blood flow has increasingly been used in newborn infants, matching the technical progress in the available equipment. The experience gathered in recent years has confirmed that Doppler US is a reliable and reproducible examination while precising the limitations and the methodology to be followed in order to prevent gross errors of assessment and interpretation. The interest this procedure has arisen, among other things, stems from being noninvasive and feasible at the patient's bed. These features enable its repeated use in newborn infants in poor clinical condition. The diagnostic and prognostic role of Doppler velocimetry has been shown in a number of neonatal diseases and the cerebral hemodynamics has been assessed in physiologic conditions as well as after drug administration. The most common equipment used in newborn infants is at present Duplex Doppler consisting of a pulsed Doppler combined with bidimensional scanner, which, with visualization of study arteries, enables precise positioning of sample volume and correction of the ultrasonic angle of incidence with respect to the direction of blood flow in the examined vessel. In this report, after a survey of the techniques and modalities of cerebral Doppler examination in newborns, a review of the present state of the art, in neonatal cerebral as well as extracranial disease, is presented.

  6. Newborn screening for non-sickling hemoglobinopathies.

    PubMed

    Hoppe, Carolyn C

    2009-01-01

    The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Non-sickling disorders are found primarily in individuals of Mediterranean, Asian and Southeast Asian ancestry. With rapid growth in the Asian and Hispanic segments of the US population, the geographic distribution of hemoglobinopathies is expected to become significantly different from what it is today. The epidemiologic changes in the prevalence of non-sickling hemoglobin disorders have important implications for future public health programs, including newborn screening. The purpose of newborn screening for hemoglobinopathies is to identify clinically significant disorders and provide early education and specialized care prior to the onset of clinical symptoms. Although newborn screening for sickle cell disease is mandated in all states, screening for non-sickling hemoglobinopathies is directed in only one state and limited to reporting of a presumptive diagnosis in most other states. Early delivery of comprehensive care, as well as new and potentially curative therapies, has significantly improved the prognosis for affected patients. This review will consider the increasing prevalence of once uncommon hemoglobinopathies in the US, highlighting the rationale for expanding newborn screening beyond sickle cell disorders.

  7. Unexpected behavioural consequences of preterm newborns' clothing.

    PubMed

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

    2015-03-17

    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.

  8. 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

  9. Sex Stereotyping in Parents' Perceptions of Newborns.

    ERIC Educational Resources Information Center

    Karraker, Katherine Hildebrandt; Vogel, Dena Ann

    This study updates and extends the findings of Rubin, Provenzano, and Luria (1974), who found that parents perceived their newborn in sex stereotyped ways as early as a few hours after birth. In addition, fathers in their study showed more extreme sex stereotyping than mothers. Participants in the present study were 20 pairs of Caucasian,…

  10. Newborn jaundice - what to ask your doctor

    MedlinePlus

    ... Kaplan M, Wong RJ, Sibley E, Stevenson DK. Neonatal jaundice and liver diseases. In: Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal Medicine . 10th ed. Philadelphia, PA: Elsevier Mosby; 2015:chap 100. Read More ... Newborn jaundice - discharge Review Date 2/ ...

  11. 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)

  12. 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…

  13. 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…

  14. 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…

  15. Congenital lower limb enlargement in a newborn.

    PubMed

    Perez-Crespo, María; Betlloch, Isabel; Martinez-Miravete, Maria Teresa; Ballester, Irene; Lucas, Ana; Mataix, Javier

    2011-01-01

    A full-term newborn presented with swelling of his right leg soon after birth. There was no alteration in Doppler. The grandmother and other relatives were said to have shown a similar history at birth. Milroy's disease was then diagnosed and compressive massage was advised.

  16. 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.

  17. 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.

  18. Guiding Restoration Principles

    DTIC Science & Technology

    2004-12-01

    restoration of important ecosystem functions requires reintegrating landscapes or restorating the func- tional aspects of landscapes ( Risser 1992...51-64. Risser , P. G. 1992. Landscape ecology approach to ecosystem rehabilitation. Pages 37-46 in M. L. Wali (ed.), Ecosystem Rehabilitation

  19. 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…

  20. 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.

  1. 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.

  2. 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 Central

    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)/Prnp0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp0/+ 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)/Prnp0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp0/0 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)/Prnp0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice, compared with RML- and 22L-inoculated Prnp0/+ 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. PMID:25330286

  3. 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.

  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. Impact of Dehydroepiandrosterone Sulfate on Newborn Leukocyte Telomere Length

    PubMed Central

    Liu, Han; Zhou, Guangdi; Chen, Qian; Ouyang, Fengxiu; Little, Julian; Zhang, Jun; Chen, Dan

    2017-01-01

    The newborn setting of leukocyte telomere length (LTL) likely has important implications for telomere dynamics over the lifespan. However, its determinants are poorly understood. Hormones play an important role during pregnancy and delivery. We hypothesized that exposure to hormones may impact the fetal telomere biology system. To test this hypothesis, cortisol, estradiol, dehydroepiandrosterone sulfate (DHEAS) and reactive oxygen species (ROS) were measured in cord blood of 821 newborns from a prospective study. After accounting for the effects of potential determinants of newborn LTL, a 10-fold increase in DHEAS concentration was associated with a 0.021 increase in T/S ratio of newborn LTL (95% confidence interval: 0.009–0.034, P = 0.0008). For newborns who fell in the lowest quartile of DHEAS level, the mean newborn LTL was estimated to be approximately 2.0% shorter than the newborns in the highest DHEAS concentration quartile (P = 0.0014). However, no association was found between newborn LTL and cortisol or estradiol. As expected, newborns with higher ROS level (ROS > 260 mol/L) had lower LTL compared to that with lower ROS level (ROS ≤ 260 mol/L) (P = 0.007). There was also an inverse relationship between DHEAS and ROS (P < 1×10−4). Our findings suggest that exposure to DHEAS may exert a “programming” effect on the newborn telomere biology system. PMID:28186106

  6. Assessing effects of serotonin precursors on newborn behavior.

    PubMed

    Yogman, M W; Zeisel, S H; Roberts, C

    While traditional studies of newborn diet have focused on the effects of malnutrition on the central nervous system, there is now interest in how qualitative differences in the composition of early newborn feeding might influence behavior. This paper reviews the available techniques for assessing newborn perception and cognition, as well as behavioral organization. The paper then focuses intensively on measures of newborn state behaviour in view of evidence in adult humans, as well as in non-human species, suggesting a relationship between sleep behavior (sleep onset, night waking) and brain serotonin levels. A study designed to examine the relationship between dietary precursors of brain serotonin (within the range of concentrations found in human milk) and newborn state behavior after feeding is described to illustrate the application of these techniques. Healthy, fullterm newborns were fed a modified formula, containing tryptophan or valine, on one day, a routine formula on another day, and observed continuously for 3 h after each feeding for the observation and recording of newborn state. Data from individual infants in the tryptophan and valine groups are presented to illustrate the findings that infants fed tryptophan entered quiet sleep and active sleep sooner than infants fed valine and spent more time in active sleep and less time alert. These results illustrate the value of newborn behavior as a sensitive dependent variable in studies of behavioral effects of diet and suggests that variations in serotonin levels in the newborn brain may modulate the newborn's sleep/wake behaviour.

  7. [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.

  8. Hospital stay for healthy term newborns.

    PubMed

    2010-02-01

    The hospital stay of the mother and her healthy term newborn infant should be long enough to allow identification of early problems and to ensure that the family is able and prepared to care for the infant at home. The length of stay should also accommodate the unique characteristics of each mother-infant dyad, including the health of the mother, the health and stability of the infant, the ability and confidence of the mother to care for her infant, the adequacy of support systems at home, and access to appropriate follow-up care. Input from the mother and her obstetrician should be considered before a decision to discharge a newborn is made, and all efforts should be made to keep mothers and infants together to promote simultaneous discharge.

  9. 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

  10. [Congenital pulmonary capillary hemangiomatosis in a newborn].

    PubMed

    Sposito Cavallo, Sandra L; Macias Sobrino, Luciano A; Marenco Altamar, Luifer J; Mejía Alquichire, Andrés F

    2017-02-01

    Pulmonary capillary hemangiomatosis is a rare entity characterized by the proliferation of capillaries into alveolar walls, interlobular septa, pleura and pulmonary interstitium, without malignant characteristics, with almost constant association with pulmonary hypertension. Until now two cases of congenital presentation have been reported in the literature. This is the third case in a newborn; he has not followed the usual pattern associated with pulmonary hypertension as occurs in most patients with this pathology; the highest incidence is among 20-40 years old. We report a preterm newborn patient of 36 weeks of gestation with progressive respiratory distress requiring mechanical ventilation by constant desaturation during his clinical evolution without clinical, radiological or ultrasonographic signs of pulmonary hypertension.

  11. Hepatic subcapsular haematoma in a premature newborn.

    PubMed

    Gonçalves, Cristina; Aguilar, Sara; Prior, Ana Rita; Oliveira, Graça

    2013-06-03

    Subcapsular haematoma of the liver rarely occurs in neonates and the diagnosis is often missed or delayed. It is a catastrophic condition that can be caused by maternal, placentar or fetal factors. A high index of suspicion is essential for early identification and stabilisation of babies with such a pathology. In a newborn with hypovolemic shock and abdominal distension, haemoperitoneum should be suspected and, along with exclusion of other aetiologies, supportive therapy should be instituted. The hepatic subcapsular haematoma has a non-specific presentation, and should be considered in very low birth weight infants with hypovolemic shock. Abdominal ultrasonography is the investigation of choice. It can delineate the lesion well, differentiate it from neoplasms, rule out rupture and aid in serial follow-up. We report a premature newborn who had this uncommon condition in the early neonatal period and survived without sequelae.

  12. 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).

  13. Genetic Disorders in the Newborn Infant

    PubMed Central

    Meschino, Wendy S.; Summers, Anne M.

    1988-01-01

    Genetic disorders in the neonate should be suspected in a number of different clinical situations, ranging from that of an infant with dysmorphic features and multiple congenital malformations to that of a previously well newborn who becomes acutely ill. An approach for the primary-care physician to the initial investigation and management of these situations is outlined. In addition neonatal screening tests for metabolic disorders and congenital hypothyroidism are briefly discussed. PMID:21253098

  14. Immunoglobulin levels in SFD newborn babies.

    PubMed

    Kobielowa, Z; Miecznikowska, M; Kubiczek, K; Michalik, R

    1975-01-01

    The IgG, IgA and IgM levels were determined by the technique of radial immunodiffusion of Mancini et al. in 40 SFD and 30 normal control newborn infants. The mean value of IgG concentrations was found to be raised but without statistical significance when compared with control. On the contrary the increased mean amounts of IgM were statistically significant.

  15. Spontaneous Splenic Hemorrhage in the Newborn

    PubMed Central

    Tiboni, Sonia; Abdulmajid, Umar; Pooboni, Suneel; Wighton, Christopher; Eradi, Balgopal; Dagash, Haitham

    2015-01-01

    Spontaneous splenic hemorrhage in the newborn is a rare entity. The presentation is usually with a triad of bleeding, abdominal distension, and hemoperitoneum. Rapid diagnosis is essential as left untreated, death is inevitable. We present a case with an unusual initial presentation of a scrotal hematocele and ultrasonography suggesting an adrenal hemorrhage. At laparotomy, splenic preservation was unsuccessful, and therefore, splenectomy was performed. The child recovered well from the procedure. PMID:26788451

  16. Principles of Wetland Restoration

    EPA Pesticide Factsheets

    the return of a degraded ecosystem to a close approximation of its remaining natural potential - is experiencing a groundswell of support across the United States. The number of stream, river, lake, wetland and estuary restoration projects grows yearly

  17. 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.

  18. The Menominee Restoration Act

    ERIC Educational Resources Information Center

    Deer, Ada E.

    1973-01-01

    The article discusses the background and current status of the Menominee Restoration Bill, which will reverse the termination of Federal responsibility effected on the Wisconsin Menominee Tribe in 1961. (KM)

  19. 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.

  20. 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

  1. Prenatal and newborn screening for hemoglobinopathies.

    PubMed

    Hoppe, C C

    2013-06-01

    The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Increased immigration of high-risk populations has prompted the implementation of prenatal and newborn screening programs for hemoglobinopathies across Europe and North America. In Canada, the UK, and other European countries, prenatal screening to identify hemoglobinopathy carriers and offer prenatal diagnostic testing to couples at risk is linked to newborn screening, while in the United States, it is still not universally performed. The structure of screening programs, whether prenatal or postnatal, universal or selective, varies greatly among these countries and within the United States. The laboratory methods used to identify hemoglobinopathies are based on the prevalence of hemoglobinopathies within the population and the type of screening performed. Advances in molecular testing have facilitated the diagnosis of complex thalassemias and sickling disorders observed in ethnically diverse populations. This review summarizes the current approaches and methods used for carrier detection, prenatal diagnosis, and newborn screening.

  2. Lysosomal Storage Disorders in the Newborn

    PubMed Central

    Staretz-Chacham, Orna; Lang, Tess C.; LaMarca, Mary E.; Krasnewich, Donna; Sidransky, Ellen

    2009-01-01

    Lysosomal storage disorders are rare inborn errors of metabolism, with a combined incidence of 1 in 1500 to 7000 live births. These relatively rare disorders are seldom considered when evaluating a sick newborn. A significant number of the >50 different lysosomal storage disorders, however, do manifest in the neonatal period and should be part of the differential diagnosis of several perinatal phenotypes. We review the earliest clinical features, diagnostic tests, and treatment options for lysosomal storage disorders that can present in the newborn. Although many of the lysosomal storage disorders are characterized by a range in phenotypes, the focus of this review is on the specific symptoms and clinical findings that present in the perinatal period, including neurologic, respiratory, endocrine, and cardiovascular manifestations, dysmorphic features, hepatosplenomegaly, skin or ocular involvement, and hydrops fetalis/congenital ascites. A greater awareness of these features may help to reduce misdiagnosis and promote the early detection of lysosomal storage disorders. Implementing therapy at the earliest stage possible is crucial for several of the lysosomal storage disorders; hence, an early appreciation of these disorders by physicians who treat newborns is essential. PMID:19336380

  3. Diet and sleep patterns in newborn infants.

    PubMed

    Yogman, M W; Zeisel, S H

    1983-11-10

    Sleep behavior is modulated by serotonergic neurons within the brain, and the synthesis and release of serotonin by such neurons is thought to be influenced by the availability of tryptophan, the amino acid precursor of serotonin. We investigated the effects on the sleep patterns of newborn infants of variations in diet designed to affect tryptophan availability. Twenty healthy newborns (two to three days of age) were randomly assigned to receive a feeding consisting either of tryptophan in 10 per cent glucose or valine in 5 per cent glucose (valine competes with tryptophan for entry into the brain). Sleep patterns during the three hours after this feeding were compared with those after a feeding of routine formula (Similac). The infants fed tryptophan entered active sleep 14.1 minutes sooner than they did after Similac, and entered quiet sleep 20 minutes sooner. Those fed valine entered active sleep 15.8 minutes later than they did after Similac, and entered quiet sleep 39 minutes later. The differences between the tryptophan and valine groups were significant (P less than 0.01 for active sleep and P less than 0.005 for quiet sleep). We conclude that variations in the composition of the diet may influence sleep behavior in newborns.

  4. 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.

  5. Brain and retinal ferroportin 1 dysregulation in polycythaemia mice.

    PubMed

    Iacovelli, Jared; Mlodnicka, Agnieska E; Veldman, Peter; Ying, Gui-Shuang; Dunaief, Joshua L; Schumacher, Armin

    2009-09-15

    Disruption of iron homeostasis within the central nervous system (CNS) can lead to profound abnormalities during both development and aging in mammals. The radiation-induced polycythaemia (Pcm) mutation, a 58-bp microdeletion in the promoter region of ferroportin 1 (Fpn1), disrupts transcriptional and post-transcriptional regulation of this pivotal iron transporter. This regulatory mutation induces dynamic alterations in peripheral iron homeostasis such that newborn homozygous Pcm mice exhibit iron deficiency anemia with increased duodenal Fpn1 expression while adult homozygotes display decreased Fpn1 expression and anemia despite organismal iron overload. Herein we report the impact of the Pcm microdeletion on iron homeostasis in two compartments of the central nervous system: brain and retina. At birth, Pcm homozygotes show a marked decrease in brain iron content and reduced levels of Fpn1 expression. Upregulation of transferrin receptor 1 (TfR1) in brain microvasculature appears to mediate the compensatory iron uptake during postnatal development and iron content in Pcm brain is restored to wild-type levels by 7 weeks of age. Similarly, changes in expression are transient and expression of Fpn1 and TfR1 is indistinguishable between Pcm homozygotes and wild-type by 12 weeks of age. Strikingly, the adult Pcm brain is effectively protected from the peripheral iron overload and maintains normal iron content. In contrast to Fpn1 downregulation in perinatal brain, the retina of Pcm homozygotes reveals increased levels of Fpn1 expression. While retinal morphology appears normal at birth and during early postnatal development, adult Pcm mice demonstrate a marked, age-dependent loss of photoreceptors. This phenotype demonstrates the importance of iron homeostasis in retinal health.

  6. Delivery of AAV2/9-Microdystrophin Genes Incorporating Helix 1 of the Coiled-Coil Motif in the C-Terminal Domain of Dystrophin Improves Muscle Pathology and Restores the Level of α1-Syntrophin and α-Dystrobrevin in Skeletal Muscles of mdx Mice

    PubMed Central

    Koo, Taeyoung; Malerba, Alberto; Athanasopoulos, Takis; Trollet, Capucine; Boldrin, Luisa; Ferry, Arnaud; Popplewell, Linda; Foster, Helen; Foster, Keith

    2011-01-01

    Abstract Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (<5 kb), truncated recombinant microdystrophin genes with deletions of most of rod and carboxyl-terminal (CT) domains of dystrophin have been developed. We have previously shown the efficiency of mRNA sequence–optimized microdystrophin (ΔR4-23/ΔCT, called MD1) with deletion of spectrin-like repeat domain 4 to 23 and CT domain in ameliorating the pathology of dystrophic mdx mice. However, the CT domain of dystrophin is thought to recruit part of the dystrophin-associated protein complex, which acts as a mediator of signaling between extracellular matrix and cytoskeleton in muscle fibers. In this study, we extended the ΔR4-23/ΔCT microdystrophin by incorporating helix 1 of the coiled-coil motif in the CT domain of dystrophin (MD2), which contains the α1-syntrophin and α-dystrobrevin binding sites. Intramuscular injection of AAV2/9 expressing CT domain–extended microdystrophin showed efficient dystrophin expression in tibialis anterior muscles of mdx mice. The presence of the CT domain of dystrophin in MD2 increased the recruitment of α1-syntrophin and α-dystrobrevin at the sarcolemma and significantly improved the muscle resistance to lengthening contraction–induced muscle damage in the mdx mice compared with MD1. These results suggest that the incorporation of helix 1 of the coiled-coil motif in the CT domain of dystrophin to the microdystrophins will substantially improve their efficiency in restoring muscle function in patients with Duchenne muscular dystrophy. PMID:21453126

  7. Evaluation of pain in healthy newborns and in newborns with developmental problems (Down syndrome).

    PubMed

    Aguilar Cordero, Maria José; Mur Villar, Norma; García García, Inmaculada

    2015-06-01

    Newborns are often subjected to invasive and painful medical procedures. This happens even more frequently when they require hospitalization. The aim of this paper was to evaluate pain in healthy newborns and in newborns with Down syndrome (DS). We performed a prospective cohort study in the neonatal service of the San Cecilio University Hospital in Granada (Spain) from January 2008 to September 2013. The universe of our study comprised a study group of 20 newborns with DS and a control group of 20 newborns without DS. All of the infants were hospitalized, and thus had to undergo painful medical procedures. The variables studied were basal recovery time (as reflected in crying and the normalization of biological constants), number of punctures, oxygen saturation, heartbeat, blood pressure, response to skin-to-skin contact, and gestational age. The evaluation was performed during blood extraction, vein canalization, and heel puncture. The significant differences in the basal recovery time between the two groups of newborns indicated that those with DS were slower to express pain, and when they did, their response was not as clearly defined as that of babies without DS. The oxygen saturation in babies with DS after the puncture was found to be significantly lower than that of the control group (p < .001). The results of this study revealed that babies with DS were not as quick to perceive pain after a puncture. However, when pain was finally perceived, it persisted for a longer time. This situation should be taken into account in the design of pharmacologic and nonpharmacologic therapies.

  8. 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...

  9. 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

  10. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

    PubMed Central

    Dowling, David J.; van Haren, Simon D.; Scheid, Annette; Bergelson, Ilana; Kim, Dhohyung; Mancuso, Christy J.; Foppen, Willemina; Fresh, Lynn; Theriot, Terese B.; Lackner, Andrew A.; Fichorova, Raina N.; Smirnov, Dmitri; Vasilakos, John P.; Beaurline, Joe M.; Tomai, Mark A.; Midkiff, Cecily C.; Alvarez, Xavier; Blanchard, James L.; Gilbert, Margaret H.; Aye, Pyone Pyone

    2017-01-01

    Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13). When admixed with PCV13 and administered i.m. on the first day of life to rhesus macaques, 3M-052 dramatically enhanced generation of Th1 CRM-197–specific neonatal CD4+ cells, activation of newborn and infant Streptococcus pneumoniae polysaccharide–specific (PnPS-specific) B cells as well as serotype-specific antibody titers, and opsonophagocytic killing. Remarkably, a single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced PnPS-specific IgG responses that were approximately 10–100 times greater than a single birth dose of PCV13 alone, rapidly exceeding the serologic correlate of protection, as early as 28 days of life. This potent immunization strategy, potentially effective with one birth dose, could represent a new paradigm in early life vaccine development. PMID:28352660

  11. 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.

  12. Counseling parents who are considering newborn male circumcision.

    PubMed

    Mielke, Ruth T

    2013-01-01

    The American Academy of Pediatrics recently issued a statement that the health benefits of newborn male circumcision exceed the risks and therefore justify access to the procedure for families who choose it. Further, clinicians are charged with providing factually correct information that communicates the risks and benefits of elective newborn male circumcision in a nonbiased manner. However, many clinicians lack adequate information to discuss the risks and benefits of male circumcision. The purpose of this review is to highlight evidence on the risks and benefits of newborn male circumcision and provide clinicians with counseling points that can be used to guide discussion with parents considering newborn male circumcision.

  13. 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

  14. 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.

  15. Feeding of newborns and infants (cultural aspects).

    PubMed

    Lala, V R; Desai, A B

    1970-07-01

    A total of 435 mothers in the postnatal ward of the Civil Hospital in Ahmedabad, India were interviewed to determine the cultural beliefs and traditional practices influencing the feeding of newborns and infants. A thorough physical and neurological examination of the newborns was conducted. All newborns and mothers were followed for a period varying from 3-7 days to detect any complications either in the newborn or the mother related to feeding patterns. The various methods of feeding were observed. In most of the cases the deciding factor to giving the 1st feed was the cry of the baby. As a 1st feed, various liquid preparations were used by the mothers. 66.2% of the mothers offered boiled water as a 1st feed. In the postnatal ward boiled water is an easily available preparation for newborns and is usually provided by the ward sister whenever the mother requests it. In most of the cases the mother herself was the initiator. 40.3% of the mothers began supplementing breast milk with milk or solid food before the age of 1 year, and 18% by the age of 1 1/2 years. 27.3% of the mothers kept their children on breast milk only until the age of 1 year, and 12.7% until the age of 2 years. 46.5% of the mothers did not give milk at all during infancy and childhood. The most common age for introducing solid food was 1-1 1/2 (61.4%); only 10.2% of the mothers introduced solid food during the 1st year of life. The various sweet carbohydrate preparations used as 1st feed are known as "Galthuthi." 25.9% of the mothers gave "Galthuthi" to their newborns during the 1st 3 days of life and 16.9% of the mothers used it as a 1st feed. Most mothers were giving it as a custom or community tradition. The infants exposed to "Galthuthi" are exposed to gastrointestinal infections. The common practice of giving fresh milk as a prelacteal feed during the 1st 3 days of life appears to be harmful to subsequent breastfeeding. It seems that prelacteal feed is not harmful as long as it is given in a

  16. Integration of the Newborn Behavioral Observations (NBO) System into Care Settings for High-Risk Newborns

    ERIC Educational Resources Information Center

    McManus, Beth M.

    2015-01-01

    Research suggests that early self-regulatory difficulties among high-risk newborns can lead to poor interactional difficulties and negative long-term cognitive and social-emotional outcomes if not identified and treated early. This article describes why an individualized, developmentally supportive, relationship-based program, such as the Newborn…

  17. Extremely low-frequency electromagnetic fields enhance the survival of newborn neurons in the mouse hippocampus.

    PubMed

    Podda, Maria V; Leone, Lucia; Barbati, Saviana A; Mastrodonato, Alessia; Li Puma, Domenica D; Piacentini, Roberto; Grassi, Claudio

    2014-03-01

    In recent years, much effort has been devoted to identifying stimuli capable of enhancing adult neurogenesis, a process that generates new neurons throughout life, and that appears to be dysfunctional in the senescent brain and in several neuropsychiatric and neurodegenerative diseases. We previously reported that in vivo exposure to extremely low-frequency electromagnetic fields (ELFEFs) promotes the proliferation and neuronal differentiation of hippocampal neural stem cells (NSCs) that functionally integrate in the dentate gyrus. Here, we extended our studies to specifically assess the influence of ELFEFs on hippocampal newborn cell survival, which is a very critical issue in adult neurogenesis regulation. Mice were injected with 5-bromo-2'-deoxyuridine (BrdU) to label newborn cells, and were exposed to ELFEFs 9 days later, when the most dramatic decrease in the number of newly generated neurons occurs. The results showed that ELFEF exposure (3.5 h/day for 6 days) enhanced newborn neuron survival as documented by double staining for BrdU and doublecortin, to identify immature neurons, or NeuN labeling of mature neurons. The effects of ELFEFs were associated with enhanced spatial learning and memory. In an in vitro model of hippocampal NSCs, ELFEFs exerted their pro-survival action by rescuing differentiating neurons from apoptotic cell death. Western immunoblot assay revealed reduced expression of the pro-apoptotic protein Bax, and increased levels of the anti-apoptotic protein Bcl-2, in the hippocampi of ELFEF-exposed mice as well as in ELFEF-exposed NSC cultures, as compared with their sham-exposed counterparts. Our results may have clinical implications for the treatment of impaired neurogenesis associated with brain aging and neurodegenerative diseases.

  18. Everglades Restoration Critiqued

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    The monitoring and assessment plan for the $7.8-billion effort to restore the hydrologic regime of the remaining wetlands of Florida's Everglades needs to be strengthened, according to a 2 April study by a committee of the National Academy of Sciences. The evolving monitoring and assessment plan of the Comprehensive Everglades Restoration Plan is grounded in current scientific theory and practice of adaptive management, according to the report. However, the least-developed aspects of the management are feedback mechanisms to connect monitoring to planning and management, the report notes.

  19. Overvoltage control during restoration

    SciTech Connect

    Adibi, M.M. ); Alexander, R.W. ); Avra-Movic, B. )

    1992-11-01

    This paper is one in a series presented on behalf of the System Operation Subcommittee with the intent of focusing industry attention on power system restoration issues. Restoration of a bulk power supply system presents the operator with unique challenges not normally encountered in daily operations. The initial, and even intermediate transmission system topologies are quite different from the well integrated systems during normal operation. There are several problems that pertain to these non-normal topologies that are of common concern to operators and need to be addressed. One of these, the problem of overvoltages, is the subject of this paper.

  20. Paraurethral Skene's duct cyst in a newborn

    PubMed Central

    Moralioğlu, Serdar; Bosnalı, Oktav; Celayir, Ayşenur Cerrah; Şahin, Ceyhan

    2013-01-01

    Paraurethral or Skene's duct cysts are rare causes of interlabial masses in neonates. The diagnosis of Skene's duct cysts in the neonatal period is based on its location, in relation to the urethra, and the demonstration of transitional epithelium in the cyst wall. The distinguishing features of paraurethral cysts are the displacement of urethral meatus by the mass and a cyst containing milky fluid. Thus, we report a case of a Skene's duct cyst in a newborn which was treated by incision and drainage. PMID:24049387

  1. A newborn with unilateral limb enlargement.

    PubMed

    Sharma, Shanel; Maino, Anna P F; Husain, Shad M; Adams, Gill G W

    2012-03-01

    On routine neonatal examination, a newborn term male was noted to have unilateral enlargement of the right lower limb, loose thickened red skin over the palm and widening of all the fingers on the right hand. His body was pinker and warmer on the right side compared with the left and he had a right undescended testicle and hypoplastic scrotum. Radiological examination of the lower limbs demonstrated the enlargement of the soft tissue of the right lower limb compared to the left (Fig. 1). Therefore, the diagnosis was unclear from this constellation of findings and an ophthalmic assessment was requested.

  2. [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.

  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 Central

    Mackenzie, Amelia C. L.; Lee, Se-Jin; Chaffin, Charles L.; Merchenthaler, István

    2016-01-01

    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. [Umbilical and peripherally inserted venous central catheterization of the newborn].

    PubMed

    Bouissou, A; Rakza, T; Storme, L; Lafarghe, A; Fily, A; Diependaele, J-F; Dalmas, S

    2008-09-01

    Umbilical venous and peripherally inserted venous central catheters are widely used to perfuse low-weight preterm and term newborns in intensive care units. This catheter must be inserted carefully and monitored rigorously to prevent complications. This paper develops today's knowledge on the use and complications in the newborn population.

  5. 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)

  6. 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…

  7. 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…

  8. 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…

  9. Spatial Effects of Sound on Visual Activity in Human Newborns.

    ERIC Educational Resources Information Center

    Mendelson, Morton J.; Haith, Marshall M.

    This study investigated the possibility of a functional relation between the auditory and visual systems in the human newborn beyond reflexive organization. Visual activity was monitored in 16 newborns through the use of infrared corneal reflection video tape recording. Infants were observed in total darkness and while monocularly viewing a…

  10. [Health assessment of newborns with congenital urinary malformation].

    PubMed

    Iushko, E I; Strotskiĭ, A V; Dubrov, V I; Tkachenko, A K

    2011-01-01

    Improvement in diagnosis of prenatal congenital urinary malformations (CUM) resulted in increased detection of CUM cases among newborns. To facilitate medical care for CUM newborns, we have developed an objective method of CUM newborns' health assessment. We studied 40 case histories of newborns with prenatally detected CUM admitted to urological clinics (20 with diagnosis of poor health and 20 with moderate condition severity) and 40 CUM newborns examined outpatiently (moderate health hazard). The computer analysis of the available data has established 13 most informative diagnostic criteria: 4 sonographic criteria, 3 lab criteria and 6 physical exam criteria estimated by 4 points - from 0 to 4. The criteria were pooled to a table which was used as a scale to assess general health condition. After delivery, CUM newborn gets inpatient health assessment by a neonatologist using 13 criteria. According to the total score, the condition is assessed as satisfactory (0-5), moderately severe (6-11), severe ( > 12). Efficacy of such health assessment was proved in a population study of 312 prenatal CUM newborns. Grouping of such newborns helps design of programs of further examination and management.

  11. 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…

  12. 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

  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. 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…

  15. 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.

  16. Nitriding of restored crankshafts

    NASA Astrophysics Data System (ADS)

    Ponukalin, V. V.; Aleksandrov, V. N.

    1984-02-01

    The following technology is recommended for restoration of steel crankshafts: facing with an Sv-08 electrode wire under an AN-348A flux with chromium and niobium introduced into the melt in accordance with the method used at automotive-repair plants and subsequent gas nitriding at (570±10)°C for 12 h.

  17. 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…

  18. [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.

  19. Red blood cell transfusion in newborn infants

    PubMed Central

    Whyte, Robin K; Jefferies, Ann L

    2014-01-01

    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

  20. 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.

  1. Challenges of newborn severe combined immunodeficiency screening among premature infants.

    PubMed

    Ward, Claire E; Baptist, Alan P

    2013-04-01

    Newborn screening for severe combined immunodeficiency (SCID) is currently being performed in many states. It is important to address diagnostic challenges while outcomes are emerging from the first several years of screening. We present the case of a premature infant whose initial newborn screen was strongly positive for SCID. Subsequent lymphocyte subset analysis by flow cytometry was difficult to interpret due to the lack of age-matched reference values, a history of prenatal corticosteroid administration, and the possibility of maternal or posttransfusion engraftment. A repeat newborn screen for SCID ultimately revealed a normal result, confirming the initial newborn screen as a false positive. This case report reveals several of the diagnostic challenges unique to newborn SCID screening in premature infants and highlights the potential for states to address the feasibility of a standard protocol in this population.

  2. Digital restoration of multichannel images

    NASA Technical Reports Server (NTRS)

    Galatsanos, Nikolas P.; Chin, Roland T.

    1989-01-01

    The Wiener solution of a multichannel restoration scheme is presented. Using matrix diagonalization and block-Toeplitz to block-circulant approximation, the inversion of the multichannel, linear space-invariant imaging system becomes feasible by utilizing a fast iterative matrix inversion procedure. The restoration uses both the within-channel (spatial) and between-channel (spectral) correlation; hence, the restored result is a better estimate than that produced by independent channel restoration. Simulations are also presented.

  3. Adaptive wiener image restoration kernel

    SciTech Connect

    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.

  4. 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…

  5. 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

  6. Hepatic lentiviral gene transfer prevents the long-term onset of hepatic tumours of glycogen storage disease type 1a in mice.

    PubMed

    Clar, Julie; Mutel, Elodie; Gri, Blandine; Creneguy, Alison; Stefanutti, Anne; Gaillard, Sophie; Ferry, Nicolas; Beuf, Olivier; Mithieux, Gilles; Nguyen, Tuan Huy; Rajas, Fabienne

    2015-04-15

    Glycogen storage disease type 1a (GSD1a) is a rare disease due to the deficiency in the glucose-6-phosphatase (G6Pase) catalytic subunit (encoded by G6pc), which is essential for endogenous glucose production. Despite strict diet control to maintain blood glucose, patients with GSD1a develop hepatomegaly, steatosis and then hepatocellular adenomas (HCA), which can undergo malignant transformation. Recently, gene therapy has attracted attention as a potential treatment for GSD1a. In order to maintain long-term transgene expression, we developed an HIV-based vector, which allowed us to specifically express the human G6PC cDNA in the liver. We analysed the efficiency of this lentiviral vector in the prevention of the development of the hepatic disease in an original GSD1a mouse model, which exhibits G6Pase deficiency exclusively in the liver (L-G6pc(-/-) mice). Recombinant lentivirus were injected in B6.G6pc(ex3lox/ex3lox). SA(creERT2/w) neonates and G6pc deletion was induced by tamoxifen treatment at weaning. Magnetic resonance imaging was then performed to follow up the development of hepatic tumours. Lentiviral gene therapy restored glucose-6 phosphatase activity sufficient to correct fasting hypoglycaemia during 9 months. Moreover, lentivirus-treated L-G6pc(-/-) mice presented normal hepatic triglyceride levels, whereas untreated mice developed steatosis. Glycogen stores were also decreased although liver weight remained high. Interestingly, lentivirus-treated L-G6pc(-/-) mice were protected against the development of hepatic tumours after 9 months of gene therapy while most of untreated L-G6pc(-/-) mice developed millimetric HCA. Thus the treatment of newborns by recombinant lentivirus appears as an attractive approach to protect the liver from the development of steatosis and hepatic tumours associated to GSD1a pathology.

  7. In vitro visualization of respiratory neuron activity in the newborn mouse ventral medulla.

    PubMed

    Onimaru, Hiroshi; Arata, Akiko; Arata, Satoru; Shirasawa, Senji; Cleary, Michael L

    2004-11-25

    To clarify the neuronal organization of the respiratory center of the mouse, we analyzed the spatio-temporal pattern of respiratory neuron activity in the ventral medulla of a newborn mouse preparation, using optical recordings. We also demonstrated optical images of the respiratory activity of two different lines of knock-out mice (Tlx3-/-, Pbx3-/-) that exhibit respiratory failure leading to neonatal death from dysfunction of central respiratory neuron activity. In the wild type mice, the respiratory neuron activity in the para-facial region of the rostral medulla appeared prior to inspiratory activity in the more caudal ventrolateral medulla. This rostral to caudal activity pattern was basically preserved in Tlx3-/- mice though the activity was more dispersed and weaker than in the wild type mice. Such an activity pattern was not clearly detected in Pbx3-/- mouse preparations. The difference in the spatio-temporal pattern between Tlx3-/- and Pbx3-/- suggests different levels of functional disorder of the respiratory center.

  8. 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…

  9. Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

    PubMed Central

    Buening, M K; Wislocki, P G; Levin, W; Yagi, H; Thakker, D R; Akagi, H; Koreeda, M; Jerina, D M; Conney, A H

    1978-01-01

    The tumorigenicities of benzo[a]pyrene and each optical enantiomer of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides derived from trans-7,8-dihydroxy-7,8-dihydrobenzol[a]pyrene were tested by sequential intraperitoneal injection of mice with 1,2, and 4 nmol, or with 2, 4, and 8 nmol of each compound on the 1st, 8th, and 15th day of life, respectively. The experiment was terminated when the animals were 34--37 weeks old. (+)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzol[a]pyrene [(+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2] had exceptional tumorigenicity, whereas benzo[a]-pyrene and the other three optically pure isomers of the benzo[a]pyrene 7,8-diol,9,10-epoxides had little or no activity. These results demonstrate differences in the carcinogenic activities of optically active isomers of a polycyclic hydrocarbon diol epoxide. Eleven percent of control mice had pulmonary tumors, whereas 71% and 100% of the mice treated with a total dose of 7 or 14 nmol of (+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2, respectively, had pulmonary tumors. Control mice had an average of 0.12 pulmonary tumors per mouse, whereas mice treated with a total dose of 7 or 14 nmol of (+)-BP-7beta,8alpha-diol-9alpha,10alpha-epoxide 2 had 1.72 and 7.67 pulmonary tumors per mouse, respectively. Mice treated with 14 nmol of (-)-BP-7alpha,8beta-diol-9beta,10beta-epoxide 2, (-)-BP-7beta,8alpha-diol-9beta,10beta-epoxide 1, or (+)-BP-7alpha,8beta-diol-9alpha,10alpha-epoxide 1 had 0.13, 0.25, and 0.34 pulmonary tumors per animal, respectively. PMID:281685

  10. Neonaticide, newborn abandonment, and denial of pregnancy--newborn victimisation associated with unwanted motherhood.

    PubMed

    Lee, A C W; Li, C H; Kwong, N S; So, K T

    2006-02-01

    We report two cases of newborn death and two cases of near-miss newborn death. One neonate was strangled to death after delivery in the hospital and one died from lethal congenital malformations. The third was found on the verge of death after being abandoned in a dumpster. The fourth was rescued from the toilet bowl by the mother's boyfriend while the mother was in a state of panic. In the three cases where the infants' maternal identities were known, the women were all primiparous and aged 22, 13, and 17 years. The paternity was extramarital, incestuous, and concealed, respectively. Denial or concealment of pregnancy was present in all cases, but none of the women had any overt psychiatric manifestations at the time of delivery. Neonaticide and newborn abandonment are closely associated with denial of pregnancy, and are serious forms of childhood victimisation. Their occurrence in Hong Kong is poorly understood and no representative figures are available. A concerted effort among the health care, social work, and judicial professionals is needed to define the scope of the problem and devise preventive measures.

  11. [Increased incidence of developmental hip dysplasia in hypertrophic newborn infants].

    PubMed

    Peschgens, T; Skopnik, H; Casser, H R; Rauschning-Sikora, K; Heimann, G

    1993-01-01

    "Lack of space" in utero is considered to be a major factor in the aetiology of the congenital dislocation of the hip. This study tries to answer the question whether hypertrophy of a newborn has to be regarded as a risk factor on the basis of the principle mentioned above. The results of postnatal clinical and sonographical examination performed on 98 large-for-gestational-age (LGA-) newborn were compared to those performed on 310 newborn children during a non selective screening program. Among the LGA-newborn pathological hip joints were found more often mainly female LGA-newborn infants were affected. It seemed that the birth weight did not correlate to the extent of the retardation of the hip joint development. It was again confirmed that the restriction to only clinical diagnostic procedures in the neonatal period is not effective in the early diagnosis of the malformation. Hypertrophy of a newborn has to be considered as a risk factor behind the development of congenital dislocation of the hip. It is recommended to examine all LGA-newborn infants post partum by clinical and most importantly also by sonographical means to recognize a retardation of hip joint development.

  12. 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.

  13. Impact of conditional cash transfers on maternal and newborn health.

    PubMed

    Glassman, Amanda; Duran, Denizhan; Fleisher, Lisa; Singer, Daniel; Sturke, Rachel; Angeles, Gustavo; Charles, Jodi; Emrey, Bob; Gleason, Joanne; Mwebsa, Winnie; Saldana, Kelly; Yarrow, Kristina; Koblinsky, Marge

    2013-12-01

    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.

  14. Phenotypic and functional characteristics of human newborns' B lymphocytes.

    PubMed

    Durandy, A; Thuillier, L; Forveille, M; Fischer, A

    1990-01-01

    It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.

  15. Jaundice in the full-term newborn.

    PubMed

    Cohen, Shannon Munro

    2006-01-01

    Jaundice is a common problem affecting over half of all full-term and most preterm infants. Jaundice describes the yellow orange hue of the skin caused by excessive circulating levels of bilirubin that accumulate in the skin. In most healthy full-term newborns, jaundice is noticed during the first week of life. Shortened hospital stays and inconsistent follow up, especially for first-time breastfeeding mothers, prompted the American Academy of Pediatrics (AAP) to update management guidelines. Health care providers need to be familiar with the diagnosis and management of jaundice to prevent brain, vision, and hearing damage. Treatment of choice for jaundice remains close observation and frequent feeding followed by phototherapy, and finally exchange transfusion for severe or refractory cases.

  16. 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

  17. 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.

  18. Nutritional support in the premature newborn

    PubMed Central

    Puntis, J W L

    2006-01-01

    The theory and practice of nutritional support in the premature newborn has assumed increasing importance with survival of greater numbers of very immature infants. After birth, many do not tolerate full enteral feeding until gastrointestinal motor function has matured. During this process some will develop necrotising enterocolitis (NEC), a devastating failure of adaptation to postnatal life that may result in death, or severe complications. The feeding strategy that minimises the risk of NEC remains to be defined. In addition, promoting growth rates and nutrient accretion equivalent to those achieved during fetal development while optimising neurodevelopmental and long term health outcomes represents an important challenge for neonatologists. This review will focus on the problems associated with enteral nutrition, the requirement for parenteral nutrition, and the long term consequences of early nutritional interventions, underlining the need for prolonged follow up in assessing the potential benefits of different approaches to feeding. PMID:16517801

  19. Dental lamina cysts in a newborn infant.

    PubMed

    Singh, Rajeev Kumar; Kumar, Rakesh; Pandey, Ramesh Kumar; Singh, Kamleshwar

    2012-10-09

    Cystic lesions of transient nature viz. Epstein pearls, Bohn's nodules and dental lamina cysts are frequently found in the oral cavities of newborn infants. These cysts arise from the developing dental tissues or from their remnants. These cystic lesions are not commonly seen by the dental surgeons due to their self-limiting nature and ignorance of the parents to seek the professional opinion. However, when contacted by anxious parents seeking treatment, dental surgeons should be able to explain and reassure the parents about the transient nature of these lesions and need for no treatment but regular follow-up. The present case report was written with the purpose to increase the awareness in dental surgeons about the peculiar clinical presentation and self-limiting nature of these cystic lesions, so that unnecessary surgical intervention can be avoided in such young infants.

  20. [Newborn with lung mass of uncommon etiology].

    PubMed

    Pellegrino Cid, Christian; Maglio, Silvana; Gentile, Luis Fernando

    2012-01-01

    Thoracic masses in neonates usually respond to congenital anomalies of the respiratory system. They comprise a large number of diseases that can compromise the development of larynx, trachea, bronchi, pulmonary parenchyma and diaphragm or chest wall. Diagnosis is carried out during prenatal period by ultrasound in most cases. In others, respiratory distress is diagnosed during post-birth examination or later as a radiological finding. We present the case of a full term newborn with prenatal diagnosis of cystic "lung mass". Physical examination was unremarkable except for decreased breath sounds on the right lung. Different image studies were carried out to characterize the lesion. The patient underwent surgery and chemotherapy at fifth month of life. Pleuropulmonary blastoma diagnosis was confirmed by pathological study of the surgical specimen. This is a rare intrathoracic malignant tumor, appearing almost exclusively in children less than 7-years-old.

  1. Newborn infants detect the beat in music

    PubMed Central

    Winkler, István; Háden, Gábor P.; Ladinig, Olivia; Sziller, István; Honing, Henkjan

    2009-01-01

    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. PMID:19171894

  2. 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)).

  3. 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)).

  4. Systematic review: intravenous Ibuprofen in preterm newborns.

    PubMed

    Aranda, J V; Thomas, Ronald

    2006-06-01

    Ibuprofen, a nonsteroidal antiinflammatory drug, widely used as antipyretic, antiinflammatory, and analgesic agent and for therapy of arthritis, exerts a dose-dependent constriction of the ductus arteriosus in newborn lambs. Two intravenous preparations, namely ibuprofen lysine and ibuprofen-THAM, have been studied in preterm newborns with patent ductus arteriosus. Clinical trials have compared IV ibuprofen to placebo, or to indomethacin. Pharmacodynamic effects of this drug before and after its administration have also been evaluated. Compared with placebo, IV ibuprofen effectively closed PDA with minimal effect on renal function. One study using intravenous ibuprofen-THAM showed decreased renal function and increased risk of NEC and PPHN. Compared with indomethacin, IV ibuprofen lysine exerted similar efficacy (75% to 93% closure). However, indomethacin increased abnormal renal function and decreased mesenteric and cerebral blood flow and bio-energetics. Two clinical trials showed that ibuprofen did not reduce the incidence of intraventricular hemorrhage compared with placebo. The drug has prolonged elimination (plasma half-life = ca 23 hours), suggesting that once daily dosing is appropriate. Dose finding studies indicate that a starting dose of 10 mg/kg followed by 5 mg/kg/d for 2 more days provides optimal efficacy with the least adverse effects. Neonatal data on ibuprofen and indomethacin indicate that, on the first day of life when IVH prevention is desired, indomethacin and not ibuprofen should be used since ibuprofen has no effect on IVH risk. On or after the second day of postnatal life, when early or therapeutic PDA closure is needed, ibuprofen and not indomethacin is probably the first choice due to its better adverse event profile.

  5. Blood alcohol levels for American Indian mothers and newborns.

    PubMed

    Kvigne, Valborg L; Randall, Brad; Simanton, Edward G; Brenneman, George; Welty, Thomas K

    2012-10-01

    Very little is known about the alcohol elimination rates of newborns who have had chronic alcohol exposure in utero. In these case reports, blood alcohol levels were taken immediately before delivery, at delivery, and postdelivery for 2 mothers who drank alcohol during their pregnancies and 3 single-birth newborns. Newborn A1 of Mother A had no physical characteristics of fetal alcohol syndrome (FAS). The initial blood alcohol level for this newborn was 38.4 mg/dL 129 minutes after birth, with a subsequent blood alcohol level of 5.5 mg/dL 304 minutes after delivery, resulting in an alcohol elimination rate of 11.3 mg/dL per hour. The blood alcohol level for Mother A was 87.4 mg/dL 66 minutes before delivery. Newborn A2 of mother A had FAS. Sixty minutes after delivery, the blood alcohol level for this newborn was 39.5 mg/dL, and the alcohol level of the mother was 42.1 mg/dL. Newborn B1 of mother B had FAS. At 67 minutes after birth, newborn B1 had a blood alcohol level of 246.5 mg/dL, which dropped to 178.7 mg/dL 302 minutes after birth, resulting in an alcohol elimination rate of 17.3 mg/dL per hour. This alcohol elimination rate is within the metabolism range (15-49 mg/dL per hour) of adults with alcoholism. The maternal blood alcohol level was 265.9 mg/dL 27 minutes before delivery. Blood alcohol levels drawn on both the mother and newborn at delivery and 2 or 3 hourly follow-up levels can provide evidence that fetal alcohol dehydrogenase activity is induced by chronic maternal alcohol use.

  6. 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)

  7. 75 FR 21645 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... of newborn screening programs fosters local control and accountability, it also gives rise to wide... about the newborn screening system, the State's policy on the potential use of residual newborn... screening system at that time. (4) All State newborn screening programs should work proactively to...

  8. 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;…

  9. Adult neurogenesis in serotonin transporter deficient mice.

    PubMed

    Schmitt, A; Benninghoff, J; Moessner, R; Rizzi, M; Paizanis, E; Doenitz, C; Gross, S; Hermann, M; Gritti, A; Lanfumey, L; Fritzen, S; Reif, A; Hamon, M; Murphy, D L; Vescovi, A; Lesch, K-P

    2007-09-01

    Serotonin (5-HT) is a regulator of morphogenetic activities during early brain development and neurogenesis, including cell proliferation, migration, differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4) mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice reduces 5-HT clearance resulting in persistently increased concentrations of synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice, including stem cell proliferation, survival, and differentiation. Using an in vivo approach, we showed an increase in proliferative capacity of hippocampal adult neural stem cells in aged 5-HTT knockout mice (approximately 14.5 months) compared to wildtype controls. In contrast, in vivo and additional in vitro analyses of younger adult 5-HTT knockout mice (approximately 7 weeks and approximately 3.0 months) did not reveal significant changes in proliferation of neural stem cells or survival of newborn cells. We showed that the cellular fate of newly generated cells in 5-HTT knockout mice is not different with respect to the total number and percentage of neurons or glial cells from wildtype controls. Our findings indicate that elevated synaptic 5-HT concentration throughout early development and later life of 5-HTT deficient mice does not induce adult neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence stem cell proliferation.

  10. [Functional state feature of erythrocytes in healthy term newborn infants].

    PubMed

    Evsiukova, I I; Iakushenko, N S; Andreeva, A A; Shevel'kova, A A; Kolesova, T A; Katiukhin, L N; Dobrylko, I A; Mandukshev, I V

    2014-01-01

    Hematological parameters and functional status of erythrocytes were studied by the osmotic and ammonium loads in healthy newborns and in adults. Mean erythrocyte volume of newborns more than in adults. Significant difference index of osmotic fragility of neonates were observed in the transition from swelling to hemolysis. Kinetic of erythrocyte's hemolysis in the ammonium load was studied by low-angle light scattering (LaSca-analyzer). The percentage of erythrocyte hemolysis is lower and the velocity of hemolysis is 2.5 times slower in newborns than in adults.

  11. Humerus Diaphysis Fracture in a Newborn during Vaginal Breech Delivery

    PubMed Central

    Kaya, Baris; Daglar, Korkut; Kirbas, Ayse; Tüten, Abdullah

    2015-01-01

    While most obstetricians are familiar with fracture of the clavicle in newborns during birth, an unlucky minority of obstetricians has encountered long-bone fractures in newborns as well. This complication is traumatic not only for the neonate, but also for the family and the obstetrician; it is also difficult to explain. Fortunately, the long-term prognosis for fracture of the long bones is excellent. Both vaginal and cesarean breech deliveries and maneuvers can be responsible for birth traumas, including long-bone fractures. This case report presents a newborn with breech presentation delivered vaginally that resulted in humerus diaphysis fracture. PMID:26770851

  12. 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

  13. [Complex etiology of acute renal failure in a newborn].

    PubMed

    Krzemień, Grazyna; Szmigielska, Agnieszka; Bieroza, Iwona; Roszkowska-Blaim, Maria

    2008-01-01

    Acute renal failure (ARF), which is diagnosed in 3.4-20% of newborns, is polyetiological in most cases. We present a newborn with non-oliguric ARF diagnosed in the first day of life, and caused by asphixia, intrauterine infection (IUI) and nephrotoxic effects of metotrexate treatment during pregnancy. Antibiotics, including netilmicin and vankomycin, were given because of IUI and infected central venous catheter. Dosage of drugs was adjusted to renal failure parameters, but monitoring of their serum levels was not available. It could cause augmented acute tubular necrosis and interstitial nephritis. Analysis of ARF risk factors in newborns helps in early diagnosis of renal damage and in prompt implementation of therapy.

  14. Nutritional support of very low birth weight newborns.

    PubMed

    Ditzenberger, Georgia

    2009-06-01

    Nutritional support to promote optimal postnatal growth for very low birth weight (VLBW) newborns less than 1500 g at birth during the initial prolonged hospitalization is a significant issue. This article reviews the concepts involved in the nutritional support of VLBW newborns, including definitions and discussions of growth, optimal postnatal growth, body composition, initial weight loss, growth expectations, growth assessment tools used during the postnatal period, the relation between inadequate nutrition and neurodevelopment, the relation between protein intake and cognitive outcome, postnatal nutrition balance, the potential for programming of future adult-onset chronic conditions, a review of fetal nutritional intake, and current recommendations for nutritional support of VLBW newborns.

  15. Introduction to resuscitation of the newborn infant. ARC and NZRC Guideline 2010.

    PubMed

    2011-08-01

    • Introduction to Resuscitation of the Newborn Infant. ARC and NZRC Guideline 2010 • Planning for Neonatal Resuscitation and Identification of the Newborn Infant at Risk. ARC and NZRC Guideline 2010 • Assessment of the Newborn Infant. ARC and NZRC Guideline 2010 • Airway Management and Mask Ventilation of the Newborn Infant. ARC and NZRC Guideline 2010 • Tracheal Intubation and Ventilation of the Newborn Infant. ARC and NZRC Guideline 2010 • Chest Compressions during Resuscitation of the Newborn Infant. ARC and NZRC Guideline 2010 • Medication or Fluids for the Resuscitation of the Newborn Infant. ARC and NZRC Guideline 2010 • The Resuscitation of the Newborn Infant in Special Circumstances. ARC and NZRC Guideline 2010 • After the Resuscitation of a Newborn Infant. ARC and NZRC Guideline 2010 • Ethical Issues in Resuscitation of the Newborn Infant. ARC and NZRC Guideline 2010.

  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. Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

    PubMed Central

    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

    2012-01-01

    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. PMID:22896664

  18. Tape Dump and Restore.

    DTIC Science & Technology

    1980-08-28

    VM/ CMS as provided at Virginia Tech and to make it possible to transfer files from this system to other computer systems , possibly machines using the...Technical Memorandum No. 80-5 DTI(-C August 28, 1980 DEC T.77w S DEC23 1980 F ABSTRACT A set of three programs to write CMS disk files on magnetic...tape in a variety of formats suitable for reading on a variety of computing systems and for restoring these tape files to disk within the restrictions

  19. 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 ...

  20. Epidermolysis Bullosa with Hypertrophic Pyloric Stenosis in a Newborn.

    PubMed

    Ben Dhaou, Mahdi; Ammar, Saloua; Louati, Hamdi; Zitouni, Hayet; Jallouli, Mohamed; Mhiri, Riadh

    2015-01-01

    Epidermolysis bullosa (EB) is an inherited blistering disorder characterized by the fragility of the skin and mucous membranes. Extracutaneous manifestations can be associated. We report a unique concomitant occurrence of EB and hypertrophic pyloric stenosis in a newborn.

  1. Epidermolysis Bullosa with Hypertrophic Pyloric Stenosis in a Newborn

    PubMed Central

    Ben Dhaou, Mahdi; Ammar, Saloua; Louati, Hamdi; Zitouni, Hayet; Jallouli, Mohamed; Mhiri, Riadh

    2015-01-01

    Epidermolysis bullosa (EB) is an inherited blistering disorder characterized by the fragility of the skin and mucous membranes. Extracutaneous manifestations can be associated. We report a unique concomitant occurrence of EB and hypertrophic pyloric stenosis in a newborn. PMID:26500857

  2. The Relation Between Audition and Vision in the Human Newborn

    ERIC Educational Resources Information Center

    Mendelson, Morton J.; Haith, Marshall M.

    1976-01-01

    Four studies were conducted to investigate the relation between audition and vision in the human newborn. In all four studies visual activity was recorded with infrared corneal-reflection techniques in 1- to 4-day-old infants. (MS)

  3. Screening for Critical Congenital Heart Disease in Newborns

    MedlinePlus

    ... critical congenital heart disease (CCHD) in newborns. 2 Physiology of Pulse Oximetry Oxygen breathed in through the ... Previous Article Next Article Jump to Article Introduction Physiology of Pulse Oximetry The Ductus Arteriosus in CCHD ...

  4. 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.

  5. Newborn Care: 10 Tips for Stressed-Out Parents

    MedlinePlus

    ... American Academy of Pediatrics Textbook of Pediatric Care. Elk Grove Village, Ill.: American Academy of Pediatrics; 2009: ... Your Newborn: From Birth to Reality. 3rd ed. Elk Grove Village, Ill.: American Academy of Pediatrics; 2015. ...

  6. Crying Baby: What to Do When Your Newborn Cries

    MedlinePlus

    Healthy Lifestyle Infant and toddler health Newborn crying jags are inevitable. Here's help soothing a crying baby — and ... own can help renew your coping strength. Make healthy lifestyle choices. Eat a healthy diet. Include physical activity ...

  7. 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)

  8. Do Newborns Have More Complications When Mom Has Asthma?

    MedlinePlus

    ... Do newborns have more complications when mom has asthma? Published Online: August 5, 2013 Asthma is fairly common in women of reproductive age ... 10% of pregnancies in the US. Mothers with asthma are known to have increased risk of pregnancy ...

  9. Diagnostic challenge of large congenital liver cyst in the newborn.

    PubMed

    Viswanathan, Sreekanth; Kumar, Deepak

    2014-04-01

    Liver cysts in the newborn often pose significant diagnostic challenges. Described herein is a case of large congenital liver cyst that was difficult to diagnose both antenatally and postnatally and which was later diagnosed as Caroli disease.

  10. [Recommendations for the care of healthy newborn infants].

    PubMed

    Figueras Aloy, J; García Alix, A; Alomar Ribes, A; Blanco Bravo, D; Esqué Ruiz, M T; Fernández Lorenzo, J R

    2001-08-01

    This article makes certain recommendations on the care of the healthy newborn. Firstly, we discuss the situations that should be reported to the pediatrician/neonatologist and the reasons why the presence of these specialists is required in the delivery room (urgent or elective cesarean section, preterm labor). Secondly, we discuss the most important guidelines to follow in the delivery room and after birth. Concerning care in the delivery room, we stress the importance of care of the newborn (especially of the umbilical cord), bonding between the mother and child, identification of the newborn, assessment of neonatal adaptation to extrauterine life, prevention of ophthalmia neonatorum and hypoprothrombinemia, placing the baby correctly in the crib and hepatitis B prophylaxis. Concerning the postnatal period, we recommend feeding (promotion of breast feeding), rooming-in with the mother if the newborn is hospitalized in the nursery screening for hypoacousia and metabolic diseases, and discharge with special surveillance in cases of early discharge.

  11. Disorders of vitamin B12 metabolism presenting through newborn screening.

    PubMed

    Fletcher, Janice

    2008-12-01

    Elevated propionyl C3 carnitine is the most common abnormality seen in tandem mass spectrometry newborn screening profiles, with an incidence of 0.15% seen in our South Australian newborn screening programme. The most common cause for this result in our population is vitamin B12 deficiency but differential diagnoses include the inherited disorders of propionic and methylmalonic acid metabolism and cobalamin deficiencies. An approach to confirmatory testing and subsequent management of infants with elevated propionic carnitine is presented.

  12. Management of neonatal abstinence syndrome in the newborn nursery.

    PubMed

    Artigas, Valarie

    2014-12-01

    Maternal drug use and neonatal abstinence syndrome (NAS) are being seen across the United States. NAS occurs with withdrawal disturbances in response to the cessation of the pregnancy exposure. The clinical presentation of a newborn with NAS can include gastrointestinal, neurologic, vasomotor and respiratory symptoms. Assessment of newborns with NAS can often present as a challenge to maternal-child nurses. Treatment can include supportive care as well as pharmacologic therapies.

  13. A Survey of Newborn Intensive Care Centers in California

    PubMed Central

    Hawes, Warren E.

    1975-01-01

    Newborn intensive care has come of age in California. Twenty-one newborn intensive care centers and 11 community level units are now approved by Crippled Children Services in California. In 1973 there were more than 6,863 patients admitted to the 20 centers surveyed, over half requiring transport from referring hospitals. This paper provides information on the distribution, admission and occupancy rates, length of stay, costs and admission diagnoses for these high risk infants. PMID:1154794

  14. 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.

  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. Intestinal apolipoprotein synthesis in the newborn piglet.

    PubMed

    Black, D D; Rohwer-Nutter, P L

    1991-01-01

    To determine the effects of dietary and biliary lipid absorption on intestinal apo B-48 and apo A-I synthesis in the newborn piglet, 2-d-old female piglets were prepared with a duodenal infusion catheter. After recovery, animals were given either low triglyceride (Vivonex; VIV group) or high triglyceride (Intralipid; FAT group) diets by continuous intraduodenal infusion for 24 h. A bile-diverted group was also studied. Segments of proximal jejunum and distal ileum were then pulse-radiolabeled in vivo with 3H-leucine. Mucosal apo B-48 and apo A-I were immunoprecipitated, and apoprotein synthesis was expressed as percentage of total protein synthesis. Mucosal apoprotein content (ng apoprotein/microgram total protein) was measured by competitive ELISA assays. In jejunum and ileum, apo B-48 synthesis was not different in the three groups. However, apo B content increased 2.4-fold in jejunum and 1.7-fold in ileum in the FAT group compared with the VIV group. Immunoblotting revealed the majority of jejunal apo B to be apo B-48, not apo B-100 from contaminating plasma lipoproteins, in all three experimental groups. Bile-diverted animals had decreased jejunal apo B content compared with the VIV group. Jejunal apo A-I synthesis and content were approximately 2-fold higher in FAT animals compared with the VIV group. Although ileal apo A-I synthesis was also 2-fold higher in the FAT group, apo A-I content was not different from the VIV group. Neither jejunal nor ileal apo A-I synthesis was significantly affected by bile diversion, even though jejunal apo A-I content was decreased by over two thirds compared with the VIV animals. In the newborn piglet, intestinal synthesis of apo B-48 and apo A-I is differentially regulated by luminal lipid absorption. Although fat feeding and bile diversion regulate mucosal apo B-48 content, synthesis is unchanged, indicating a posttranslational regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Immediate newborn care practices delay thermoregulation and breastfeeding initiation

    PubMed Central

    Sobel, Howard L; Silvestre, Maria Asuncion A; Mantaring, Jacinto Blas V; Oliveros, Yolanda E; Nyunt-U, Soe

    2011-01-01

    Aim A deadly nosocomial outbreak in a Philippine hospital drew nationwide attention to neonatal sepsis. Together with specific infection control measures, interventions that protect newborns against infection-related mortality include drying, skin-to-skin contact, delayed cord clamping, breastfeeding initiation and delayed bathing. This evaluation characterized hospital care in the first hours of life with the intent to drive policy change, strategic planning and hospital reform. Methods Trained physicians observed 481 consecutive deliveries in 51 hospitals using a standardized tool to record practices and timing of immediate newborn care procedures. Results Drying, weighing, eye care and vitamin K injections were performed in more than 90% of newborns. Only 9.6% were allowed skin-to-skin contact. Interventions were inappropriately sequenced, e.g. immediate cord clamping (median 12 sec), delayed drying (96.5%) and early bathing (90.0%). While 68.2% were put to the breast, they were separated two minutes later. Unnecessary suctioning was performed in 94.9%. Doctors trained in neonatal resuscitation were 2.5 (1.1–5.7) times more likely to unnecessarily suction vigorous newborns. Two per cent died and 5.7% developed sepsis/pneumonia. Conclusions This minute-by-minute observational assessment revealed that performance and timing of immediate newborn care interventions are below WHO standards and deprive newborns of basic protections against infection and death. PMID:21375583

  18. Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke

    PubMed Central

    Zhang, Wenting; Wang, Hailian; Zhang, Hui; Leak, Rehana K.; Shi, Yejie; Hu, Xiaoming; Gao, Yanqin; Chen, Jun

    2015-01-01

    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 35 days 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 to not only protect against ischemic injury for the long term but also to actively promote neurovascular restorative dynamics and brain repair. PMID:25771800

  19. Magistral drugs in hospitalized newborns and children

    PubMed Central

    Pereira, Agueda Cabral de Souza; Miranda, Elaine Silva; de Castilho, Selma Rodrigues; Futuro, Débora Omena; Teixeira, Lenise Arneiro; de Paula, Geraldo Renato

    2016-01-01

    Abstract Objective: Study the use of magistral oral solutions and suspensions in infants and children at a university hospital. Methods: This is a descriptive study based on the analysis of the assessed hospital's magistral drug request forms regarding the patients in the neonatal ICU, Obstetrics, Pediatrics and Pediatric Emergency from January 2012 to December 2013. The frequency of drug requests and dispensation was evaluated and the consumption of each active ingredient of the preparations was expressed as number of “infant defined daily dose” (iDDD) and of iDDD/100 bed-days. Results: A total of 657 forms were analyzed - a monthly average of 27 pediatric preparations. The neonatal ICU accounted for 69.6% of these requests. Twenty-one drug items were used, of which the most common were folinic acid (88 requests), sulfadiazine (85) and captopril (73). The consumption of the active principle in these preparations varied in number of iDDD, from 7.5 (hydralazine) to 16,520.0 (folic acid), and in number of iDDD/100 bed-days in the neonatal ICU, from 0.1 (zinc sulfate) to 146.1 (folic acid). Conclusions: The constant consumption of magistral oral solutions and suspensions by newborns and children of the assessed hospital indicates the need for such preparations as a pediatric therapeutic alternative in this hospital. PMID:27131897

  20. Different Viewpoints: International Perspectives on Newborn Screening

    PubMed Central

    Pollitt, Rodney J

    2015-01-01

    Summary Newborn blood-spot screening to detect potentially treatable disorders is widely practiced across the globe. However, there are great variations in practice, both in terms of disorders covered, screening technologies, disease definition, information provision, parental informed consent, and storage and disposal of residual specimens, partly reflecting the degree to which screening is the subject of explicit legislation (and thus public and media pressure) or is embedded in a general health care system and managed at an executive level. It is generally accepted that disorders to be screened for should comply with the ten Wilson and Jungner criteria, but the way that compliance is assessed ranges from broadly-based opinion surveys to detailed analysis of quantitative data. Consequently, even countries with comparable levels of economic development and health care show large differences in the number of disorders screened for. There are several areas on which there are no generally accepted guidelines: how should parents be informed about screening and to what extent should they be encouraged to regard screening as an option to choose to refuse? Is DNA mutation analysis acceptable as part of a screening protocol? How soon should the blood samples be destroyed once screening has been completed? As technology advances and the potential scope of screening expands at both the metabolite and genome level, challenging policy issues will have to be faced. PMID:28356819