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Sample records for normal adult mice

  1. Lepidium meyenii (Maca increases litter size in normal adult female mice

    Directory of Open Access Journals (Sweden)

    Gasco Manuel

    2005-05-01

    Full Text Available Abstract Background Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Methods Adult female Balb/C mice were divided at random into three main groups: i Reproductive indexes group, ii Implantation sites group and iii Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Results Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Conclusion Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to

  2. Development of intraepithelial T lymphocytes in the intestine of irradiated SCID mice by adult liver hematopoietic stem cells from normal mice

    International Nuclear Information System (INIS)

    Yamagiwa, Satoshi; Seki, Shuhji; Shirai, Katsuaki; Yoshida, Yuhei; Miyaji, Chikako; Watanabe, Hisami; Abo, Toru

    1999-01-01

    Background/Aims: We recently reported the adult mouse liver to contain c-kit + stem cells that can give rise to multilineage leukocytes. This study was designed to determine whether or not adult mouse liver stem cells can generate intraepithelial T cells in the intestine as well as to examine the possibility that adult liver c-kit + stem cells originate from the fetal liver. Methods: Adult liver mononuclear cells, bone marrow (BM) cells, liver c-kit + cells or bone BM c-kit + cells of BALB/c mice were i.v. transferred into 4 Gy irradiated CB17/-SCID mice. In other experiments, fetal liver cells from Ly5.1 C57BL/6 mice and T cell depleted adult BM cells from Ly5.2 C57BL/6 mice were simultaneously transferred into irradiated C57BL/6 SCID mice (Ly5.2). At 1 to 8 weeks after cell transfer, the SCID mice were examined. Results: Not only BM cells and BM c-kit + cells but also liver mononuclear cells and liver c-kit + cells reconstituted γδT cells, CD4 + CD8 + double-positive T cells and CDiα + β - T cells of intestinal intraepithelial lymphocytes of SCID mice. Injection of a mixture of fetal liver cells from Ly5.1 C57BL/6 mice and adult BM cells from Ly5.2 C57BL/6 mice into Ly5.2 C57BL/6 SCID mice induced both Ly5.1 and Ly5.2 T cells, while also generating c-kit + cells of both Ly5.1 and Ly5.2 origins in the liver. Conclusions: Adult mouse liver stem cells were able to generate intestinal intraepithelial T cells of the SCID mice, and it is thus suggested that some adult liver stem cells may indeed be derived from the fetal liver. (au)

  3. Neurokinin B is critical for normal timing of sexual maturation but dispensable for adult reproductive function in female mice.

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    True, Cadence; Nasrin Alam, Sayeda; Cox, Kimberly; Chan, Yee-Ming; Seminara, Stephanie B

    2015-04-01

    Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of pubertal development than adult reproductive function. NKB receptor-deficient mice are hypogonadotropic but have no defects in the timing of sexual maturation. The current study has performed the first phenotypic evaluation of mice bearing mutations in Tac2, the gene encoding the NKB ligand, to determine whether they have impaired sexual development similar to their human counterparts. Male Tac2-/- mice showed no difference in the timing of sexual maturation or fertility compared with wild-type littermates and were fertile. In contrast, Tac2-/- females had profound delays in sexual maturation, with time to vaginal opening and first estrus occurring significantly later than controls, and initial abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2-/- females were fertile, although they produced fewer pups per litter. Thus, female Tac2-/- mice parallel humans harboring NKB pathway mutations, with delayed sexual maturation and activation of the reproductive cascade later in life. Moreover, direct comparison of NKB ligand and receptor-deficient females confirmed that only NKB ligand-deficient animals have delayed sexual maturation, suggesting that in the absence of the NKB receptor, NKB may regulate the timing of sexual maturation through other tachykinin receptors.

  4. Normal Conducting RF Cavity for MICE

    International Nuclear Information System (INIS)

    Li, D.; DeMello, A.; Virostek, S.; Zisman, M.; Summers, D.

    2010-01-01

    Normal conducting RF cavities must be used for the cooling section of the international Muon Ionization Cooling Experiment (MICE), currently under construction at Rutherford Appleton Laboratory (RAL) in the UK. Eight 201-MHz cavities are needed for the MICE cooling section; fabrication of the first five cavities is complete. We report the cavity fabrication status including cavity design, fabrication techniques and preliminary low power RF measurements.

  5. Mast cell distribution in normal adult skin

    NARCIS (Netherlands)

    A.S. Janssens (Artiena Soe); R. Heide (Rogier); J.C. den Hollander (Jan); P.G.M. Mulder (P. G M); B. Tank (Bhupendra); A.P. Oranje (Arnold)

    2005-01-01

    markdownabstract__AIMS:__ To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. __METHODS:__ Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults.

  6. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  7. Mast cell distribution in normal adult skin.

    Science.gov (United States)

    Janssens, A S; Heide, R; den Hollander, J C; Mulder, P G M; Tank, B; Oranje, A P

    2005-03-01

    To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

  8. [Quantification of acetabular coverage in normal adult].

    Science.gov (United States)

    Lin, R M; Yang, C Y; Yu, C Y; Yang, C R; Chang, G L; Chou, Y L

    1991-03-01

    Quantification of acetabular coverage is important and can be expressed by superimposition of cartilage tracings on the maximum cross-sectional area of the femoral head. A practical Autolisp program on PC AutoCAD has been developed by us to quantify the acetabular coverage through numerical expression of the images of computed tomography. Thirty adults (60 hips) with normal center-edge angle and acetabular index in plain X ray were randomly selected for serial drops. These slices were prepared with a fixed coordination and in continuous sections of 5 mm in thickness. The contours of the cartilage of each section were digitized into a PC computer and processed by AutoCAD programs to quantify and characterize the acetabular coverage of normal and dysplastic adult hips. We found that a total coverage ratio of greater than 80%, an anterior coverage ratio of greater than 75% and a posterior coverage ratio of greater than 80% can be categorized in a normal group. Polar edge distance is a good indicator for the evaluation of preoperative and postoperative coverage conditions. For standardization and evaluation of acetabular coverage, the most suitable parameters are the total coverage ratio, anterior coverage ratio, posterior coverage ratio and polar edge distance. However, medial coverage and lateral coverage ratios are indispensable in cases of dysplastic hip because variations between them are so great that acetabuloplasty may be impossible. This program can also be used to classify precisely the type of dysplastic hip.

  9. Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.

    Science.gov (United States)

    Maier, Jennifer A; Harfe, Brian D

    2011-11-15

    The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles. To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi. Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice. Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.

  10. Body surface area prediction in normal, hypermuscular, and obese mice.

    Science.gov (United States)

    Cheung, Michael C; Spalding, Paul B; Gutierrez, Juan C; Balkan, Wayne; Namias, Nicholas; Koniaris, Leonidas G; Zimmers, Teresa A

    2009-05-15

    Accurate determination of body surface area (BSA) in experimental animals is essential for modeling effects of burn injury or drug metabolism. Two-dimensional surface area is related to three-dimensional body volume, which in turn can be estimated from body mass. The Meeh equation relates body surface area to the two-thirds power of body mass, through a constant, k, which must be determined empirically by species and size. We found older values of k overestimated BSA in certain mice; thus we determined empirically k for various strains of normal, obese, and hypermuscular mice. BSA was computed from digitally scanned pelts and nonlinear regression analysis was used to determine the best-fit k. The empirically determined k for C57BL/6J mice of 9.82 was not significantly different from other inbred and outbred mouse strains of normal body composition. However, mean k of the nearly spheroid, obese lepr(db/db) mice (k = 8.29) was significantly lower than for normals, as were values for dumbbell-shaped, hypermuscular mice with either targeted deletion of the myostatin gene (Mstn) (k = 8.48) or with skeletal muscle specific expression of a dominant negative myostatin receptor (Acvr2b) (k = 8.80). Hypermuscular and obese mice differ substantially from normals in shape and density, resulting in considerably altered k values. This suggests Meeh constants should be determined empirically for animals of altered body composition. Use of these new, improved Meeh constants will allow greater accuracy in experimental models of burn injury and pharmacokinetics.

  11. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  12. Protein Degradation in Normal and Beige (Chediak-Higashi) Mice

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    Lyons, Robert T.; Pitot, Henry C.

    1978-01-01

    The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [14C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting 125I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of 125I-bovine serum albumin (t½ = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t½ = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t½ = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [3H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed. PMID:202611

  13. Diffraction enhanced imaging of normal and arthritic mice feet

    International Nuclear Information System (INIS)

    Crittell, Suzanne; Cheung, K.C.; Hall, Chris; Ibison, Mark; Nolan, Paul; Page, Robert; Scraggs, David; Wilkinson, Steve

    2007-01-01

    The aim of this experiment was to produce X-ray images of mice feet using the diffraction-enhanced imaging (DEI) system at the UK Synchrotron Radiation Source (SRS) at Daresbury. There were two broad types of mice feet samples studied: normal and arthritic. The two types of samples were imaged using several views and compared in order to determine whether it would be possible to detect the early morphological changes linked with this form of arthritis. We found that the DEI images produced were indeed of sufficient quality to show the presence of some osteoarthritic changes

  14. Core temperature rhythms in normal and tumor-bearing mice.

    Science.gov (United States)

    Griffith, D J; Busot, J C; Lee, W E; Djeu, D J

    1993-01-01

    The core temperature temporal behavior of DBA/2 mice (11 normal and 13 with an ascites tumor) was studied using surgically implanted radio telemetry transmitters. Normal mice continuously displayed a stable 24 hour temperature rhythm. Tumor-bearers displayed a progressive deterioration of the temperature rhythm following inoculation with tumor cells. While such disruptions have been noted by others, details on the dynamics of the changes have been mostly qualitative, often due to time-averaging or steady-state analysis of the data. The present study attempts to quantify the dynamics of the disruption of temperature rhythm (when present) by continuously monitoring temperatures over periods up to a month. Analysis indicated that temperature regulation in tumor-bearers was adversely affected during the active period only. Furthermore, it appears that the malignancy may be influencing temperature regulation via pathways not directly attributable to the energy needs of the growing tumor.

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  16. Lyplal1 is dispensable for normal fat deposition in mice

    Directory of Open Access Journals (Sweden)

    Rachel A. Watson

    2017-12-01

    Full Text Available Genome-wide association studies (GWAS have detected association between variants in or near the Lysophospholipase-like 1 (LYPLAL1 locus and metabolic traits, including central obesity, fatty liver and waist-to-hip ratio. LYPLAL1 is also known to be upregulated in the adipose tissue of obese patients. However, the physiological role of LYPLAL1 is not understood. To investigate the function of Lyplal1 in vivo we investigated the phenotype of the Lyplal1tm1a(KOMPWtsi homozygous mouse. Body composition was unaltered in Lyplal1 knockout mice as assessed by dual-energy X-ray absorptiometry (DEXA scanning, both on normal chow and on a high-fat diet. Adipose tissue distribution between visceral and subcutaneous fat depots was unaltered, with no change in adipocyte cell size. The response to both insulin and glucose dosing was normal in Lyplal1tm1a(KOMPWtsi homozygous mice, with normal fasting blood glucose concentrations. RNAseq analysis of liver, muscle and adipose tissue confirmed that Lyplal1 expression was ablated with minimal additional changes in gene expression. These results suggest that Lyplal1 is dispensable for normal mouse metabolic physiology and that despite having been maintained through evolution Lyplal1 is not an essential gene, suggesting possible functional redundancy. Further studies will be required to clarify its physiological role.

  17. The normal acid-base status of mice.

    Science.gov (United States)

    Iversen, Nina K; Malte, Hans; Baatrup, Erik; Wang, Tobias

    2012-03-15

    Rodent models are commonly used for various physiological studies including acid-base regulation. Despite the widespread use of especially genetic modified mice, little attention have been made to characterise the normal acid-base status in these animals in order to reveal proper control values. Furthermore, several studies report blood gas values obtained in anaesthetised animals. We, therefore, decided to characterise blood CO(2) binding characteristic of mouse blood in vitro and to characterise normal acid-base status in conscious BALBc mice. In vitro CO(2) dissociation curves, performed on whole blood equilibrated to various PCO₂ levels in rotating tonometers, revealed a typical mammalian pK' (pK'=7.816-0.234 × pH (r=0.34)) and a non-bicarbonate buffer capacity (16.1 ± 2.6 slyke). To measure arterial acid-base status, small blood samples were taken from undisturbed mice with indwelling catheters in the carotid artery. In these animals, pH was 7.391 ± 0.026, plasma [HCO(3)(-)] 18.4 ± 0.83 mM, PCO₂ 30.3 ± 2.1 mm Hg and lactate concentration 4.6 ± 0.7 mM. Our study, therefore, shows that mice have an arterial pH that resembles other mammals, although arterial PCO₂ tends to be lower than in larger mammals. However, pH from arterial blood sampled from mice anaesthetised with isoflurane was significantly lower (pH 7.239 ± 0.021), while plasma [HCO(3)(-)] was 18.5 ± 1.4 mM, PCO₂ 41.9 ± 2.9 mm Hg and lactate concentration 4.48 ± 0.67 mM. Furthermore, we measured metabolism and ventilation (V(E)) in order to determine the ventilation requirements (VE/VO₂) to answer whether small mammals tend to hyperventilate. We recommend, therefore, that studies on acid-base regulation in mice should be based on samples taken for indwelling catheters rather than cardiac puncture of terminally anaesthetised mice. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Myogenin regulates exercise capacity but is dispensable for skeletal muscle regeneration in adult mdx mice.

    Directory of Open Access Journals (Sweden)

    Eric Meadows

    Full Text Available Duchenne muscular dystrophy (DMD is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myog(flox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myog(flox/flox mice (mdx, Myog(flox/flox mice (wild-type, and mdx:Myog(floxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted. mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  20. Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice.

    Science.gov (United States)

    Ojewole, J A O; Adewunmi, C O

    2003-01-01

    Diabetes mellitus is a debilitating hormonal disorder in which strict glycemic control and prevention of associated complications are of crucial importance. This study was designed to evaluate the hypoglycemic effect of methanolic extract of mature, green fruits of Musa paradisiaca (MEMP) in normal (normoglycemic) and streptozotocin (STZ)-treated, diabetic (hyperglycemic) mice, using chlorpropamide as the reference antidiabetic agent. MEMP (100-800 mg/kg p.o.) induced significant, dose-related (p < 0.05-0.001) reductions in the blood glucose concentrations of both normal and diabetic mice. Chlorpropamide (250 mg/kg p.o.) also produced significant (p < 0.01-0.001) reductions in the blood glucose concentrations of normal and diabetic mice. The results of this experimental study indicate that, in the mammalian model used, MEMP possesses hypoglycemic activity. Although the precise mechanism of the hypoglycemic action of MEMP is still unclear and will have to await further studies, it could be due, at least in part, to stimulation of insulin production and subsequent glucose utilization. Nevertheless, the findings of this experimental animal study indicate that MEMP possesses hypoglycemic activity, and thus lends credence to the suggested folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetic mellitus among the Yoruba-speaking people of South-Western Nigeria.

  1. Ratio of organs to blood of mercury during its uptake by normal and acatalasemic mice

    International Nuclear Information System (INIS)

    Ogata, M.; Aikoh, H.

    1987-01-01

    The brain/blood, liver/blood, and heart/blood ratios of acatalasemic mice after intraperitoneal injection of labelled metallic mercury or after exposure to labelled metallic mercury vapor were significantly higher than those of normal mice. These ratios of normal or acatalasemic mice after injection with metallic mercury or exposure to metallic mercury vapor were significantly higher than those of normal and acatalasemic mice injected with mercuric ion. The amount of metallic mercury exhaled from acatalasemic mice injected with metallic mercury was greater than that from normal mice, indicating that the level of metallic mercury in blood of the former was higher than that of the latter. Actually, metallic mercury in the blood of acatalasemic mice injected with metallic mercury is higher than that in the blood of normal mice, suggesting that metallic mercury is easily transferred from blood to brain, liver, kidney, and heart

  2. Normal function of immunologic stem cells from aged mice

    International Nuclear Information System (INIS)

    Harrison, D.E.; Doubleday, J.W.

    1975-01-01

    Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

  3. Normal isometric strength of rotator cuff muscles in adults

    OpenAIRE

    Chezar, A.; Berkovitch, Y.; Haddad, M.; Keren, Y.; Soudry, M.; Rosenberg, N.

    2013-01-01

    Objectives The most prevalent disorders of the shoulder are related to the muscles of rotator cuff. In order to develop a mechanical method for the evaluation of the rotator cuff muscles, we created a database of isometric force generation by the rotator cuff muscles in normal adult population. We hypothesised the existence of variations according to age, gender and dominancy of limb. Methods A total of 400 healthy adult volunteers were tested, classified into groups of 50 men and women for e...

  4. The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

    OpenAIRE

    Berger, Katja; Schulte, Kevin; Boor, Peter; Kuppe, Christoph; van Kuppevelt, Toin H.; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J.

    2014-01-01

    Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman’s capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glo...

  5. The regenerative potential of parietal epithelial cells in adult mice

    NARCIS (Netherlands)

    Berger, K.; Schulte, K.; Boor, P.; Kuppe, C.; Kuppevelt, T.H. van; Floege, J.; Smeets, B.; Moeller, M.J.

    2014-01-01

    Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically

  6. Radiologic study of patellofemoral congruence in normal adults

    International Nuclear Information System (INIS)

    Diedrichs, L.C.

    1986-01-01

    In order to establish the normal position of the patella, in relation to the intercondilar sulcus, we have evaluated 72 adults patients, making use of the FICAT view in axial radiographys at 30 0 : a simple and accurate technique adopted to measure the congrunce angle in the detection of sub-luxation of the patella. The value of +9 0 was used as the normal pattern for the maximal lateral position of the patella in the intercondilar sulcus. (Author) [pt

  7. SEC23B is required for pancreatic acinar cell function in adult mice

    Science.gov (United States)

    Khoriaty, Rami; Vogel, Nancy; Hoenerhoff, Mark J.; Sans, M. Dolors; Zhu, Guojing; Everett, Lesley; Nelson, Bradley; Durairaj, Haritha; McKnight, Brooke; Zhang, Bin; Ernst, Stephen A.; Ginsburg, David; Williams, John A.

    2017-01-01

    Mice with germline absence of SEC23B die perinatally, exhibiting massive pancreatic degeneration. We generated mice with tamoxifen-inducible, pancreatic acinar cell–specific Sec23b deletion. Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in decreased overall pancreatic weights from pancreatic cell loss (decreased pancreatic DNA, RNA, and total protein content), as well as degeneration of exocrine cells, decreased zymogen granules, and alterations in the endoplasmic reticulum (ER), ranging from vesicular ER to markedly expanded cisternae with accumulation of moderate-density content or intracisternal granules. Acinar Sec23b deletion results in induction of ER stress and increased apoptosis in the pancreas, potentially explaining the loss of pancreatic cells and decreased pancreatic weight. These findings demonstrate that SEC23B is required for normal function of pancreatic acinar cells in adult mice. PMID:28539403

  8. Study of trace element metabolism in normal and cancerous mice using multitracer technique

    International Nuclear Information System (INIS)

    Wang Xiao; Kong Fuquan; Zhao Kui; Zhang Xiang; Qin Zhi

    2008-01-01

    A radioactive multitracer solution of the 24 elements, e.g. Be, Na, K, Rb, Mg, Ca, Sr, Ga, As, Sc, V, Cr, Mn, Co, Fe, Zn, Y, Zr, Mo, Nb, To, Ru, Ag and In, was obtained from the nuclear reaction of 25 MeV/u 40 Ar + Se with a series of chemical process. The multitracer solution was orally administered to normal and muscular turnout-bearing mice of male Balb/c mice. Urine and faeces samples of mice were collected. The two group mice were saerificed after 96 h. The uptake of 17 elements, Na, Rb, Ga, As, Sc, V, Cr, Mn, Co, Fe, Zn, Y, Zr, Tc, Ru, Ag and In, were simultaneously detected in normal mice while 15 elements, Na, Rb, Ga, Sc, V, Cr, Mn, Co, Fe, Y, Zr, Tc, Ru, Ag and In, were simultaneously detected in tumour-bearing mice. Our results indicate that the majority of the detected elements were distributed in liver, kidney, pelt, turnout while a small fraction of the biotrace elements were distributed in heart and spleen. (tumour-bearing mice) in the two groups of mice. The higher concentrations of Fe, Na, Mn were detected in heart or kidney of normal mice. Na, Mn, Fe and Co showed better absorption in most tissues in the normal mice, except for Na and Mn in heart. (authors)

  9. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Carl Johan Drott

    Full Text Available Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1, that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.

  10. Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

    Directory of Open Access Journals (Sweden)

    Charlton HM

    2003-02-01

    Full Text Available Abstract During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI, 17β-hydroxysteroid dehydrogenase type III (17βHSD III, prostaglandin D (PGD-synthetase and oestrogen sulphotransferase (EST is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH.

  11. Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

    Directory of Open Access Journals (Sweden)

    Xiaoli Zhang

    Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

  12. Normal CT characteristics of the thymus in adults

    Energy Technology Data Exchange (ETDEWEB)

    Simanovsky, Natalia, E-mail: natalias@hadassah.org.il [Department of Medical Imaging, Hadassah - Hebrew University Medical Center, Jerusalem (Israel); Hiller, Nurith; Loubashevsky, Natali; Rozovsky, Katya [Department of Medical Imaging, Hadassah - Hebrew University Medical Center, Jerusalem (Israel)

    2012-11-15

    Background: The thymus changes with age. Its shape and the proportion of solid tissue and fat vary between individuals, yet there is no comprehensive work describing the size and morphology of the normal thymus on CT. As a result, many adults with some preserved soft tissue in the thymus may undergo extensive work-up to exclude mediastinal tumor. Our aim was to quantify CT characteristics of the normal thymus in an adult population. Methods: CT chest scans of 194 trauma patients aged 14-78 years (mean 52.6 years), were retrospectively reviewed. The density, volume, shape and predominant side of the thymus were recorded for 56 patients in whom some solid tissue was preserved. Statistical analysis of these characteristics according to the patient age and gender was performed. Results: Thymic density and volume decreased progressively with age. No solid tissue component was seen in the thymus in patients older than 54 years. In the majority of patients, the thymus had an arrowhead shape, with middle position. However, great variability in thymic shape and border were noted. There was a highly significant relationship between density and patient age (p < 0.0001). Conclusion: We hope that our work will help in the definition of normal thymic CT parameters in adults, help to prevent unnecessary and expensive imaging procedures, and reduce patient exposure to ionizing radiation.

  13. Normal CT characteristics of the thymus in adults

    International Nuclear Information System (INIS)

    Simanovsky, Natalia; Hiller, Nurith; Loubashevsky, Natali; Rozovsky, Katya

    2012-01-01

    Background: The thymus changes with age. Its shape and the proportion of solid tissue and fat vary between individuals, yet there is no comprehensive work describing the size and morphology of the normal thymus on CT. As a result, many adults with some preserved soft tissue in the thymus may undergo extensive work-up to exclude mediastinal tumor. Our aim was to quantify CT characteristics of the normal thymus in an adult population. Methods: CT chest scans of 194 trauma patients aged 14–78 years (mean 52.6 years), were retrospectively reviewed. The density, volume, shape and predominant side of the thymus were recorded for 56 patients in whom some solid tissue was preserved. Statistical analysis of these characteristics according to the patient age and gender was performed. Results: Thymic density and volume decreased progressively with age. No solid tissue component was seen in the thymus in patients older than 54 years. In the majority of patients, the thymus had an arrowhead shape, with middle position. However, great variability in thymic shape and border were noted. There was a highly significant relationship between density and patient age (p < 0.0001). Conclusion: We hope that our work will help in the definition of normal thymic CT parameters in adults, help to prevent unnecessary and expensive imaging procedures, and reduce patient exposure to ionizing radiation.

  14. Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

    Science.gov (United States)

    Tan, Siang-Yang

    1986-01-01

    Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

  15. The regenerative potential of parietal epithelial cells in adult mice.

    Science.gov (United States)

    Berger, Katja; Schulte, Kevin; Boor, Peter; Kuppe, Christoph; van Kuppevelt, Toin H; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J

    2014-04-01

    Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glomerular hypertrophy was induced by progressive partial nephrectomies. Again, no significant podocyte replenishment was observed. Rather, labeled PECs exclusively invaded segments of the tuft affected by glomerulosclerosis, consistent with our previous findings. We next reassessed PEC recruitment in juvenile mice using a different reporter mouse and confirmed significant recruitment of labeled PECs onto the glomerular tuft. Moreover, some labeled cells on Bowman's capsule expressed podocyte markers, and cells on Bowman's capsule were also directly labeled in juvenile podocyte-specific Pod-rtTA transgenic mice. In 6-week-old mice, however, cells on Bowman's capsule no longer expressed podocyte-specific markers. Similarly, in human kidneys, some cells on Bowman's capsule expressed the podocyte marker synaptopodin from 2 weeks to 2 years of age but not at 7 years of age. In summary, podocyte regeneration from PECs could not be detected in aging mice or models of glomerular hypertrophy. We propose that a small fraction of committed podocytes reside on Bowman's capsule close to the vascular stalk and are recruited onto the glomerular tuft during infancy to adolescence in mice and humans.

  16. Safety of disclosing amyloid status in cognitively normal older adults.

    Science.gov (United States)

    Burns, Jeffrey M; Johnson, David K; Liebmann, Edward P; Bothwell, Rebecca J; Morris, Jill K; Vidoni, Eric D

    2017-09-01

    Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid). There was no difference in depressive symptoms across groups over time. There was a significant group by time interaction in anxiety, although post hoc analyses revealed no group differences at any time point, suggesting a minimal nonsustained increase in anxiety symptoms immediately postdisclosure in the elevated group. Slight but measureable increases in test-related distress were present after disclosure and were related to greater baseline levels of anxiety and depression. Disclosing amyloid imaging results to cognitively normal adults in the clinical research setting with pre- and postdisclosure counseling has a low risk of psychological harm. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  17. Kinetics of small lymphocytes in normal and nude mice after splenectomy

    DEFF Research Database (Denmark)

    Hougen, H P; Hansen, F; Jensen, E K

    1977-01-01

    Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed...... thymic activity and diminished numbers of T lymphocytes in peripheral lymphoid tissues. The total number of cells in these tissues as well as the blast cell activity, were within normal limits. Bone marrow lymphocyte numbers and kinetics as well as blood lymphocyte levels in splenectomized and sham......-splenectomized normal animals were comparable. Blood lymphocyte numbers were at normal levels in splenectomized nude mice, in spite of reduced numbers of bone marrow and thoracic duct lymphocytes. It is suggested that increased number of newly-formed lymphocytes, found in lymph nodes and blood of splenectomized mice...

  18. Effect of hormone treatment on spontaneous and radiation-induced chromosomal breakage in normal and dwarf mice

    International Nuclear Information System (INIS)

    Buul, P.P.W. van; Buul-Offers, S. van

    1982-01-01

    Treatment of dwarf mice with growth hormone, insulin and testosterone had no effect on the spontaneous frequencies of micronuclei (MN) in bone-marrow cells, whereas thyroxine decreased these frequencies. The induction of MN by X-rays and mitomycin C was significantly lower in dwarf mice than in normal mice. Treatment with thyroxine plus growth hormone restored normal radiosensitivity in dwarfs. (orig.)

  19. Residual haematopoietic damage in adult and 8 day-old mice exposed to 7 Gy of x-rays

    International Nuclear Information System (INIS)

    Grande, T.; Bueren, J.A.; Gaitan, S.; Tejero, C.

    1993-01-01

    The authors' experiments have focused on the analysis of residual haematopoietic damage in 8-day-old and 12-week-old mice X-irradiated with a single dose of 7 Gy. In the case of adult mice, analysis of femoral and splenic CFU-S, CFU-GM and BFU-E showed a persistent depletion of these haematopoietic progenitor cells after irradiation. In contrast, in 1-week-old irradiated mice, a progressive recovery of the femoral haematopoietic progenitors was observed, achieving essentially normal values 1 year after irradiation. The spleens of these mice, however, contained significantly less haematopoietic progenitors than the control group, mainly as a consequence of the size reduction of this organ. In the peripheral blood, normal cellularity values were observed in most cases, although in the adult group a decline in numbers or circulating cells was noted after the first year following irradiation. (author)

  20. The acyl-CoA binding protein is required for normal epidermal barrier function in mice

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Bek, Signe; Marcher, Ann-Britt

    2012-01-01

    (+/+) and ACBP(-/-) mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP(-/-) mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC......The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling...... with age. Morphology and development of skin and appendages are normal in ACBP(-/-) mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP...

  1. Sonographic Measurement of Normal Splenic Length in Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sang Bum; Cheon, Byung Kook; Kim, Jong Min; Oh, Kyung Seoung; Jung, Gyoo Sik; Huh, Jin Do; Joh, Young Duk [Kosin University College of Medicine, Busan (Korea, Republic of)

    1996-12-15

    To establish upper limit of normal splenic length of Korean adults on ultrasonography and to determice the degree of interobserver and intraobserver variation. Ultrasonographic scans were performed to measure the maximum length of spleen in 105 of 150 adults selected by convenience sampling. Remained 45 cases with any conditions that could alter splenic size were excluded from this study. The maximum length of spleen was measured and correlated with body surface area, patient height, weight, age and sex. In 31 of the 105 adults we evaluated the interobserver and intraobserver variations in sonographic measurements of splenic length obtained by three radiologists in blind fashion. The mean splenic length in 105 adults was 8.56cm ({+-} 0.95). The splenic length positively correlated with body surface area, patient height and weight (P <0.001), and negatively correlated with patient age (P < 0.01). Male spleen (8.87 cm {+-} 1.07) was longer than female spleen (8.35 cm {+-} 0.81) (P < 0.05). The following guidelines are proposed for the upper limit of normal splenic length at different groups of body surface area: no longer than 10 cm at 1.20{approx}1.59 m{sup 2}, 11 cm at1.60{approx}1.79 m{sup 2}, and 12 cm at 1.80{approx}1.99 m{sup 2}. The mean interobserver variation between any two radiologists ranged from 0.32 cm ({+-} 0.29) to 0.39 cm ({+-} 0.33) and interobserver variations were within 1 cm in 96%. The mean intraobserver variations were within 0.5 cm in 91%. The splenic length closely correlated with body surface area, patient height, weight and age. Particularly the upper limit of normal splenic length changed according to body surface area. Interobserver variation about 1 cm and intraobserver variation about 0.5 cm should be considered in the measurement of the splenic length on ultrasonography

  2. Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

    Science.gov (United States)

    Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

    2013-07-01

    It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  3. 2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

    International Nuclear Information System (INIS)

    Skillman, C.A.; Fletcher, H.P.

    1986-01-01

    The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

  4. Palatal shelf epithelium: a morphologic and histochemical study in X-irradiated and normal mice

    International Nuclear Information System (INIS)

    Gartner, L.P.; Hiatt, J.L.; Provenza, D.V.

    1978-01-01

    The palatal shelf epithelium of normal and irradiated mice was examined morphologically and histochemically, utilizing the periodic acid-Schiff (PAS) technique for the demonstration of the basement membrane and the Nitro BT method for succinate dehydrogenase activity in order to demonstrate the metabolic competence of its cells. The 'programmed cell death theory' was not supported by the present investigation, since the cells of the medial ridge epithelium retained their structural and metabolic integrity even subsequent to the formation of cell nests. Additionally, the medial ridge epithelium of mice with radiation-induced cleft palates demonstrated normal structural and metabolic integrity long past the prospective time of fusion. (author)

  5. Dichotic and dichoptic digit perception in normal adults.

    Science.gov (United States)

    Lawfield, Angela; McFarland, Dennis J; Cacace, Anthony T

    2011-06-01

    Verbally based dichotic-listening experiments and reproduction-mediated response-selection strategies have been used for over four decades to study perceptual/cognitive aspects of auditory information processing and make inferences about hemispheric asymmetries and language lateralization in the brain. Test procedures using dichotic digits have also been used to assess for disorders of auditory processing. However, with this application, limitations exist and paradigms need to be developed to improve specificity of the diagnosis. Use of matched tasks in multiple sensory modalities is a logical approach to address this issue. Herein, we use dichotic listening and dichoptic viewing of visually presented digits for making this comparison. To evaluate methodological issues involved in using matched tasks of dichotic listening and dichoptic viewing in normal adults. A multivariate assessment of the effects of modality (auditory vs. visual), digit-span length (1-3 pairs), response selection (recognition vs. reproduction), and ear/visual hemifield of presentation (left vs. right) on dichotic and dichoptic digit perception. Thirty adults (12 males, 18 females) ranging in age from 18 to 30 yr with normal hearing sensitivity and normal or corrected-to-normal visual acuity. A computerized, custom-designed program was used for all data collection and analysis. A four-way repeated measures analysis of variance (ANOVA) evaluated the effects of modality, digit-span length, response selection, and ear/visual field of presentation. The ANOVA revealed that performances on dichotic listening and dichoptic viewing tasks were dependent on complex interactions between modality, digit-span length, response selection, and ear/visual hemifield of presentation. Correlation analysis suggested a common effect on overall accuracy of performance but isolated only an auditory factor for a laterality index. The variables used in this experiment affected performances in the auditory modality to a

  6. The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

    Science.gov (United States)

    Berger, Katja; Schulte, Kevin; Boor, Peter; Kuppe, Christoph; van Kuppevelt, Toin H.; Floege, Jürgen; Smeets, Bart

    2014-01-01

    Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman’s capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glomerular hypertrophy was induced by progressive partial nephrectomies. Again, no significant podocyte replenishment was observed. Rather, labeled PECs exclusively invaded segments of the tuft affected by glomerulosclerosis, consistent with our previous findings. We next reassessed PEC recruitment in juvenile mice using a different reporter mouse and confirmed significant recruitment of labeled PECs onto the glomerular tuft. Moreover, some labeled cells on Bowman’s capsule expressed podocyte markers, and cells on Bowman’s capsule were also directly labeled in juvenile podocyte-specific Pod-rtTA transgenic mice. In 6-week-old mice, however, cells on Bowman’s capsule no longer expressed podocyte-specific markers. Similarly, in human kidneys, some cells on Bowman’s capsule expressed the podocyte marker synaptopodin from 2 weeks to 2 years of age but not at 7 years of age. In summary, podocyte regeneration from PECs could not be detected in aging mice or models of glomerular hypertrophy. We propose that a small fraction of committed podocytes reside on Bowman’s capsule close to the vascular stalk and are recruited onto the glomerular tuft during infancy to adolescence in mice and humans. PMID:24408873

  7. Effects of Kerack used in addict Iranian people on fertility of adult mice

    Directory of Open Access Journals (Sweden)

    Mehdi Amini

    2013-08-01

    Full Text Available Background: Infertility is one of the most serious social problems. Illicit drug use can be an important cause of male factor infertility. Kerack which its use is rising up in Iran refers to a high purity street-level heroin (heroin Kerack. Heroin Kerack used in Iran is an opioid and has harmful effects on body organs. The aim of this study is to investigate the effects of Kerack used in Iran on fertility adult mice.Methods: In this study, 25 male mice were divided into five groups (control, sham and three experimental. Experimental groups of Kerack-dependent mice (received ascend-ing dose of Kerack for seven days were divided into three categories, experimental I, II and III. Experimental I was given Kerack at a dose of 5 mg/kg, experimental II 35 mg/kg and experimental III 70 mg/kg, intraperitoneally twice a day for a period of 35 days. The sham group received normal saline and lemon juice (2.6 µl/ml whilst the control group just received water and food. Mice were then scarified and sperm removed from cauda epididymis were analyzed for sperm count, motility, morphology (normal/abnormal and viability. Testes were also removed, weighed and processed for light microscopic studies.Results: The results showed that fertility were significantly decreased in addicted mice compared with control groups (P≤0.05. Epididymal sperm parameters and thickness of seminiferous epithelium were significantly decreased in experimental groups (dose-dependent compared with sham and control groups (P≤0.05. Gonadosomatic index was significantly reduced with high dose Kerack injected (70 mg/kg in comparison with control testes (P≤0.05.Conclusion: This study has shown the deleterious effects of Kerack used in addicted Iranian people on fertility for the first time. This effect is especially on epididymal sperm parameters in adult mice.

  8. Digital ranges of motion: normal values in young adults.

    Science.gov (United States)

    Mallon, W J; Brown, H R; Nunley, J A

    1991-09-01

    Analysis of the range of motion of fingers was done in young (eighteen to thirty-five year old) adult volunteers with no history of previous injury to their hands. The data show that there are slight differences between the individual digits. Notably, metacarpophalangeal flexion and total active motion increase linearly in proceeding from the index to the small finger. There were also minor differences in comparing sexes. Women have greater extension at the metacarpophalangeal joint in both active and passive motion and have a greater total active motion at all digits as a result. A significant tenodesis effect was found at the distal interphalangeal joint in normal subjects. No differences were found that could be attributable to handedness.

  9. Dosimetric Studies in Normal Mice of 177Lu-DOTA-SP and 177Lu-DOTA-His2-MG

    International Nuclear Information System (INIS)

    Puerta Yepes, N.; Rojo, A.M.; Lopez Bularte, A.C.; Nevares, N.; Zapata, M.; Perez, J.H.; Crudo, J.

    2010-01-01

    DOTA-Substance-P (SP) and DOTA-minigastrin (His2-MG) labeled with 177 Lu could be used in peptide receptor radionuclide therapy (PRRT) for treatment of various tumour species. Biodistribution studies of both radiopharmaceuticals in normal mice were performed at different times. Absorbed doses in mouse organs were estimated and extrapolated to humans. Dosimetric calculations showed that kidneys received the highest dose, for both radiopharmaceuticals. The Maximum Tolerated Activity (MTA) of 177 Lu-DOTA-SP that can be administered without kidney toxicity are 414 and 422 MBq/kg for the standard adult man and woman, respectively. In the same way, the MTA of 177 Lu-DOTA-His2-MG are 488 and 518 MBq/kg for the standard adult man and woman, respectively. (authors)

  10. Normal isometric strength of rotatorcuff muscles in adults.

    Science.gov (United States)

    Chezar, A; Berkovitch, Y; Haddad, M; Keren, Y; Soudry, M; Rosenberg, N

    2013-01-01

    The most prevalent disorders of the shoulder are related to the muscles of rotator cuff. In order to develop a mechanical method for the evaluation of the rotator cuff muscles, we created a database of isometric force generation by the rotator cuff muscles in normal adult population. We hypothesised the existence of variations according to age, gender and dominancy of limb. A total of 400 healthy adult volunteers were tested, classified into groups of 50 men and women for each decade of life. Maximal isometric force was measured at standardised positions for supraspinatus, infraspinatus and subscapularis muscles in both shoulders in every person. Torque of the force was calculated and normalised to lean body mass. The profiles of mean torque-time curves for each age and gender group were compared. Our data showed that men gradually gained maximal strength in the fifth decade, and showed decreased strength in the sixth. In women the maximal strength was gained in the fourth decade with gradual decline to the sixth decade of life. The dominant arm was stronger in most of the tested groups. The torque profiles of the rotator cuff muscles in men at all ages were significantly higher than that in women. We found previously unrecognised variations of rotator cuff muscles' isometric strength according to age, gender and dominancy in a normal population. The presented data may serve as a basis for the future studies for identification of the abnormal patterns of muscle isometric strength in patients with pathology of the rotator cuff muscles. Cite this article: Bone Joint Res 2013;2:214-19.

  11. Adaptation of enterovirus 71 to adult interferon deficient mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  12. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Science.gov (United States)

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  13. Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice.

    Science.gov (United States)

    Schultz, C J; Blanchette-Mackie, E J; Scow, R O

    2000-02-01

    Combined lipase deficiency (cld) is a recessive mutation in mice that causes a severe lack of lipoprotein lipase (LPL) and hepatic lipase (HL) activities, hyperlipemia, and death within 3 days after birth. Earlier studies showed that inactive LPL and HL were synthesized by cld/cld tissues and that LPL synthesized by cld/cld brown adipocytes was retained in their ER. We report here a study of HL in liver, adrenal, and plasma of normal newborn and cld/cld mice. Immunofluorescence studies showed HL was present in extracellular space, but not in cells, in liver and adrenal of both normal and cld/cld mice. When protein secretion was blocked with monensin, HL was retained intracellularly in liver cell cultures and in incubated adrenal tissues of both groups of mice. These findings demonstrated that HL was synthesized and secreted by liver and adrenal cells in normal newborn and cld/cld mice. HL activities in liver, adrenal, and plasma in cld/cld mice were very low, cld/cld cells was inactive. Livers of both normal newborn and cld/cld mice synthesized LPL, but the level of LPL activity in cld/cld liver was very low, cld/cld mice, indicating that LPL was synthesized but not secreted by cld/cld liver cells. Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL. Livers of both groups of mice contained an unidentified alkaline lipase activity which accounted for 34-54% of alkaline lipase activity in normal and 65% of that in cld/cld livers. Our findings indicate that liver and adrenal cells synthesized and secreted HL in both normal newborn and cld/cld mice, but the lipase was inactive in cld/cld mice. That cld/cld liver cells secreted inactive HL while retaining inactive LPL indicates that these closely related lipases were processed differently.

  14. [Performance of normal young adults in two temporal resolution tests].

    Science.gov (United States)

    Zaidan, Elena; Garcia, Adriana Pontin; Tedesco, Maria Lucy Fraga; Baran, Jane A

    2008-01-01

    temporal auditory processing is defined as the perception of sound or of sound alteration within a restricted time interval and is considered a fundamental ability for the auditory perception of verbal and non verbal sounds, for the perception of music, rhythm, periodicity and in the discrimination of pitch, duration and of phonemes. to compare the performance of normal Brazilian adults in two temporal resolution tests: the Gaps-in-Noise Test (GIN) and the Random Gap Detection Test (RGDT), and to analyze potential differences of performance in these two tests. twenty-five college students with normal hearing (11 males and 14 females) and no history of educational, neurological and/or language problems, underwent the GIN and RGDT at 40dB SL. statistically significant gender effects for both tests were found, with female participants showing poorer performance on both temporal processing tests. In addition, a comparative analysis of the results obtained in the GIN and RGDT revealed significant differences in the threshold measures derived for these two tests. In general, significantly better gap detection thresholds were observed for both male and female participants on the GIN test when compared to the results obtained for the RGDT. male participants presented better performances on both RGDT and GIN, when compared to the females. There were no differences in performance between right and left ears on the GIN test. Participants of the present investigation, males and females, performed better on the GIN when compared to the RGDT. The GIN presented advantages over the RGDT, not only in terms of clinical validity and sensibility, but also in terms of application and scoring.

  15. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. Growth restriction, leptin, and the programming of adult behavior in mice.

    Science.gov (United States)

    Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

    2014-12-15

    Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, phormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Roentgenographic studies of Korean adults profile with normal occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1972-11-15

    A roentgraphic cephalometric study was made on the soft and hard tissue profile of Korean adults. The subject consisted of 52 males and 54 females from 17 to 22 years of age and with normal occlusion and acceptable profile. Twenty one landmarks were plotted and two oriented lines named SnH line and SnV line were drawn on the tracings of all cephalograms. The means and the standard deviations from the subjects were calculated in each measuring category and the means were compared with those of male and female samples. The results were obtained as follow: 1. In depth and height, individual variations and sex differences of the lower facial profile were larger than the upper face. 2. The sex differences of upper facial profile were larger in height than depth. 3. The individual variations and sex differences of the top of nose were the smallest in all measuring points. 4. The thickness of the soft tissue of upper face and upper lip in male sample were larger than those of female, but the same matter were not found in mental region.

  18. Metabolic alterations due to caloric restriction and every other day feeding in normal and growth hormone receptor knockout mice.

    Science.gov (United States)

    Westbrook, Reyhan; Bonkowski, Michael S; Arum, Oge; Strader, April D; Bartke, Andrzej

    2014-01-01

    Mutations causing decreased somatotrophic signaling are known to increase insulin sensitivity and extend life span in mammals. Caloric restriction and every other day (EOD) dietary regimens are associated with similar improvements to insulin signaling and longevity in normal mice; however, these interventions fail to increase insulin sensitivity or life span in growth hormone receptor knockout (GHRKO) mice. To investigate the interactions of the GHRKO mutation with caloric restriction and EOD dietary interventions, we measured changes in the metabolic parameters oxygen consumption (VO2) and respiratory quotient produced by either long-term caloric restriction or EOD in male GHRKO and normal mice. GHRKO mice had increased VO2, which was unaltered by diet. In normal mice, EOD diet caused a significant reduction in VO2 compared with ad libitum (AL) mice during fed and fasted conditions. In normal mice, caloric restriction increased both the range of VO2 and the difference in minimum VO2 between fed and fasted states, whereas EOD diet caused a relatively static VO2 pattern under fed and fasted states. No diet significantly altered the range of VO2 of GHRKO mice under fed conditions. This provides further evidence that longevity-conferring diets cause major metabolic changes in normal mice, but not in GHRKO mice.

  19. Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

    Science.gov (United States)

    Nakanishi, S T; Whelan, P J

    2010-05-01

    During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

  20. Catalase induction in normal and tumorigenic mice using x-rays, clofibrate, ethanol, or hydrogen peroxide

    International Nuclear Information System (INIS)

    Alexander, L.; Oberley, L.

    1985-01-01

    The authors studied catalase induction in normal male Swiss mice as well as in male mice harboring H-6 hepatomas. The induction patterns many suggest reasons why tumor cells have lower catalase activity than normal cells. X-rays, hydrogen peroxide, ethanol, and clofibrate were used as inducing agents. X-rays interact with tissue and cause free radical formation. This results in an increase in hydrogen peroxide concentration, which ought to induce catalase. Oral administration of hydrogen peroxide should induce catalase similarly. Ethanol can be a substrate for catalase, forming acetalehyde; and as such may induce catalase. Ethanol can also restore inactive catalase compound II to useful catalase. Clofibrate is a hypolipidemic agent which induces catalase, most likely because of its ability to accelerate lipid breakdown, which raises peroxide concentration

  1. Preparation of 177Lu-DTPA-BIS-BIOTIN and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Du Jin

    2010-01-01

    The labeling method for 177 Lu-DTPA-BIS-BIOTIN was established, and the biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice was carried out as well. Under the optimal experimental condition (DTPA-BIS-BIOTIN 25 μg, pH=4.5 reacting at 80 degree C for 20 min), the labeling yield of 177 Lu-DTPA-BIS-BIOTIN is more than 99.0%. 177 Lu-DTPA-BIS-BIOTIN shows pretty good in vitro stability. The biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice shows a rapid blood clearance. The uptake of 177 Lu-DTPA-BIS-BIOTIN is mainly accumulated in liver, spleen and kidney. 177 Lu-DTPA-BIS-BIOTIN is excreted by kidney. The results provide the basis for further study on 177 Lu-DTPA-BIS-BIOTIN used in pretargeted radioimage and radiotherapy of cancer. (authors)

  2. Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

    Directory of Open Access Journals (Sweden)

    Andrea R. Durrant

    2012-06-01

    Full Text Available The cholinesterases, acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase, are abundant in the nervous system and in other tissues. The role of acetylcholinesterase in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates acetylcholinesterase and butyrylcholinesterase in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While acetylcholinesterase in mdx-sera is elevated, butyrylcholinesterase is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T is a negative modulator of butyrylcholinesterase, but not of acetylcholinesterase, in male mouse sera. T-removal elevated both butyrylcholinesterase activity and the butyrylcholinesterase/acetylcholinesterase ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

  3. Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

    Directory of Open Access Journals (Sweden)

    Mekayla A. Storer

    2018-05-01

    Full Text Available Summary: Circulating systemic factors can regulate adult neural stem cell (NSC biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6, since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. : In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions. Keywords: interleukin-6, neural stem cell, adult neurogenesis, CNS cytokines, postnatal brain development, stem cell depletion, neural stem cell niche, circulating stem cell factors, olfactory bulb

  4. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

    Science.gov (United States)

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  5. Effect of Tamoxifen on Seminiferous Tubules Structure during Pregnancy in Adult Mice

    Directory of Open Access Journals (Sweden)

    J Soleimani Rad

    2016-03-01

    Full Text Available Introduction: Tamoxifen is a nonsteroidal drug which mainly treats breast cancer. It is also applied for stimulation of ovulation and remedy of infertility. Regarding the tamoxifen binding to estrogen receptors and the possible role of estrogens in spermatogenesis, the present study aimed to histologically evaluate spermatogenesis in the seminiferous ducts of mice, whose mothers had received tamoxifen during pregnancy. Methods: In the present study, 30 female and 15 male mice of NMRI race were selected for mating. Since 13th day of pregnancy, the experimental group received tamoxifen with the dosage of 5 mg/kg intra-peritoneally for 7 days, wherease the control group received normal saline. After childbirth of the mated mice, male infants were selected and monitored in the standard laboratory conditions. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation, and the testes were removed for histological evaluation of spermatogenesis. After routine histological processing, the samples were studied by the light microscope. Results: Histological studies showed that spermatogenic and Sertoli cells in the seminiferous tubules in control and experimental groups were significantly different, though no difference was observed in the number of Leydig cells in the both groups. Conclusion: The findings of the present study showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility in the male rat.

  6. Effect of extract of Hibiscus on the ultrastructure of the testis in adult mice.

    Science.gov (United States)

    Mahmoud, Yomna Ibrahim

    2012-07-01

    Hibiscus sabdariffa extract is a popular beverage in many tropical and sub-tropical countries. Although, Hibiscus tea is known for its medicinal effects for thousands of years, scientific evidence of its systemic safety is very limited. The current study aimed to assess the potential adverse effects of H. sabdariffa extract on sperm morphology and testicular ultrastructure of albino mice. Thirty adult male albino mice were divided into three equal groups and were given: (a) distilled water, (b) cold Hibiscus aqueous extract, and (c) boiled Hibiscus aqueous extract. Hibiscus extract was administered orally daily for 4 weeks in a dose of 200 mg/kg body weight/mouse. Twenty-four hours after the last treatment, mice were decapitated and the testes and epididymides were excised and processed for transmission electron microscopy to assess ultrastructural and sperm abnormalities. The results clearly demonstrate that aqueous extracts from dried calyx of H. sabdariffa, either cold or boiled, alter normal sperm morphology and testicular ultrastructure and adversely influence the male reproductive fertility in albino mice. The current data suggest that Hibiscus extract should be consumed with caution, and reasonable estimates of the human risk associated with its consumption should be provided. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Mice lacking the p75 receptor fail to acquire a normal complement of taste buds and geniculate ganglion neurons by adulthood

    OpenAIRE

    Krimm, Robin F.

    2006-01-01

    Brain derived neurotrophic factor and neurotrophin-4 are required for normal taste bud development. Although these neurotrophins normally function via the tyrosine kinase receptor, trkB, they also bind to the pan-neurotrophin receptor, p75. The goal of the present study was to determine whether the p75 receptor is required for the development or maintenance of a full complement of adult taste buds. Mice with p75 null mutations lose 34% of their circumvallate taste buds, 36% of their fungiform...

  8. Normal mitochondrial respiratory function is essential for spatial remote memory in mice

    Directory of Open Access Journals (Sweden)

    Tanaka Daisuke

    2008-12-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice with heteroplasmy for wild-type and pathogenically deleted (Δ mtDNA; the "low" group carried 50% or less ΔmtDNA, and the "high" group carried more than 50% ΔmtDNA. Results Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII, a protein important for the establishment of spatial remote memory. Conclusion Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.

  9. [Calbindin and parvalbumin distribution in spinal cord of normal and rabies-infected mice].

    Science.gov (United States)

    Monroy-Gómez, Jeison; Torres-Fernández, Orlando

    2013-01-01

    Rabies is a fatal infectious disease of the nervous system; however, the knowledge about the pathogenic neural mechanisms in rabies is scarce. In addition, there are few studies of rabies pathology of the spinal cord. To study the distribution of calcium binding proteins calbindin and parvalbumin and assessing the effect of rabies virus infection on their expression in the spinal cord of mice. MATERIALES Y METHODS: Mice were inoculated with rabies virus, by intracerebral or intramuscular route. The spinal cord was extracted to perform some crosscuts which were treated by immunohistochemistry with monoclonal antibodies to reveal the presence of the two proteins in normal and rabies infected mice. We did qualitative and quantitative analyses of the immunoreactivity of the two proteins. Calbindin and parvalbumin showed differential distribution in Rexed laminae. Rabies infection produced a decrease in the expression of calbindin. On the contrary, the infection caused an increased expression of parvalbumin. The effect of rabies infection on the two proteins expression was similar when comparing both routes of inoculation. The differential effect of rabies virus infection on the expression of calbindin and parvalbumin in the spinal cord of mice was similar to that previously reported for brain areas. This result suggests uniformity in the response to rabies infection throughout the central nervous system. This is an important contribution to the understanding of the pathogenesis of rabies.

  10. A 201-MHz Normal Conducting RF Cavity for the International MICE Experiment

    International Nuclear Information System (INIS)

    Li, D.; DeMello, A.J.; Virostek, Steve; Zisman, Michael S.; Rimmer, Robert

    2008-01-01

    MICE is a demonstration experiment for the ionization cooling of muon beams. Eight RF cavities are proposed to be used in the MICE cooling channel. These cavities will be operated in a strong magnetic field; therefore, they must be normal conducting. The cavity design and construction are based on the successful experience and techniques developed for a 201-MHz prototype cavity for the US MUCOOL program. Taking advantage of a muon beamΛ s penetration property, the cavity employs a pair of curved thin beryllium windows to terminate conventional beam irises and achieve higher cavity shunt impedance. The cavity resembles a round, closed pillbox cavity. Two half-shells spun from copper sheets are joined by e-beam welding to form the cavity body. There are four ports on the cavity equator for RF couplers, vacuum pumping and field probes. The ports are formed by means of an extruding technique.

  11. The experience of weight management in normal weight adults.

    Science.gov (United States)

    Hernandez, Cheri Ann; Hernandez, David A; Wellington, Christine M; Kidd, Art

    2016-11-01

    No prior research has been done with normal weight persons specific to their experience of weight management. The purpose of this research was to discover the experience of weight management in normal weight individuals. Glaserian grounded theory was used. Qualitative data (focus group) and quantitative data (food diary, study questionnaire, and anthropometric measures) were collected. Weight management was an ongoing process of trying to focus on living (family, work, and social), while maintaining their normal weight targets through five consciously and unconsciously used strategies. Despite maintaining normal weights, the nutritional composition of foods eaten was grossly inadequate. These five strategies can be used to develop new weight management strategies that could be integrated into existing weight management programs, or could be developed into novel weight management interventions. Surprisingly, normal weight individuals require dietary assessment and nutrition education to prevent future negative health consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Ocular Axial Length Measurement Among Normal Adults Using ...

    African Journals Online (AJOL)

    2017-07-26

    Jul 26, 2017 ... eye is the AL and report from previous studies suggest that in an adult, the average ... 2017 Nigerian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow ..... Parel JM, Gelender H, Trefers WF, Norton EW.

  13. Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

    Directory of Open Access Journals (Sweden)

    Astha Malik

    Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

  14. The Forkhead Transcription Factor, FOXP3, Is Required for Normal Pituitary Gonadotropin Expression in Mice1

    Science.gov (United States)

    Jung, Deborah O.; Jasurda, Jake S.; Egashira, Noboru; Ellsworth, Buffy S.

    2012-01-01

    ABSTRACT The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3sf/Y). Although the gonadotroph cells appear to be intact in Foxp3sf/Y mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3sf/Y males. Treatment of Foxp3sf/Y males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3sf/Y males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3sf/Y males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by

  15. Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice

    OpenAIRE

    Sugasini, Dhavamani; Thomas, Riya; Yalagala, Poorna C. R.; Tai, Leon M.; Subbaiah, Papasani V.

    2017-01-01

    Docosahexaenoic acid (DHA) is uniquely concentrated in the brain, and is essential for its function, but must be mostly acquired from diet. Most of the current supplements of DHA, including fish oil and krill oil, do not significantly increase brain DHA, because they are hydrolyzed to free DHA and are absorbed as triacylglycerol, whereas the transporter at blood brain barrier is specific for phospholipid form of DHA. Here we show that oral administration of DHA to normal adult mice as lysopho...

  16. NORMAL AXIAL ANGLES OF THE KNEE JOINT IN ADULT ...

    African Journals Online (AJOL)

    hi-tech

    2003-08-01

    Aug 1, 2003 ... Conclusion: Our study has demonstrated comparative variations in means and ranges of normal axial angles .... population was significantly different from the mean ... case, however, the angle also exhibits racial variations.

  17. Normal values for quantitative muscle ultrasonography in adults.

    NARCIS (Netherlands)

    Arts, I.M.P.; Pillen, S.; Schelhaas, H.J.; Overeem, S.; Zwarts, M.J.

    2010-01-01

    Ultrasonography can detect structural muscle changes caused by neuromuscular disease. Quantitative analysis is the preferred method to determine if ultrasound findings are within normal limits, but normative data are incomplete. The purpose of this study was to provide normative muscle

  18. Ocular axial length measurement among normal adults using ...

    African Journals Online (AJOL)

    , as visual compromise is a major consequence if they are not diagnosed and managed appropriately. Aim and Objectives: To use magnetic resonance imaging, to determine the normal AL of the eyeball and to establish the association, if any, ...

  19. Synthesis and biodistribution of 2-[123I]iodomelatonin in normal mice

    International Nuclear Information System (INIS)

    Al-Jammaz, I.; Al-Otaibi, B.; Aboul-Enein, H.; Amartey, J.K.

    2006-01-01

    Melatonin demands that this hormone and its receptors be well understood. With this aim in mind, synthetic melatonin was radioiodinated with no-carrier-added (n.c.a.) sodium iodide-123 using in situ generated peracetic acid as oxidizing agent for electrophilic iodination at room temperature. The radiochemical yield was typically greater than 80% after 20 min reaction time especially when relatively small amounts of activities were used (10 mCi). Biological evaluation was performed in normal mice. The distribution of the tracer did not reveal any specificity during the time frame studied. There was no significant retention in the whole brain

  20. Synthesis and biodistribution of 2-[{sup 123}I]iodomelatonin in normal mice

    Energy Technology Data Exchange (ETDEWEB)

    Al-Jammaz, I. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)]. E-mail: jammaz@kfshrc.edu.sa; Al-Otaibi, B. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Aboul-Enein, H. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Amartey, J.K. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)

    2006-01-01

    Melatonin demands that this hormone and its receptors be well understood. With this aim in mind, synthetic melatonin was radioiodinated with no-carrier-added (n.c.a.) sodium iodide-123 using in situ generated peracetic acid as oxidizing agent for electrophilic iodination at room temperature. The radiochemical yield was typically greater than 80% after 20 min reaction time especially when relatively small amounts of activities were used (10 mCi). Biological evaluation was performed in normal mice. The distribution of the tracer did not reveal any specificity during the time frame studied. There was no significant retention in the whole brain.

  1. Mice Lacking Pannexin 1 Release ATP and Respond Normally to All Taste Qualities.

    Science.gov (United States)

    Vandenbeuch, Aurelie; Anderson, Catherine B; Kinnamon, Sue C

    2015-09-01

    Adenosine triphosphate (ATP) is required for the transmission of all taste qualities from taste cells to afferent nerve fibers. ATP is released from Type II taste cells by a nonvesicular mechanism and activates purinergic receptors containing P2X2 and P2X3 on nerve fibers. Several ATP release channels are expressed in taste cells including CALHM1, Pannexin 1, Connexin 30, and Connexin 43, but whether all are involved in ATP release is not clear. We have used a global Pannexin 1 knock out (Panx1 KO) mouse in a series of in vitro and in vivo experiments. Our results confirm that Panx1 channels are absent in taste buds of the knockout mice and that other known ATP release channels are not upregulated. Using a luciferin/luciferase assay, we show that circumvallate taste buds from Panx1 KO mice normally release ATP upon taste stimulation compared with wild type (WT) mice. Gustatory nerve recordings in response to various tastants applied to the tongue and brief-access behavioral testing with SC45647 also show no difference between Panx1 KO and WT. These results confirm that Panx1 is not required for the taste evoked release of ATP or for neural and behavioral responses to taste stimuli. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  3. Age and Gender Effects on Wideband Absorbance in Adults with Normal Outer and Middle Ear Function

    Science.gov (United States)

    Mazlan, Rafidah; Kei, Joseph; Ya, Cheng Li; Yusof, Wan Nur Hanim Mohd; Saim, Lokman; Zhao, Fei

    2015-01-01

    Purpose: This study examined the effects of age and gender on wideband energy absorbance in adults with normal middle ear function. Method: Forty young adults (14 men, 26 women, aged 20-38 years), 31 middle-aged adults (16 men, 15 women, aged 42-64 years), and 30 older adults (20 men, 10 women, aged 65-82 years) were assessed. Energy absorbance…

  4. Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF-transgenic mice

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Fenger, Christina; Nielsen, Helle H

    2004-01-01

    degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus in TNF-transgenic mice with the response in genetically normal mice. Transectioning of the entorhino-dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly...... larger levels in the TNF-transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF-transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed...

  5. Radioprotection of normal tissues in tumor-bearing mice by troxerutin

    International Nuclear Information System (INIS)

    Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

    2004-01-01

    The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

  6. Normal range values for thromboelastography in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    S. Scarpelini

    2009-12-01

    Full Text Available Thromboelastography (TEG® provides a functional evaluation of coagulation. It has characteristics of an ideal coagulation test for trauma, but is not frequently used, partially due to lack of both standardized techniques and normal values. We determined normal values for our population, compared them to those of the manufacturer and evaluated the effect of gender, age, blood type, and ethnicity. The technique was standardized using citrated blood, kaolin and was performed on a Haemoscope 5000 device. Volunteers were interviewed and excluded if pregnant, on anticoagulants or having a bleeding disorder. The TEG® parameters analyzed were R, K, α, MA, LY30, and coagulation index. All volunteers outside the manufacturer’s normal range underwent extensive coagulation investigations. Reference ranges for 95% for 118 healthy volunteers were R: 3.8-9.8 min, K: 0.7-3.4 min, α: 47.8-77.7 degrees, MA: 49.7-72.7 mm, LY30: -2.3-5.77%, coagulation index: -5.1-3.6. Most values were significantly different from those of the manufacturer, which would have diagnosed coagulopathy in 10 volunteers, for whom additional investigation revealed no disease (81% specificity. Healthy women were significantly more hypercoagulable than men. Aging was not associated with hypercoagulability and East Asian ethnicity was not with hypocoagulability. In our population, the manufacturer’s normal values for citrated blood-kaolin had a specificity of 81% and would incorrectly identify 8.5% of the healthy volunteers as coagulopathic. This study supports the manufacturer’s recommendation that each institution should determine its own normal values before adopting TEG®, a procedure which may be impractical. Consideration should be given to a multi-institutional study to establish wide standard values for TEG®.

  7. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  8. Differential effects of social isolation in adolescent and adult mice on behavior and cortical gene expression.

    Science.gov (United States)

    Lander, Sharon S; Linder-Shacham, Donna; Gaisler-Salomon, Inna

    2017-01-01

    Intact function of the medial prefrontal cortex (mPFC) function relies on proper development of excitatory and inhibitory neuronal populations and on integral myelination processes. Social isolation (SI) affects behavior and brain circuitry in adulthood, but previous rodent studies typically induced prolonged (post-weaning) exposure and failed to directly compare between the effects of SI in adolescent and adulthood. Here, we assessed the impact of a 3-week SI period, starting in mid-adolescence (around the onset of puberty) or adulthood, on a wide range of behaviors in adult male mice. Additionally, we asked whether adolescent SI would differentially affect the expression of excitatory and inhibitory neuronal markers and myelin-related genes in mPFC. Our findings indicate that mid-adolescent or adult SI increase anxiogenic behavior and locomotor activity. However, SI in adolescence uniquely affects the response to the psychotomimetic drug amphetamine, social and novelty exploration and performance in reversal and attentional set shifting tasks. Furthermore, adolescent but not adult SI increased the expression of glutamate markers in the adult mPFC. Our results imply that adolescent social deprivation is detrimental for normal development and may be particularly relevant to the investigation of developmental psychopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

    DEFF Research Database (Denmark)

    Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

    2004-01-01

    Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells...... and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

  10. Neurologic function during developmental and adult stages in Dab1(scm) (scrambler) mutant mice.

    Science.gov (United States)

    Jacquelin, C; Strazielle, C; Lalonde, R

    2012-01-01

    Homozygous Dab1(scm) mouse mutants with cell ectopias in cerebellar cortex, hippocampus, and neocortex were compared to non-ataxic controls on the SHIRPA primary screening battery on postnatal days 8, 15, and 22, as well as in the adult period. Dab1(scm) mutants were distinguished from non-ataxic controls as early as postnatal day 8 based on body tremor, gait anomalies, and body weight. On postnatal day 15, motor coordination deficits were evident on horizontal bar and inclined or vertical grid tests in association with a weaker grip strength. Likewise, mutants were distinguished from controls on drop righting and hindpaw clasping tests. Further differences were detected on postnatal day 22 in the form of fewer visual placing, touch escape, trunk curl, freezing, and vocalization responses, as well as squares traversed in the open-field. Evaluation at the adult age demonstrated similar impairments, indicative of permanent motor alterations. Neuronal metabolic activity was estimated by cytochrome oxidase histochemistry on cerebellar sections. Cerebellar cortical layers and efferent deep nuclei of Dab1(scm) mice appeared hypometabolic relative to non-ataxic mice despite normal metabolism in both regular and ectopic Purkinje cells. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. CT appearance of the normal appendix in adults

    International Nuclear Information System (INIS)

    Tamburrini, Stefania; Brunetti, Arturo; Brown, Michele; Sirlin, Claude B.; Casola, Giovanna

    2005-01-01

    The aims of this study were to identify (1) the normal range of the appendix on computed tomography (CT), (2) the correlation of patient age and sex with the visibility and appearance of the appendix on CT, and (3) the normal variations in wall thickness, intraluminal content, and location of the appendix. Three hundred seventy-two outpatients underwent abdominopelvic CT. The scans were reviewed on the picture archiving and communication system and appendiceal outer-to-outer wall diameter, wall thickness, location, content and its correlation with appendix diameter were analyzed. The appendix was visualized in 305/372 patients. Its location relative to the cecum was highly variable. The diameter range was 3-10 mm; in 42% of cases the diameter was greater than 6 mm. When the intraluminal content (185/305) was visualized, the diameter was slightly superior to the mean (p=0.0156). In 329 CT scans in which oral contrast material was given, the appendix was filled by contrast material in 74/329 patients. The appendix wall thickness was measurable in 22/305 patients (average 0.15 cm). There is significant overlap between the normal and abnormal CT appearance of the appendix. Consequently the diagnosis of acute appendicitis should be based not only on the appearance of the appendix but also on the presence of secondary signs. (orig.)

  12. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    International Nuclear Information System (INIS)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo; Lee, Jae Sung

    2002-01-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5±3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis

  13. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo [Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Jae Sung [Seoul national University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5{+-}3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis.

  14. Glycogen distribution in adult and geriatric mice brains

    KAUST Repository

    Alrabeh, Rana

    2017-05-01

    Astrocytes, the most abundant glial cell type in the brain, undergo a number of roles in brain physiology; among them, the energetic support of neurons is the best characterized. Contained within astrocytes is the brain’s obligate energy store, glycogen. Through glycogenolysis, glycogen, a storage form of glucose, is converted to pyruvate that is further reduced to lactate and transferred to neurons as an energy source via MCTs. Glycogen is a multi-branched polysaccharide synthesized from the glucose uptaken in astrocytes. It has been shown that glycogen accumulates with age and contributes to the physiological ageing process in the brain. In this study, we compared glycogen distribution between young adults and geriatric mice to understand the energy consumption of synaptic terminals during ageing using computational tools. We segmented and densely reconstructed neuropil and glycogen granules within six (three 4 month old old and three 24 month old) volumes of Layer 1 somatosensory cortex mice brains from FIB-SEM stacks, using a combination of semi-automated and manual tools, ilastik and TrakEM2. Finally, the 3D visualization software, Blender, was used to analyze the dataset using the DBSCAN and KDTree Nearest neighbor algorithms to study the distribution of glycogen granules compared to synapses, using a plugin that was developed for this purpose. The Nearest Neighbors and clustering results of 6 datasets show that glycogen clusters around excitatory synapses more than inhibitory synapses and that, in general, glycogen is found around axonal boutons more than dendritic spines. There was no significant accumulation of glycogen with ageing within our admittedly small dataset. However, there was a homogenization of glycogen distribution with age and that is consistent with published literature. We conclude that glycogen distribution in the brain is not a random process but follows a function distribution.

  15. Bowman Capsule Volume and Related Factors in Adults With Normal Renal Function

    Directory of Open Access Journals (Sweden)

    Takaya Sasaki

    2018-03-01

    Conclusion: In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.

  16. Inhibiting effect of plasma from normal and tumour bearing mice on the mitotic rate of regenerating liver.

    Science.gov (United States)

    Echave Llanos, J M; Moreno, F R; Badrán, A F

    1986-01-01

    Plasma from normal mice and from mice bearing the ES2 transplantable malignant tumour was injected intraperitoneally at a dose of 0.01 ml/g body weight in partially hepatectomized mice. Control animals were injected with a solution of sodium citrate in saline. The recipients were killed at the first (14:00 hours/48 h). These times are the time of day and the number of h after partial hepatectomy and second (14:00 hours/72 h) peak times after partial hepatectomy. The number of colchicine metaphases per 1000 nuclei was determined for hepatocytes and litoral cells. A different effect was obtained with plasma from tumour-bearing compared with normal mice. Plasma from both sources when injected 26 h after partial hepatectomy (16:00 hours/26 h) inhibited the mitotic activity of hepatocytes at the next peak of regenerative activity (14:00 hours/48 h). The plasma from tumour-bearing mice also inhibited the peak on the following day (14:00 hours/72 h), whereas plasma from normal mice had no inhibitory effect and, indeed, a compensatory wave was observed at this time. Furthermore, plasma from tumour-bearing mice also showed an inhibitory effect at the first peak (14:00 hours/48 h) when injected at the time of partial hepatectomy (14:00 hours/00 h) or at 22 h before partial hepatectomy (16:00 hours/-22 h) whereas the injection of plasma from normal mice at these times had no inhibitory effect. In the litoral cells the injection of plasma from tumour-bearing mice made 22 h before hepatectomy (16:00 hours/-22 h) led to a stimulation of mitotic activity which was controlled at 14:00 hours/48 h.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Synthesis and kinetics of [18F]4'-fluoroantipyrine in normal mice

    International Nuclear Information System (INIS)

    Robbins, P.J.; Fortman, D.L.; Scholz, K.L.; Fusaro, G.A.; Sodd, V.J.

    1978-01-01

    Antipyrine labeled with radioiodine has proven useful for studying the symmetry of human brain perfusion by gamma-camera techniques. The feasibility of preparing F-18-labeled antipyrine for eventual use with a positron camera was investigated. The preparation of [ 18 F] 4'-fluoroantipyrine and its distribution in normal mice were used to evaluate this potential. 4'-Fluoroantipyrine was prepared in 7 to 20% chemical yield by the pyrolysis of the 4'-diazonium fluoroborate salt of antipyrine. This Schiemann salt was prepared by a five-step synthesis from 1-(4'-nitrophenyl)-3-methyl-5-chloro-pyrazole. Fluorine-18 labeling of the diazonium fluoroborate salt by exchange with aqueous F-18 and pyrolysis of the dried labeled salt produced [ 18 F] 4'-fluoroantipyrine with specific activities of 0.83 to 2.7 μCi/mg. The incorporated F-18 activity ranged from 0.53 to 1.9%. The labeling procedure took about 3 hr. The labeled antipyrine was administered by tail vein to fasting female Swiss-Cox mice. Distribution of F-18 at 12, 30, 60, and 120 sec, and 10 min, after injection showed that radioactivity persisted in the brain up to 120 sec at a level greater than that of the skin and the bone. (Skin and bone samples were chosen as representative of activities in the scalp and skull surrounding the brain.) Thus, perfusion imaging of the CNS should be possible when greater quantities of high-specific-activity F-18-labeled antipyrine becomes available

  18. Markers of Alzheimer’s Disease in Primary Visual Cortex in Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    Luis Fernando Hernández-Zimbrón

    2017-01-01

    Full Text Available Aging is the principal risk factor for the development of Alzheimer’s disease (AD. The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42 and abnormal hyperphosphorylation of Tau (p-Tau protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP, and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the visual cortex; they also show an increase of the expression of GFAP and presenilin-2 in this region. These results provide a comprehensive framework for the role of Aβ42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging.

  19. Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice

    International Nuclear Information System (INIS)

    Feinstein, R.N.; Fry, R.J.M.; Staffeidt, E.F.

    1978-01-01

    Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carcinogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in γ-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H 2 O 2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H 2 O 2

  20. Genome-wide expression analysis comparing hypertrophic changes in normal and dysferlinopathy mice

    Directory of Open Access Journals (Sweden)

    Yun-Sil Lee

    2015-12-01

    Full Text Available Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use. One potential concern is that in muscle degenerative diseases, inducing hypertrophy may increase stress on dystrophic fibers. Our study shows that blocking this pathway in dysferlin deficient mice results in early improvement in histopathology but ultimately accelerates muscle degeneration. Hence, benefits of this approach should be weighed against these potential detrimental effects. Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015. Our data sets have been deposited in the Gene Expression Omnibus (GEO database (GSE62945 and are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62945. Our data provide a resource for exploring molecular mechanisms that are related to hypertrophy-induced, accelerated muscular degeneration in dysferlinopathy.

  1. Motivation to Address Self-Reported Hearing Problems in Adults with Normal Hearing Thresholds

    Science.gov (United States)

    Alicea, Carly C. M.; Doherty, Karen A.

    2017-01-01

    Purpose: The purpose of this study was to compare the motivation to change in relation to hearing problems in adults with normal hearing thresholds but who report hearing problems and that of adults with a mild-to-moderate sensorineural hearing loss. Factors related to their motivation were also assessed. Method: The motivation to change in…

  2. Characteristics and function of bone marrow stromal adherent cells in normal and irradiated mice and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Changyu, Zheng; Ji, Liu; Xiaoying, Bi

    1986-04-01

    It has been shown from cytochemical and other characteristic studies of bone marrow stromal cells in CFU-F that there are seven types of stromal cells in the stromal adherent cell layer of normal and irradiated C/sub 57/ mice whereas there are only six types in guinea pigs. On the other hand, a radioresistant cell subtype appears in adherent layer after irradiation of both C/sub 57/ mice and guinea pig since the supernatant of cultured CFU-F of the normal and irradiated C/sub 57/ mice can stimulate production of CFU-Gm. It is justifiable that the bone marrow stromal adherent cells of the C/sub 57/ mice could produce CSF.

  3. Toxicity of benzyl alcohol in adult and neonatal mice

    International Nuclear Information System (INIS)

    McCloskey, S.E.

    1987-01-01

    Benzyl alcohol (BA) is an aromatic alcohol, which is used as a bacteriostat in a variety of parenteral preparations. In 1982, it was implicated as the agent responsible for precipitating The Gasping Syndrome in premature neonates. The investigate further this toxicity, BA was administered, intraperiotoneally, to adult and neonatal CD-1 male mice. Gross behavioral changes were monitored. Low doses produced minimal toxic effects within an initial 4 hour observation period. At the end of this time, the LD 50 was determined to be 1000 mg/kg for both age groups. Death was due to respiratory arrest in all cases. Rapid absorption and conversion of BA to its primary metabolite, benzaldehyde, was demonstrated by gas chromatographic analysis of plasma from both experimental groups. The conversion of BA to benzaldehyde was confirmed in in vitro by using both horse-liver and mouse liver ADH. The inhibition of alcohol dehydrogenase (ADH) by pyrazole was similarly demonstrated in both enzyme systems. 14 C-labelled BA was utilized to determine the distribution of BA and its metabolites in the body, and to possibly pinpoint a target organ of toxicity

  4. A study of several normal values of Korean healthy adults on chest roentgenograms

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Byung Chull [Choong Nam University College of Medicine, Taejeon (Korea, Republic of)

    1975-06-15

    Determination of several normal values were carried out healthy 1805 cases of Korean adults, 1436 cases of male and 369 cases of female, by the drawing and calculation on chest roentgenograms. In many instances, the change of normal values provides an important clinical values, and often is decisive to evaluate the diagnosis, treatment and prognosis of pulmonary, cardiac and mediastinal disease.

  5. Normal anatomy and histology of the adult zebrafish.

    Science.gov (United States)

    Menke, Aswin L; Spitsbergen, Jan M; Wolterbeek, Andre P M; Woutersen, Ruud A

    2011-08-01

    The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals such as rodents. However, before we can fully realize the potential of the zebrafish as an animal model for understanding human development, disease, and toxicology, we must first greatly advance our knowledge of normal zebrafish physiology, anatomy, and histology. To further this knowledge, we describe, in the present article, location and histology of the major zebrafish organ systems with a brief description of their function.

  6. Anti-diabetic effects of Inonotus obliquus polysaccharides-chromium (III) complex in type 2 diabetic mice and its sub-acute toxicity evaluation in normal mice.

    Science.gov (United States)

    Wang, Cong; Chen, Zhongqin; Pan, Yuxiang; Gao, Xudong; Chen, Haixia

    2017-10-01

    Polysaccharides are important bioactive ingredients from Inonotus obliquus. This study aimed to synthesize and characterize a novel I. obliquus polysaccharides-chromium (III) complex (UIOPC) and investigate the anti-diabetic effects in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) mice and sub-acute toxicity in normal mice. The molecular weight of UIOPC was about 11.5 × 10 4  Da with the chromium content was 13.01% and the chromium was linked with polysaccharides through coordination bond. After treatment of UIOPC for four weeks, the body weight, fasting blood glucose (FBG) levels, plasma insulin levels of the diabetic mice were significantly reduced when compared with those of the diabetic mice (p < 0.05). The results on serum profiles and antioxidant enzymes activities revealed that UIOPC had a positive effect on hypoglycemic and antioxidant ability. Histopathology results showed that UIOPC could effectively alleviate the STZ-lesioned tissues in diabetic mice. Furthermore, high dose administration of UIOPC had no obviously influence on serum profiles levels and antioxidant ability of the normal mice and the organ tissues maintained organized and integrity in the sub-acute toxicity study. These results suggested that UIOPC might be a good candidate for the functional food or pharmaceuticals in the treatment of T2DM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Learning and memory deficits in male adult mice treated with a benzodiazepine sleep-inducing drug during the juvenile period

    Directory of Open Access Journals (Sweden)

    Yusuke Furukawa

    2016-07-01

    Full Text Available Gamma-aminobutyric acid (GABA, the major inhibitory neurotransmitter in the mammalian central nervous system, is also known to be important for brain development. Therefore, disturbances of GABA receptor (GABA-R mediated signaling (GABA-R signal during brain development may influence normal brain maturation and cause late-onset brain malfunctions. In this study, we examined whether the temporal stimulation of the GABA-R signal during brain development induces late-onset adverse effects on the brain in adult male mice. To stimulate the GABA-R signal, we used either the benzodiazepine sleep-inducing drug triazolam (TZ or the non-benzodiazepine drug zolpidem (ZP. We detected deficits in learning and memory in mice treated with TZ during the juvenile period, as seen in the fear conditioning test. On the other hand, ZP administration during the juvenile period had little effect. In addition, decreased protein expression of GluR1 and GluR4, which are excitatory neurotransmitter receptors, was detected in the hippocampi of mice treated with TZ during the juvenile period. We measured mRNA expression of the immediate early genes (IEGs, which are neuronal activity markers, in the hippocampus shortly after the administration of TZ or ZP to juvenile mice. Decreased IEG expression was detected in mice with juvenile TZ administration, but not in mice with juvenile ZP administration. Our findings demonstrate that TZ administration during the juvenile period can induce irreversible brain dysfunction in adult mice. It may need to take an extra care for the prescription of benzodiazepine sleep-inducing drugs to juveniles because it might cause late onset learning and memory defects.

  8. Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds123

    Science.gov (United States)

    Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun

    2015-01-01

    Abstract Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood. PMID:26730405

  9. Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds.

    Science.gov (United States)

    Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun; Krimm, Robin F

    2015-01-01

    Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood.

  10. ARGINASE ENZYMES IN ISOLATED AIRWAYS FROM NORMAL AND NITRIC OXIDE SYNTHASE 2-KNOCKOUT MICE EXPOSED TO OVALBUMIN

    Science.gov (United States)

    Bratt, Jennifer M.; Franzi, Lisa M.; Linderholm, Angela L.; Last, Michael S.; Kenyon, Nicholas J.; Last, Jerold A.

    2009-01-01

    Arginase has been suggested to compete with nitric oxide synthase (NOS) for their common substrate, L-arginine. To study the mechanisms underlying this interaction, we compared arginase expression in isolated airways and the consequences of inhibiting arginase activity in vivo with NO production, lung inflammation, and lung function in both C57BL/6 and NOS2 knockout mice undergoing ovalbumin-induced airway inflammation, a mouse model of asthma. Arginases I and II were measured by western blot in isolated airways from sensitized C57BL/6 mice exposed to ovalbumin aerosol. Physiological and biochemical responses---inflammation, lung compliance, airway hyperreactivity, exhaled NO concentration, arginine concentration--were compared with the responses of NOS2 knockout mice. NOS2 knockout mice had increased total cells in lung lavage, decreased lung compliance, and increased airway hyperreactivity. Both arginase I and arginase II were constitutively expressed in the airways of normal C57BL/6 mice. Arginase I was up-regulated approximately 8-fold in the airways of C57BL/6 mice exposed to ovalbumin. Expression of both arginase isoforms were significantly upregulated in NOS2 knockout mice exposed to ovalbumin, with about 40- and 4-fold increases in arginases I and II, respectively. Arginine concentration in isolated airways was not significantly different in any of the groups studied. Inhibition of arginase by systemic treatment of C57BL/6 mice with a competitive inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA), significantly decreased the lung inflammatory response to ovalbumin in these animals. We conclude that NOS2 knockout mice are more sensitive to ovalbumin-induced airway inflammation and its sequelae than are C57BL/6 mice, as determined by increased total cells in lung lavage, decreased lung compliance, and increased airway hyperreactivity, and that these findings are strongly correlated with increased expression of both arginase isoforms in the airways of the NOS2

  11. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

    Science.gov (United States)

    Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

    2018-03-16

    Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  12. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice

    Directory of Open Access Journals (Sweden)

    Kayla A. Quirin

    2018-03-01

    Full Text Available Recombinant adeno-associated virus (rAAV-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9 expressing GFP in a self-complementary (sc AAV vector under an EF1α promoter (scAAV.GFP following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 1012 viral genomes (vg. Intraductal delivery of 1 × 1011 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 1011 vg. In a KrasG12D-driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  13. Characteristics of multi-organ lymphangiectasia resulting from temporal deletion of calcitonin receptor-like receptor in adult mice.

    Directory of Open Access Journals (Sweden)

    Samantha L Hoopes

    Full Text Available Adrenomedullin (AM and its receptor complexes, calcitonin receptor-like receptor (Calcrl and receptor activity modifying protein 2/3, are highly expressed in lymphatic endothelial cells and are required for embryonic lymphatic development. To determine the role of Calcrl in adulthood, we used an inducible Cre-loxP system to temporally and ubiquitously delete Calcrl in adult mice. Following tamoxifen injection, Calcrl(fl/fl/CAGGCre-ER™ mice rapidly developed corneal edema and inflammation that was preceded by and persistently associated with dilated corneoscleral lymphatics. Lacteals and submucosal lymphatic capillaries of the intestine were also dilated, while mesenteric collecting lymphatics failed to properly transport chyle after an acute Western Diet, culminating in chronic failure of Calcrl(fl/fl/CAGGCre-ER™ mice to gain weight. Dermal lymphatic capillaries were also dilated and chronic edema challenge confirmed significant and prolonged dermal lymphatic insufficiency. In vivo and in vitro imaging of lymphatics with either genetic or pharmacologic inhibition of AM signaling revealed markedly disorganized lymphatic junctional proteins ZO-1 and VE-cadherin. The maintenance of AM signaling during adulthood is required for preserving normal lymphatic permeability and function. Collectively, these studies reveal a spectrum of lymphatic defects in adult Calcrl(fl/fl/CAGGCre-ER™ mice that closely recapitulate the clinical symptoms of patients with corneal, intestinal and peripheral lymphangiectasia.

  14. Characteristics of multi-organ lymphangiectasia resulting from temporal deletion of calcitonin receptor-like receptor in adult mice.

    Science.gov (United States)

    Hoopes, Samantha L; Willcockson, Helen H; Caron, Kathleen M

    2012-01-01

    Adrenomedullin (AM) and its receptor complexes, calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2/3, are highly expressed in lymphatic endothelial cells and are required for embryonic lymphatic development. To determine the role of Calcrl in adulthood, we used an inducible Cre-loxP system to temporally and ubiquitously delete Calcrl in adult mice. Following tamoxifen injection, Calcrl(fl/fl)/CAGGCre-ER™ mice rapidly developed corneal edema and inflammation that was preceded by and persistently associated with dilated corneoscleral lymphatics. Lacteals and submucosal lymphatic capillaries of the intestine were also dilated, while mesenteric collecting lymphatics failed to properly transport chyle after an acute Western Diet, culminating in chronic failure of Calcrl(fl/fl)/CAGGCre-ER™ mice to gain weight. Dermal lymphatic capillaries were also dilated and chronic edema challenge confirmed significant and prolonged dermal lymphatic insufficiency. In vivo and in vitro imaging of lymphatics with either genetic or pharmacologic inhibition of AM signaling revealed markedly disorganized lymphatic junctional proteins ZO-1 and VE-cadherin. The maintenance of AM signaling during adulthood is required for preserving normal lymphatic permeability and function. Collectively, these studies reveal a spectrum of lymphatic defects in adult Calcrl(fl/fl)/CAGGCre-ER™ mice that closely recapitulate the clinical symptoms of patients with corneal, intestinal and peripheral lymphangiectasia.

  15. Position and width of normal adult optic chiasm as measured in coronal MRI

    International Nuclear Information System (INIS)

    Kim, Myung Soon; Park, Jin Sook

    1994-01-01

    To evaluate the position and transverse dimension of the adult optic chiasm in normal Korean adult. The authors analysed 3D coronal volume images (TR/TE=30/13, flip angle=30 .deg. ) of 136 normal adult subjects without known visual abnormality. All MRI examinations were performed using a 0.5T system. MRI was reviewed retrospectively to determine the position (horizontal and tilted) of the potic chiosm and the transverse dimension of the optic chiasm was measured. Seventy- five (55%) of the 136 normal subjects had horizontal position, and sixty-one (45%) had tilted position. Thirty- eight (62%) of 61 with tilted position showed higher position on the right side, and twenty-three (38%) showed higher position on the side. The average transverse dimension(mean SD) was 15.2 ± 0.7mm in men and 14.6 ± 1.0mm in women. The difference of transverse dimension between men and women was statistically significant. Tilted position of the adult optic chiasm on coronal MRI was seen in approximately half of normal adults. The average of transverse dimension of normal optic chiasm was 15mm

  16. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

    Science.gov (United States)

    Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

    2015-05-01

    Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. Myosin heavy chain isoform expression in adult and juvenile mini-muscle mice bred for high-voluntary wheel running.

    Science.gov (United States)

    Talmadge, Robert J; Acosta, Wendy; Garland, Theodore

    2014-11-01

    The myosin heavy chain (MyHC) isoform composition of locomotor and non-locomotor muscles of mini-muscle mice were assessed at the protein and mRNA levels in both adult and juvenile (21 day old) mice. Mini-muscle mice are one outcome of a replicated artificial selection experiment in which four lines of mice were bred for high voluntary wheel running (HR lines). Two of the lines responded with an increase in frequency of a single nucleotide polymorphism in an intron in the MyHC-2b gene (myh4) that when homozygous causes a dramatic reduction in triceps surae mass. We found that both locomotor and non-locomotor muscles of adult mini-muscle mice displayed robust reductions, but not elimination, of the MyHC-2b isoform at both the protein and mRNA levels, with commensurate increases in MyHC-2x and sometimes MyHC-2a, as compared with either a line of HR mice that does not display the mini-muscle phenotype or inbred C57Bl6 mice. Immunohistochemical analyses revealed that locomotor muscles of mini-muscle mice contain fibers that express the MyHC-2b isoform, which migrates normally in SDS-PAGE gels. However, these MyHC-2b positive fibers are generally smaller than the surrounding fibers and smaller than the MyHC-2b positive fibers of non-mini-muscle mice, resulting in characteristically fast muscles that lack a substantial MyHC-2b positive (superficial) region. In contrast, the masseter, a non-locomotor muscle of mini-muscle mice contained MyHC-2b positive fibers that stained more lightly for MyHC-2b, but appeared normal in size and distribution. In adults, many of the MyHC-2b positive fibers in the mini-muscle mice also display central nuclei. Only a small proportion of small MyHC-2b fibers in mini-muscle mice stained positive for the neural cell adhesion molecule, suggesting that anatomical innervation was not compromised. In addition, weanling (21 day old), but not 5 day old mice, displayed alterations in MyHC isoform content at both the protein and mRNA levels, including

  18. Normal weight obesity among young adults in Trinidad and Tobago: prevalence and associated factors.

    Science.gov (United States)

    Ramsaran, Cherrita; Maharaj, Rohan G

    2017-04-01

    Patients with normal weight obesity (NWO) have a normal body mass index (BMI) but elevated body fat percentage (BF%), thereby increasing their risk of cardiovascular and metabolic disorders. The purpose of this research was to determine the prevalence of NWO and its associated factors in a sample of young adults in Trinidad and Tobago (T&T). A cross sectional study involving a convenience non-voluntary sample of participants with a normal BMI of 18.5-24.9 kg/m2 was conducted. The following information was collected: history, basic anthropometric measurements, including BF% via the Tanita Ironman Body Composition Analyzer (BC554), physical examination and basic blood investigations. Participants were divided into two groups; normal BF% (young adult population was found to have NWO. Long-term studies are recommended to study the full implications of these findings.

  19. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

    DEFF Research Database (Denmark)

    Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

    2014-01-01

    to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

  20. Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

    Science.gov (United States)

    Wierman, Margaret E; Xu, Mei; Pierce, A; Bliesner, B; Bliss, S P; Roberson, M S

    2012-01-01

    Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron. Copyright © 2011 S. Karger AG, Basel.

  1. Uptake of elemental mercury and activity of catalase in rat, hamster, guinea-pig, normal and acatalasemic mice

    International Nuclear Information System (INIS)

    Eide, I.; Syversen, T.L.M.

    1982-01-01

    Uptake of elemental mercury after inhalation (3.5 mg/m 3 ) and the activity of catalase in brain, liver, kidney and blood were investigated in rat, hamster, guinea-pig, and normal and acatalasemic mice. The uptake of mercury in the species investigated varied considerably, being highest in the two strains of mice, followed by rat and hamster, and lowest in the guinea-pig. The uptake seemed to be more dependent on pulmonary ventilation than on the activity of catalase. The two strains of mice were exposed to a wide range of mercury concentrations in air (0.002-3.5 mg/m 3 ). The content of mercury in brain, liver and kidney was linearly dependent on the mercury concentration in the air, whereas in blood this relationship was exponential. At the lower concentraions of mercury in the inhaled air, the mercury level in blood was significantly lower, and in kidney higher in the acatalasemic mice compared to the normal ones. In acatalasemic mice the mercury content in the liver has higher at all concentrations investigated, whereas in brain no difference between the two strains was found. (author)

  2. Long-lasting Effects of Minocycline on Behavior in Young but not Adult Fragile X Mice

    Science.gov (United States)

    Dansie, Lorraine E.; Phommahaxay, Kelly; Okusanya, Ayodeji G.; Uwadia, Jessica; Huang, Mike; Rotschafer, Sarah E.; Razak, Khaleel A.; Ethell, Douglas W.; Ethell, Iryna M.

    2013-01-01

    Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder (OCD). Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in “fragile X mental retardation gene” knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines - postsynaptic sites for excitatory synapses - in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4 and 8 week long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model. PMID:23660195

  3. Increasing the effectiveness of intracerebral injections in adult and neonatal mice: a neurosurgical point of view.

    Science.gov (United States)

    Mathon, Bertrand; Nassar, Mérie; Simonnet, Jean; Le Duigou, Caroline; Clemenceau, Stéphane; Miles, Richard; Fricker, Desdemona

    2015-12-01

    Intracerebral injections of tracers or viral constructs in rodents are now commonly used in the neurosciences and must be executed perfectly. The purpose of this article is to update existing protocols for intracerebral injections in adult and neonatal mice. Our procedure for stereotaxic injections in adult mice allows the investigator to improve the effectiveness and safety, and save time. Furthermore, for the first time, we describe a two-handed procedure for intracerebral injections in neonatal mice that can be performed by a single operator in a very short time. Our technique using the stereotaxic arm allows a higher precision than freehand techniques previously described. Stereotaxic injections in adult mice can be performed in 20 min and have >90% efficacy in targeting the injection site. Injections in neonatal mice can be performed in 5 min. Efficacy depends on the difficulty of precisely localizing the injection sites, due to the small size of the animal. We describe an innovative, effortless, and reproducible surgical protocol for intracerebral injections in adult and neonatal mice.

  4. Assessment of various hilar measurements on PA chest of Korean normal adults

    International Nuclear Information System (INIS)

    Ro, Hee Jeong; Kim, Hyun; Kang, Si Won; Park, Seog Hee; Bahk, Yong Whee

    1990-01-01

    Appreciation of the normal position of the hila is essential in screening and diagnosis of the diseases of the chest. Many authors assessed the hilar position in normal adults using PA chest roentgenograms. However there have been no previous publication regarding consolidated assessment of various measurements. The authors carried out the present study to evaluate various hilar measurements including hilar points, hilar distances, difference between both hilar heights, hilar height ratio, and the relationship between the level of the clavicle and hila on the 500 normal PA chest roentgenograms

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

    OpenAIRE

    Vidal Gómez, José

    2013-01-01

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

  6. Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

    Science.gov (United States)

    Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

    2013-01-31

    Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

  7. Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

    Science.gov (United States)

    Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K

    1995-08-01

    The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

  8. Attitudes of Overweight and Normal Weight Adults Regarding Exercise at a Health Club

    Science.gov (United States)

    Miller, Wayne C.; Miller, Todd A.

    2010-01-01

    Objective: To compare attitudes of overweight (OW) and normal weight (NW) adults regarding health club exercise. Design: A 46-item survey (23 pairs of attitude/value statements) measured attitudes toward exercising at a health club 30 minutes, twice a week, for a month. Setting: Survey posted on surveymonkey.com. Respondents (men = 730, women =…

  9. Cell Proliferation during Lymphopoiesis in the Thymus of Normal and Continuously Irradiated Mice

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J. I. [Department of Radiological Science, Johns Hopkins University, Baltimore, MD (United States)

    1968-08-15

    The patterns of lymphoid cell proliferation in the thymus and spleen in normal and continuously irradiated young C57BL mice have been examined with techniques of flash and repeated labelling with tritiated thymidine and high resolution autoradiography. Changes in percentage labelling indices and labelled mitoses data have provided information on sites and rates of lymphoid cell proliferation in the thymus cortex (reticular cells, large, medium and small lymphocytes) and the spleen white pulp (germinal centre cells, large, medium and small lymphocytes). Labelling rates were fastest in the more primitive cell forms; in both lymphoid organs, the stem-cell labelling - reticular cells and germinal centre cells - reached 100% rapidly, whereas this was not the case for the different lymphocyte populations, and thymic lymphopoiesis was more rapid than splenic lymphopoiesis. Mean cycle times for thymus lymphoid cells were {approx} 12.5 hours for reticular cells, {approx} 9.5 hours for large lymphocytes, and {approx} 10.0 hours for medium and small lymphocytes; in the spleen, representative cycle times were significantly longer. Small lymphocytes were replaced at a greater rate in the thymus than in the spleen. Under continuous {gamma}-irradiation (caesium-137) at 45 rad/day and 75 rad/day for 15 days, there was a progressive depopulation of all lymphoid cell classes, an increase in the relative proportion of the more primitive forms, and a marked decrease in the numbers of small lymphocytes in both tissues. In the thymus and in the spleen, there was an increase in proliferation rates in both stem-cell populations and in all lymphoid cell forms, a decrease in mean cell cycle times to shorter values and a possible reduction in the spread of cell cycle times. In irradiated tissues, there was little evidence for lymphoid cell emigration. Tentative patterns of lymphopoiesis in the normal thymus and spleen based on the autoradiographic data aredescribed and changes in the

  10. Effects of acute exposure to chlorpyrifos on cholinergic and non-cholinergic targets in normal and high-fat fed male C57BL/6J mice.

    Science.gov (United States)

    Kondakala, Sandeep; Lee, Jung Hwa; Ross, Matthew K; Howell, George E

    2017-12-15

    The prevalence of obesity is increasing at an alarming rate in the United States with 36.5% of adults being classified as obese. Compared to normal individuals, obese individuals have noted pathophysiological alterations which may alter the toxicokinetics of xenobiotics and therefore alter their toxicities. However, the effects of obesity on the toxicity of many widely utilized pesticides has not been established. Therefore, the present study was designed to determine if the obese phenotype altered the toxicity of the most widely used organophosphate (OP) insecticide, chlorpyrifos (CPS). Male C57BL/6J mice were fed normal or high-fat diet for 4weeks and administered a single dose of vehicle or CPS (2.0mg/kg; oral gavage) to assess cholinergic (acetylcholinesterase activities) and non-cholinergic (carboxylesterase and endocannabinoid hydrolysis) endpoints. Exposure to CPS significantly decreased red blood cell acetylcholinesterase (AChE) activity, but not brain AChE activity, in both diet groups. Further, CPS exposure decreased hepatic carboxylesterase activity and hepatic hydrolysis of a major endocannabinoid, anandamide, in a diet-dependent manner with high-fat diet fed animals being more sensitive to CPS-mediated inhibition. These in vivo studies were corroborated by in vitro studies using rat primary hepatocytes, which demonstrated that fatty acid amide hydrolase and CES activities were more sensitive to CPS-mediated inhibition than 2-arachidonoylglycerol hydrolase activity. These data demonstrate hepatic CES and FAAH activities in high-fat diet fed mice were more potently inhibited than those in normal diet fed mice following CPS exposure, which suggests that the obese phenotype may exacerbate some of the non-cholinergic effects of CPS exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Reaffirming normal: the high risk of pathologizing healthy adults when interpreting the MMPI-2-RF.

    Science.gov (United States)

    Odland, Anthony P; Lammy, Andrew B; Perle, Jonathan G; Martin, Phillip K; Grote, Christopher L

    2015-01-01

    Monte Carlo simulations were utilized to determine the proportion of the normal population expected to have scale elevations on the MMPI-2-RF when multiple scores are interpreted. Results showed that when all 40 MMPI-2-RF scales are simultaneously considered, approximately 70% of normal adults are likely to have at least one scale elevation at or above 65 T, and as many as 20% will have five or more elevated scales. When the Restructured Clinical (RC) Scales are under consideration, 34% of normal adults have at least one elevated score. Interpretation of the Specific Problem Scales and Personality Psychopathology Five Scales--Revised also yielded higher than expected rates of significant scores, with as many as one in four normal adults possibly being miscategorized as having features of a personality disorder by the latter scales. These findings are consistent with the growing literature on rates of apparently abnormal scores in the normal population due to multiple score interpretation. Findings are discussed in relation to clinical assessment, as well as in response to recent work suggesting that the MMPI-2-RF's multiscale composition does not contribute to high rates of elevated scores.

  12. Effects of cage density on behavior in young adult mice.

    Science.gov (United States)

    Davidson, Lauren P; Chedester, Alan L; Cole, Marlene N

    2007-08-01

    Optimal housing conditions for mice can be achieved by minimizing environmental variables, such as those that may contribute to anxiety-like behavior. This study evaluated the effects of cage size on juvenile mice through assessment of differences in weaning weight, locomotor skills, and anxiety-like behavior. Eighteen pairs of male and pregnant female Swiss-Webster (Cr:SW) mice were housed in 3 different caging scenarios, providing 429, 505, or 729 cm2 of space. Litters were standardized to 10 pups per litter in each cage. Mice reared in each caging scenario were assessed with the open-field, light-dark exploration, and elevated plus-maze tests. No differences in weaning weight were noted. Mice reared in the 505- and 729-cm2 cages explored a significantly larger area of the open-field arena than did those in the 429-cm2 cages. Those reared in the 505-cm2 cages spent more time in the center of the open field than did those in the 729-cm2 cages, suggesting that anxiety-like behavior may be increased in the animals housed in the larger cages. This study did not establish a consistent link between decreased floor space and increased anxiety-like behavior; neither does there appear to be a consistent effect of available floor area on the development of locomotor skills on mouse pups.

  13. Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

    Science.gov (United States)

    Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

    1991-02-01

    In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

  14. In vivo P-31 MR spectroscopic studies of liver in normal adults and cirrhotic patients

    International Nuclear Information System (INIS)

    Ban, N.; Moriyasu, F.; Tamada, T.

    1986-01-01

    The author performed in vivo P-31 MR spectroscopic studies of normal and diseased human liver using an experimental 2.0-T whole-body MR imager. Then normal adults and ten cirrhotic patients in the fasting state were studied. Spatially localized in vivo P-31 MR spectra of human liver were obtained in combination with the use of a surface coil and gradient magnetic field. Six spectral peaks were observed in both groups and were assigned, from left to right, to phosphomonoester, inorganic phosphate, phosophodiester, γ-ATP, α-ATP, and β-ATP, on the basis of the chemical shifts. There were no definite differences between the spectral patterns of normal adults and those of cirrhotic patients in the fasting state

  15. Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

    Science.gov (United States)

    Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

    2017-05-30

    We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast

  16. Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice.

    Directory of Open Access Journals (Sweden)

    Budd A Tucker

    2011-04-01

    Full Text Available This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs, could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease.

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

    Directory of Open Access Journals (Sweden)

    Nye David J

    2010-09-01

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

  18. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    Science.gov (United States)

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

    Directory of Open Access Journals (Sweden)

    Fei He

    Full Text Available Disorders of sexual development (DSD encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E18.5 and adult mice revealed shortened anogenital distance (AGD, open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans.

  20. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

    Science.gov (United States)

    Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

    2017-09-05

    Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Mechanism of infectivity of a murine leukemia virus in adult mice

    International Nuclear Information System (INIS)

    Levy, R.L.; Barrington, M.H.; Lerner, R.A.; Dixon, F.J.

    1976-01-01

    Infection of adult BALB/c mice with murine leukemia virus (MuLV) induces typical thymic lymphomas. Expression of virus was measured by using a radioimmunoassay for murine P-30, a virion core protein. Nineteen days after injection of MuLV-S into adult mice, there were 0.3μg P-30/ml of serum. X-irradiation permitted the early expression of high levels of viremia, when given before or after MuLV-S administration, and it also hastened the development of lymphomas. Seventeen to 21 days after injection of MuLV-S into x-irradiated (600 rads) adult mice, there were 2.7 μg of P-30/ml of serum. The virus produced by infected adult mice was infectious and oncogenic when given to newborn mice. Several lines of evidence are presented that suggest the mechanism by which x-irradiation permits early expession of virion proteins and lymphomas is not immunosuppression

  2. Preparation, distribution, stability and tumor imaging properties of [62Zn] Bleomycin complex in normal and tumor-bearing mice

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Fateh, B.; Ghergherehchi, M.; Karimian, A.; Matloobi, M.; Moradkhani, S.; Kamalidehghan, M.; Tabeie, F.

    2003-01-01

    Backgrounds: Bleomycin (BLM) has been labeled with radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [ 62 Zn] zinc chloride for oncologic PET studies. Materials and methods: The complex was obtained at the P H=2 normal saline at 90 d eg C in 60 min. Radio-TLC showed on overall radiochemical yield of 95-97% (radiochemical purity>97%). Stability of complex was checked in vitro in mice and human plasma/urine. Results: Preliminary in vitro studies performed to determined complex stability and distribution of [ 62 Zn] BLM in normal and fibrosarcoma tumors in mice according to bio-distribution/imaging studies. Conclusion: [ 62 Zn] BLM can be used in PET oncology studies due to its suitable physico-chemical propertied as a diagnostic complex behavior in higher animals

  3. Brain regional uptake of radioactive Sc, Mn, Zn, Se, Rb and Zr tracers into normal mice during aging

    International Nuclear Information System (INIS)

    Amano, R.; Enomoto, S.

    2001-01-01

    Radioactive multitracer technique was applied to study the brain regional uptake of trace elements by the normal mice during aging. The brain regional radioactivities of 46 Sc, 54 Mn, 65 Zn, 75 Se, 83 Rb and 88 Zr were measured 48 hours after intraperitoneal injection of a solution in normal mice aged 6 to 52 weeks to evaluate the brain regional (corpus striatum, cerebellum, cerebral cortex, hippocampus, and pons and medulla) uptakes. The radioactive distributions of 46 Sc, 54 Mn and 88 Zr tracers were variable and region-specific in the brain, while those of 65 Zn, 75 Se and 83 Rb tracers were comparable among all regions of interest. The brain regional uptakes of all tracers slightly increased with age from 10 to 28 weeks, and then remained constant during aging after 28 weeks. These uptake variations may be involved in the functional degenerative process of the blood-brain barrier during aging. (author)

  4. Static and dynamic postural control in low-vision and normal-vision adults.

    Science.gov (United States)

    Tomomitsu, Mônica S V; Alonso, Angelica Castilho; Morimoto, Eurica; Bobbio, Tatiana G; Greve, Julia M D

    2013-04-01

    This study aimed to evaluate the influence of reduced visual information on postural control by comparing low-vision and normal-vision adults in static and dynamic conditions. Twenty-five low-vision subjects and twenty-five normal sighted adults were evaluated for static and dynamic balance using four protocols: 1) the Modified Clinical Test of Sensory Interaction on Balance on firm and foam surfaces with eyes opened and closed; 2) Unilateral Stance with eyes opened and closed; 3) Tandem Walk; and 4) Step Up/Over. The results showed that the low-vision group presented greater body sway compared with the normal vision during balance on a foam surface (p≤0.001), the Unilateral Stance test for both limbs (p≤0.001), and the Tandem Walk test. The low-vision group showed greater step width (p≤0.001) and slower gait speed (p≤0.004). In the Step Up/Over task, low-vision participants were more cautious in stepping up (right p≤0.005 and left p≤0.009) and in executing the movement (p≤0.001). These findings suggest that visual feedback is crucial for determining balance, especially for dynamic tasks and on foam surfaces. Low-vision individuals had worse postural stability than normal-vision adults in terms of dynamic tests and balance on foam surfaces.

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

    Science.gov (United States)

    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.

  6. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

    Science.gov (United States)

    Kilpatrick, L A; Li, Q; Yang, J; Goddard, J C; Fekete, D M; Lang, H

    2011-06-01

    Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

  7. Bone marrow cellularity in normal and polycythemic mice estimated by DNA incorporation of /sup 3/H-TdR

    Energy Technology Data Exchange (ETDEWEB)

    Blackwell, L.H.; Ledney, G.D.

    1982-07-01

    Nucleated bone marrow cell numbers in normal and polycythemic mice were determined using /sup 3/H-thymidine (/sup 3/H-TdR). The cellularities were estimated by extrapolating the exponential disappearance of labeled cells after a single injection of /sup 3/H-TdR to the time of injection. Dermestid beetles (Anthrenus piceus) were used to prepare tissue-free skeletons labeled with /sup 3/H-TdR. The correlation between tritium activity in bone marrow DNA and tritium derived from the combusted skeleton was determined. The total skeletal cellularity determined by isotope dilution analysis in both normal and polycythemic mice was 2.6 x 10(8) cells/mouse or 17.6 x 10(9) cells/kg body weight. Although the red cell component of the marrow was reduced in the polycythemic mouse, the total numbers of nucleated cells in both types of animals were similar. The differential distribution of cells in the polycythemic animal showed a twofold increase in granulocytic cells, which may explain the identical nucleated cell count in normal and in polycythemic mice.

  8. Different perception levels of histamine-induced itch sensation in young adult mice.

    Science.gov (United States)

    Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

    2018-05-01

    Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Food restriction increases long-term memory persistence in adult or aged mice.

    Science.gov (United States)

    Talhati, F; Patti, C L; Zanin, K A; Lopes-Silva, L B; Ceccon, L M B; Hollais, A W; Bizerra, C S; Santos, R; Tufik, S; Frussa-Filho, R

    2014-04-03

    Food restriction (FR) seems to be the unique experimental manipulation that leads to a remarkable increase in lifespan in rodents. Evidences have suggested that FR can enhance memory in distinct animal models mainly during aging. However, only few studies systemically evaluated the effects FR on memory formation in both adult (3-month-old) and aged (18-24-month-old) mice. Thus, the aim of the present study was to investigate the effects of acute (12h) or repeated (12h/day for 2days) FR protocols on learning and memory of adult and aged mice evaluated in the plus-maze discriminative avoidance task (PM-DAT), an animal model that concurrently (but independently) evaluates learning and memory, anxiety and locomotion. We also investigated the possible role of FR-induced stress by the corticosterone concentration in adult mice. Male mice were kept at home cage with food ad libitum (CTRL-control condition) or subjected to FR during the dark phase of the cycle for 12h/day or 12h/2days. The FR protocols were applied before training, immediately after it or before testing. Our results demonstrated that only FR for 2days enhanced memory persistence when applied before training in adults and before testing in aged mice. Conversely, FR for 2days impaired consolidation and exerted no effects on retrieval irrespective of age. These effects do not seem to be related to corticosterone concentration. Collectively, these results indicate that FR for 2days can promote promnestic effects not only in aged mice but also in adults. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Effect of acetylsalicylic acid on spermatogenesis in adult albino mice

    International Nuclear Information System (INIS)

    Ameer, M.K.; Tahrir, M.

    2015-01-01

    Spermatogenesis in male albino mice. Study Design: Laboratory based randomized controlled trial. Place and Duration of Study: Department of Anatomy University of Health Sciences, Lahore from Apr, 2012 to Dec, 2012. Material and Methods: Thirty nine male albino mice, 6-8 weeks old weighing 30 - 5 gm, were used; these were randomly divided into three groups having thirteen mice in each using random numbers table. Group A served as a control and was given distilled water orally via oral gavage 10 ml per kg for 30 days. Group B was given acetylsalicylic acid 100 mg/kg dissolved in 10 ml distilled orally for a period of 30 days. Group C was given acetylsalicylic acid 25 mg/kg dissolved in 2.5 ml distilled orally for a period of 30 days. Animals were sacrificed 24 hours after the last dose and the testes were removed, fixed in Bouin's fixative for 48 hours. Five microns thick sections of processed tissue were stained with H and E and PAS for calculation of Johnsen score and diameter of seminiferous tubules. Serum testosterone level was measured by testosterone enzyme immunoassay test kits. Results: Microscopic examination demonstrated that ASA treatment lead to statistically significant increase in the mean Johnsen score and mean diameter of seminiferous tubules. Conclusion: It was concluded from the current study that ASA treatment enhances spermatogenesis. (author)

  11. Studies by radioiodination of normal adult, fetal and leukemic cell membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kannourakis, G; Cauchi, M N [Department of Pathology and Immunology, Monash Medical School, Melbourne, Australia

    1978-01-01

    A comparison was made between cord blood lymphocytes, normal adult lymphocytes and leukemic cells after membrane iodination with lactoperoxidase. A double-labeling technique using lactoperoxidase iodination with /sup 125/I and /sup 131/I followed by analysis on polyacrylamide gel electrophoresis revealed a number of membrane differences between leukemic, normal and fetal cells. There was a reduction in the 70,000 molecular weight component in cord blood cells compared to adult lymphocytes, and an increase in membrane peptides with molecular weights of 35,000, 20,000, 9,000 and 4,000. Although smaller molecular weight peptides were also present in chronic lymphatic leukemia as well as acute myeloid leukemia, these were shown to be distinct from fetal type membrane components.

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

    Directory of Open Access Journals (Sweden)

    Kirsten Madsen

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

  13. P2Y2 receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb

    Directory of Open Access Journals (Sweden)

    Rita Delgado Marques

    2013-10-01

    Full Text Available Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleotides on ion transport in the thick ascending limb. In the medullary thick ascending limb (mTAL, basolateral P2X receptors markedly (~25% inhibit NaCl absorption. Although this segment does express both apical and basolateral P2Y2 receptors, acute activation of the basolateral P2Y2 receptors had no apparent effect on transepithelial ion transport. Here we studied, if the absence of the P2Y2 receptor causes chronic alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated transepithelial transport rates. We used perfused mouse mTALs to electrically measure NaCl absorption in juvenile (35 days male mice. Using microelectrodes, we determined the transepithelial voltage (Vte and the transepithelial resistance (Rte and thus, transepithelial NaCl absorption (equivalent short circuit current, I’sc.We find that mTALs from adult wild type (WT mice have significantly lower NaCl absorption rates when compared to mTALs from juvenile WT mice. This could be attributed to significantly higher Rte values in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y2 receptor knockout (KO mice. In addition, adult P2Y2 receptor KO mTALs have significantly lower Vte values compared to the juvenile. No difference in absolute I´sc was observed when comparing mTALs from WT and KO mice. AVP stimulated the mTALs to similar increases of NaCl absorption irrespective of the absence of the P2Y2 receptor. No difference was observed in the medullary expression level of NKCC2 in between the genotypes.These data indicate that the lack of P2Y2 receptors does not cause substantial differences in resting and AVP-stimulated NaCl absorption in

  14. Gender Dependence in Mouth Opening Dimensions in Normal Adult Malaysians Population

    OpenAIRE

    Shaari, Ramizu; Hwa, Teoh Eng; Rahman, Shaifulizan Abdul

    2011-01-01

    While measurement of mouth opening is an important clinica examination in diagnosis and management of oral disease, data on non-Western populations are limited. This study was therefore conducted to determine the range of mouth opening in normal Malaysian male and female adults. A total of 34 dental students of Universiti Sains Malaysia (USM) were chosen randomly and their maximum mouth opening was measured after being asked to open their mouth sufficiently to accommodate three fingers. Measu...

  15. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

    Science.gov (United States)

    La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

    2016-11-01

    Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

  16. Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells.

    Science.gov (United States)

    Qiu, Xiaoliang; Dowling, Abigail R; Marino, Joseph S; Faulkner, Latrice D; Bryant, Benjamin; Brüning, Jens C; Elias, Carol F; Hill, Jennifer W

    2013-03-01

    Pubertal onset only occurs in a favorable, anabolic hormonal environment. The neuropeptide kisspeptin, encoded by the Kiss1 gene, modifies GnRH neuronal activity to initiate puberty and maintain fertility, but the factors that regulate Kiss1 neurons and permit pubertal maturation remain to be clarified. The anabolic factor insulin may signal nutritional status to these neurons. To determine whether insulin sensing plays an important role in Kiss1 neuron function, we generated mice lacking insulin receptors in Kiss1 neurons (IR(ΔKiss) mice). IR(ΔKiss) females showed a delay in vaginal opening and in first estrus, whereas IR(ΔKiss) males also exhibited late sexual maturation. Correspondingly, LH levels in IR(ΔKiss) mice were reduced in early puberty in both sexes. Adult reproductive capacity, body weight, fat composition, food intake, and glucose regulation were comparable between the 2 groups. These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states.

  17. Esophageal Clearance Patterns in Normal Older Adults as Documented with Videofluoroscopic Esophagram

    Directory of Open Access Journals (Sweden)

    Janice Jou

    2009-01-01

    Full Text Available Normal esophageal bolus transport in asymptomatic healthy older adults has not been well defined, potentially leading to ambiguity in differentiating esophageal swallowing patterns of dysphagic and healthy individuals. This pilot study of 24 young (45–64 years and old (65+years men and women was designed to assess radiographic esophageal bolus movement patterns in healthy adults using videofluoroscopic recording. Healthy, asymptomatic adults underwent videofluoroscopic esophagram to evaluate for the presence of ineffective esophageal clearance, namely, intraesophageal stasis and intraesophageal reflux. Intraesophageal stasis and intraesophageal reflux were visualized radiographically in these normal subjects. Intraesophageal stasis occurred significantly more frequently with semisolid (96% compared with liquid (16% barium, suggesting that a variety of barium consistencies, as opposed to only the traditional fluids, would better define the spectrum of esophageal transport. Intraesophageal reflux was observed more frequently in older males than in their younger counterparts. The rates of intraesophageal stasis and intraesophageal reflux were potentially high given that successive bolus presentations were spaced 10 seconds apart. These findings suggest a need for a more comprehensive definition regarding the range of normal esophageal bolus transport to (a prevent misdiagnosis of dysphagia and (b to enhance generalization to functional eating, which involves solid foods in addition to liquids.

  18. Sonographic determination of normal spleen size in an adult African population

    Energy Technology Data Exchange (ETDEWEB)

    Mustapha, Zainab; Tahir, Abdulrahman [Department of Radiology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State (Nigeria); Tukur, Maisaratu [Department of Human Physiology, University of Maiduguri, Maiduguri, Borno State (Nigeria); Bukar, Mohammed [Department of Obstetrics and Gynaecology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State (Nigeria); Lee, Wai-Kit, E-mail: leewk33@hotmail.co [Department of Medical Imaging, St. Vincent' s Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065 (Australia)

    2010-07-15

    Objective: The purpose of this study was to determine the normal range of spleen size in an adult African population, and compare the findings to published data to determine any correlation with ethnicity. Materials and methods: Three hundred and seventy-four African adults without conditions that can affect the spleen or splenic abnormalities were evaluated with ultrasonography. Spleen length, width and thickness were measured and spleen volume calculated. Spleen size was correlated with age, gender, height, weight, and body mass index. Results: The mean spleen volume was 120 cm{sup 3}. Spleen volume correlated with spleen width (r = 0.85), thickness (r = 0.83) and length (r = 0.80). Men had a larger mean spleen volume than women. No correlation was found between spleen volume and age, weight, height, or body mass index. Conclusion: Mean spleen volume in African adults is smaller than data from Western sources, and cannot be explained by difference in body habitus.

  19. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    International Nuclear Information System (INIS)

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-01-01

    Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

  20. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

    Science.gov (United States)

    Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

    2014-08-01

    The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance

    Science.gov (United States)

    Ghrelin and the ghrelin receptor (GH secretagogue receptor, GHS-R) are believed to have important roles in energy homeostasis. We describe results from the first studies to be conducted in congenic (N10) adult ghrelin(-/-) and Ghsr(-/-) mice under conditions of both positive (high-fat diet) and nega...

  2. Effects of recombinant human interleukin-8 (rhIL-8) on the bone marrow cells of normal BALB/c mice

    International Nuclear Information System (INIS)

    Liu Yulong; Zhou Jianying; Wang Guoquan; Dai Hong; Duan Yingying; Guo Xiaokui

    2001-01-01

    Objective: To observe the colony formation ability of recombinant human interleukin-8 (rhIL-8) on bone marrow cells (BMCs) of normal mice in vivo. Methods: By means of cells culture and flow cytometry (FCM), the colony-stimulating activity of rhIL-8 on BMCs of normal mice was studied. Results: The experimental studies in vivo demonstrated that rhIL-8 could not changed the counts of CFU-GM and distribution of cell cycle in BMCs. Conclusion: rhIL-8 has no colony-stimulating activity to BMCs of normal mice

  3. [Relationship between the Mandarin acceptable noise level and the personality traits in normal hearing adults].

    Science.gov (United States)

    Wu, Dan; Chen, Jian-yong; Wang, Shuo; Zhang, Man-hua; Chen, Jing; Li, Yu-ling; Zhang, Hua

    2013-03-01

    To evaluate the relationship between the Mandarin acceptable noise level (ANL) and the personality trait for normal-hearing adults. Eighty-five Mandarin speakers, aged from 21 to 27, participated in this study. ANL materials and the Eysenck Personality Questionnaire (EPQ) questionnaire were used to test the acceptable noise level and the personality trait for normal-hearing subjects. SPSS 17.0 was used to analyze the results. ANL were (7.8 ± 2.9) dB in normal hearing participants. The P and N scores in EPQ were significantly correlated with ANL (r = 0.284 and 0.318, P 0.05). Listeners with higher ANL were more likely to be eccentric, hostile, aggressive, and instabe, no ANL differences were found in listeners who were different in introvert-extravert or lying.

  4. The research on biodistribution of 131I-iodosennoside A in normal mice and to evaluate myocardial activity

    International Nuclear Information System (INIS)

    Wang Junhu; Yin Zhiqi; Jiang Cuihua; Jiang Xiao; Li Yue; Zhang Jian; Sun Ziping; Ni Yicheng

    2013-01-01

    Purpose: The objective of this project is to evaluate biodistribution of [ 131 I]-Iodosennoside A in normal mice and explore the feasibility on the diagnosis of myocardial infarction. Methods: Iodogen method was used to radioiodinate sennoside A with 131 I. [ 131 I] Iodosennoside A was intravenously injected into mice. Three groups of mice were killed at 4 h, 24 h and 48 h post injection respectively and the radioactive uptake in major organs were calculated. Rats were subjected to left anterior descending (LAD) coronary artery ligation to induce acute myocardial infarction. Rat models of myocardial infarction were intravenously injected [ 131 I] iodosennoside A. 24 h after injection of [ 131 I] iodosennoside A, the regional distribution of radioiodinated sennoside A was determined by radioactivity counting technique. 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and autoradiography were per- formed with 2 mm thick sections of hearts for postmortem verifications. Results: The study showed high uptake of [ 131 I] iodosennoside A in kidneys and fast blood clearance. At 24 h post injection, radioactivity concentration in infarcted myocardium was over 11.9 times higher than in normal myocardium. Preferential uptake of the [ 131 I] iodosennoside A in necrotic tissue was confirmed by perfect match of images from TTC staining and autoradiography. Conclusion: The result proved that [ 131 I] iodosennoside A has myocardial necrosis affinity and may serve as a marker on the diagnosis of myocardial infarction. (authors)

  5. Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin aα null mice

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Reddy, Ramesh N; Price, S Russ

    2013-01-01

    to thrive and early lethality of most null pups. Work in our laboratory led to the rescue of CnAα-/- mice by supplemental feeding to compensate for a defect in salivary enzyme secretion. The data revealed that, without intervention, knockout mice suffer from severe caloric restriction. Since nutritional...... deprivation is known to significantly alter development, it is imperative that previous conclusions based on CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development...... and function persist in adult CnAα-/- mice including a significant decrease in glomerular filtration rate and an increase in blood urea nitrogen levels. These data indicate that impaired renal development we previously reported was not due to caloric restriction but rather a specific role for CnAα in renal...

  6. Hearts of dystonia musculorum mice display normal morphological and histological features but show signs of cardiac stress.

    Directory of Open Access Journals (Sweden)

    Justin G Boyer

    2010-03-01

    Full Text Available Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue. Based on this localization pattern, we tested whether dystonin-deficiency leads to structural defects in cardiac muscle. Desmin intermediate filament, microfilament, and microtubule subcellular organization appeared normal in dt hearts. Nevertheless, increased transcript levels of atrial natriuretic factor (ANF, 66% beta-myosin heavy chain (beta-MHC, 95% and decreased levels of sarcoplasmic reticulum calcium pump isoform 2A (SERCA2a, 26%, all signs of cardiac muscle stress, were noted in dt hearts. Hearts from two-week old dt mice were assessed for the presence of morphological and histological alterations. Heart to body weight ratios as well as left ventricular wall thickness and left chamber volume measurements were similar between dt and wild-type control mice. Hearts from dt mice also displayed no signs of fibrosis or calcification. Taken together, our data provide new insights into the intricate structure of the sarcomere by situating dystonin in cardiac muscle fibers and suggest that dystonin does not significantly influence the structural organization of cardiac muscle fibers during early postnatal development.

  7. Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor-bearing mice is involved in the immune response.

    Science.gov (United States)

    Xu, Qingyu; Gu, Junfei; Lv, You; Yuan, Jiarui; Yang, Nan; Chen, Juan; Wang, Chunfei; Hou, Xuefeng; Jia, Xiaobin; Feng, Liang; Yin, Guowen

    2018-03-01

    Tumor vascular normalization involved in immune response is beneficial to the chemotherapy of tumors. Recombinant human endostatin (Endostar), an angiogenesis inhibitor, has been demonstrated to be effective in hepatocellular cancer (HCC). However, its vascular normalization in HCC and the role of the immune response in angiogenesis were unclear. In the present study, effects of Endostar on tumor vascular normalization were evaluated in hepatoma 22 (H22) tumor-bearing mice. Endostar was able to inhibit the proliferation and infiltration of tumor cells and improve α-fetoprotein, tumor necrosis factor-α and cyclic adenosine 5'-phosphate levels in the serum of H22-bearing mice, as well as the protein expression levels of the immune factors interferon-γ and cluster of differentiation (CD)86 in liver tissue. Endostar also exhibited more marked downregulation of the levels of vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)-2, MMP-9 and interleukin-17 during day 3-9 treatment, resulting in short-term normalization of tumor blood vessels. The period of vascular normalization was 3-9 days. The results of the present study demonstrated that Endostar was able to induce the period of vascular normalization, contributing to a more efficacious means of HCC treatment combined with other chemotherapy, and this effect was associated with the immune response. It may be concluded that Endostar inhibited immunity-associated angiogenesis behaviors of vascular endothelial cells in response to HCC. The results of the present study provided more reasonable possibility for the combination therapy of Endostar for the treatment of HCC.

  8. Recognition of "real-world" musical excerpts by cochlear implant recipients and normal-hearing adults.

    Science.gov (United States)

    Gfeller, Kate; Olszewski, Carol; Rychener, Marly; Sena, Kimberly; Knutson, John F; Witt, Shelley; Macpherson, Beth

    2005-06-01

    The purposes of this study were (a) to compare recognition of "real-world" music excerpts by postlingually deafened adults using cochlear implants and normal-hearing adults; (b) to compare the performance of cochlear implant recipients using different devices and processing strategies; and (c) to examine the variability among implant recipients in recognition of musical selections in relation to performance on speech perception tests, performance on cognitive tests, and demographic variables. Seventy-nine cochlear implant users and 30 normal-hearing adults were tested on open-set recognition of systematically selected excerpts from musical recordings heard in real life. The recognition accuracy of the two groups was compared for three musical genre: classical, country, and pop. Recognition accuracy was correlated with speech recognition scores, cognitive measures, and demographic measures, including musical background. Cochlear implant recipients were significantly less accurate in recognition of previously familiar (known before hearing loss) musical excerpts than normal-hearing adults (p genre. Implant recipients were most accurate in the recognition of country items and least accurate in the recognition of classical items. There were no significant differences among implant recipients due to implant type (Nucleus, Clarion, or Ineraid), or programming strategy (SPEAK, CIS, or ACE). For cochlear implant recipients, correlations between melody recognition and other measures were moderate to weak in strength; those with statistically significant correlations included age at time of testing (negatively correlated), performance on selected speech perception tests, and the amount of focused music listening following implantation. Current-day cochlear implants are not effective in transmitting several key structural features (i.e., pitch, harmony, timbral blends) of music essential to open-set recognition of well-known musical selections. Consequently, implant

  9. Effect of acetylation on monoclonal antibody ZCE-025 Fab': Distribution in normal and tumor-bearing mice

    International Nuclear Information System (INIS)

    Tarburton, J.P.; Halpern, S.E.; Hagan, P.L.; Sudora, E.; Chen, A.; Fridman, D.M.; Pfaff, A.E.

    1990-01-01

    Studies were performed to determine in vitro and in vivo effects of acetylation on Fab' fragments of ZCE-025, a monoclonal anti-CEA antibody. Isoelectric focusing revealed a drop in isoelectric point of 1.7 pI units following acetylation. Biodistribution studies of acetylated and nonacetylated [111In]Fab' were performed in normal BALB/c mice and in nude mice bearing the T-380 CEA-producing human colon tumor. The acetylated fragments remained in the vascular compartment longer and had significantly diminished renal uptake of 111In compared to controls. While acetylation itself effected a 50% drop in immunoreactivity, tumor uptake of the acetylated and nonacetylated 111In-labeled Fab' fragments was comparable, with the exception of one data point, through 72 h

  10. Immunomodulatory activities of different solvent extracts from Tricholoma matsutake (S. Ito et S. Imai) singer (higher basidiomycetes) on normal mice.

    Science.gov (United States)

    Yin, Xiulian; You, Qinghong; Jiang, Zhonghai

    2012-01-01

    The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.

  11. Intake of Wild Blueberry Powder Improves Episodic-Like and Working Memory during Normal Aging in Mice.

    Science.gov (United States)

    Beracochea, Daniel; Krazem, Ali; Henkouss, Nadia; Haccard, Guillaume; Roller, Marc; Fromentin, Emilie

    2016-08-01

    The number of Americans older than 65 years old is projected to more than double in the next 40 years. Cognitive changes associated to aging can affect an adult's day-to-day functioning. Among these cognitive changes, reasoning, episodic memory, working memory, and processing speed decline gradually over time. Early memory changes include a decline in both working and episodic memory. The aim of the present study was to determine whether chronic (up to 75 days) daily administration of wild blueberry extract or a wild blueberry full spectrum powder would help prevent memory failure associated with aging in tasks involving various forms of memory. Both blueberry ingredients were used in a study comparing young mice (6 months old) to aged mice (18 months old). At this age, mice exhibit memory decline due to aging, which is exacerbated first by a loss in working and contextual (episodic-like) memory. Contextual memory (episodic-like memory) was evaluated using the contextual serial discrimination test. Working and spatial memory were evaluated using the Morris-Water maze test and the sequential alternation test. Statistical analysis was performed using an ANOVA with the Bonferroni post-hoc test. Supplementation with wild blueberry full spectrum powder and wild blueberry extract resulted in significant improvement of contextual memory, while untreated aged mice experienced a decline in such memory. Only the wild blueberry full spectrum powder significantly contributed to an improvement of spatial and working memory versus untreated aged mice. These improvements of cognitive performance may be related to brain oxidative status, acetylcholinesterase activity, neuroprotection, or attenuation of immunoreactivity. Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

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

    2012-03-01

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

  13. Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons.

    Science.gov (United States)

    Ailanen, Liisa; Bezborodkina, Natalia N; Virtanen, Laura; Ruohonen, Suvi T; Malova, Anastasia V; Okovityi, Sergey V; Chistyakova, Elizaveta Y; Savontaus, Eriika

    2018-04-01

    Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPY D βH ) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance. Glycogen structure was characterized by cytofluorometric analysis in isolated hepatocytes and mRNA expression of key enzymes by qPCR. OE-NPY D βH mice displayed decreased labile glycogen fraction relative to stabile fraction (the intermediate form of glycogen) suggesting enhanced glycogen cycling. This was supported by decreased filling of glucose residues in the 10th outer tier of the glycogen molecule, which suggests accelerated glycogen phosphorylation. Metformin reduced fat mass gain in both genotypes, but glucose tolerance was improved mostly in wild-type mice. However, metformin inhibited glycogen accumulation and normalized the ratio between glycogen structures in OE-NPY D βH mice indicating decreased glycogen synthesis. Furthermore, the presence of glucose residues in the 11th tier together with decreased glycogen phosphorylase expression suggested inhibition of glycogen degradation. In conclusion, structural changes in glycogen of OE-NPY D βH mice point to increased glycogen metabolism, which may predispose them to prediabetes. Metformin treatment normalizes these changes and suppresses both glycogen synthesis and phosphorylation, which may contribute to its preventive effect on the onset of diabetes.

  14. An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism.

    Science.gov (United States)

    Meziane, Hamid; Schaller, Fabienne; Bauer, Sylvian; Villard, Claude; Matarazzo, Valery; Riet, Fabrice; Guillon, Gilles; Lafitte, Daniel; Desarmenien, Michel G; Tauber, Maithé; Muscatelli, Françoise

    2015-07-15

    Mutations of MAGEL2 have been reported in patients presenting with autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a neurodevelopmental genetic disorder. This study aimed to determine the behavioral phenotype of Magel2-deficient adult mice, to characterize the central oxytocin (OT) system of these mutant mice, and to test the curative effect of a peripheral OT treatment just after birth. We assessed the social and cognitive behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated or not by a postnatal administration of OT, and determined the effect of this treatment on the brain. Magel2 inactivation induces a deficit in social recognition and social interaction and a reduced learning ability in adult male mice. In these mice, we reveal anatomical and functional modifications of the OT system and show that these defects change from birth to adulthood. Daily administration of OT in the first postnatal week was sufficient to prevent deficits in social behavior and learning abilities in adult mutant male mice. We show that this OT treatment partly restores a normal OT system. Thus, we report that an alteration of the OT system around birth has long-term consequences on behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient pups has a curative effect. Our study reveals that OT plays a crucial role in setting social behaviors during a period just after birth. An early OT treatment in this critical period could be a novel therapeutic approach for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome and autism. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. A study on normal value of eyeball protrusion in Korean adult using CT

    International Nuclear Information System (INIS)

    Song, Chi Sung; Chang, Kee Hyun

    1984-01-01

    CT may be valuably used in determination of proptosis. Normal value of eyeball protrusion was measured in normal Koreans using CT. Among 86 Koreans, 26 have normal both eyes, but 60 have one normal eye with one abnormal eye (chiefly, proptosis and and eyeball tumor). The results of 112 eyes are as follows: Absolute measurement of 'a', that is, the distance between cornea and IZL (interzygomatic line) is 16.0±3.4 mm in male (for 63 eye), 15.7±4.0 mm in female for 49 eyes. Ratio of 'a' over 'A' (A-P diameter of eyeball) is 57±12% is male (for 63 eye), 57±14% in female (for 49 eye) Discrepancy of eyeball protrusion between both eyes is 0.67±1.5 mm (for 26 adults). Practically, normal range of eyeball prtotrusion ('a') is 12.6 mm < male < 19.4 mm, 11.7 mm < female < 19.7 mm. 'a/A' ratio over 70% and over 2mm discrepancy between both eyes are also suggested as genuine exophthalmos

  16. Changes in radiation dose with variations in human anatomy: larger and smaller normal-stature adults.

    Science.gov (United States)

    Marine, Patrick M; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

    2010-05-01

    A systematic evaluation has been performed to study how specific absorbed fractions (SAFs) vary with changes in adult body size, for persons of different size but normal body stature. A review of the literature was performed to evaluate how individual organ sizes vary with changes in total body weight of normal-stature individuals. On the basis of this literature review, changes were made to our easily deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed; SAFs for photons were generated for 10th, 25th, 75th, and 90th percentile adults; and comparisons were made to the reference (50th) percentile SAF values. Differences in SAFs for organs irradiating themselves were between 0.5% and 1.0%/kg difference in body weight, from 15% to 30% overall, for organs within the trunk. Differences in SAFs for organs outside the trunk were not greater than the uncertainties in the data and will not be important enough to change calculated doses. For organs irradiating other organs within the trunk, differences were significant, between 0.3% and 1.1%/kg, or about 8%-33% overall. The differences are interesting and can be used to estimate how different patients' dosimetry might vary from values reported in standard dose tables.

  17. The refinement of ipsilateral eye retinotopic maps is increased by removing the dominant contralateral eye in adult mice.

    Directory of Open Access Journals (Sweden)

    Spencer L Smith

    2010-03-01

    Full Text Available Shortly after eye opening, initially disorganized visual cortex circuitry is rapidly refined to form smooth retinotopic maps. This process asymptotes long before adulthood, but it is unknown whether further refinement is possible. Prior work from our lab has shown that the retinotopic map of the non-dominant ipsilateral eye develops faster when the dominant contralateral eye is removed. We examined whether input from the contralateral eye might also limit the ultimate refinement of the ipsilateral eye retinotopic map in adults. In addition, we examined whether the increased refinement involved the recruitment of adjacent cortical area.By surgically implanting a chronic optical window over visual cortex in mice, we repeatedly measured the degree of retinotopic map refinement using quantitative intrinsic signal optical imaging over four weeks. We removed the contralateral eye and observed that the retinotopic map for the ipsilateral eye was further refined and the maximum magnitude of response increased. However, these changes were not accompanied by an increase in the area of responsive cortex.Since the retinotopic map was functionally refined to a greater degree without taking over adjacent cortical area, we conclude that input from the contralateral eye limits the normal refinement of visual cortical circuitry in mice. These findings suggest that the refinement capacity of cortical circuitry is normally saturated.

  18. Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

    Science.gov (United States)

    An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

    2016-09-01

    1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

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

    Science.gov (United States)

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

    2012-01-01

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

  20. Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury.

    Science.gov (United States)

    Gao, Yang; Xu, Siyi; Cui, Zhenwen; Zhang, Mingkun; Lin, Yingying; Cai, Lei; Wang, Zhugang; Luo, Xingguang; Zheng, Yan; Wang, Yong; Luo, Qizhong; Jiang, Jiyao; Neale, Joseph H; Zhong, Chunlong

    2015-07-01

    Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild-type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI-induced deficits in long-term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors. © 2015 International Society for Neurochemistry.

  1. Global gene expression patterns in the post-pneumonectomy lung of adult mice

    Directory of Open Access Journals (Sweden)

    Ingenito Edward P

    2009-10-01

    Full Text Available Abstract Background Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration. Methods Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points. Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days and analyzed using microarray technology. Results The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1, as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis. Conclusion These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.

  2. Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior.

    Science.gov (United States)

    Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Luo, Hai-Yun; Bobrovskaya, Larisa; Zhou, Xin-Fu

    2016-07-01

    Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established. Here, we aimed to investigate the role of sortilin in regulating mood-related behaviors and its role in the proBDNF-mediated mood abnormality in mice. We found that sortilin was up-regulated in neocortex (by 78.3%) and hippocampus (by 111%) of chronically stressed mice as assessed by western blot analysis. These changes were associated with decreased mobility in the open field test and increased depression-like behavior in the forced swimming test. We also found that sortilin deficiency in mice resulted in hyperlocomotion in the open field test and increased anxiety-like behavior in both the open field and elevated plus maze tests. No depression-like behavior in the forced swimming test and no deficit in spatial cognition in the Morris water maze test were found in the Sort1-deficient mice. Moreover, the intracellular and extracellular levels of mature BDNF and proBDNF were not changed when sortilin was absent in vivo and in vitro. Finally, we found that both WT and Sort1-deficient mice injected with proBDNF in lateral ventricle displayed increased depression-like behavior in the forced swimming test but not anxiety-like behaviors in the open field and elevated plus maze tests. The present study suggests that sortilin functions as a negative regulator of mood performance and can be a therapeutic target for the treatment of mental illness. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  3. Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

    Science.gov (United States)

    Bárez-López, Soledad; Bosch-García, Daniel; Gómez-Andrés, David; Pulido-Valdeolivas, Irene; Montero-Pedrazuela, Ana; Obregon, Maria Jesus; Guadaño-Ferraz, Ana

    2014-01-01

    Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms. This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed. The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

  4. Exploring the Factor Structure of Financial Capacity in Cognitively Normal and Impaired Older Adults.

    Science.gov (United States)

    Gerstenecker, Adam; Triebel, Kristen; Eakin, Amanda; Martin, Roy; Marson, Daniel

    2018-01-01

    To investigate the factor structure of financial capacity using a direct-performance measure of financial skills (The Financial Capacity Instrument [FCI]) as a proxy for the financial capacity construct. The study sample was composed of 440 older adults who represented the cognitive spectrum from normal cognitive aging to mild cognitive impairment (MCI) to mild dementia: 179 healthy older adults, 149 participants with MCI, and 112 participants with mild Alzheimer's dementia (AD). Both Velicer's Minimum Average Partial test and Horn's parallel analysis supported a four-factor solution which accounted for 46% of variance. The four extracted factors were interpreted as: (1) Basic Monetary Knowledge and Calculation Skills, (2) Financial Judgment, (3) Financial Conceptual Knowledge, and (4) Financial Procedural Knowledge. The study findings represent an important first step in empirically articulating the financial capacity construct in aging. The four identified factors can guide both clinical practice and future instrument utilization and development. Cognitively impaired older adults with MCI and mild AD dementia are likely to show financial changes in one or more of the four identified financial factors. Clinicians working with older adults should routinely examine for potential changes in these four areas of financial function.

  5. Telomere erosion varies during in vitro aging of normal human fibroblasts from young and adult donors.

    Science.gov (United States)

    Figueroa, R; Lindenmaier, H; Hergenhahn, M; Nielsen, K V; Boukamp, P

    2000-06-01

    The life span of normal fibroblasts in vitro (Hayflick limit) depends on donor age, and telomere shortening has been proposed as a potential mechanism. By quantitative fluorescence in situ hybridization and Southern blot analysis, we show progressive telomere loss to about 5 kb mean telomere restriction fragment length in fibroblasts from two adult donors within 40 population doublings, whereas in fibroblasts from two infant donors, telomere erosion is reduced, leaving a mean telomere restriction fragment length of approximately 7 kb at senescence (after approximately 60 population doublings). Aging of fibroblasts from both infant and adult donors was not accompanied by chromosomal abnormalities but was correlated with increased telomere repeat-binding factor 2 expression at both the protein and transcriptional level.

  6. Cellulose supplementation early in life ameliorates colitis in adult mice.

    Directory of Open Access Journals (Sweden)

    Dorottya Nagy-Szakal

    Full Text Available Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC] where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001], and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]. Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation.

  7. Cellulose Supplementation Early in Life Ameliorates Colitis in Adult Mice

    Science.gov (United States)

    Nagy-Szakal, Dorottya; Hollister, Emily B.; Luna, Ruth Ann; Szigeti, Reka; Tatevian, Nina; Smith, C. Wayne; Versalovic, James; Kellermayer, Richard

    2013-01-01

    Decreased consumption of dietary fibers, such as cellulose, has been proposed to promote the emergence of inflammatory bowel diseases (IBD: Crohn disease [CD] and ulcerative colitis [UC]) where intestinal microbes are recognized to play an etiologic role. However, it is not known if transient fiber consumption during critical developmental periods may prevent consecutive intestinal inflammation. The incidence of IBD peaks in young adulthood indicating that pediatric environmental exposures may be important in the etiology of this disease group. We studied the effects of transient dietary cellulose supplementation on dextran sulfate sodium (DSS) colitis susceptibility during the pediatric period in mice. Cellulose supplementation stimulated substantial shifts in the colonic mucosal microbiome. Several bacterial taxa decreased in relative abundance (e.g., Coriobacteriaceae [p = 0.001]), and other taxa increased in abundance (e.g., Peptostreptococcaceae [p = 0.008] and Clostridiaceae [p = 0.048]). Some of these shifts persisted for 10 days following the cessation of cellulose supplementation. The changes in the gut microbiome were associated with transient trophic and anticolitic effects 10 days following the cessation of a cellulose-enriched diet, but these changes diminished by 40 days following reversal to a low cellulose diet. These findings emphasize the transient protective effect of dietary cellulose in the mammalian large bowel and highlight the potential role of dietary fibers in amelioration of intestinal inflammation. PMID:23437211

  8. Natural killer activity and suppressor cells in irradiated mice repopulated with a mixture of cells from normal and 89Sr-treated donors

    International Nuclear Information System (INIS)

    Levy, E.M.; Kumar, V.; Bennett, M.

    1981-01-01

    Mice that have been injected with 89 Sr have fairly normal B and T cell function, but are abnormal in that they lack natural killer (NK) activity and other functions that require an intact bone marrow. These mice also have an increased potential for suppressor cell activity. We had previously shown that spleen cells from 89 Sr-treated mice could transfer low NK activity and increased suppressor cell function to lethally irradiated syngeneic recipients. To investigate the mechanisms involved in perpetuating these defects, groups of normal spleen or bone marrow cells. Recipients were assayed for their NK activity and suppressor cell function 5 to 14 wk later. it was found that the addition of normal cells in the donor inoculum resulted in normal NK activity. This indicates that low NK activity in 89 Sr-treated mice was not due to the presence of a suppressor cell that prevented NK cell generation. It was additionally found that low NK activity in recipient mice could be boosted by interferon inducers. This would indicate that NK activity in the recipients was not due to a lack of interferon-sensitive pre-NK cells. Suppressor cell function in recipient mice depended on the type and number of normal cells in the donor inoculum. Bone marrow cells were very efficient in overcoming the tendency to produce suppressor cells. It took approximately 20 times more normal spleen cells to produce the same results. The implications of these findings are discussed

  9. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach

    International Nuclear Information System (INIS)

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Baghban Khojasteh, Nasrin

    2012-01-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. - Highlights: ► Boron distribution in male and female rats' normal brain was studied in this research. ► Coronal sections of animal tissue samples were irradiated with thermal neutrons. ► Alpha and Lithium tracks were counted using alpha autoradiography. ► Different boron concentration was seen in brain sections of male and female rats. ► The highest boron concentration was seen in 4 h after boron compound injection.

  10. Normal reference values for vertebral artery flow volume by color Doppler sonography in Korean adults

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hyun Sook; Cha, Jang Gyu; Park, Seong Jin; Joh, Joon Hee; Park, Jai Soung; Kim, Dae Ho; Lee, Hae Kyung; Ahn, Hyun Cheol [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2003-09-15

    Vertebrobasilar ischemia has been attributed to a reduction of net vertebral artery flow volume. This study was to establish the reference values for the flow volume of the vertebral artery using color Doppler sonography in the normal Korea adults. Thirty five normal Korea adults without any underlying disease including hypertension, hyperlipidemia, diabetes, heart disease, obesity (body mas index>30), or carotid artery stenosis was included. There were 17 males and 18 females, age ranged from 20 to 53 years (average=32.86 years). Flow velocities and vessel diameters were recorded in the intertransverse (V2) segment, usually at C5-6 level, bilaterally. The flow volume (Q) was calculated. (Q=time averaged mean velocity x cross sectional area of vessel) A lower Flow velocity and smaller vessel diameter were measured on the right side compared to those of the left side, resulting in a lower flow volume. The calculated flow volumes using the equation were 77.0 +- 39.7 ml/min for the right side and 127.6 +- 71.0 ml/min for the left side (p=0.0001) while the net vertebral artery flow volume was 204.6 +- 81.8 ml/min. Decrease in the vertebral artery flow volume was statistically significant with advanced age. (r=-0.36, p=0.032). Vertebral artery blood flow volume was 191.20 +- 59.19 ml/min in male, and 217.28 +- 98.67 ml/min in female (p=0.6). The normal range for the net vertebral artery flow volume defined by the 5th to 95th percentiles was between 110.06 and 364.1 ml/min. The normal range for the net vertebral artery flow volume was between 110.06 and 364.1 ml/min. Vertebral artery flow volume decreased with the increase of age. However, gender did not affect the blood flow volume.

  11. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

    Directory of Open Access Journals (Sweden)

    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  12. ASCT2 (SLC1A5-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production

    Directory of Open Access Journals (Sweden)

    Etienne Masle-Farquhar

    2017-05-01

    Full Text Available SLC1A5 (solute carrier family 1, member 5 is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients.

  13. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  14. Comparison between β-thalassemia minor and normal individuals using the Wechsler Adult Intelligence Scale.

    Science.gov (United States)

    Zangiabadi, Nasser; Yarahmadi, Fahimeh; Darekordi, Ali; Shabani, Mohammad; Dadgar, Mehrak Memaran

    2013-01-01

    The present study aimed at investigating and comparing patients suffering from β-thalassemia (β-thal) minor with normal individuals in regard to their performances in the short version of the Wechsler Adult Intelligence Scale (WAIS) test. Patients with β-thal minor are carriers of β-thal genes. They have mild microcytic and hypochromic anemia and are usually asymptomatic. In this cross-sectional study, a total of 60 individuals were divided into two equal groups of β-thal minor and normal subjects; they were then studied by the WAIS subscales. The mean performance scores of the normal group in the subtests of arithmetic and vocabulary (p <0.01) and picture completion (p <0.05) were higher than those of the thalassemia group. The mean performance score and ability of the normal group on the verbal scale was higher in comparison to the thalassemia group (p <0.05), while on the non verbal scale, there was no significant difference between the two groups. It can be concluded that β-thal minor negatively influences verbal fluency, reasoning and conceptualization, and sequencing tasks, perceptual skill, prediction of social situations and abstract thinking.

  15. Normal mast cell numbers in the tissues of AhR-deficient mice.

    Science.gov (United States)

    Pilz, Caroline; Feyerabend, Thorsten; Sonner, Jana; Redaelli, Chiara; Peter, Katharina; Kunze, Anja; Haas, Katharina; Esser, Charlotte; Schäkel, Knut; Wick, Wolfgang; Rodewald, Hans-Reimer; Lanz, Tobias V; Platten, Michael

    2016-01-01

    The transcription factor aryl hydrocarbon receptor (AhR) acts as an immunomodulatory molecule in several immune cell lineages. Recently, it has been implicated in development and maintenance of immune cells in barrier tissues such as skin and mucosa. To investigate its role on mast cell development and maintenance in skin, peritoneal exudate cells (PECs) and lymph nodes, we studied in depth their phenotype in AhR-deficient mice. Our findings do not provide any evidence for a suspected role of the AhR in mast cell homeostasis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

    Energy Technology Data Exchange (ETDEWEB)

    Mosier, D.E.; Mond, J.J.; Goldings, E.A.

    1977-12-01

    The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.

  17. Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

    International Nuclear Information System (INIS)

    Mosier, D.E.; Mond, J.J.; Goldings, E.A.

    1977-01-01

    The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other

  18. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-03-01

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

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  1. High Mutation Levels are Compatible with Normal Embryonic Development in Mlh1-Deficient Mice.

    Science.gov (United States)

    Fan, Xiaoyan; Li, Yan; Zhang, Yulong; Sang, Meixiang; Cai, Jianhui; Li, Qiaoxia; Ozaki, Toshinori; Ono, Tetsuya; He, Dongwei

    2016-10-01

    To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12.5 dpc in fetuses of Mlh1 +/+ and Mlh1 -/- mice showed their own unique spectra, suggesting that deletion mutations were the main causes in the deficiency of the Mlh1 gene. Of note, fetuses of irradiated mice exhibited marked differences such as post-implantation loss and Mendelian distribution. Collectively, these results strongly suggest that high mutation ofMlh1 -/- -deficient fetuses has little effect on the fetuses during their early developmental stages, whereas Mlh1 -/- -deficient fetuses from X-ray irradiated mothers are clearly effected.

  2. Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway.

    Science.gov (United States)

    Zhao, Yong-Na; Li, Wei-Feng; Li, Fei; Zhang, Zhen; Dai, Yun-Dong; Xu, Ai-Li; Qi, Cui; Gao, Ji-Min; Gao, Jun

    2013-06-14

    Resveratrol (RSV) is a natural compound found in grapes and red wine. It has been well known for its beneficial effects as a dietary supplement in prevention of cardiovascular diseases and cancer. Recently, in vitro studies have reported the neuroprotective role of RSV in neurodegenerative process in Alzheimer's disease (AD). However, in vivo effects of RSV on the decline of brain function accompanying the aging process, especially those on cognitive loss, have not been not investigated. Here we report that, after intraventricular injection of RSV for one week in 8-9 month-old mice, the long-term memory formation and the LTP induction from hippocampus CA1 were improved. The RSV enhancement effects were blocked in SIRT1 mutant mice. Additional experiments suggest that RSV effects are likely to be mediated through reduced expressions of miR-134 and miR-124, which may in turn up-regulate CREB levels to subsequently promote BDNF synthesis. These findings demonstrate a role for RSV in cognition and a microRNA-CREB-BDNF mechanism by which RSV regulates these processes, demonstrating its value as a potential therapeutic target against CNS disorders in aging. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Normally occurring intersexuality and testosterone induced plasticity in the copulatory system of adult leopard geckos.

    Science.gov (United States)

    Holmes, Melissa M; Putz, Oliver; Crews, David; Wade, Juli

    2005-04-01

    The copulatory neuromuscular system of lizards is highly sexually dimorphic. Adult males possess bilateral penises called hemipenes, which are independently controlled by two muscles, the retractor penis magnus (RPM) and transversus penis (TPN). These structures are not obvious in adult females. However, in adult female leopard geckos (Eublepharis macularius), testosterone induces hemipene growth. We investigated whether these structures develop de novo in adulthood or are histologically present as rudimentary structures in the female leopard gecko. We also investigated the extent of sexual dimorphisms and plasticity in the associated neuromuscular components. To do this, we compared copulatory morphology (sizes of hemipenes, RPM and TPN muscle fibers, and associated motoneurons, as well as motoneuron and RPM fiber number) in adult females treated with testosterone, control females, and control males. All of the geckos possessed hemipenes, RPMs and TPNs, but these structures were indeed vestigial in control females. Testosterone induced striking increases in hemipene and copulatory muscle fiber size in females, but not to levels equivalent to control males. In parallel, males with increased levels of androgenic activity had larger hemipenes, suggesting naturally occurring steroid-induced plasticity. Copulatory motoneurons were not sexually dimorphic in size or number, and these measures did not respond to testosterone. The data demonstrate that the copulatory system of leopard geckos, in which gonadal sex is determined by egg incubation temperature, differs from that of many species (both reptilian and mammalian) with genotypic sex determination. Indeed, the system is remarkable in that adult females have normally occurring intersex characteristics and they exhibit substantial steroid-induced morphological plasticity in adulthood.

  4. Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β.

    Science.gov (United States)

    Ekmark-Lewén, Sara; Flygt, Johanna; Fridgeirsdottir, Gudrun A; Kiwanuka, Olivia; Hånell, Anders; Meyerson, Bengt J; Mir, Anis K; Gram, Hermann; Lewén, Anders; Clausen, Fredrik; Hillered, Lars; Marklund, Niklas

    2016-04-01

    Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1β has not been established in TAI. An IL-1β-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham-injured controls (n = 20) and untreated, naive mice (n = 9). The anti-IL-1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 μg/brain tissue) at 24 h post-injury in both cFPI (n = 5) and sham-injured (n = 3) mice, with lower concentrations at 72 h post-injury (up to ~18 μg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post-injury, and the Morris water maze (MWM) at 14-21 days post-injury. Following TAI, the IL-1β-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1β-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1β is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Clearance of a monoclonal anti-DNA antibody following administration of DNA in normal and autoimmune mice

    International Nuclear Information System (INIS)

    Jones, F.S.; Pisetsky, D.S.; Kurlander, R.J.

    1986-01-01

    To study the assembly of DNA-anti-DNA complexes in vivo, we have measured the clearance from blood and organ localization of a murine IgG2a monoclonal anti-DNA antibody, called 6/0, following the infusion of DNA intravenously or intraperitoneally. Intraperitoneal DNA caused a profound acceleration of 6/0 anti-DNA clearance that was dose dependent and demonstrable after the infusion of as little as 1.9 microgram per gram of body weight of single-stranded DNA. The antibody was cleared primarily in the liver without increased deposition in the kidney. Intraperitoneal infusions of DNA also accelerated the clearance of 6/0 in autoimmune MRL-lpr/lpr mice. In contrast, intravenous DNA given in comparable doses caused only a slight increase in 6/0 antibody clearance; this accelerated clearance was seen only at low antigen doses and only during the first 10 min following DNA infusion. Using double-radiolabeling techniques, 6/0 and Cl.18, an IgG2ak myeloma protein without anti-DNA activity, were found to disappear from blood at a comparable rate in both B6D2 mice and MRL-lpr/lpr mice. These results suggest that the DNA-anti-DNA immune complexes can form in vivo but that this process is profoundly affected by the manner in which DNA enters the circulation. In addition, the results suggest that DNA-dependent clearance is not a major pathway for anti-DNA metabolism in normal or at least one strain of autoimmune mice

  6. Variation in normal and tumor tissue sensitivity of mice to ionizing radiation-induced DNA strand breaks in vivo

    International Nuclear Information System (INIS)

    Meyn, R.E.; Jenkins, W.T.

    1983-01-01

    The efficiency of DNA strand break formation in normal and tumor tissues of mice was measured using the technique of alkaline elution coupled with a microfluorometric determination of DNA. This methodology allowed measurement of the DNA strand breaks produced in tissues irradiated in vivo with doses of radiation comparable to those used in radiotherapy (i.e., 1.0 gray) without the necessity for the cells to be dividing and incorporating radioactive precursors to label the DNA. The results showed that substantial differences existed among various tissues in terms of the amount of DNA strand break damage produced for a given dose of radiation. Of the normal tissues, the most breaks were produced in bone marrow and the least were produced in gut. Furthermore, strand break production was relatively inefficient in the tumor compared to the normal tissues. The efficiency of DNA strand break formation measured in the cells from the tissues irradiated in vitro was much more uniform and considerably greater than that measured in vivo, suggesting that the normal tissues in the animal may be radiobiologically hypoxic

  7. Neonatal blockade of GABA-A receptors alters behavioral and physiological phenotypes in adult mice.

    Science.gov (United States)

    Salari, Ali-Akbar; Amani, Mohammad

    2017-04-01

    Gamma-aminobutyric acid (GABA) plays an inhibitory role in the mature brain, and has a complex and bidirectional effect in different parts of the immature brain which affects proliferation, migration and differentiation of neurons during development. There is also increasing evidence suggesting that activation or blockade of the GABA-A receptors during early life can induce brain and behavioral abnormalities in adulthood. We investigated whether neonatal blockade of the GABA-A receptors by bicuculline can alter anxiety- and depression-like behaviors, body weight, food intake, corticosterone and testosterone levels in adult mice (postnatal days 80-95). To this end, neonatal mice were treated with either DMSO or bicuculline (70, 150 and 300μg/kg) during postnatal days 7, 9 and 11. When grown to adulthood, mice were exposed to behavioral tests to measure anxiety- (elevated plus-maze and light-dark box) and depression-like behaviors (tail suspension test and forced swim test). Stress-induced serum corticosterone and testosterone levels, body weight and food intake were also evaluated. Neonatal bicuculline exposure at dose of 300μg/kg decreased anxiety-like behavior, stress-induced corticosterone levels and increased testosterone levels, body weight and food intake, without significantly influencing depression-like behavior in adult male mice. However, no significant changes in these parameters were observed in adult females. These findings suggest that neonatal blockade of GABA-A receptors affects anxiety-like behavior, physiological and hormonal parameters in a sex-dependent manner in mice. Taken together, these data corroborate the concept that GABA-A receptors during early life have an important role in programming neurobehavioral phenotypes in adulthood. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  8. Behavioral neurotoxicity in adolescent and adult mice exposed to fenproporex during pregnancy.

    Science.gov (United States)

    Moreira, C Q; Faria, M J S S; Moreira, E G

    2005-08-01

    We investigated the effects of gestational exposure to fenproporex, one of the most used anorectic drugs in Brazil, on the behavior of adolescent and adult pups (30 and 60 days of age, respectively). Pregnant Swiss mice were treated daily, by gavage, with 15 mg/kg of fenproporex chloride or water during the whole gestational period. Male pups were submitted to open-field, forced swimming test, tail suspension test and fenproporex-induced stereotyped behavior. The results demonstrated that gestational exposure to fenproporex induces antidepressant-like effect and decreases fenproporex-induced stereotyped behavior in both adolescent and adult pups. Moreover, fenproporex-exposed adolescent pups tended (P= 0.06) to be more active than control pups. Our data show, for the first time, that gestational exposure to fenproporex leads to long-lasting behavioral toxicity in male mice characteristic of altered dopaminergic transmission.

  9. Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

    Science.gov (United States)

    Batista, Thiago M.; Alonso-Magdalena, Paloma; Vieira, Elaine; Amaral, Maria Esmeria C.; Cederroth, Christopher R.; Nef, Serge; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2012-01-01

    Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. PMID:22470480

  10. An anatomical study of normal variations of circle of Willis in 132 fetus, newborn and adult

    Directory of Open Access Journals (Sweden)

    Bateni F

    2009-09-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Several studies have investigated the variations in the anatomy of each segment of circle of Willis whereas a few have addressed the variations of this arterial circle as a whole. In this study the entire circle of Willis and its variations were studied in a cohort of Iranian people and compared with previous reports."n"nMethods: Anatomical variations of the circle of Willis in 132 brains of Iranian cadavers (102 male adults and 30 fetuses and infants were studied. The dissection process was digitally filmed for further studies. Using computer software the external diameters of the vessels were measured and the circle variations were classified. The variations of the circle as a whole and segmental variations were compared with previous studies. "n"nResults: Uni-and bilateral hypoplasia of posterior communicating arteries (PcoAs constituted the most common variation in our study which was similar to previous works. Aplasia of the anterior cerebral artery (A1 and the posterior cerebral artery (P1 were not observed. In 3.3% of fetuses and infants and 3% of adult instances both right and left posterior communicating arteries were absent. There was one case of anterior communicating artery (AcoA aplasia in

  11. Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

    Science.gov (United States)

    Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

    2016-10-01

    Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. Copyright © 2016. Published by Elsevier Inc.

  12. Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

    OpenAIRE

    Lazarini, Fran?oise; Mouthon, Marc-Andr?; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, St?phanie; Abrous, Djoher Nora; Boussin, Fran?ois D.; Lledo, Pierre-Marie

    2009-01-01

    International audience; BACKGROUND: In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we irradiated adult mice to impair c...

  13. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    International Nuclear Information System (INIS)

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-01-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting 3 H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities

  14. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  15. Factors influencing the vaccinia-specific cytotoxic response of thymocytes from normal and chimeric mice

    International Nuclear Information System (INIS)

    Doherty, P.C.; Schwartz, D.H.; Bennink, J.R.; Korngold, R.

    1981-01-01

    Following adoptive transfer into irradiated recipients, thymocytes can be induced to respond strongly to vaccinia virus. High levels of cytotoxic T-lymphocyte (CTL) activity may be generated from thymus, but not from spleen, of 3-day-old mice. The capacity of thymocytes to differentiate into effector CTL tends to be lost with age. Some of this loss may reflect positive suppression: a single, low dose of cyclophosphamide allows the reemergence of responsiveness in at least one mouse strain. Thymocytes from [A leads to (A x B)F1] and [(A x B)F1 leads to A] chimeras show the response patterns that would by predicted from previous studies of lymph node and spleen cells. However, thymic function seems to be rapidly lost in the [A leads to (A x B)F1] Chimeras

  16. The effects of aerobic exercise on depression-like, anxiety-like, and cognition-like behaviours over the healthy adult lifespan of C57BL/6 mice.

    Science.gov (United States)

    Morgan, Julie A; Singhal, Gaurav; Corrigan, Frances; Jaehne, Emily J; Jawahar, Magdalene C; Baune, Bernhard T

    2018-01-30

    Preclinical studies have demonstrated exercise improves various types of behaviours such as anxiety-like, depression-like, and cognition-like behaviours. However, these findings were largely conducted in studies utilising short-term exercise protocols, and the effects of lifetime exercise on these behaviours remain unknown. This study investigates the behavioural effects of lifetime exercise in normal healthy ageing C57BL/6 mice over the adult lifespan. 12 week-old C57BL/6 mice were randomly assigned to voluntary wheel running or non-exercise (control) groups. Exercise commenced at aged 3 months and behaviours were assessed in young adult (Y), early middle age (M), and old (O) mice (n=11-17/group). The open field and elevated zero maze examined anxiety-like behaviours, depression-like behaviours were quantified with the forced swim test, and the Y maze and Barnes maze investigated cognition-like behaviours. The effects of lifetime exercise were not simply an extension of the effects of chronic exercise on anxiety-like, depression-like, and cognition-like behaviours. Exercise tended to reduce overt anxiety-like behaviours with ageing, and improved recognition memory and spatial learning in M mice as was expected. However, exercise also increased anxiety behaviours including greater freezing behaviour that extended spatial learning latencies in Y female mice in particular, while reduced distances travelled contributed to longer spatial memory and cognitive flexibility latencies in Y and O mice. Lifetime exercise may increase neurogenesis-associated anxiety. This could be an evolutionary conserved adaptation that nevertheless has adverse impacts on cognition-like function, with particularly pronounced effects in Y female mice with intact sex hormones. These issues require careful investigation in future rodent studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Adult opossums (Didelphis virginiana) demonstrate near normal locomotion after spinal cord transection as neonates.

    Science.gov (United States)

    Wang, X M; Basso, D M; Terman, J R; Bresnahan, J C; Martin, G F

    1998-05-01

    When the thoracic spinal cord of the North American opossum (Didelphis virginiana) is transected on postnatal day (PD) 5, the site of injury becomes bridged by histologically recognizable spinal cord and axons which form major long tracts grow through the lesion. In the present study we asked whether opossums lesioned on PD5 have normal use of the hindlimbs as adults and, if so, whether that use is dependent upon axons which grow through the lesion site. The thoracic spinal cord was transected on PD5 and 6 months later, hindlimb function was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. All animals supported their weight with the hindlimbs and used their hindlimbs normally during overground locomotion. In some cases, the spinal cord was retransected at the original lesion site or just caudal to it 6 months after the original transection and paralysis of the hindlimbs ensued. Surprisingly, however, these animals gradually recovered some ability to support their weight and to step with the hindlimbs. Similar recovery was not seen in animals transected only as adults. In order to verify that descending axons which grew through the lesion during development were still present in the adult animal, opossums subjected to transection of the thoracic cord on PD5 were reoperated and Fast blue was injected several segments caudal to the lesion. In all cases, neurons were labeled rostral to the lesion in each of the spinal and supraspinal nuclei labeled by comparable injections in unlesioned, age-matched controls. The results of orthograde tracing studies indicated that axons which grew through the lesion innervated areas that were appropriate for them. Copyright 1998 Academic Press.

  18. Amyloid burden and incident depressive symptoms in cognitively normal older adults.

    Science.gov (United States)

    Harrington, Karra D; Gould, Emma; Lim, Yen Ying; Ames, David; Pietrzak, Robert H; Rembach, Alan; Rainey-Smith, Stephanie; Martins, Ralph N; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

    2017-04-01

    Several studies have reported that non-demented older adults with clinical depression show changes in amyloid-β (Aβ) levels in blood, cerebrospinal fluid and on neuroimaging that are consistent with those observed in patients with Alzheimer's disease. These findings suggest that Aβ may be one of the mechanisms underlying the relation between the two conditions. We sought to determine the relation between elevated cerebral Aβ and the presence of depression across a 54-month prospective observation period. Cognitively normal older adults from the Australian Imaging Biomarkers and Lifestyle study who were not depressed and had undergone a positron emission tomography scan to classify them as either high Aβ (n = 81) or low Aβ (n = 278) participated. Depressive symptoms were assessed using the Geriatric Depression Scale - Short Form at 18-month intervals over 54 months. Whilst there was no difference in probable depression between groups at baseline, incidence was 4.5 (95% confidence interval [CI] 1.3-16.4) times greater within the high Aβ group (9%) than the low Aβ group (2%) by the 54-month assessment. Results of this study suggest that elevated Aβ levels are associated with a 4.5-fold increased likelihood of developing clinically significant depressive symptoms on follow-up in preclinical Alzheimer's disease. This underscores the importance of assessing, monitoring and treating depressive symptoms in older adults with elevated Aβ. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Effect of cyclophosphamide on the course of Candida albicans infection in normal and vaccinated mice

    International Nuclear Information System (INIS)

    Japoni, A.; Alborzi, A.; Farshad, S.; Hayati, M.; Dehyadegari, Mohammad A.; Mehrabani, D.

    2006-01-01

    To evaluate the immunomodulating effect of cyclophosphamide (Cy) on the course of Candida albicans (C. albicans). We performed this study in the Shiraz Medical School, Shiraz, Iran during April to November 2003. Five groups of 10 mice (vaccinated group) were immunized by 5 equal injections of 2x105, 2.5x105 and 3x105 of the organism intraperitoneally. Then, the group received Cy on day zero and was challenged with lethal doses of C. albicans (7.74x105 colony forming unit) on days zero, one, 3, 6 and 12 post-Cy injection. Another 5 equal groups of 10 mice (non-vaccinated group) received Cy on day zero and similar to vaccinated ones were challenged with lethal doses of the organism too. The control groups received just Cy on day zero and were sacrificed on days zero, one, 3, 6 and 12 days post-Cy injection. We performed the hemogram and the spleen and studied the renal tissues microscopically and macroscopically. In vaccinated group, we observed an increase in survival time and in spleen and renal weights were visible while in non-vaccinated ones, a significant decrease was also observed on days one and 3 and an increased on days 6 and 12 post-Cy injection. We observed atrophy and necrosis in the spleen while inflammation and necrosis were also observed in the kidneys on days one and 3. We noticed a significant hyperplasia in the white pulp on days 6 and 12 post-Cy injection. We conclude that hyperplasia in the white pulp of spleen and the increase in peripheral polymorphonuclears due to selective effects of Cy could effectively protect the animal against C. albicans infection. (author)

  20. CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

    DEFF Research Database (Denmark)

    Gad, M; Brimnes, J; Claesson, Mogens Helweg

    2003-01-01

    Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4......+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow......-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...

  1. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults.

    Science.gov (United States)

    Magistrelli, Ashley; Chezem, Jo Carol

    2012-11-01

    In healthy normal-weight adults, cinnamon reduces blood glucose concentration and enhances insulin sensitivity. Insulin resistance, resulting in increased fasting and postprandial blood glucose and insulin levels, is commonly observed in obese individuals. The objective of the study was to compare declines in postprandial glycemic response in normal-weight and obese subjects with ingestion of 6 g ground cinnamon. In a crossover study, subjects consumed 50 g available carbohydrate in instant farina cereal, served plain or with 6 g ground cinnamon. Blood glucose concentration, the main outcome measure, was assessed at minutes 0, 15, 30, 45, 60, 90, and 120. Repeated-measures analysis of variance evaluated the effects of body mass index (BMI) group, dietary condition, and time on blood glucose. Paired t-test assessed blood glucose at individual time points and glucose area under the curve (AUC) between dietary conditions. Thirty subjects between the ages of 18 and 30 years, 15 with BMIs between 18.5 and 24.9 and 15 with BMIs of 30.0 or more, completed the study. There was no significant difference in blood glucose between the two BMI groups at any time point. However, in a combined analysis of all subjects, the addition of cinnamon to the cereal significantly reduced 120-minute glucose AUC (P=0.008) and blood glucose at 15 (P=0.001), 30 (Pblood glucose was significantly higher with cinnamon consumption (Pglucose response in normal weight and obese adults. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  2. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    International Nuclear Information System (INIS)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei

    2008-01-01

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6±5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  3. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    Energy Technology Data Exchange (ETDEWEB)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei [Shimane Univ., Faculty of Medicine, Izumo, Shimane (Japan)

    2008-03-15

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6{+-}5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  4. Repeatability and consistency of individual behaviour in juvenile and adult Eurasian harvest mice

    Science.gov (United States)

    Schuster, Andrea C.; Carl, Teresa; Foerster, Katharina

    2017-04-01

    Knowledge on animal personality has provided new insights into evolutionary biology and animal ecology, as behavioural types have been shown to affect fitness. Animal personality is characterized by repeatable and consistent between-individual behavioural differences throughout time and across different situations. Behavioural repeatability within life history stages and consistency between life history stages should be checked for the independence of sex and age, as recent data have shown that males and females in some species may differ in the repeatability of behavioural traits, as well as in their consistency. We measured the repeatability and consistency of three behavioural and one cognitive traits in juvenile and adult Eurasian harvest mice ( Micromys minutus). We found that exploration, activity and boldness were repeatable in juveniles and adults. Spatial recognition measured in a Y Maze was only repeatable in adult mice. Exploration, activity and boldness were consistent before and after maturation, as well as before and after first sexual contact. Data on spatial recognition provided little evidence for consistency. Further, we found some evidence for a litter effect on behaviours by comparing different linear mixed models. We concluded that harvest mice express animal personality traits as behaviours were repeatable across sexes and consistent across life history stages. The tested cognitive trait showed low repeatability and was less consistent across life history stages. Given the rising interest in individual variation in cognitive performance, and in its relationship to animal personality, we suggest that it is important to gather more data on the repeatability and consistency of cognitive traits.

  5. Seeing the Talker's Face Improves Free Recall of Speech for Young Adults with Normal Hearing but Not Older Adults with Hearing Loss

    Science.gov (United States)

    Rudner, Mary; Mishra, Sushmit; Stenfelt, Stefan; Lunner, Thomas; Rönnberg, Jerker

    2016-01-01

    Purpose: Seeing the talker's face improves speech understanding in noise, possibly releasing resources for cognitive processing. We investigated whether it improves free recall of spoken two-digit numbers. Method: Twenty younger adults with normal hearing and 24 older adults with hearing loss listened to and subsequently recalled lists of 13…

  6. Talker Differences in Clear and Conversational Speech: Perceived Sentence Clarity for Young Adults with Normal Hearing and Older Adults with Hearing Loss

    Science.gov (United States)

    Ferguson, Sarah Hargus; Morgan, Shae D.

    2018-01-01

    Purpose: The purpose of this study is to examine talker differences for subjectively rated speech clarity in clear versus conversational speech, to determine whether ratings differ for young adults with normal hearing (YNH listeners) and older adults with hearing impairment (OHI listeners), and to explore effects of certain talker characteristics…

  7. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    International Nuclear Information System (INIS)

    Guizar-Sahagun, G.; Rivera, F.; Babinski, E.; Berlanga, E.; Madrazo, M.; Franco-Bourland, R.; Grijalva, I.; Gonzalez, J.; Contreras, B.; Madrazo, I.

    1994-01-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  8. Commingling effect of gynoid and android fat patterns on cardiometabolic dysregulation in normal weight American adults.

    Science.gov (United States)

    Okosun, I S; Seale, J P; Lyn, R

    2015-05-18

    To determine the independent and commingling effect of android and gynoid percent fat (measured using Dual Energy X-Ray Absorptiometry) on cardiometabolic dysregulation in normal weight American adults. The 2005-2006 data (n=1802) from the United States National Health and Nutritional Examination Surveys (NHANES) were used in this study. Associations of android percent fat, gynoid percent fat and their joint occurrence with risks of cardiometabolic risk factors were estimated using prevalence odds ratios from logistic regression analyses. Android-gynoid percent fat ratio was more highly correlated with cardiometabolic dysregulation than android percent fat, gynoid percent fat or body mass index. Commingling of android and gynoid adiposities was associated with much greater odds of cardiometabolic risk factors than either android or gynoid adiposities. Commingling of android and gynoid adiposities was associated with 1.75 (95% confidence interval (CI)=1.42-2.93), 1.48 (95% CI=1.32-1.91), 1.61 (95% CI=1.50-1.89), 3.56 (95% CI=2.91-4.11) and 1.86 (95% CI=1.49-1.96) increased odds of elevated glucose, elevated blood pressure, elevated low-density lipoprotein-cholesterol, elevated triglyceride and low high-density lipoprotein-cholesterol, respectively. Normal weight subjects who present with both android and gynoid adiposities should be advised of the associated health risks. Both android and gynoid fat accumulations should be considered in developing public health strategies for reducing cardiometabolic disease risk in normal weight subjects.

  9. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico); Rivera, F [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Babinski, E [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Berlanga, E [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Madrazo, M [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Franco-Bourland, R [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico); Grijalva, I [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  10. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Science.gov (United States)

    Jain, Nidhi; Oswal, Neelam; Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Bal, Vineeta; Medigeshi, Guruprasad R

    2017-02-01

    Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  11. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

    Directory of Open Access Journals (Sweden)

    Nidhi Jain

    2017-02-01

    Full Text Available Following Japanese encephalitis virus (JEV infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null are highly susceptible and die over 10-18 day period as compared to the wild-type (WT mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB. Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

  12. Administration of midazolam in infancy does not affect learning and memory of adult mice.

    Science.gov (United States)

    Xu, Hua; Liu, Zhi-Qiang; Liu, Yi; Zhang, Wei-Shi; Xu, Bo; Xiong, Yuan-Chang; Deng, Xiao-Ming

    2009-12-01

    1. Midazolam is a common fast-acting GABA(A) receptor agonist. Recent data suggest that exposure to midazolam in early life may cause long-term effects on brain function through stable epigenetic reprogramming. The aim of the present study was to determine whether the administration of midazolam to infant mice would affect their learning and memory in adulthood. 2. An open-field test was conducted before and then 3, 24, 48 and 72 h after administration of midazolam (50 mg/kg, i.p.) to infant mice. Saline control mice received an equal volume of saline i.p. 3 h before the open-field test. Total movements, total movement time, total movement distance and velocity were analysed. Novel object recognition (NOR), Morris water-maze and passive avoidance tests were performed when the treated mice grew to adulthood (105 days of age). 3. The results of open-field test showed that midazolam significantly reduced locomotor activity (total movements, total movement time, total movement distance and velocity) in infant mice 3 and 24 h after drug administration and that these effects had disappeared by 72 h after drug administration. The results of the water-maze, NOR and passive avoidance tests in adulthood (at 105 days of age) indicated that administration of midazolam in infancy had no long-term effects on the learning and memory behaviours of adult mice compared with the saline control. 4. Acute midazolam administration to infant mice affected spontaneous locomotor activity for approximately 2 days, but did not seem to have any significant impact on cognitive functioning that lasted into adulthood.

  13. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

    Directory of Open Access Journals (Sweden)

    Xiaodi Yang

    Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

  14. Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status

    DEFF Research Database (Denmark)

    Greibe, Eva; Mahalle, Namita; Bhide, Vijayshri

    2017-01-01

    PURPOSE: To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. METHODS: We included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotran...

  15. Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Herbrecht Evelyn

    2009-06-01

    Full Text Available Abstract Background Individuals with autism spectrum disorders (ASDs often display symptoms from other diagnostic categories. Studies of clinical and psychosocial outcome in adult patients with ASDs without concomitant intellectual disability are few. The objective of this paper is to describe the clinical psychiatric presentation and important outcome measures of a large group of normal-intelligence adult patients with ASDs. Methods Autistic symptomatology according to the DSM-IV-criteria and the Gillberg & Gillberg research criteria, patterns of comorbid psychopathology and psychosocial outcome were assessed in 122 consecutively referred adults with normal intelligence ASDs. The subjects consisted of 5 patients with autistic disorder (AD, 67 with Asperger's disorder (AS and 50 with pervasive developmental disorder not otherwise specified (PDD NOS. This study group consists of subjects pooled from two studies with highly similar protocols, all seen on an outpatient basis by one of three clinicians. Results Core autistic symptoms were highly prevalent in all ASD subgroups. Though AD subjects had the most pervasive problems, restrictions in non-verbal communication were common across all three subgroups and, contrary to current DSM criteria, so were verbal communication deficits. Lifetime psychiatric axis I comorbidity was very common, most notably mood and anxiety disorders, but also ADHD and psychotic disorders. The frequency of these diagnoses did not differ between the ASD subgroups or between males and females. Antisocial personality disorder and substance abuse were more common in the PDD NOS group. Of all subjects, few led an independent life and very few had ever had a long-term relationship. Female subjects more often reported having been bullied at school than male subjects. Conclusion ASDs are clinical syndromes characterized by impaired social interaction and non-verbal communication in adulthood as well as in childhood. They also

  16. Mercury uptake in vivo by normal and acatalasemic mice exposed to metallic mercury vapor (203Hg degrees) and injected with metallic mercury or mercuric chloride (203HgCl2)

    International Nuclear Information System (INIS)

    Ogata, M.; Kenmotsu, K.; Hirota, N.; Meguro, T.; Aikoh, H.

    1985-01-01

    Levels of mercury in the brain and liver of acatalasemic mice immediately following exposure to metallic mercury vapor or injection of metallic mercury were higher than those found in normal mice. Acatalasemic mice had decreased levels of mercury in the blood and kidneys when the levels were compared with those of normal mice, which indicated that catalase plays a role in oxidizing and taking up mercury. Thus, the brain/blood or liver/blood ratio of mercury concentration in acatalasemic mice was significantly higher than that of normal mice. These results suggest that metallic mercury in the blood easily passed through the blood-brain or blood-liver barrier. The levels of mercury distribution to the kidneys of normal and acatalasemic mice, 1 hr after injection of mercuric chloride solution, were higher than that of normal and acatalasemic mice, respectively, 1 hr after injection of metallic mercury

  17. Radiation genetic injury and metabolic difference of tritiated thymidine in testis of young and adult mice

    Energy Technology Data Exchange (ETDEWEB)

    Mingyue, Lun; Shoupeng, Zhu

    1990-04-01

    The radiogenetoxicological effects on the adult testis and the metabolic difference of tritiated thymidine between the testis of young and adult BALB/C mice were studied. When 0.037 MBq/g.b.w. of tritiated thymidine was given i.v. to mice, the initial burden of tritium in the adult was larger than that of tritium in the young. But the retention of tritium in testis of the young gradually become larger than that of tritium in the adult with the passing time. Tritiated thymidine which was incorporated into DNA of the male germ cell nuclei damaged the genetic materials and caused the rising of the rates of the dominant lethal and the dominant mutation which produced skeletal abnomalities in the offspring. The relationship between the dominant lethal mutation index (Y) and the injected activity of tritiated thymidine (I, MBq/g.b.w.) is described by Y = 74.13 + 80.20 I (r = 0.95). The relationship between the incidence of the dominant skeletal mutation in the offspring (B) and the injected activity is B = 0.16 + 0.079 I ( r = 0.85).

  18. Radiation genetic injury and metabolic difference of tritiated thymidine in testis of young and adult mice

    International Nuclear Information System (INIS)

    Lun Mingyue; Zhu Shoupeng.

    1990-01-01

    The radiogenetoxicological effects on the adult testis and the metabolic difference of tritiated thymidine between the testis of young and adult BALB/C mice were studied. When 0.037 MBq/g.b.w. of tritiated thymidine was given i.v. to mice, the initial burden of tritium in the adult was larger than that of tritium in the young. But the retention of tritium in testis of the young gradually become larger than that of tritium in the adult with the passing time. Tritiated thymidine which was incorporated into DNA of the male germ cell nuclei damaged the genetic materials and caused the rising of the rates of the dominant lethal and the dominant mutation which produced skeletal abnomalities in the offspring. The relationship between the dominant lethal mutation index (Y) and the injected activity of tritiated thymidine (I, MBq/g.b.w.) is described by Y = 74.13 + 80.20 I (r = 0.95). The relationship between the incidence of the dominant skeletal mutation in the offspring (B) and the injected activity is B = 0.16 + 0.079 I ( r = 0.85)

  19. Membrane potential dye imaging of ventromedial hypothalamus neurons from adult mice to study glucose sensing.

    Science.gov (United States)

    Vazirani, Reema P; Fioramonti, Xavier; Routh, Vanessa H

    2013-11-27

    Studies of neuronal activity are often performed using neurons from rodents less than 2 months of age due to the technical difficulties associated with increasing connective tissue and decreased neuronal viability that occur with age. Here, we describe a methodology for the dissociation of healthy hypothalamic neurons from adult-aged mice. The ability to study neurons from adult-aged mice allows the use of disease models that manifest at a later age and might be more developmentally accurate for certain studies. Fluorescence imaging of dissociated neurons can be used to study the activity of a population of neurons, as opposed to using electrophysiology to study a single neuron. This is particularly useful when studying a heterogeneous neuronal population in which the desired neuronal type is rare such as for hypothalamic glucose sensing neurons. We utilized membrane potential dye imaging of adult ventromedial hypothalamic neurons to study their responses to changes in extracellular glucose. Glucose sensing neurons are believed to play a role in central regulation of energy balance. The ability to study glucose sensing in adult rodents is particularly useful since the predominance of diseases related to dysfunctional energy balance (e.g. obesity) increase with age.

  20. Protective effects of vitamin E and Cornus mas fruit extract on methotrexate-induced cytotoxicity in sperms of adult mice

    Directory of Open Access Journals (Sweden)

    Leila Zarei

    2014-03-01

    Full Text Available This study was aimed to assess the protective effects of Cornus mas fruit extract (CMFE and vitamin E (Vit E on sperm quality parameters in the methotrexate (MTX-treated mice. Forty-eight young adult male mice (8-12 weeks were randomly divided into six groups including control and test groups. The control group received normal saline orally , and the test groups were treated MTX (20 mg kg-1, ip, once weekly, MTX + CMFE (250 mg kg-1, MTX + CMFE (500 mg kg-1, MTX + CMFE (1000 mg kg-1, and MTX + Vit E (100 IU kg-1, po for 35 consecutive days. On day 35, after euthanasia the epididymal sperms were isolated. Then the total mean sperm count, sperm viability and motility were determined. The total antioxidant capacity (TAOC of all experimental groups were also evaluated. The MTX-treated animals showed a significant changes in all parameters of sperm quality assessment compared to the control group. Both Vit E and CMFE were able to protect from MTX-induced effects on sperm maturity and DNA damage. Co-administration of MTX and CMFE and/or Vit E resulted in protection from MTX-reduced TAOC. In conclusion, these data suggested that MTX administration could adversely affect the sperm quality. Moreover, the protective effect of Vit E and CMFE on MTX-induced sperm toxicity was also documented.

  1. Normal reference values for vertebral artery flow volume by color Doppler sonography in Korean adults

    International Nuclear Information System (INIS)

    Hong, Hyun Sook; Cha, Jang Gyu; Park, Seong Jin; Joh, Joon Hee; Park, Jai Soung; Kim, Dae Ho; Lee, Hae Kyung; Ahn, Hyun Cheol

    2003-01-01

    Vertebrobasilar ischemia has been attributed to a reduction of net vertebral artery flow volume. This study was to establish the reference values for the flow volume of the vertebral artery using color Doppler sonography in the normal Korea adults. Thirty five normal Korea adults without any underlying disease including hypertension, hyperlipidemia, diabetes, heart disease, obesity (body mas index>30), or carotid artery stenosis was included. There were 17 males and 18 females, age ranged from 20 to 53 years (average=32.86 years). Flow velocities and vessel diameters were recorded in the intertransverse (V2) segment, usually at C5-6 level, bilaterally. The flow volume (Q) was calculated. (Q=time averaged mean velocity x cross sectional area of vessel) A lower Flow velocity and smaller vessel diameter were measured on the right side compared to those of the left side, resulting in a lower flow volume. The calculated flow volumes using the equation were 77.0 ± 39.7 ml/min for the right side and 127.6 ± 71.0 ml/min for the left side (p=0.0001) while the net vertebral artery flow volume was 204.6 ± 81.8 ml/min. Decrease in the vertebral artery flow volume was statistically significant with advanced age. (r=-0.36, p=0.032). Vertebral artery blood flow volume was 191.20 ± 59.19 ml/min in male, and 217.28 ± 98.67 ml/min in female (p=0.6). The normal range for the net vertebral artery flow volume defined by the 5th to 95th percentiles was between 110.06 and 364.1 ml/min. The normal range for the net vertebral artery flow volume was between 110.06 and 364.1 ml/min. Vertebral artery flow volume decreased with the increase of age. However, gender did not affect the blood flow volume.

  2. Pediatric and adult MRI atlas of bone marrow. Normal appearances, variants and diffuse disease states

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Sundaram, Murali [Cleveland Clinic Lerner College of Medicine, OH (United States); Cleveland Clinic Department of Radiology, OH (United States)

    2016-08-01

    This comprehensive atlas is unique in being devoted to the MRI appearances of bone marrow in the axial and appendicular skeleton of adults and children. Normal MRI findings, including common variants and degenerative changes, are first documented. MRI appearances in the entire spectrum of neoplastic and non-neoplastic infiltrative marrow disorders are then presented, with accompanying explanatory text. Among the conditions considered are multiple myeloma, the acute and chronic leukemias, diffuse metastases, diffuse lymphomas, the anemias, polycythemia vera, myelofibrosis, storage disorders, and infections. Characteristic changes to bone marrow following various forms of treatment are also displayed and discussed. The selected images reflect the use of a variety of sequences and techniques, such as fat suppression, and contrast-enhanced imaging.

  3. Special proliferative sites are not needed for seeding and proliferation of transfused bone marrow cells in normal syngeneic mice

    International Nuclear Information System (INIS)

    Brecher, G.; Ansell, J.D.; Micklem, H.S.; Tjio, J.H.; Cronkite, E.P.

    1982-01-01

    The widely held view that transfused bone marrow cells will not proliferate in normal mice, not exposed to irradiation or other forms of bone marrow ablation, was reinvestigated. Forty million bone marrow cells from male donors were given to female recipients on each of 5 consecutive days, 5 to 10 times the number customarily used in the past. When the recipients were examined 2-13 weeks after the last transfusion, donor cells were found to average 16-25% of total marrow cells. Similar percentages of donor cells were found when variants of the enzyme phosphoglycerate kinase determined electrophoretically were used for identification of donor and recipient cells. Evidence is presented that the proportion of donor cells is compatible with a nonlinear dependence on the number of cells transfused over the range tested - i.e., 20-200 million bone marrow cells injected intravenously. Special proliferative sites thus do not appear to be required

  4. Radioresistant CD4+ T cells in normal, unprimed mice, with verification of the Bergonie-Tribondeau law

    International Nuclear Information System (INIS)

    Makidono, Reiko; Ito, Akira.

    1997-01-01

    This is the first report on radioresistant CD4+ T cells found in normal, unprimed mice. After sublethal whole body irradiation, regular CD4+ as well as primitive NK1.1+ CD4+ T cells were enriched in the spleen. Since it has been well established that virgin T and B cells are highly radiosensitive, these cells were once assumed to be a unique lymphocyte population for which radiosensitivity does not follow the general law of radiation sensitivity for mammalian cells (Bergonie-Tribondeau law). These cells exhibited higher proliferative response to accessory cells than the non-irradiated control cells in the syngeneic mixed leukocyte reaction (SMLR). This indicated that virgin CD4+ T cells sensitized to, and readily respond to self-MHC class II molecules are radioresistant, and that their radioresistance, as activated cells, is consistent with the Bergonie-Tribondeau law. (author)

  5. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    Science.gov (United States)

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  6. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults.

    Science.gov (United States)

    Taylor, Matthew K; Sullivan, Debra K; Swerdlow, Russell H; Vidoni, Eric D; Morris, Jill K; Mahnken, Jonathan D; Burns, Jeffrey M

    2017-12-01

    Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging. Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults. Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing. Results: Amyloid was elevated in 26% ( n = 33) of participants. HGLDiet pattern adherence ( P = 0.01), sugar intake ( P = 0.03), and carbohydrate intake ( P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level ( P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education. Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer

  7. Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization

    Directory of Open Access Journals (Sweden)

    Giulia Ottaviani

    2016-09-01

    Full Text Available Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.

  8. Increased anxiety and fear memory in adult mice lacking type 2 deiodinase.

    Science.gov (United States)

    Bárez-López, Soledad; Montero-Pedrazuela, Ana; Bosch-García, Daniel; Venero, César; Guadaño-Ferraz, Ana

    2017-10-01

    A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3'-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which is secreted to circulating blood, however, most actions of THs are mediated by T3, the transcriptionally active form. In the brain, intracellular concentrations of T3 are modulated by the activity of type 2 (D2) and type 3 (D3) deiodinases. In the present work, we evaluated learning and memory capabilities and anxiety-like behavior at adult stages in mice lacking D2 (D2KO) and we analyzed the impact of D2-deficiency on TH content and on the expression of T3-dependent genes in the amygdala and the hippocampus. We found that D2KO mice do not present impairments in spatial learning and memory, but they display emotional alterations with increased anxiety-like behavior as well as enhanced auditory-cued fear memory and spontaneous recovery of fear memory following extinction. D2KO mice also presented reduced T3 content in the hippocampus and decreased expression of the T3-dependent gene Dio3 in the amygdala suggesting a hypothyroid status in this structure. We propose that the emotional dysfunctions found in D2KO mice can arise from the reduced T3 content in their brain, which consequently leads to alterations in gene expression with functional consequences. We found a downregulation in the gene encoding for the calcium-binding protein calretinin (Calb2) in the amygdala of D2KO mice that could affect the GABAergic transmission. The current findings in D2KO mice can provide insight into emotional disorders present in humans with DIO2 polymorphisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults.

    Science.gov (United States)

    Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

    2016-05-20

    Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage spondylolysis group and the control group with independent-sample t- test. There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P spondylolysis group than those in the control group, but STA was lower (P spondylolysis group. Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population.

  10. Analysis of serum and cerebrospinal fluid in clinically normal adult miniature donkeys.

    Science.gov (United States)

    Mozaffari, A A; Samadieh, H

    2013-09-01

    To establish reference intervals for serum and cerebrospinal fluid (CSF) parameters in clinically healthy adult miniature donkeys. Experiments were conducted on 10 female and 10 male clinically normal adult miniature donkeys, randomly selected from five herds. Lumbosacral CSF collection was performed with the sedated donkey in the standing position. Cell analysis was performed immediately after the samples were collected. Blood samples were obtained from the jugular vein immediately after CSF sample collection. Sodium, potassium, glucose, urea nitrogen, total protein, calcium, chloride, phosphorous and magnesium concentrations were measured in CSF and serum samples. A paired t-test was used to compare mean values between female and male donkeys. The CSF was uniformly clear, colourless and free from flocculent material, with a specific gravity of 1.002. The range of total nucleated cell counts was 2-4 cells/μL. The differential white cell count comprised only small lymphocytes. No erythrocytes or polymorphonuclear cells were observed on cytological examination. Reference values were obtained for biochemical analysis of serum and CSF. Gender had no effect on any variables measured in serum or CSF (p>0.05). CSF analysis can provide important information in addition to that gained by clinical examination. CSF analysis has not previously been performed in miniature donkeys; this is the first report on the subject. In the present study, reference intervals for total nucleated cell count, total protein, glucose, urea nitrogen, sodium, potassium, chloride, calcium, phosphorous and magnesium concentrations of serum and CSF were determined for male and female miniature donkeys.

  11. Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

    Directory of Open Access Journals (Sweden)

    Soledad Bárez-López

    Full Text Available BACKGROUND: Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4 but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2. To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO did not find gross neurological alterations, possibly due to compensatory mechanisms. AIM: This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. RESULTS: Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice. No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction and skeletal muscle (33% reduction, but not in the cerebellum where other deiodinase (type 1 is expressed. CONCLUSIONS: The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

  12. Age-related changes in normal adult pancreas: MR imaging evaluation

    International Nuclear Information System (INIS)

    Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Sone, Teruki; Noda, Yasufumi; Higaki, Atsushi; Kanki, Akihiko; Tanimoto, Daigo; Higashi, Hiroki

    2012-01-01

    Objective: To investigate age-related changes in normal adult pancreas as identified by magnetic resonance imaging (MRI). Materials and methods: We examined 115 patients without pancreatic diseases (21–90 years) who underwent upper abdominal MRI to evaluate the normal pancreatic MRI findings related to aging. The parameters examined were the pancreatic anteroposterior (AP) diameter, pancreatic lobulation, pancreatic signal intensity (SI), depiction of the main pancreatic duct (MPD), grade of the visual SI decrease on the opposed-phase T1-weighted images compared with in-phase images, and enhancement effect of the pancreas in the arterial phase of dynamic imaging. Results: The pancreatic AP diameter significantly reduced (head, p = 0.0172; body, p = 0.0007; tail, p < 0.0001), and lobulation (p < 0.0001) and parenchymal fatty change (p < 0.0001) became more evident with aging. No significant correlation was observed between aging and pancreatic SI, however the SI on the in-phase T1-weighted images tended to decrease with aging. No significant correlation was observed between aging and the depiction of the MPD as well as aging and contrast enhancement. Conclusion: MRI findings of pancreatic atrophy, lobulation, and fatty degeneration are characteristic changes related to aging, and it is necessary to recognize these changes in the interpretation of abdominal MRI in patients with and without pancreatic disease

  13. The monoclonal antitoxin antibodies (actoxumab-bezlotoxumab treatment facilitates normalization of the gut microbiota of mice with Clostridium difficile infection

    Directory of Open Access Journals (Sweden)

    Mária Džunková

    2016-10-01

    detected by the end of the experiments. In conclusion, MK-3415A (actoxumab-bezlotoxumab treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota.

  14. Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

    Science.gov (United States)

    Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

    2017-10-01

    Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD). Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD. Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography. Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice ( P vitamin E/kg. Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

  15. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain of function mutations

    DEFF Research Database (Denmark)

    Galan-Diez, Marta; Isa, Adiba; Ponzetti, Marco

    2016-01-01

    of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5...... mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation...... of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM...

  16. Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

    Science.gov (United States)

    Shechter, M; Ginsberg, S; Scheinowitz, M; Feinberg, M S; Laron, Z

    2007-04-01

    Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

  17. Regular-, irregular-, and pseudo-character processing in Chinese: The regularity effect in normal adult readers

    Directory of Open Access Journals (Sweden)

    Dustin Kai Yan Lau

    2014-03-01

    Full Text Available Background Unlike alphabetic languages, Chinese uses a logographic script. However, the pronunciation of many character’s phonetic radical has the same pronunciation as the character as a whole. These are considered regular characters and can be read through a lexical non-semantic route (Weekes & Chen, 1999. Pseudocharacters are another way to study this non-semantic route. A pseudocharacter is the combination of existing semantic and phonetic radicals in their legal positions resulting in a non-existing character (Ho, Chan, Chung, Lee, & Tsang, 2007. Pseudocharacters can be pronounced by direct derivation from the sound of its phonetic radical. Conversely, if the pronunciation of a character does not follow that of the phonetic radical, it is considered as irregular and can only be correctly read through the lexical-semantic route. The aim of the current investigation was to examine reading aloud in normal adults. We hypothesized that the regularity effect, previously described for alphabetical scripts and acquired dyslexic patients of Chinese (Weekes & Chen, 1999; Wu, Liu, Sun, Chromik, & Zhang, 2014, would also be present in normal adult Chinese readers. Method Participants. Thirty (50% female native Hong Kong Cantonese speakers with a mean age of 19.6 years and a mean education of 12.9 years. Stimuli. Sixty regular-, 60 irregular-, and 60 pseudo-characters (with at least 75% of name agreement in Chinese were matched by initial phoneme, number of strokes and family size. Additionally, regular- and irregular-characters were matched by frequency (low and consistency. Procedure. Each participant was asked to read aloud the stimuli presented on a laptop using the DMDX software. The order of stimuli presentation was randomized. Data analysis. ANOVAs were carried out by participants and items with RTs and errors as dependent variables and type of stimuli (regular-, irregular- and pseudo-character as repeated measures (F1 or between subject

  18. Characterization of intrinsic properties of cingulate pyramidal neurons in adult mice after nerve injury

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    Chen Tao

    2009-12-01

    Full Text Available Abstract The anterior cingulate cortex (ACC is important for cognitive and sensory functions including memory and chronic pain. Glutamatergic excitatory synaptic transmission undergo long-term potentiation in ACC pyramidal cells after peripheral injury. Less information is available for the possible long-term changes in neuronal action potentials or intrinsic properties. In the present study, we characterized cingulate pyramidal cells in the layer II/III of the ACC in adult mice. We then examined possible long-term changes in intrinsic properties of the ACC pyramidal cells after peripheral nerve injury. In the control mice, we found that there are three major types of pyramidal cells according to their action potential firing pattern: (i regular spiking (RS cells (24.7%, intrinsic bursting (IB cells (30.9%, and intermediate (IM cells (44.4%. In a state of neuropathic pain, the population distribution (RS: 21.3%; IB: 31.2%; IM: 47.5% and the single action potential properties of these three groups were indistinguishable from those in control mice. However, for repetitive action potentials, IM cells from neuropathic pain animals showed higher initial firing frequency with no change for the properties of RS and IB neurons from neuropathic pain mice. The present results provide the first evidence that, in addition to synaptic potentiation reported previously, peripheral nerve injury produces long-term plastic changes in the action potentials of cingulate pyramidal neurons in a cell type-specific manner.

  19. Effects of cigarette smoking on cerebral blood flow in normal adults

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    Shinohara, Takao [Tokyo Medical Coll. (Japan)

    1997-11-01

    To elucidate the pharmacological effects of cigarette smoking on cerebral function and blood flow in normal adults, cerebral blood flow (CBF) was measured by positron emission tomography (PET) in 10 right-handed male healthy volunteers with a smoking habit after 12-hour abstinence. By the oxygen-15 intravenous injection method, quantitative CBF was measured repeatedly 6 times; during normal breathing (baseline), 5% CO{sub 2} inhalation and cigarette smoking. Sham smoking was performed during baseline and CO{sub 2} inhalation. To eliminate the effects from PaCO{sub 2}, CBF was adjusted based on the vascular reactivity to CO{sub 2} and PaCO{sub 2} during smoking. Pulse rate, systemic blood pressure and arterial nicotine level were increased during smoking. In the overall comparison, there was no significant change in the mean CBF during smoking as compared with baseline. Out of 19 sessions, CBF increased significantly in 7 sessions, while CBF decreased in 7 sessions and was unchanged in 5 sessions. The arterial concentration of nicotine correlated inversely with CBF. When the baseline CBF was relatively low, CBF increased during smoking, while it decreased when the baseline value was high. In the 3-dimensional statistical analysis of normalized CBF, a significant increase was seen in the nucleus accumbens, which is assumed to be related to the drug habits or addiction in previous studies. In the first smoking after abstinence, CBF increased in the orbitofrontal gyri, and this can be linked to reward or relaxation. By contrast, a significant decrease was observed in the occipital lobes and paracentral areas. (author)

  20. Effects of cigarette smoking on cerebral blood flow in normal adults

    International Nuclear Information System (INIS)

    Shinohara, Takao

    1997-01-01

    To elucidate the pharmacological effects of cigarette smoking on cerebral function and blood flow in normal adults, cerebral blood flow (CBF) was measured by positron emission tomography (PET) in 10 right-handed male healthy volunteers with a smoking habit after 12-hour abstinence. By the oxygen-15 intravenous injection method, quantitative CBF was measured repeatedly 6 times; during normal breathing (baseline), 5% CO 2 inhalation and cigarette smoking. Sham smoking was performed during baseline and CO 2 inhalation. To eliminate the effects from PaCO 2 , CBF was adjusted based on the vascular reactivity to CO 2 and PaCO 2 during smoking. Pulse rate, systemic blood pressure and arterial nicotine level were increased during smoking. In the overall comparison, there was no significant change in the mean CBF during smoking as compared with baseline. Out of 19 sessions, CBF increased significantly in 7 sessions, while CBF decreased in 7 sessions and was unchanged in 5 sessions. The arterial concentration of nicotine correlated inversely with CBF. When the baseline CBF was relatively low, CBF increased during smoking, while it decreased when the baseline value was high. In the 3-dimensional statistical analysis of normalized CBF, a significant increase was seen in the nucleus accumbens, which is assumed to be related to the drug habits or addiction in previous studies. In the first smoking after abstinence, CBF increased in the orbitofrontal gyri, and this can be linked to reward or relaxation. By contrast, a significant decrease was observed in the occipital lobes and paracentral areas. (author)

  1. Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.

    Science.gov (United States)

    Li, Ge; Mayer, Cynthia L; Morelli, Daniel; Millard, Steven P; Raskind, Wendy H; Petrie, Eric C; Cherrier, Monique; Fagan, Anne M; Raskind, Murray A; Peskind, Elaine R

    2017-09-19

    To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ 42 , total tau, and p-tau 181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status. Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ 42 , total tau, and p-tau 181 , respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau 181 ( p = 0.003), where greater decreases from baseline in CSF p-tau 181 concentrations were associated with higher baseline LDL level for the simvastatin group. Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia. © 2017 American Academy of Neurology.

  2. CT measurement of normal pericardial thickness in adults on computed tomography

    International Nuclear Information System (INIS)

    Choi, Young Woo; Park, Chan Sup; Jeon, Yong Sun; Bae, In Young; Choi, Sung Gyu; Koo, Jin Hoe; Chung, Won Kyun

    1998-01-01

    The purpose of this study was to establish, using computed tomography, the normal thickness of the pericardium in adults. Materials and Methods: CT scans of 50 patients, including sections through the level of the heart, were reviewed. Patients were excluded if there were any suspicions of pericardial abnormality such as infectious or neoplastic diseases. Twenty-four of the 50 were men and 26 were women; their mean age was 47.0(range,18-76) years. We measured pericardial thickness at the level of the right ventricle, interventricular septum and left ventricle, and also compared pericardial thickness in terms of age and sex. Results: In all patients, the pericardium was observed in the right ventricular region; in 41 (82%) at the interventricular septum; and in 41 (82%) along the left ventricle. The mean thickness of normal pericardium at the level of the right ventricle, interventricular septum, and left ventricle was 1.8 mm ± 0.5 mm, 1.8 mm ± 0.4 mm, and 1.7 mm ± 0.5 mm, respectively. No statistically significant correlation was apparent between pericardial thickness and age group (p > 0.63, ANOVA test). Mean pericardial thickness was 1.9 mm ± 0.6 mm in males and 1.7 mm ± 0.4 mm in females; thus, no statistically significant correlation was apparent between pericardial thickness and sex (p >0.29, Student's t-test). Conclusion: The pericardium was best visualized in sections through the right ventricle.The mean thickness of normal pericardium was 1.8 mm ± 0.5 mm and pericardial thickness did not differ according to age or sex

  3. Contrast sensitivity measured by two different test methods in healthy, young adults with normal visual acuity.

    Science.gov (United States)

    Koefoed, Vilhelm F; Baste, Valborg; Roumes, Corinne; Høvding, Gunnar

    2015-03-01

    This study reports contrast sensitivity (CS) reference values obtained by two different test methods in a strictly selected population of healthy, young adults with normal uncorrected visual acuity. Based on these results, the index of contrast sensitivity (ICS) is calculated, aiming to establish ICS reference values for this population and to evaluate the possible usefulness of ICS as a tool to compare the degree of agreement between different CS test methods. Military recruits with best eye uncorrected visual acuity 0.00 LogMAR or better, normal colour vision and age 18-25 years were included in a study to record contrast sensitivity using Optec 6500 (FACT) at spatial frequencies of 1.5, 3, 6, 12 and 18 cpd in photopic and mesopic light and CSV-1000E at spatial frequencies of 3, 6, 12 and 18 cpd in photopic light. Index of contrast sensitivity was calculated based on data from the three tests, and the Bland-Altman technique was used to analyse the agreement between ICS obtained by the different test methods. A total of 180 recruits were included. Contrast sensitivity frequency data for all tests were highly skewed with a marked ceiling effect for the photopic tests. The median ICS for Optec 6500 at 85 cd/m2 was -0.15 (95% percentile 0.45), compared with -0.00 (95% percentile 1.62) for Optec at 3 cd/m2 and 0.30 (95% percentile 1.20) FOR CSV-1000E. The mean difference between ICSFACT 85 and ICSCSV was -0.43 (95% CI -0.56 to -0.30, p<0.00) with limits of agreement (LoA) within -2.10 and 1.22. The regression line on the difference of average was near to zero (R2=0.03). The results provide reference CS and ICS values in a young, adult population with normal visual acuity. The agreement between the photopic tests indicated that they may be used interchangeably. There was little agreement between the mesopic and photopic tests. The mesopic test seemed best suited to differentiate between candidates and may therefore possibly be useful for medical selection purposes.

  4. Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritoneal leukocytes in mice under normal conditions and during acute inflammatory reaction

    International Nuclear Information System (INIS)

    van't Wout, J.W.; Linde, I.; Leijh, P.C.; van Furth, R.

    1989-01-01

    In order to develop a suitable model for studying the role of granulocytes and monocytes in resistance against pathogenic microorganisms, we investigated the effect of irradiation and cytostatic treatment (cyclophosphamide and VP-16) on the number of both peripheral blood and peritoneal leukocytes in male Swiss mice. Irradiation and cyclophosphamide treatment severely decreased the number of both granulocytes and monocytes in peripheral blood, whereas VP-16 only lowered the number of blood monocytes to a significant degree and had little effect on the number of blood granulocytes or lymphocytes. When normal mice were injected intraperitoneally with newborn calf serum (NBCS) the number of peritoneal granulocytes rose about 100-fold within 6 h. In irradiated and cyclophosphamide-treated mice, this influx of granulocytes into the peritoneal cavity was virtually eliminated, as was the concomitant increase in the number of blood granulocytes; in VP-16-treated mice, on the other hand, the number of peripheral blood and peritoneal granulocytes increased to the same degree as in normal mice. An increase in the number of peripheral blood monocytes and peritoneal macrophages occurred 24-48 h after injection of NBCS in normal mice. This increase was significantly impaired by irradiation as well as by treatment with cyclophosphamide or VP-16

  5. Comparative study of two different Bombesin derivates labeled with 111In and biodistribution in normal mice

    International Nuclear Information System (INIS)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly 5 -BBN (6-14) ) and (DTPA-Phe-Gly 2 -BBN (6-14 )) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of 111 InCl 3 at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of 111 InCl 3 activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly 5 -BBN (6-14 ). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of 111 In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled peptides was 1.85 MBq/ μg. The maximum specific

  6. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  7. Detection of normal plantar fascia thickness in adults via the ultrasonographic method.

    Science.gov (United States)

    Abul, Kadir; Ozer, Devrim; Sakizlioglu, Secil Sezgin; Buyuk, Abdul Fettah; Kaygusuz, Mehmet Akif

    2015-01-01

    Heel pain is a prevalent concern in orthopedic clinics, and there are numerous pathologic abnormalities that can cause heel pain. Plantar fasciitis is the most common cause of heel pain, and the plantar fascia thickens in this process. It has been found that thickening to greater than 4 mm in ultrasonographic measurements can be accepted as meaningful in diagnoses. Herein, we aimed to measure normal plantar fascia thickness in adults using ultrasonography. We used ultrasonography to measure the plantar fascia thickness of 156 healthy adults in both feet between April 1, 2011, and June 30, 2011. These adults had no previous heel pain. The 156 participants comprised 88 women (56.4%) and 68 men (43.6%) (mean age, 37.9 years; range, 18-65 years). The weight, height, and body mass index of the participants were recorded, and statistical analyses were conducted. The mean ± SD (range) plantar fascia thickness measurements for subgroups of the sample were as follows: 3.284 ± 0.56 mm (2.4-5.1 mm) for male right feet, 3.3 ± 0.55 mm (2.5-5.0 mm) for male left feet, 2.842 ± 0.42 mm (1.8-4.1 mm) for female right feet, and 2.8 ± 0.44 mm (1.8-4.3 mm) for female left feet. The overall mean ± SD (range) thickness for the right foot was 3.035 ± 0.53 mm (1.8-5.1 mm) and for the left foot was 3.053 ± 0.54 mm (1.8-5.0 mm). There was a statistically significant and positive correlation between plantar fascia thickness and participant age, weight, height, and body mass index. The plantar fascia thickness of adults without heel pain was measured to be less than 4 mm in most participants (~92%). There was no statistically significant difference between the thickness of the right and left foot plantar fascia.

  8. Comparison of Fatty Acid and Gene Profiles in Skeletal Muscle in Normal and Obese C57BL/6J Mice before and after Blunt Muscle Injury

    Directory of Open Access Journals (Sweden)

    Jens-Uwe Werner

    2018-01-01

    Full Text Available Injury and obesity are two major health burdens affecting millions of people worldwide. Obesity is recognized as a state of chronic inflammation accompanied by various co-morbidities like T2D or cardiovascular diseases. There is increasing evidence that obesity impairs muscle regeneration, which is mainly due to chronic inflammation and to excessive accumulation of lipids in adipose and non-adipose tissue. To compare fatty acid profiles and changes in gene expression at different time points after muscle injury, we used an established drop tower-based model with a defined force input to damage the extensor iliotibialis anticus on the left hind limb of female C57BL/6J mice of normal weight and obese mice. Although most changes in fatty acid content in muscle tissue are diet related, levels of eicosaenoic (normal weight and DHG-linolenic acid (obese in the phospholipid and docosahexaenoic acid (normal weight in the triglyceride fraction are altered after injury. Furthermore, changes in gene transcription were detected in 3829 genes in muscles of normal weight mice, whereas only 287 genes were altered in muscles of obese mice after trauma. Alterations were found within several pathways, among them notch-signaling, insulin-signaling, sonic hedgehog-signaling, apoptosis related pathways, fat metabolism related cholesterol homeostasis, fatty acid biosynthetic process, fatty acid elongation, and acyl-CoA metabolic process. We could show that genes involved in fat metabolism are affected 3 days after trauma induction mostly in normal weight but not in obese mice. The strongest effects were observed in normal weight mice for Alox5ap, the activating protein for leukotriene synthesis, and Apobec1, an enzyme substantial for LDL synthesis. In summary, we show that obesity changes the fat content of skeletal muscle and generally shows a negative impact upon blunt muscle injury on various cellular processes, among them fatty acid related metabolism, notch

  9. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    Science.gov (United States)

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  10. Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

    Science.gov (United States)

    Bale, Laurie K; West, Sally A; Conover, Cheryl A

    2017-08-01

    Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  11. Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

    Directory of Open Access Journals (Sweden)

    Lyu C

    2017-08-01

    Full Text Available Chuang Lyu,1,2 Gong-Wei Lyu,3 Aurora Martinez,4 Tie-Jun Sten Shi4 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of China; 2Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; 3Department of Neurology, 1st Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Biomedicine, University of Bergen, Bergen, Norway Background: The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice. Methods: A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery. Results: There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice. Conclusion: Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self

  12. Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking.

    Science.gov (United States)

    Holstein, Sarah E; Spanos, Marina; Hodge, Clyde W

    2011-10-01

    Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl). Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during

  13. Enriched expression of the ciliopathy gene Ick in cell proliferating regions of adult mice.

    Science.gov (United States)

    Tsutsumi, Ryotaro; Chaya, Taro; Furukawa, Takahisa

    2018-04-07

    Cilia are essential for sensory and motile functions across species. In humans, ciliary dysfunction causes "ciliopathies", which show severe developmental abnormalities in various tissues. Several missense mutations in intestinal cell kinase (ICK) gene lead to endocrine-cerebro-osteodysplasia syndrome or short rib-polydactyly syndrome, lethal recessive developmental ciliopathies. We and others previously reported that Ick-deficient mice exhibit neonatal lethality with developmental defects. Mechanistically, Ick regulates intraflagellar transport and cilia length at ciliary tips. Although Ick plays important roles during mammalian development, roles of Ick at the adult stage are poorly understood. In the current study, we investigated the Ick gene expression in adult mouse tissues. RT-PCR analysis showed that Ick is ubiquitously expressed, with enrichment in the retina, brain, lung, intestine, and reproductive system. In the adult brain, we found that Ick expression is enriched in the walls of the lateral ventricle, in the rostral migratory stream of the olfactory bulb, and in the subgranular zone of the hippocampal dentate gyrus by in situ hybridization analysis. We also observed that Ick staining pattern is similar to pachytene spermatocyte to spermatid markers in the mature testis and to an intestinal stem cell marker in the adult small intestine. These results suggest that Ick is expressed in proliferating regions in the adult mouse brain, testis, and intestine. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. The Intrauterine and Nursing Period Is a Window of Susceptibility for Development of Obesity and Intestinal Tumorigenesis by a High Fat Diet in Min/+ Mice as Adults

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    Ha Thi Ngo

    2015-01-01

    Full Text Available We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia/+ mice. The mice were given a 10% fat diet throughout life (negative control or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+ or 23 weeks for obesogenic effect (wild-type. Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

  15. Amyloid β Is Not the Major Factor Accounting for Impaired Adult Hippocampal Neurogenesis in Mice Overexpressing Amyloid Precursor Protein

    Directory of Open Access Journals (Sweden)

    Hongyu Pan

    2016-10-01

    Full Text Available Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP. However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid β (Aβ or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG of adult mice overexpressing wild-type hAPP (hAPP-I5 compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aβ. Furthermore, reducing Aβ levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aβ was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.

  16. A study on brain ventricle measurements of normal Korean adults using computed tomography

    International Nuclear Information System (INIS)

    Kim, Ung Jin; Chang, Kee Hyun; Han, Man Chung

    1981-01-01

    The study was undertaken to assess the ventricular system of the brain in normal Korean adults on the base of computed tomography. The computerized tomographic examinations of 334 Korean adults between ages of 15 to 50 years, performed at Seoul National University Hospital, were evaluated. The cerebro- or cerebello-ventricular ratio, between ventricular size and brain parenchyme width, has been known to be reliable indicator of the ventricular size. This ratio was measured at the level of the lateral, third and fourth ventricles respectively. The shape of the quardigeminal and suprasellar cistern was analyzed. The results are as follows: 1. The cerebroventricular ratios of the lateral ventricle at the level of the widest bifrontal and bicaudate diameters were 0.30 ± 0.04 and 0.14 ± 0.02, respectively. The lateral ventricle was asymmetric in 12.6%, of which the left side was usually larger than the right. 2. There was correlation between the cerebroventricular ratio and age, i.e., with increase of age, the C-V ratio increased slightly. 3. The cerebrocventricular ratio of the third ventricle was 0.03 ± 0.01. 4. The cerebroventricular ratio of the fourth ventricle in width and height was 0.14 ± 0.02 and 0.10 ± 0.03, respectively. The anteroposterior position index of the fourth ventricle was 0.42 ± 0.04. 5. The quadrigeminal cistern showed W-shape in 76.6% and U-shaped in 23.4%. 6. The suprasellar cistern showed pentagonal shape in 61.1%, round in 28.4% and hexagonal in 10.5%. 7. There was no significant difference between male and female according to the above results

  17. A study on brain ventricle measurement of normal Korean adults using computed tomography

    International Nuclear Information System (INIS)

    Kim, Ung Jin; Chang, Kee Hyun; Han, Man Chung

    1981-01-01

    The study was undertaken to assess the ventricular system of the brain in normal Korean adults on the base of computed tomography. The computerized tomographic examinations of 334 Korean adults between ages of 15 to 50 years, performed at Seoul National University Hospital, were evaluated. The cerebro- or cerebello-ventricular ratio, between ventricular size and brain parenchyme width, has been known to be a reliable indicator of the ventricular size. This ratio was measured at the level of the lateral, third and fourth ventricles respectively. The shape of the quardigeminal and suprasellar cistern was analyzed. The results are as follows: 1. The cerebroventricular ratios of the lateral ventricle at the level of the widest bifrontal and bicaudate diameters were 0.30 ± 0.04 and 0.14 ± 0.02, respectively. The lateral ventricle was asymmetric in 12.6%, of which the left side was usually larger than the right. 2. There was correlation between the cerebroventricular ratio and age, i.e., with increase of age, the C-V ratio increased slightly. 3. The cerebroventricular ratio of the third ventricle was 0.03 ± 0.01. 4. The cerebroventricular ratio of the fourth ventricle in width and height was 0.14± 0.02 and 0.10 ± 0.03, respectively. The anteroposterior position index of the fourth ventricle was 0.42 ± 0.04. 5. The quadrigeminal cistern showed W-shape in 76.6% and U-shape in 23.4%. 6. The suprasellar cistern showed pentagonal shape in 61.1%, round in 28.4% and hexagonal in 10.5%. 7. There was no significant difference between male and female according to the above results

  18. Effects of noise exposure on young adults with normal audiograms I: Electrophysiology.

    Science.gov (United States)

    Prendergast, Garreth; Guest, Hannah; Munro, Kevin J; Kluk, Karolina; Léger, Agnès; Hall, Deborah A; Heinz, Michael G; Plack, Christopher J

    2017-02-01

    Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18-36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3-6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in

  19. Association of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults.

    Science.gov (United States)

    Donovan, Nancy J; Okereke, Olivia I; Vannini, Patrizia; Amariglio, Rebecca E; Rentz, Dorene M; Marshall, Gad A; Johnson, Keith A; Sperling, Reisa A

    2016-12-01

    Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ε4 (APOEε4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOEε4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n = 25). Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness). The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOEε4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOEε4, socioeconomic

  20. Chronic Giardia muris infection in anti-IgM-treated mice. I. Analysis of immunoglobulin and parasite-specific antibody in normal and immunoglobulin-deficient animals.

    Science.gov (United States)

    Snider, D P; Gordon, J; McDermott, M R; Underdown, B J

    1985-06-01

    To investigate the role of B cells and antibody in the immune response of mice to the murine intestinal parasite Giardia muris, we used mice treated from birth with rabbit anti-IgM antisera (aIgM). Such mice developed in serum and in gut secretions extreme Ig deficiency (IgM, IgA, and IgG) relative to control animals. The aIgM-treated mice showed no anti-G. muris antibody in serum or in gut wash material. Infections of G. muris in these mice were chronic, with a high load of parasite present in the small bowel, as reflected by prolonged cyst excretion (greater than 11 wk) and high trophozoite counts. In contrast, normal, untreated mice or NRS-treated animals developed anti-parasite IgA and IgG antibody in serum, demonstrated IgA antibody against the parasite in gut washings, and expelled the parasite within 9 wk. These effects of aIgM treatment on the murine response to primary infection with G. muris were demonstrated in two strains of mice: BALB/c and (C57BL/6 X C3H/He) F1. It was also observed that the response to G. muris infection in untreated animals was characterized by higher than normal total secretion of IgA into the gut and a concomitant increase in the serum polymeric IgA level. Mice treated with aIgM had a marked decrease of both monomeric and polymeric IgA in serum, and little detectable IgA in the intestinal lumen. These experiments provide the first demonstration that anti-IgM treatment suppresses a specific intestinal antibody response to antigen, and provide evidence that B cells and antibody play a role in the development of an effective response to a primary infection with G. muris in mice.

  1. Speech Recognition in Real-Life Background Noise by Young and Middle-Aged Adults with Normal Hearing

    OpenAIRE

    Lee, Ji Young; Lee, Jin Tae; Heo, Hye Jeong; Choi, Chul-Hee; Choi, Seong Hee; Lee, Kyungjae

    2015-01-01

    Background and Objectives People usually converse in real-life background noise. They experience more difficulty understanding speech in noise than in a quiet environment. The present study investigated how speech recognition in real-life background noise is affected by the type of noise, signal-to-noise ratio (SNR), and age. Subjects and Methods Eighteen young adults and fifteen middle-aged adults with normal hearing participated in the present study. Three types of noise [subway noise, vacu...

  2. Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

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    Katherine J. Bangen

    2017-06-01

    Full Text Available Cerebral blood flow (CBF alterations and amyloid-β (Aβ accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer’s disease (AD within a sample of older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI study. Sixty-two cognitively normal participants (mean age = 72 years underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity was determined based on established cutoffs (Landau et al., 2013. The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory

  3. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    International Nuclear Information System (INIS)

    Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

    1988-01-01

    The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

  4. Development of the adult neurogenic niche in the hippocampus of mice

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    Zeina eNicola

    2015-05-01

    Full Text Available When does adult hippocampal neurogenesis begin? We describe the development of the neurogenic niche in the subgranular zone (SGZ of the hippocampal dentate gyrus. We did so from the perspective of the situation in the adult.Ontogeny of the dentate gyrus is complex and results in an ectopic neurogenic niche that lifelong generates new granule cells. Neurogenesis during the fetal and early postnatal periods builds the dentate gyrus and gives way to activity-dependent adult neurogenesis. We used markers most relevant to adult neurogenesis research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2, Doublecortin (DCX, NeuroD1 and Prox1. We found that massive changes and a local condensation of proliferating precursor cells occurs between postnatal day 7 (P7, near the peak in proliferation, and P14. Before and around P7, the spatial distribution of cells and the co-localization of markers were distinct from the situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the radial glial marker BLBP were not overlapping during embryonic development, presumably indicating different types of radial glia-like cells. Before P7 GFAP-positive cells in the hilus lacked the radial orientation that is characteristic of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3 progenitor cells and early postmitotic neurons in the adult, showed diffuse expression before P7. Intermediate progenitor cell marker Tbr2 became restricted to the SGZ but was found in the granule cell layer and hilus before. Lineage markers NeuroD1 and Prox1 confirmed this pattern.We conclude that the neurogenic niche of adult neurogenesis is in place well before true adulthood. This might indicate that consistent with the hypothesized function of adult neurogenesis in activity-dependent plasticity, the early transition from postnatal neurogenesis to adult neurogenesis coincides with the time, when the young mice start to become active themselves.

  5. [Imprinting as a mechanism of information memorizing in the adult BALB/c mice].

    Science.gov (United States)

    Nikol'skaia, K A; Berezhnoĭ, D S

    2011-09-01

    Study of spatial learning in adult BALB/c mice revealed that a short exposition to the environment (from 3 to 8 minutes) could be enough for spatial information to be fixed in the long-term memory, and affected subsequent learning process in the new environment. Control group, learning in the same maze, followed the "shortest path" principle during formation of the optimal food-obtaining habit. Experimental animals, learning in a slightly changed environment, were unable to apply this rule due to persistent coupling of the new spatial information with the old memory traces which led to constant errors. The obtained effect was observed during the whole learning period and depended neither on frequency nor on interval of repetition during the initial information acquisition. The obtained data testify that memorizing in adult state share the properties with the imprinting process inherent in the early ontogeny. The memory fixation on all development stages seems to be based on a universal mechanism.

  6. Sex-comparative study of mouse cerebellum physiology under adult-onset hypothyroidism: The significance of GC-MS metabolomic data normalization in meta-analysis.

    Science.gov (United States)

    Maga-Nteve, Christoniki; Vasilopoulou, Catherine G; Constantinou, Caterina; Margarity, Marigoula; Klapa, Maria I

    2017-01-15

    A systematic data quality validation and normalization strategy is an important component of the omic profile meta-analysis, ensuring comparability of the profiles and exclusion of experimental biases from the derived biological conclusions. In this study, we present the normalization methodology applied on the sets of cerebellum gas chromatography-mass spectrometry metabolic profiles of 124days old male and female animals in an adult-onset-hypothyroidism (AOH) mouse model before combining them into a sex-comparative analysis. The employed AOH model concerns the monitoring of the brain physiology of Balb/cJ mice after eight-week administration of 1%w/v KClO 4 in the drinking water, initiated on the 60th day of their life. While originating from the same animal study, the tissues of the two sexes were processed and their profiles acquired and analyzed at different time periods. Hence, the previously published profile set of male mice was first re-annotated based on the presently available resources. Then, after being validated as acquired under the same analytical conditions, both profiles sets were corrected for derivatization biases and filtered for low-confidence measurements based on the same criteria. The final normalized 73-metabolite profiles contribute to the currently few available omic datasets of the AOH effect on brain molecular physiology, especially with respect to sex differentiation. Multivariate statistical analysis indicated one (unknown) and three (succinate, benzoate, myristate) metabolites with significantly higher and lower, respectively, cerebellum concentration in the hypothyroid compared to the euthyroid female mice. The respective numbers for the males were two and 24. Comparison of the euthyroid cerebellum metabolic profiles between the two sexes indicated 36 metabolites, including glucose, myo- and scyllo-inositol, with significantly lower concentration in the females versus the males. This implies that the female mouse cerebellum has

  7. Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults.

    Science.gov (United States)

    Beyer, Peter L; Caviar, Elena M; McCallum, Richard W

    2005-10-01

    Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with

  8. Gender Difference in TEOAEs and Contralateral Suppression of TEOAEs in Normal Hearing Adults

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    Farzaneh Zamiri Abdollahi

    2011-10-01

    Full Text Available Objectives: Otoacoustic emissions (OAEs are sounds that originate in cochlea and are measured in external auditory canal and provide a simple, efficient and non-invasive objective indicator of healthy cochlear function. Olivo cochlear bundle (OCB or auditory efferent system is a neural feedback pathway which originated from brain stem and terminated in the inner ear and can be evaluated non-invasively by applying a contralateral acoustic stimulus and simultaneously measuring reduction of OAEs amplitude. In this study gender differences in TEOAE amplitude and suppression of TEOAE were investigated. Methods: This study was performed at Akhavan rehabilitation centre belonging to the University of Social welfare and rehabilitation sciences, Tehran, Iran in 2011. 60 young adults (30 female and 30 male between 21 and 27 years old (mean=24 years old, SD=1.661 with normal hearing criteria were selected. Right ear of all cases were tested to neutralize side effect if there is any. Results: According to Independent t-test, TEOAE amplitude was significantly greater in females with mean value of 24.98 dB (P<0.001 and TEOAE suppression was significantly greater in males with mean value of 2.07 dB (P<0.001. Discussion: This study shows that there is a significant gender difference in adult’s TEOAE (cochlear mechanisms and TEOAE suppression (auditory efferent system. The exact reason for these results is not clear. According to this study different norms for males and females might be necessary.

  9. Is There Evidence for Myelin Modeling by Astrocytes in the Normal Adult Brain?

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    Alfredo Varela-Echevarría

    2017-09-01

    Full Text Available A set of astrocytic process associated with altered myelinated axons is described in the forebrain of normal adult rodents with confocal, electron microscopy, and 3D reconstructions. Each process consists of a protuberance that contains secretory organelles including numerous lysosomes which polarize and open next to disrupted myelinated axons. Because of the distinctive asymmetric organelle distribution and ubiquity throughout the forebrain neuropil, this enlargement is named paraxial process (PAP. The myelin envelope contiguous to the PAP displays focal disruption or disintegration. In routine electron microscopy clusters of large, confluent, lysosomes proved to be an effective landmark for PAP identification. In 3D assemblies lysosomes organize a series of interconnected saccules that open up to the plasmalemma next to the disrupted myelin envelope(s. Activity for acid hydrolases was visualized in lysosomes, and extracellularly at the PAP-myelin interface and/or between the glial and neuronal outer aspects. Organelles in astrocytic processes involved in digesting pyknotic cells and debris resemble those encountered in PAPs supporting a likewise lytic function of the later. Conversely, processes entangling tripartite synapses and glomeruli were devoid of lysosomes. Both oligodendrocytic and microglial processes were not associated with altered myelin envelopes. The possible roles of the PAP in myelin remodeling in the context of the oligodendrocyte-astrocyte interactions and in the astrocyte's secretory pathways are discussed.

  10. Diet enriched with fresh coconut decreases blood glucose levels and body weight in normal adults.

    Science.gov (United States)

    Vijayakumar, Venugopal; Shankar, Nagashree R; Mavathur, Ramesh; Mooventhan, A; Anju, Sood; Manjunath, N K

    2018-02-20

    Background There exist controversies about the health effects of coconut. Fresh coconut consumption on human health has not been studied substantially. Fresh coconut consumption is a regular part of the diet for many people in tropical countries like India, and thus there is an increasing need to understand the effects of fresh coconut on various aspects of health. Aim To compare the effects of increased saturated fatty acid (SFA) and fiber intake, provided by fresh coconut, versus monounsaturated fatty acid (MUFA) and fiber intake, provided by a combination of groundnut oil and groundnuts, on anthropometry, serum insulin, glucose levels and blood pressure in healthy adults. Materials Eighty healthy volunteers, randomized into two groups, were provided with a standardized diet along with either 100 g fresh coconut or an equivalent amount of groundnuts and groundnut oil for a period of 90 days. Assessments such as anthropometric measurements, blood pressure, blood sugar and insulin levels were performed before and after the supplementation period. Results Results of this study showed a significant reduction in fasting blood sugar (FBS) in both the groups. However, a significant reduction in body weight was observed in the coconut group, while a significant increase in diastolic pressure was observed in the groundnut group. Conclusions Results of this study suggest that fresh coconut-added diet helps reduce blood glucose levels and body weight in normal healthy individuals.

  11. Searching for sources of variance in speech recognition: Young adults with normal hearing

    Science.gov (United States)

    Watson, Charles S.; Kidd, Gary R.

    2005-04-01

    In the present investigation, sensory-perceptual abilities of one thousand young adults with normal hearing are being evaluated with a range of auditory, visual, and cognitive measures. Four auditory measures were derived from factor-analytic analyses of previous studies with 18-20 speech and non-speech variables [G. R. Kidd et al., J. Acoust. Soc. Am. 108, 2641 (2000)]. Two measures of visual acuity are obtained to determine whether variation in sensory skills tends to exist primarily within or across sensory modalities. A working memory test, grade point average, and Scholastic Aptitude Test scores (Verbal and Quantitative) are also included. Preliminary multivariate analyses support previous studies of individual differences in auditory abilities (e.g., A. M. Surprenant and C. S. Watson, J. Acoust. Soc. Am. 110, 2085-2095 (2001)] which found that spectral and temporal resolving power obtained with pure tones and more complex unfamiliar stimuli have little or no correlation with measures of speech recognition under difficult listening conditions. The current findings show that visual acuity, working memory, and intellectual measures are also very poor predictors of speech recognition ability, supporting the independence of this processing skill. Remarkable performance by some exceptional listeners will be described. [Work supported by the Office of Naval Research, Award No. N000140310644.

  12. Subcategory learning in normal and language learning-disabled adults: how much information do they need?

    Science.gov (United States)

    Richardson, Jessica; Harris, Laurel; Plante, Elena; Gerken, Louann

    2006-12-01

    The purpose of this experiment was to determine if nonreferential morphophonological information was sufficient to facilitate the learning of gender subcategories (i.e., masculine vs. feminine) in individuals with normal language (NL) and those with a history of language-based learning disabilities (HLD). Thirty-two adults listened for 18 min to a familiarization set of Russian words that included either 1 (single-marked) or 2 (double-marked) morphophonological markers indicating gender. Participants were then tested on their knowledge of both trained and untrained members of each gender subcategory. Testing indicated that morphophonological information is sufficient for lexical subcategory learning in both NL and HLD groups, although the HLD group had lower overall accuracy. The HLD group benefited from double-marking relative to single-marking for subcategory learning. The results demonstrated that learning through implicit mechanisms occurred after a relatively brief exposure to the language stimuli. In addition, the weaker overall learning by the HLD group was facilitated when multiple cues to linguistic subcategory were available in the input group members received.

  13. Changes in Olfactory Sensory Neuron Physiology and Olfactory Perceptual Learning After Odorant Exposure in Adult Mice.

    Science.gov (United States)

    Kass, Marley D; Guang, Stephanie A; Moberly, Andrew H; McGann, John P

    2016-02-01

    The adult olfactory system undergoes experience-dependent plasticity to adapt to the olfactory environment. This plasticity may be accompanied by perceptual changes, including improved olfactory discrimination. Here, we assessed experience-dependent changes in the perception of a homologous aldehyde pair by testing mice in a cross-habituation/dishabituation behavioral paradigm before and after a week-long ester-odorant exposure protocol. In a parallel experiment, we used optical neurophysiology to observe neurotransmitter release from olfactory sensory neuron (OSN) terminals in vivo, and thus compared primary sensory representations of the aldehydes before and after the week-long ester-odorant exposure in individual animals. Mice could not discriminate between the aldehydes during pre-exposure testing, but ester-exposed subjects spontaneously discriminated between the homologous pair after exposure, whereas home cage control mice cross-habituated. Ester exposure did not alter the spatial pattern, peak magnitude, or odorant-selectivity of aldehyde-evoked OSN input to olfactory bulb glomeruli, but did alter the temporal dynamics of that input to make the time course of OSN input more dissimilar between odorants. Together, these findings demonstrate that odor exposure can induce both physiological and perceptual changes in odor processing, and suggest that changes in the temporal patterns of OSN input to olfactory bulb glomeruli could induce differences in odor quality. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Nigral dopaminergic neuron replenishment in adult mice through VE-cadherin-expressing neural progenitor cells

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    Abir A Rahman

    2017-01-01

    Full Text Available The function of dopaminergic neurons in the substantia nigra is of central importance to the coordination of movement by the brain's basal ganglia circuitry. This is evidenced by the loss of these neurons, resulting in the cardinal motor deficits associated with Parkinson's disease. In order to fully understand the physiology of these key neurons and develop potential therapies for their loss, it is essential to determine if and how dopaminergic neurons are replenished in the adult brain. Recent work has presented evidence for adult neurogenesis of these neurons by Nestin+/Sox2– neural progenitor cells. We sought to further validate this finding and explore a potential atypical origin for these progenitor cells. Since neural progenitor cells have a proximal association with the vasculature of the brain and subsets of endothelial cells are Nestin+, we hypothesized that dopaminergic neural progenitors might share a common cell lineage. Therefore, we employed a VE-cadherin promoter-driven CREERT2:THlox/THlox transgenic mouse line to ablate the tyrosine hydroxylase gene from endothelial cells in adult animals. After 26 weeks, but not 13 weeks, following the genetic blockade of tyrosine hydroxylase expression in VE-cadherin+ cells, we observed a significant reduction in tyrosine hydroxylase+ neurons in the substantia nigra. The results from this genetic lineage tracing study suggest that dopaminergic neurons are replenished in adult mice by a VE-cadherin+ progenitor cell population potentially arising from an endothelial lineage.

  15. Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice.

    Science.gov (United States)

    Tien, Yun-Chen; Piekos, Stephanie C; Pope, Chad; Zhong, Xiao-Bo

    2017-03-01

    Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. The goal of this study was to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered up through adult life. We selected a mouse model to test phenobarbital exposure at a neonatal age and its impact on efficacy of omeprazole in adult life. The results of our experiment show an observed decrease in omeprazole's ability to raise gastric pH in adult mice that received single or multiple doses of phenobarbital at a neonatal age. This effect may be associated with the permanent induction of cytochrome P450 enzymes in adult liver after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt re-evaluation of how DDIs are viewed and how to avoid long-term DDIs in clinical practice. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Redox proteomic analysis of the gastrocnemius muscle from adult and old mice

    Directory of Open Access Journals (Sweden)

    Brian McDonagh

    2015-09-01

    Full Text Available The data provides information in support of the research article, “Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging”, Journal of Proteome Research, 2014, 13 (11, 2008–21 [1]. Raw data is available from ProteomeXchange [2] with identifier PDX001054. The proteome of gastrocnemius muscle from adult and old mice was analyzed by global label-free proteomics and the relative quantification of specific reduced and reversibly oxidized Cysteine (Cys residues was performed using Skyline [3]. Briefly, reduced Cysteine (Cys containing peptides was alkylated using N-ethylmalemide (d0-NEM. Samples were desalted and reversibly oxidized Cys residues were reduced using tris(2-carboxyethylphosphine (TCEP and the newly formed reduced Cys residues were labeled with heavy NEM( d5-NEM. Label-free analysis of the global proteome of adult (n=5 and old (n=4 gastrocnemius muscles was performed using Peaks7™ mass spectrometry data analysis software [4]. Relative quantification of Cys containing peptides that were identified as reduced (d(0 NEM labeled and reversibly oxidized d(5–NEM labeled was performed using the intensity of their precursor ions in Skyline. Results indicate that muscles from old mice show reduced redox flexibility particularly in proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response.

  17. Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

    Science.gov (United States)

    Lazarini, Françoise; Mouthon, Marc-André; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, Stéphanie; Abrous, Djoher Nora; Boussin, François D.; Lledo, Pierre-Marie

    2009-01-01

    Background In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. Methodology/Principal Findings In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation. Conclusion/Significance These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces. PMID:19753118

  18. Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice.

    Directory of Open Access Journals (Sweden)

    Françoise Lazarini

    2009-09-01

    Full Text Available In mammals, new neurons are added to the olfactory bulb (OB throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.

  19. Perinatal exposure to methoxychlor enhances adult cognitive responses and hippocampal neurogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Mariangela eMartini

    2014-06-01

    Full Text Available During perinatal life, sex steroids, such as estradiol, have marked effects on the development and function of the nervous system. Environmental estrogens or xenoestrogens are man-made chemicals, which animal and human population encounter in the environment and which are able to disrupt the functioning of the endocrine system. Scientific interest in the effects of exposure to xenoestrogens has focused more on fertility and reproductive behaviors, while the effects on cognitive behaviors have received less attention. Therefore, the present study explored whether the organochlorine insecticide Methoxychlor (MXC, with known xenoestrogens properties, administered during the perinatal period (from gestational day 11 to postnatal day 8 to pregnant-lactating females, at an environmentally relevant dose (20µg/kg (body weight/day, would also affect learning and memory functions depending on the hippocampus of male and female offspring mice in adulthood. When tested in adulthood, MXC perinatal exposure led to an increase in anxiety-like behavior and in short-term spatial working memory in both sexes. Emotional learning was also assessed using a contextual fear paradigm and MXC treated male and female mice showed an enhanced freezing behavior compared to controls. These results were correlated with an increased survival of adult generated cells in the adult hippocampus. In conclusion, our results show that perinatal exposure to an environmentally relevant dose of MXC has an organizational effect on hippocampus-dependent memory and emotional behaviors.

  20. Glucose transporters GLUT4 and GLUT8 are upregulated after facial nerve axotomy in adult mice.

    Science.gov (United States)

    Gómez, Olga; Ballester-Lurbe, Begoña; Mesonero, José E; Terrado, José

    2011-10-01

    Peripheral nerve axotomy in adult mice elicits a complex response that includes increased glucose uptake in regenerating nerve cells. This work analyses the expression of the neuronal glucose transporters GLUT3, GLUT4 and GLUT8 in the facial nucleus of adult mice during the first days after facial nerve axotomy. Our results show that whereas GLUT3 levels do not vary, GLUT4 and GLUT8 immunoreactivity increases in the cell body of the injured motoneurons after the lesion. A sharp increase in GLUT4 immunoreactivity was detected 3 days after the nerve injury and levels remained high on Day 8, but to a lesser extent. GLUT8 also increased the levels but later than GLUT4, as they only rose on Day 8 post-lesion. These results indicate that glucose transport is activated in regenerating motoneurons and that GLUT4 plays a main role in this function. These results also suggest that metabolic defects involving impairment of glucose transporters may be principal components of the neurotoxic mechanisms leading to motoneuron death. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

  1. Culture of normal human blood cells in diffusion chamber systems. I. Granulocyte survival and proliferation. [X radiation, mice

    Energy Technology Data Exchange (ETDEWEB)

    Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Cronkite, E.P.

    1978-01-01

    Blood cells from four normal volunteers were cultured in diffusion chambers (DC), made of Millipore (MDC) or Nuclepore (NDC) filters, in the peritoneal cavities of whole body X-irradiated (700 rad) mice. The total nucleated cell recovery from the two types of DC over 18 days indicates that the cells in DC persist and proliferate. The mature neutrophilic cells, metamyelocytes (M/sub 5/) + band forms (M/sub 6/) + segmented forms (M/sub 7/), survived with T/sup 1///sub 2/ of 29 and 34 h in MDC and NDC, respectively. The reduction of the cells in the DC was surmised to be due to degeneration and death of the M/sub 7/. The /sup 3/H-diisopropylfluorophosphate (/sup 3/HDFP) labeled M/sub /sub 6/+/sub 7// survival in MDC was slightly shorter than that of unlabeled cells, which may be explained on the basis of the loss of /sup 3/HDFP (5.1%/day) from the cells. The eosinophils survived with an average T/sup 1///sub 2/ of 7.2 days (range 4.8 to 9.6), and the results were comparable in both types of DC. Formation of myeloblasts, promyelocytes, and neutrophilic, eosinophilic and basophilic myelocytes, occasional megakaryocytes and rare normoblasts in DC indicated that the normal human blood contains progenitors (pluripotent and/or committed stem cells) of hemopoietic cells. The neutrophilic cell recovery pattern was similar from both types of DC, but the total number recovered was always greater from NDC than from MDC.

  2. Growing into obesity: patterns of height growth in those who become normal weight, overweight, or obese as young adults.

    Science.gov (United States)

    Stovitz, Steven D; Demerath, Ellen W; Hannan, Peter J; Lytle, Leslie A; Himes, John H

    2011-01-01

    To study whether patterns of height growth differ by adult obesity status, and determine the contribution of subcutaneous fatness as an explanatory variable for any differences. A multicenter, prospective longitudinal cohort assessed in 3rd grade (8.8 years), 5th grade (11.1 years), 8th grade (14.1 years), and 12th grade (18.3 years). Exposures were young adult obesity status classified by CDC adult BMI categories at 12th grade. Skinfolds were measured in third, fifth, and eighth grades. Outcome was mean height (cm) at the four measurements using repeated-measures ANCOVA for young adult obesity status, and height increments between grades by adult obesity status in sequential models including initial height and, secondarily, initial skinfolds. Adjusted for age, and race/ethnicity, young adult obesity status explained a small, but statistically significant amount of height growth among both females and males within each of the three intervals. Compared with normal weight young adults, overweight or obese young adults stood taller in childhood, but had relatively less growth in height throughout the teenage years. There was no association between adult height and weight status. Skinfolds explained only a small amount of the height patterns in the three weight groups. Childhood and adolescent height growth patterns differ between those who become young adults who are normal weight and those who become overweight or obese. Since differences in fatness explain only a small amount of these height growth patterns, research is needed to identify other determinants. Copyright © 2011 Wiley-Liss, Inc.

  3. UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

    Science.gov (United States)

    Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

    2015-10-10

    A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice

    Science.gov (United States)

    Zinker, Bradley A.; Rondinone, Cristina M.; Trevillyan, James M.; Gum, Rebecca J.; Clampit, Jill E.; Waring, Jeffrey F.; Xie, Nancy; Wilcox, Denise; Jacobson, Peer; Frost, Leigh; Kroeger, Paul E.; Reilly, Regina M.; Koterski, Sandra; Opgenorth, Terry J.; Ulrich, Roger G.; Crosby, Seth; Butler, Madeline; Murray, Susan F.; McKay, Robert A.; Bhanot, Sanjay; Monia, Brett P.; Jirousek, Michael R.

    2002-01-01

    The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA1C. Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, were increased and PI3-kinase p85α expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes. PMID:12169659

  5. Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice

    OpenAIRE

    Kiran Chaudhari; Jessica M. Wong; Philip H. Vann; Nathalie Sumien

    2014-01-01

    Purpose: The purpose of this study was to determine if antioxidant supplementation, moderate exercise, and the combination of both treatments could ameliorate cognitive performance in adult mice and whether the apolipoprotein E (APOE) genotype as well as sex could influence the functional outcomes of the treatments. Methods: For a period of 16 weeks, separate groups of male and female mice expressing either the human APOE3 or APOE4 isoforms were fed either a control diet (NIH-31) or the co...

  6. Flow-regulated versus differential pressure-regulated shunt valves for adult patients with normal pressure hydrocephalus

    DEFF Research Database (Denmark)

    Ziebell, Morten; Wetterslev, Jørn; Tisell, Magnus

    2013-01-01

    Since 1965 many ventriculo-peritoneal shunt systems have been inserted worldwide to treat hydrocephalus. The most frequent indication in adults is normal pressure hydrocephalus (NPH), a condition that can be difficult to diagnose precisely. Surgical intervention with flow-regulated and differential...

  7. The effects of familiarity and complexity on appraisal of complex songs by cochlear implant recipients and normal hearing adults.

    Science.gov (United States)

    Gfeller, Kate; Christ, Aaron; Knutson, John; Witt, Shelley; Mehr, Maureen

    2003-01-01

    The purposes of this study were (a) to develop a test of complex song appraisal that would be suitable for use with adults who use a cochlear implant (assistive hearing device) and (b) to compare the appraisal ratings (liking) of complex songs by adults who use cochlear implants (n = 66) with a comparison group of adults with normal hearing (n = 36). The article describes the development of a computerized test for appraisal, with emphasis on its theoretical basis and the process for item selection of naturalistic stimuli. The appraisal test was administered to the 2 groups to determine the effects of prior song familiarity and subjective complexity on complex song appraisal. Comparison of the 2 groups indicates that the implant users rate 2 of 3 musical genres (country western, pop) as significantly more complex than do normal hearing adults, and give significantly less positive ratings to classical music than do normal hearing adults. Appraisal responses of implant recipients were examined in relation to hearing history, age, performance on speech perception and cognitive tests, and musical background.

  8. Skeletal myofiber VEGF regulates contraction-induced perfusion and exercise capacity but not muscle capillarity in adult mice.

    Science.gov (United States)

    Knapp, Amy E; Goldberg, Daniel; Delavar, Hamid; Trisko, Breanna M; Tang, Kechun; Hogan, Michael C; Wagner, Peter D; Breen, Ellen C

    2016-07-01

    A single bout of exhaustive exercise signals expression of vascular endothelial growth factor (VEGF) in the exercising muscle. Previous studies have reported that mice with life-long deletion of skeletal myofiber VEGF have fewer capillaries and a severe reduction in endurance exercise. However, in adult mice, VEGF gene deletion conditionally targeted to skeletal myofibers limits exercise capacity without evidence of capillary regression. To explain this, we hypothesized that adult skeletal myofiber VEGF acutely regulates skeletal muscle perfusion during muscle contraction. A tamoxifen-inducible skeletal myofiber-specific VEGF gene deletion mouse (skmVEGF-/-) was used to reduce skeletal muscle VEGF protein by 90% in adult mice. Three weeks after inducing deletion of the skeletal myofiber VEGF gene, skmVEGF-/- mice exhibited diminished maximum running speed (-10%, P Contraction-induced perfusion measured by optical imaging during a period of electrically stimulated muscle contraction was 85% lower in skmVEGF-/- than control mice. No evidence of capillary rarefication was detected in the soleus, gastrocnemius, and extensor digitorum longus (EDL) up to 8 wk after tamoxifen-induced VEGF ablation, and contractility and fatigue resistance of the soleus measured ex vivo were also unchanged. The force-frequency of the EDL showed a small right shift, but fatigue resistance did not differ between EDL from control and skmVEGF-/- mice. These data suggest myofiber VEGF is required for regulating perfusion during periods of contraction and may in this manner affect endurance capacity. Copyright © 2016 the American Physiological Society.

  9. Zinc deficiency with reduced mastication impairs spatial memory in young adult mice.

    Science.gov (United States)

    Kida, Kumiko; Tsuji, Tadataka; Tanaka, Susumu; Kogo, Mikihiko

    2015-12-01

    Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22 weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4 weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency

  10. Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

    Science.gov (United States)

    Daliri, Ayoub; Max, Ludo

    2018-02-01

    Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre

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

    Directory of Open Access Journals (Sweden)

    Dani Smith

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

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    Directory of Open Access Journals (Sweden)

    Alessandro Ieraci

    2016-01-01

    Full Text Available Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

  14. Delayed and transient increase of adult hippocampal neurogenesis by physical exercise in DBA/2 mice.

    Directory of Open Access Journals (Sweden)

    Rupert W Overall

    Full Text Available This study builds on the findings that physical activity, such as wheel running in mice, enhances cell proliferation and neurogenesis in the adult hippocampus of the common mouse strain C57BL/6, and that the baseline level of neurogenesis varies by strain, being considerably lower in DBA/2. Because C57BL/6 and DBA/2 are important as the parental strains of the BXD recombinant inbred cross which allows the detection of genetic loci regulating phenotypes such as adult neurogenesis, we performed the current study to investigate the gene x environment interactions regulating neurogenesis. At equal distances and times run DBA/2J mice lacked the acute increase in precursor cell proliferation known from C57BL/6. In DBA/2J proliferation even negatively correlated with the distance run. This was neither due to a stress response (to running itself or single housing nor differences in estrous cycle. DBA/2 animals exhibited a delayed and weaker pro-neurogenic response with a significant increase in numbers of proliferating cells first detectable after more than a week of wheel running. The proliferative response to running was transient in both strains, the effect being undetectable by 6 weeks. There was also a small transient increase in the production of new neurons in DBA/2J, although these extra cells did not survive. These findings indicate that the comparison between C57BL/6 and DBA/2, and by extension the BXD genetic reference population derived from these strains, should provide a powerful tool for uncovering the complex network of modifier genes affecting the activity-dependent regulation of adult hippocampal neurogenesis. More generally, our findings also describe how the external physical environment interacts with the internal genetic environment to produce different responses to the same behavioral stimuli.

  15. Instrument development in the measurement of unsupported arm exercise endurance in normal adult subjects.

    Science.gov (United States)

    Breslin, E H; Adams, E; Lutz, A; Roy, C

    1993-06-01

    Many daily activities, from basic grooming to employment tasks, require adequate unsupported arm endurance (UAE). We developed an electromechanical device to measure UAE endurance. The purpose of this study was to standardize the instrument for two rates of arm motion, moderate and slow, in 18 normal adult subjects (FEVI = 3.7L +/- .78, FVC = 4.2L +/- .74, FEV1/FVC = 1.1 +/- .08). Exercise endurance limits, and the following metabolic, ventilatory, and sensation responses were determined at rest prior to exercise and at end-exercise limits for both rates of UAE:minute ventilation (Ve), tidal volume (VT), respiratory rate (RR), duty cycle (Ti/Ttot), oxygen uptake (VO2), carbon dioxide production (VCO2), inspiratory flow (VT/Ti), heart rate (HR), and visual analog scale measurements (VAS) of dyspnea (D), respiratory effort (RE), and arm fatigue (AF). Significance increases from baseline rest were shown at the endurance limits for both rates of UAE in: VO2, VCO2, Ve, VT, RR, VT/Ti, HR, VAS-D, VAS-RE, and VAS-AF. There were no changes in Ti/Ttot and SaO2 with UAE. Peak VO2, RR, Ve, VT/Ti, and VAS-D with moderate exercise were significantly greater than slow UAE; and there was a trend increase in peak HR for moderate as opposed to slow rate UAE. Despite these differences, the endurance time between the two rates of UAE were similar. These data provide standards against which UAE in COPD can be evaluated.

  16. Right dorsal colon ultrasonography in normal adult ponies and miniature horses

    Science.gov (United States)

    Zak, Agnieszka; Baron, Monika; Cylna, Marta; Borowicz, Hieronim

    2017-01-01

    The aim of this study was to determine the normal location, wall thickness and motility of the right dorsal colon in adult ponies and miniature horses. The abdominal ultrasonography examination was performed in a study group consisting of 23 ponies and miniature horses and in a control group comprising ten Thoroughbred horses. The procedure was performed in unsedated standing animals. The location and the thickness of the right dorsal colonic wall was examined on the right side of the abdomen between the 10th and the 14th intercostal space. The contractility was recorded in the 12th intercostal space. A comparative analysis between the study group and control group was carried out using the Student’s t-test. Pearson’s linear correlation coefficient was used to calculate the correlation between the thickness of the colonic wall as well as the number of peristaltic movements and age, wither height and body mass of the animals. The right dorsal colon was identified in all the horses in the 12th intercostal space. In all the intercostal spaces the mean ± standard deviation (SD) wall thickness of the right dorsal colon was 0.27 ± 0.03 cm in the horses from the study group and 0.37 ± 0.03 cm in the control horses. The mean number of peristaltic contractions was 4.05 ± 1.07 per minute in the animals from the study group and 1.7 ± 0.46 contractions per minute in the control group. The values of the ultrasonographic wall thickness and peristaltic motility in small breed horses in the present study were different from the values obtained for large breed horses. The study also found that the right dorsal colon in small breed horses is physiologically located in the 12th intercostal space. This suggests that different reference values should be used in small horse breeds when performing an ultrasound examination. PMID:29065146

  17. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    International Nuclear Information System (INIS)

    Choi, Du Hyok; Chung, June Key; Lee, Hong Kyu; Koh, Chang Soon; Hong, Kee Suk

    1983-01-01

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean±S.D. of Group I was 91.1±3.2 mg%, while that of Group II is 82.5±4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean±S.D. of 14.7±3.0 μU/ml while Group II shows that of 7.0±2.6 μU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7±10.8 μU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  18. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Du Hyok; Chung, June Key; Lee, Hong Kyu; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Kee Suk [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1983-03-15

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean+-S.D. of Group I was 91.1+-3.2 mg%, while that of Group II is 82.5+-4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean+-S.D. of 14.7+-3.0 muU/ml while Group II shows that of 7.0+-2.6 muU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7+-10.8 muU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  19. Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.

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    Natalie J Groves

    Full Text Available Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD deficiency in BALB/c mice was associated with (a adult hippocampal neurogenesis at baseline, b following 6 weeks of voluntary wheel running and (c a depressive-like phenotype on the forced swim test (FST, which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX, and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

  20. Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

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    Zhu PL

    2015-02-01

    Full Text Available Pei-Li Zhu,1 Si-Yuan Pan,1 Shu-Feng Zhou,2 Yi Zhang,1 Xiao-Yan Wang,1 Nan Sun,1 Zhu-Sheng Chu,1 Zhi-Ling Yu,3 Kam-Ming Ko41Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 4Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of ChinaBackground: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF, a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb pulp (AqSF-P or an SF-related synthetic analog, bicyclol (BY, on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL mice.Methods: Male mice obtained from the Institute of Cancer Research (ICR were fed on a normal diet (ND or high cholesterol/bile salt (0.5%/0.15%, w/w diet (HCBD containing FF (0.03% or 0.1%, w/w with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w or BY (0.025%, w/w for 10 days. Then serum lipid levels and alanine aminotransferase (ALT activity, as well as hepatic triglyceride (TG, total cholesterol (TC, and glucose levels, were measured.Results: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79% in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67% and in HCBD-fed mice (up to 54%, when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was

  1. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

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    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  2. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

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    Saurabh Chattopadhyay

    Full Text Available 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.

  3. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

    Science.gov (United States)

    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.

  4. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice.

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    Alice Chaplin

    Full Text Available The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute to body weight regulation. Adult mice were fed either a normal fat (NF, 12% kJ content as fat or a high-fat (HF, 43% kJ content as fat diet. In the latter case, half of the animals received daily oral supplementation of CLA. Expression and content of stomach proteins and specific bacterial populations from caecum were analysed. CLA supplementation was associated with an increase in stomach protein expression, and exerted a prebiotic action on both Bacteroidetes/Prevotella and Akkermansia muciniphila. However, CLA supplementation was not able to override the negative effects of HF diet on Bifidobacterium spp., which was decreased in both HF and HF+CLA groups. Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species.

  5. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice.

    Science.gov (United States)

    Chaplin, Alice; Parra, Pilar; Serra, Francisca; Palou, Andreu

    2015-01-01

    The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA) have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute to body weight regulation. Adult mice were fed either a normal fat (NF, 12% kJ content as fat) or a high-fat (HF, 43% kJ content as fat) diet. In the latter case, half of the animals received daily oral supplementation of CLA. Expression and content of stomach proteins and specific bacterial populations from caecum were analysed. CLA supplementation was associated with an increase in stomach protein expression, and exerted a prebiotic action on both Bacteroidetes/Prevotella and Akkermansia muciniphila. However, CLA supplementation was not able to override the negative effects of HF diet on Bifidobacterium spp., which was decreased in both HF and HF+CLA groups. Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species.

  6. Effect of maternal and post weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult Apc+/Min and wild type mice.

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    Jill Ann Mckay

    2011-05-01

    Full Text Available Increasing evidence supports the developmental origins of adult health and disease hypothesis which argues for a causal relationship between adverse early life nutrition and increased disease risk in adulthood. Modulation of epigenetic marks, e.g. DNA methylation and consequential altered gene expression, has been proposed as a mechanism mediating these effects. Via its role as a methyl donor, dietary folate supply may influence DNA methylation. As aberrant methylation is an early event in colorectal cancer (CRC pathogenesis, we hypothesised low maternal and/or post-weaning folate intake may influence methylation of genes involved in CRC development. We investigated the effects of maternal folate depletion during pregnancy and lactation on selected gene methylation in the small intestine (SI of wild type (WT and Apc+/Min mice at weaning and as adults. We also investigated the effects of folate depletion post-weaning on gene methylation in adult mice. Female C57Bl6/J mice were fed low or normal folate diets from mating with Apc+/Min males to the end of lactation. A sub set of offspring were killed at weaning. Remaining offspring were weaned on to low or normal folate diets, resulting in 4 treatment groups of Apc+/Min and WT mice. p53 was more methylated in weaning and adult WT compared with Apc+/Min mice (p>0.001. Igf2 and Apc were hypermethylated in adult Apc+/Mi n compared with WT mice (p=0.004 & p=0.012 respectively. Low maternal folate reduced p53 methylation in adults (p=0.04. Low post-weaning folate increased Apc methylation in Apc+/Min mice only (p=0.008 for interaction. These observations demonstrate that folate depletion in early life can alter epigenetic marks in a gene specific manner. Also, the differential effects of altered folate supply on DNA methylation in WT and Apc+/Min mice suggest that genotype may modulate epigenetic responses to environmental cues and may have implications for the development of personalised nutrition.

  7. Novel approach to select genes from RMA normalized microarray data using functional hearing tests in aging mice

    Science.gov (United States)

    D'Souza, Mary; Zhu, Xiaoxia; Frisina, Robert D.

    2008-01-01

    Presbycusis – age-related hearing loss – is the number one communicative disorder and one of the top three chronic medical condition of our aged population. High-throughput technologies potentially can be used to identify differentially expressed genes that may be better diagnostic and therapeutic targets for sensory and neural disorders. Here we analyzed gene expression for a set of GABA receptors in the cochlea of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing measures were made, including auditory brainstem response (ABR) thresholds and distortion-product otoacoustic emission (DPOAE) amplitudes (four age groups). Four specific criteria were used to assess gene expression changes from RMA normalized microarray data (40 replicates). Linear regression models were used to fit the neurophysiological hearing measurements to probe-set expression profiles. These data were first subjected to one-way ANOVA, and then linear regression was performed. In addition, the log signal ratio was converted to fold change, and selected gene expression changes were confirmed by relative real-time PCR. Major findings: expression of GABA-A receptor subunit α6 was upregulated with age and hearing loss, whereas subunit α1 was repressed. In addition, GABA-A receptor associated protein like-1 and GABA-A receptor associated protein like-2 were strongly downregulated with age and hearing impairment. Lastly, gene expression measures were correlated with pathway/network relationships relevant to the inner ear using Pathway Architect, to identify key pathways consistent with the gene expression changes observed. PMID:18455804

  8. Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care.

    Science.gov (United States)

    Yamada, Shigeki; Ishikawa, Masatsune; Yamamoto, Kazuo

    2017-01-01

    In spite of growing evidence of idiopathic normal-pressure hydrocephalus (NPH), a viewpoint about clinical care for idiopathic NPH is still controversial. A continuous divergence of viewpoints might be due to confusing classifications of idiopathic and adult-onset congenital NPH. To elucidate the classification of NPH, we propose that adult-onset congenital NPH should be explicitly distinguished from idiopathic and secondary NPH. On the basis of conventional CT scan or MRI, idiopathic NPH was defined as narrow sulci at the high convexity in concurrent with enlargement of the ventricles, basal cistern and Sylvian fissure, whereas adult-onset congenital NPH was defined as huge ventricles without high-convexity tightness. We compared clinical characteristics and cerebrospinal fluid distribution among 85 patients diagnosed with idiopathic NPH, 17 patients with secondary NPH, and 7 patients with adult-onset congenital NPH. All patients underwent 3-T MRI examinations and tap-tests. The volumes of ventricles and subarachnoid spaces were measured using a 3D workstation based on T2-weighted 3D sequences. The mean intracranial volume for the patients with adult-onset congenital NPH was almost 100 mL larger than the volumes for patients with idiopathic and secondary NPH. Compared with the patients with idiopathic or secondary NPH, patients with adult-onset congenital NPH exhibited larger ventricles but normal sized subarachnoid spaces. The mean volume ratio of the high-convexity subarachnoid space was significantly less in idiopathic NPH than in adult-onset congenital NPH, whereas the mean volume ratio of the basal cistern and Sylvian fissure in idiopathic NPH was >2 times larger than that in adult-onset congenital NPH. The symptoms of gait disturbance, cognitive impairment, and urinary incontinence in patients with adult-onset congenital NPH tended to progress more slowly compared to their progress in patients with idiopathic NPH. Cerebrospinal fluid distributions and

  9. Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice.

    Science.gov (United States)

    Fonseca, Tatiana L; Teixeira, Marilia B C G; Miranda-Rodrigues, Manuela; Rodrigues-Miranda, Manuela; Silva, Marcos V; Martins, Gisele M; Costa, Cristiane C; Arita, Danielle Y; Perez, Juliana D; Casarini, Dulce E; Brum, Patricia C; Gouveia, Cecilia H A

    2014-08-15

    To investigate whether thyroid hormone (TH) interacts with the sympathetic nervous system (SNS) to modulate bone mass and structure, we studied the effects of daily T3 treatment in a supraphysiological dose for 12 wk on the bone of young adult mice with chronic sympathetic hyperactivity owing to double-gene disruption of adrenoceptors that negatively regulate norepinephrine release, α(2A)-AR, and α(2C)-AR (α(2A/2C)-AR(-/-) mice). As expected, T3 treatment caused a generalized decrease in the areal bone mineral density (aBMD) of WT mice (determined by DEXA), followed by deleterious effects on the trabecular and cortical bone microstructural parameters (determined by μCT) of the femur and vertebra and on the biomechanical properties (maximum load, ultimate load, and stiffness) of the femur. Surprisingly, α(2A/2C)-AR(-/-) mice were resistant to most of these T3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T3 in the bone of α(2A/2C)-AR(-/-) and WT mice, respectively. β1-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T3 treatment only in α(2A/2C)-AR(-/-) mice. As expected, T3 inhibited the cell growth of calvaria-derived osteoblasts isolated from WT mice, but this effect was abolished or reverted in cells isolated from KO mice. Collectively, these findings support the hypothesis of a TH-SNS interaction to control bone mass and structure of young adult mice and suggests that this interaction may involve α2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology. Copyright © 2014 the American Physiological Society.

  10. Cutoff Values of Serum Carcinoembryonic Antigen (CEA) in Normal Korean Adults and Factors Influencing Serum CEA Level

    International Nuclear Information System (INIS)

    Kim, Jong Soon; Kim, Sun Wook; Chung, June Key; Lee, Dong Soo

    1994-01-01

    Carcinoembryonic Antigen is one of most frequently checked tumor markers in cancer management. We performed statistical analysis with serum CEA data of 2626 persons who received regular health examination and were thought to be free of active disease to determine the cutoff values of serum CEA level in normal Korean adults and to study the factors influencing serum CEA levels in normal subjects. 1) The cutoff values of serum CEA in normal Korean adults in general were 9.28 ng/ml for men, 5.90 ng/ml for women. 2) Serum CEA level was influenced by age, present smoking history, sex, and abnormal findings in chest X ray. 3) Serum CEA level had no correlation with the history of amount of alcohol consumption or obesity. 4) Cutoff values of serum CEA in normal Korean adults were tabulated according to age, sex, and smoking history. Serum CEA level was influenced by age, sex, present smoking history and abnormal findings in chest X ray and cutoff values of serum CEA were tabulated according to age, sex, and smoking history.

  11. A rare presentation of patent ductus arteriosus in an adult patient with normal pulmonary hypertension and limb edema

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    Bahram Pishgoo

    2014-09-01

    Full Text Available BACKGROUND: Patent ductus arteriosus (PDA at childhood is one of the five major and frequent congenital abnormalities, but it can be rarely seen in adults. Pulmonary hypertension (PHTN and other presentations such as heart failure and edema are the identified complications of longstanding PDA, but adult case with no permanent heart symptoms and PHTN was rare. We reported a rare case of with an obvious PDA and normal pulmonary pressure. CASE REPORT: A 61-year-old woman presented with dyspnea (New York Heart Association class 2, chest pain, and lower limb edema. Echocardiogram showed; normal left ventricular chamber size and function, normal size of both atria. Furthermore, an obvious PDA (diameter = 6-7 mm connecting the aortic arch to the pulmonary artery was reported in echocardiography. No lung congestion and evidence for PHTN was reported by computed tomographic angiography [Pulmonary capillary wedge pressure (PCWP = 30 mmHg]. The patient was treated with antihypertensive drugs and after 1 and 3 months follow-up, edema and other symptoms were resolved. CONCLUSION: Finally, we conclude that PDA in adulthood can present with nonspecific cardiovascular symptoms, and it seems that PHTN is not a fixed echocardiographic finding in these patients.   Keywords: Adults, Edema, Patent Ductus Arteriosus eri, Pulmonary Hypertension  Normal 0 false false false EN-US X-NONE AR-SA

  12. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins

    NARCIS (Netherlands)

    Schinkel, A. H.; Mayer, U.; Wagenaar, E.; Mol, C. A.; van Deemter, L.; Smit, J. J.; van der Valk, M. A.; Voordouw, A. C.; Spits, H.; van Tellingen, O.; Zijlmans, J. M.; Fibbe, W. E.; Borst, P.

    1997-01-01

    The mdr1-type P-glycoproteins (P-gps) confer multidrug resistance to cancer cells by active extrusion of a wide range of drugs from the cell. To study their physiological roles, we have generated mice genetically deficient in the mdr1b gene [mdr1b (-/-) mice] and in both the mdr1a and mdr1b genes

  13. Speed-Dependent Modulation of the Locomotor Behavior in Adult Mice Reveals Attractor and Transitional Gaits.

    Science.gov (United States)

    Lemieux, Maxime; Josset, Nicolas; Roussel, Marie; Couraud, Sébastien; Bretzner, Frédéric

    2016-01-01

    Locomotion results from an interplay between biomechanical constraints of the muscles attached to the skeleton and the neuronal circuits controlling and coordinating muscle activities. Quadrupeds exhibit a wide range of locomotor gaits. Given our advances in the genetic identification of spinal and supraspinal circuits important to locomotion in the mouse, it is now important to get a better understanding of the full repertoire of gaits in the freely walking mouse. To assess this range, young adult C57BL/6J mice were trained to walk and run on a treadmill at different locomotor speeds. Instead of using the classical paradigm defining gaits according to their footfall pattern, we combined the inter-limb coupling and the duty cycle of the stance phase, thus identifying several types of gaits: lateral walk, trot, out-of-phase walk, rotary gallop, transverse gallop, hop, half-bound, and full-bound. Out-of-phase walk, trot, and full-bound were robust and appeared to function as attractor gaits (i.e., a state to which the network flows and stabilizes) at low, intermediate, and high speeds respectively. In contrast, lateral walk, hop, transverse gallop, rotary gallop, and half-bound were more transient and therefore considered transitional gaits (i.e., a labile state of the network from which it flows to the attractor state). Surprisingly, lateral walk was less frequently observed. Using graph analysis, we demonstrated that transitions between gaits were predictable, not random. In summary, the wild-type mouse exhibits a wider repertoire of locomotor gaits than expected. Future locomotor studies should benefit from this paradigm in assessing transgenic mice or wild-type mice with neurotraumatic injury or neurodegenerative disease affecting gait.

  14. Cellular origins of cold-induced brown adipocytes in adult mice.

    Science.gov (United States)

    Lee, Yun-Hee; Petkova, Anelia P; Konkar, Anish A; Granneman, James G

    2015-01-01

    This work investigated how cold stress induces the appearance of brown adipocytes (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, α polypeptide (PDGFRα) by 3- to 4-fold. Surprisingly, brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT. Although cold stress did not increase proliferation in inguinal white adipose tissue (ingWAT), the percentage of BAs, defined as multilocular adipocytes that express uncoupling protein 1, rose from undetectable to 30% of total adipocytes. To trace the origins of cold-induced BAs, we genetically tagged PDGFRα(+) cells and adipocytes prior to cold exposure, using Pdgfra-Cre recombinase estrogen receptor T2 fusion protein (CreER(T2)) and adiponectin-CreER(T2), respectively. In iBAT, cold stress triggered the proliferation and differentiation of PDGFRα(+) cells into BAs. In contrast, all newly observed BAs in ingWAT (5207 out of 5207) were derived from unilocular adipocytes tagged by adiponectin-CreER(T2)-mediated recombination. Surgical denervation of iBAT reduced cold-induced brown adipogenesis by >85%, whereas infusion of norepinephrine (NE) mimicked the effects of cold in warm-adapted mice. NE-induced de novo brown adipogenesis in iBAT was eliminated in mice lacking β1-adrenergic receptors. These observations identify a novel tissue niche for brown adipogenesis in iBAT and further define depot-specific mechanisms of BA recruitment. © FASEB.

  15. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice.

    Science.gov (United States)

    Fox, Donald A; Hamilton, W Ryan; Johnson, Jerry E; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B; O'Callaghan, James P

    2011-11-01

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ~25 and ~40 μg/dL, respectively, on PN10 and by PN30 all were ≤ 1 μg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice.

    Science.gov (United States)

    Khalyfa, Abdelnaby; Cortese, Rene; Qiao, Zhuanhong; Ye, Honggang; Bao, Riyue; Andrade, Jorge; Gozal, David

    2017-04-15

    Late gestation during pregnancy has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia, a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis and metabolic function in offspring. Here we show that late gestation intermittent hypoxia induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in visceral white adipose tissue. Fetal perturbations by OSA during pregnancy impose long-term detrimental effects manifesting as metabolic dysfunction in adult male offspring. Pregnancy, particularly late gestation (LG), has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesized that IH during late pregnancy (LG-IH) may increase the propensity for metabolic dysregulation and obesity in adult offspring via epigenetic modifications. Time-pregnant female C57BL/6 mice were exposed to LG-IH or room air (LG-RA) during days 13-18 of gestation. At 24 weeks, blood samples were collected from offspring mice for lipid profiles and insulin resistance, indirect calorimetry was performed and visceral white adipose tissues (VWAT) were assessed for inflammatory cells as well as for differentially methylated gene regions (DMRs) using a methylated DNA immunoprecipitation on chip (MeDIP-chip). Body weight, food intake, adiposity index, fasting insulin, triglycerides and cholesterol levels were all significantly higher in LG-IH male but not female offspring. LG-IH also altered metabolic expenditure and locomotor activities in male offspring, and increased number of pro-inflammatory macrophages emerged in VWAT along with 1520 DMRs (P < 0.0001), associated with 693

  17. Subregion-Specific Proteomic Signature in the Hippocampus for Recognition Processes in Adult Mice

    Directory of Open Access Journals (Sweden)

    Lukas M. von Ziegler

    2018-03-01

    Full Text Available Summary: The hippocampal formation is a brain structure essential for higher-order cognitive functions. It has a complex anatomical organization and cellular composition, and hippocampal subregions have different properties and functional roles. In this study, we used SWATH-MS to determine whether the proteomes of hippocampus areas CA1 and CA3 can explain the commonalities or specificities of these subregions in basal conditions and after recognition memory. We show that the proteomes of areas CA1 and CA3 are largely different in basal conditions and that differential changes and dynamics in protein expression are induced in these areas after recognition of an object or object location. While changes are consistent across both recognition paradigms in area CA1, they are not in area CA3, suggesting distinct proteomic responses in areas CA1 and CA3 for memory formation. : How does the proteome differ in hippocampus areas CA1 and CA3? von Ziegler et al. identify the proteomes of areas CA1 and CA3 and characterize their dynamics during different recognition processes in adult mice. Keywords: hippocampus, areas CA1 and CA3, proteome, dynamics, object memory, object location memory, mass spectrometry, SWATH-MS, mice, bioinformatic tools

  18. Conditional deletion of pejvakin in adult outer hair cells causes progressive hearing loss in mice.

    Science.gov (United States)

    Harris, Suzan L; Kazmierczak, Marcin; Pangršič, Tina; Shah, Prahar; Chuchvara, Nadiya; Barrantes-Freer, Alonso; Moser, Tobias; Schwander, Martin

    2017-03-06

    Mutations in the Pejvakin (Pjvk) gene cause autosomal recessive hearing loss DFNB59 with audiological features of auditory neuropathy spectrum disorder (ANSD) or cochlear dysfunction. The precise mechanisms underlying the variable clinical phenotypes of DFNB59 remain unclear. Here, we demonstrate that mice with conditional ablation of the Pjvk gene in all sensory hair cells or only in outer hair cells (OHCs) show similar auditory phenotypes with early-onset profound hearing loss. By contrast, loss of Pjvk in adult OHCs causes a slowly progressive hearing loss associated with OHC degeneration and delayed loss of inner hair cells (IHCs), indicating a primary role for pejvakin in regulating OHC function and survival. Consistent with this model, synaptic transmission at the IHC ribbon synapse is largely unaffected in sirtaki mice that carry a C-terminal deletion mutation in Pjvk. Using the C-terminal domain of pejvakin as bait, we identified in a cochlear cDNA library ROCK2, an effector for the small GTPase Rho, and the scaffold protein IQGAP1, involved in modulating actin dynamics. Both ROCK2 and IQGAP1 associate via their coiled-coil domains with pejvakin. We conclude that pejvakin is required to sustain OHC activity and survival in a cell-autonomous manner likely involving regulation of Rho signaling. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Effects of 60Co γ-radiation on brain hippocampal tissue of adult mice

    International Nuclear Information System (INIS)

    Liu Yongbao; Rao Yongqing; Xu Luxi

    2000-01-01

    Objective: To study neuro-pathological changes of hippocampus tissue in adult mice following a series of irradiation with 60 Co γ-rays. Methods: Male mice of Kunming strain in experimental group (n = 8) were exposed total-bodily to 60 Co γ-rays at 2.0 Gy once every two days. A histopathological imaging analysis of the mouse brain tissue was carried out after paraffin embedding and a series of sections were made and stained with Nissl and Weil staining methods. Results: In the irradiation group (the cumulative dose = 26 Gy) loss of pyramidal cells in hippocampus was significant when compared with the control group. Neuro-pathological changes were characterised by reduced neuron size, nuclear pyknosis and karyolysis. The neurofibrillar density of the pyramidal layer in the irradiation group was much lower than that of the control group (P CA2>CA3>CA4 in the hippocampus. Conclusion: The neuronal damage in hippocampus after 60 Co irradiation could form a pathological basis in reduction of memorial and learning ability

  20. Ultrasonic vocalizations of adult male Foxp2-mutant mice: behavioral contexts of arousal and emotion.

    Science.gov (United States)

    Gaub, S; Fisher, S E; Ehret, G

    2016-02-01

    Adult mouse ultrasonic vocalizations (USVs) occur in multiple behavioral and stimulus contexts associated with various levels of arousal, emotion and social interaction. Here, in three experiments of increasing stimulus intensity (water; female urine; male interacting with adult female), we tested the hypothesis that USVs of adult males express the strength of arousal and emotion via different USV parameters (18 parameters analyzed). Furthermore, we analyzed two mouse lines with heterozygous Foxp2 mutations (R552H missense, S321X nonsense), known to produce severe speech and language disorders in humans. These experiments allowed us to test whether intact Foxp2 function is necessary for developing full adult USV repertoires, and whether mutations of this gene influence instinctive vocal expressions based on arousal and emotion. The results suggest that USV calling rate characterizes the arousal level, while sound pressure and spectrotemporal call complexity (overtones/harmonics, type of frequency jumps) may provide indices of levels of positive emotion. The presence of Foxp2 mutations did not qualitatively affect the USVs; all USV types that were found in wild-type animals also occurred in heterozygous mutants. However, mice with Foxp2 mutations displayed quantitative differences in USVs as compared to wild-types, and these changes were context dependent. Compared to wild-type animals, heterozygous mutants emitted mainly longer and louder USVs at higher minimum frequencies with a higher occurrence rate of overtones/harmonics and complex frequency jump types. We discuss possible hypotheses about Foxp2 influence on emotional vocal expressions, which can be investigated in future experiments using selective knockdown of Foxp2 in specific brain circuits. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  1. Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice.

    Science.gov (United States)

    Moon, Minho; Jeong, Hyun Uk; Choi, Jin Gyu; Jeon, Seong Gak; Song, Eun Ji; Hong, Seon-Pyo; Oh, Myung Sook

    2016-09-15

    It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose-dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice.

    Science.gov (United States)

    Caulfield, Jasmine I; Caruso, Michael J; Michael, Kerry C; Bourne, Rebecca A; Chirichella, Nicole R; Klein, Laura C; Craig, Timothy; Bonneau, Robert H; August, Avery; Cavigelli, Sonia A

    2017-05-30

    Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function. To mimic symptoms of allergic asthma in young BALB/cJ mice (postnatal days [P] 7-57; N=98), we induced lung inflammation with repeated intranasal administration of house dust mite extract (most common aeroallergen for humans) and bronchoconstriction with aerosolized methacholine (non-selective muscarinic receptor agonist). Three experimental groups, in addition to a control group, included: (1) "Airway inflammation only", allergen exposure 3 times/week, (2) "Labored breathing only", methacholine exposure once/week, and (3) "Airway inflammation+Labored breathing", allergen and methacholine exposure. Compared to controls, mice that experienced methacholine-induced labored breathing during adolescence displayed a ∼20% decrease in time on open arms of the elevated plus maze in early adulthood (P60), a ∼30% decrease in brainstem serotonin transporter (SERT) mRNA expression and a ∼50% increase in hippocampal serotonin receptor 1a (5Htr1a) and corticotropin releasing hormone receptor 1 (Crhr1) expression in adulthood (P75). This is the first evidence that experimentally-induced clinical symptoms of adolescent asthma alter adult anxiety-related behavior and brain function several weeks after completion of asthma manipulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice.

    Science.gov (United States)

    Kirkpatrick, Meg; Benoit, Janina; Everett, Wyll; Gibson, Jennifer; Rist, Michael; Fredette, Nicholas

    2015-09-01

    Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Indicated prevention of adult obesity: reference data for weight normalization in overweight children

    Science.gov (United States)

    Background: Pediatric obesity is a major risk factor for adult obesity. Indicated prevention--that is, helping overweight or obese youth attain non-overweight status--has been suggested to prevent adult obesity. This study aimed to support the notion of indicated prevention by demonstrating that rel...

  5. Assessment of Metabolic Flexibility of Old and Adult Mice Using Three Noninvasive, Indirect Calorimetry-Based Treatments

    NARCIS (Netherlands)

    Duivenvoorde, L.P.M.; Schothorst, van E.M.; Swarts, J.J.M.; Keijer, J.

    2015-01-01

    Indirect calorimetry (InCa) can potentially be used to noninvasively assess metabolic and age-related flexibility. To assess the use of InCa for this purpose, we tested the sensitivity and response stability over time of three InCa-based treatments in old versus adult mice. Diurnal patterns of

  6. Sex-specific positive and negative consequences of avoidance training during childhood on adult active avoidance learning in mice

    Directory of Open Access Journals (Sweden)

    Almuth eSpröwitz

    2013-10-01

    Full Text Available In humans and animals cognitive training during childhood plays an important role in shaping neural circuits and thereby determines learning capacity later in life. Using a negative feedback learning paradigm, the two-way active avoidance (TWA learning, we aimed to investigate in mice (i the age-dependency of TWA learning, (ii the consequences of pretraining in childhood on adult learning capacity and (iii the impact of sex on the learning paradigm in mice. Taken together, we show here for the first time that the beneficial or detrimental outcome of pretraining in childhood depends on the age during which TWA training is encountered, indicating that different, age-dependent long-term memory traces might be formed, which are recruited during adult TWA training and thereby either facilitate or impair adult TWA learning. While pretraining during infancy results in learning impairment in adulthood, pretraining in late adolescence improved avoidance learning.The experiments revealed a clear sex difference in the group of late-adolescent mice: female mice showed better avoidance learning during late adolescence compared to males, and the beneficial impact of late-adolescent pretraining on adult learning was more pronounced in females compared to males.

  7. In vivo imaging of oxidative stress in the kidney of diabetic mice and its normalization by angiotensin II type 1 receptor blocker

    International Nuclear Information System (INIS)

    Sonta, Toshiyo; Inoguchi, Toyoshi; Matsumoto, Shingo; Yasukawa, Keiji; Inuo, Mieko; Tsubouchi, Hirotaka; Sonoda, Noriyuki; Kobayashi, Kunihisa; Utsumi, Hideo; Nawata, Hajime

    2005-01-01

    This study was undertaken to evaluate oxidative stress in the kidney of diabetic mice by electron spin resonance (ESR) imaging technique. Oxidative stress in the kidney was evaluated as organ-specific reducing activity with the signal decay rates of carbamoyl-PROXYL probe using ESR imaging. The signal decay rates were significantly faster in corresponding image pixels of the kidneys of streptozotocin-induced diabetic mice than in those of controls. This technique further demonstrated that administration of angiotensin II type 1 receptor blocker (ARB), olmesartan (5 mg/kg), completely restored the signal decay rates in the diabetic kidneys to control values. In conclusion, this study provided for the first time the in vivo evidence for increased oxidative stress in the kidneys of diabetic mice and its normalization by ARB as evaluated by ESR imaging. This technique would be useful as a means of further elucidating the role of oxidative stress in diabetic nephropathy

  8. Long-term Treatment with Low-Dose Caffeine Worsens BPSD-Like Profile in 3xTg-AD Mice Model of Alzheimer’s Disease and Affects Mice with Normal Aging

    Directory of Open Access Journals (Sweden)

    Raquel Baeta-Corral

    2018-02-01

    Full Text Available Coffee or caffeine has recently been suggested as prophylaxis for dementia. Although memory problems are hallmarks of Alzheimer’s disease, this dementia is also characterized by neuropsychiatric symptoms called Behavioral and Psychological Symptoms of Dementia (BPSD. The impact of preventive/therapeutic strategies on both cognitive and non-cognitive symptoms can be addressed in the 3xTg-AD mice, since they exhibit cognitive but also BPSD-like profiles. Here, we studied the long-term effects of a low dose of caffeine in male 3xTg-AD mice and as compared to age-matched non-transgenic (NTg counterparts with normal aging. Animals were treated (water or caffeine in drinking water from adulthood (6 months of age until middle-aged (13 months of age, that in 3xTg-AD mice correspond to onset of cognitive impairment and advanced stages, respectively. The low caffeine dosing used (0.3 mg/ml was previously found to give a plasma concentration profile in mice roughly equivalent to that of a human coffee drinker. There were significant effects of caffeine on most behavioral variables, especially those related to neophobia and other anxiety-like behaviors, emotionality, and cognitive flexibility. The 3xTg-AD and NTg mice were differently influenced by caffeine. Overall, the increase of neophobia and other anxiety-related behaviors resulted in an exacerbation of BPSD-like profile in 3xTg-AD mice. Learning and memory, strongly influenced by anxiety in 3xTg-AD mice, got little benefit from caffeine, only shown after a detailed analysis of navigation strategies. The worsened pattern in NTg mice and the use of search strategies in 3xTg-AD mice make both groups more similar. Circadian motor activity showed genotype differences, which were found to be enhanced by caffeine. Selective effects of caffeine on NTg were found in the modulation of behaviors related to emotional profile and risk assessment. Caffeine normalized splenomegaly of 3xTg-AD mice, a physical

  9. Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.

    Science.gov (United States)

    Yau, Suk Yu; Chiu, Christine; Vetrici, Mariana; Christie, Brian R

    2016-10-01

    Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

    Science.gov (United States)

    Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

    2014-01-01

    There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

  11. Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.

    Directory of Open Access Journals (Sweden)

    Thomas W Elston

    Full Text Available There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.

  12. Do Adults with Cochlear Implants Rely on Different Acoustic Cues for Phoneme Perception than Adults with Normal Hearing?

    Science.gov (United States)

    Moberly, Aaron C.; Lowenstein, Joanna H.; Tarr, Eric; Caldwell-Tarr, Amanda; Welling, D. Bradley; Shahin, Antoine J.; Nittrouer, Susan

    2014-01-01

    Purpose: Several acoustic cues specify any single phonemic contrast. Nonetheless, adult, native speakers of a language share weighting strategies, showing preferential attention to some properties over others. Cochlear implant (CI) signal processing disrupts the salience of some cues: In general, amplitude structure remains readily available, but…

  13. Human CD4 restores normal T cell development and function in mice deficient in murine CD4

    OpenAIRE

    1994-01-01

    The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positiv...

  14. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Donald A., E-mail: dafox@uh.edu [College of Optometry, University of Houston, Houston, TX (United States); Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX (United States); Hamilton, W. Ryan [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Johnson, Jerry E. [Department of Natural Sciences, University of Houston-Downtown, Houston, TX (United States); Xiao, Weimin [College of Optometry, University of Houston, Houston, TX (United States); Chaney, Shawntay; Mukherjee, Shradha [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Miller, Diane B.; O' Callaghan, James P. [Toxicology and Molecular Biology Branch, Health Effects Research Laboratory, Centers for Disease Control and Prevention-NIOSH, Morgantown, WV USA (United States)

    2011-11-15

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1, {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black

  15. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    International Nuclear Information System (INIS)

    Fox, Donald A.; Hamilton, W. Ryan; Johnson, Jerry E.; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B.; O'Callaghan, James P.

    2011-01-01

    Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ∼ 25 and ∼ 40 μg/dL, respectively, on PN10 and by PN30 all were ≤ 1 μg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: ► Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: ≤ 1, ≤ 10, 25 and 40 μg/dL ► Gestational lead exposure dose-dependently decreased the number of TH

  16. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    Science.gov (United States)

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

  17. Adult vitamin D deficiency exacerbates impairments caused by social stress in BALB/c and C57BL/6 mice.

    Science.gov (United States)

    Groves, Natalie J; Zhou, Mei; Jhaveri, Dhanisha J; McGrath, John J; Burne, Thomas H J

    2017-12-01

    Vitamin D deficiency is prevalent in adults throughout the world. Epidemiological studies have shown significant associations between vitamin D deficiency and an increased risk of various neuropsychiatric and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease and cognitive impairment. However, studies based on observational epidemiology cannot address questions of causality; they cannot determine if vitamin D deficiency is a causal factor leading to the adverse health outcome. The main aim of this study was to determine if AVD deficiency would exacerbate the effects of a secondary exposure, in this case social stress, in BALB/c mice and in the more resilient C57BL/6 mice. Ten-week old male BALB/c and C57BL/6 mice were fed a control or vitamin D deficient diet for 10 weeks, and the mice were further separated into one of two groups for social treatment, either Separated (SEP) or Social Defeat (DEF). SEP mice were placed two per cage with a perforated Plexiglas divider, whereas the DEF mice underwent 10days of social defeat prior to behavioural testing. We found that AVD-deficient mice were more vulnerable to the effects of social stress using a social avoidance test, and this was dependent on strain. These results support the hypothesis that vitamin D deficiency may exacerbate behavioural outcomes in mice vulnerable to stress, a finding that can help guide future studies. Importantly, these discoveries support the epidemiological link between vitamin D deficiency and neuropsychiatric and neurodegenerative disorders; and has provided clues that can guide future studies related to unravelling the mechanisms of action linking adult vitamin D deficiency and adverse brain related outcomes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  18. Loss of long-term depression in the insular cortex after tail amputation in adult mice.

    Science.gov (United States)

    Liu, Ming-Gang; Zhuo, Min

    2014-01-08

    The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.

  19. Taste Bud Labeling in Whole Tongue Epithelial Sheet in Adult Mice.

    Science.gov (United States)

    Venkatesan, Nandakumar; Boggs, Kristin; Liu, Hong-Xiang

    2016-04-01

    Molecular labeling in whole-mount tissues provides an efficient way to obtain general information about the formation, maintenance, degeneration, and regeneration of many organs and tissues. However, labeling of lingual taste buds in whole tongue tissues in adult mice has been problematic because of the strong permeability barrier of the tongue epithelium. In this study, we present a simple method for labeling taste buds in the intact tongue epithelial sheet of an adult mouse. Following intralingual protease injection and incubation, immediate fixation of the tongue on mandible in 4% paraformaldehyde enabled the in situ shape of the tongue epithelium to be well maintained after peeling. The peeled epithelium was accessible to taste bud labeling with a pan-taste cell marker, keratin 8, and a type II taste cell marker, α-gustducin, in all three types of taste papillae, that is, fungiform, foliate, and circumvallate. Overnight incubation of tongue epithelial sheets with primary and secondary antibodies was sufficient for intense labeling of taste buds with both fluorescent and DAB visualizations. Labeled individual taste buds were easy to identify and quantify. This protocol provides an efficient way for phenotypic analyses of taste buds, especially regarding distribution pattern and number.

  20. Effect of dose on lead retention and distribution in suckling and adult female mice

    International Nuclear Information System (INIS)

    Keller, C.A.; Doherty, R.A.

    1980-01-01

    Single doses of lead (trace to 445 mg/kg) were administered per os to suckling and adult mice. Both groups exhibited dose-independent lead retention when doses of 4 to 445 mg/kg were administered. However, developmental differences in the fraction of initial dose (FID) retained were evident for all doses administered. A much larger FID was retained in both age groups following administration of carrier-free 203 Pb. The results are consistent with a mechanism of gastrointestinal lead absorption comprising two or more processes. Developmental differences were also observed in organ lead concentration relative to whole body concentration for kidneys, skull and brain 6 days following lead administration. Lead retentions (relative to whole body retention) in brain and in bone were linearly related to dose of lead administered in both suckling and adult age groups. Though uptake of lead into brain and into femur was observed to be directly related to dose over a wide range, relative blood lead concentrations were not linearly correlated with dose administered. The relationships between lead concentrations of blood and organ(s) were also shown to be nonlinear relative to dose. However, blood lead concentration was found to be a reliable indicator of kidney and liver lead concentrations following an acute lead exposure

  1. Successful small intestine colonization of adult mice by Vibrio cholerae requires ketamine anesthesia and accessory toxins.

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    Verena Olivier

    2009-10-01

    Full Text Available Vibrio cholerae colonizes the small intestine of adult C57BL/6 mice. In this study, the physical and genetic parameters that facilitate this colonization were investigated. Successful colonization was found to depend upon anesthesia with ketamine-xylazine and neutralization of stomach acid with sodium bicarbonate, but not streptomycin treatment. A variety of common mouse strains were colonized by O1, O139, and non-O1/non-O139 strains. All combinations of mutants in the genes for hemolysin, the multifunctional, autoprocessing RTX toxin (MARTX, and hemagglutinin/protease were assessed, and it was found that hemolysin and MARTX are each sufficient for colonization after a low dose infection. Overall, this study suggests that, after intragastric inoculation, V. cholerae encounters barriers to infection including an acidic environment and an immediate immune response that is circumvented by sodium bicarbonate and the anti-inflammatory effects of ketamine-xylazine. After initial adherence in the small intestine, the bacteria are subjected to additional clearance mechanisms that are evaded by the independent toxic action of hemolysin or MARTX. Once colonization is established, it is suggested that, in humans, these now persisting bacteria initiate synthesis of the major virulence factors to cause cholera disease. This adult mouse model of intestinal V. cholerae infection, now well-characterized and fully optimized, should serve as a valuable tool for studies of pathogenesis and testing vaccine efficacy.

  2. Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

    Science.gov (United States)

    Ahmed, Zaghloul

    2017-10-01

    Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

  3. Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice.

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    Thomas Lundåsen

    Full Text Available Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2 and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c. Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.

  4. A high-fat, high-protein diet attenuates the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters in adult mice.

    Science.gov (United States)

    Zhao, Jing-Lu; Zhao, Yu-Yun; Zhu, Wei-Jie

    2017-10-01

    The interaction between obesity and chronic inflammation has been studied. Diet-induced obesity or chronic inflammation could reduce the testicular functions of males. However, the mechanism underlying the reproductive effects of fattening foods in males with or without chronic inflammation still needs further discussion. This study was aimed to investigate the effects of high-fat, high-protein diet on testicular steroidogenesis and sperm parameters in adult mice under physiological and chronic inflammatory conditions. Because casein can trigger a non-infectious systemic inflammatory response, we used casein injection to induce chronic inflammation in male adult Kunming mice. Twenty-four mice were randomly and equally divided into four groups: (i) normal diet+saline (Control); (ii) normal diet+casein (ND+CS); (iii) high-fat, high-protein diet+saline (HFPD+SI); (iv) high-fat, high-protein diet+casein (HFPD+CS). After 8weeks, there was a significant increase in body weight for groups HFPD+SI and HFPD+CS and a decrease in group ND+CS compared with the control. The serum levels of tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) and lipid profiles were increased markedly in groups ND+CS, HFPD+SI and HFPD+CS compared with the control. A remarkable reduction of serum adiponectin level occurred in group HFPD+CS compared with group ND+CS. Sperm parameters (sperm count, viability and abnormality) were also adversely affected in groups ND+CS and HFPD+SI. Groups ND+CS and HFPD+SI showed severe pathological changes in testicular tissues. Semiquantitative RT-PCR, Western blot and immunohistochemical staining also showed significant reductions in both testicular mRNA and protein levels of steroidogenic acute regulatory (StAR) and cytochrome P450scc (CYP11A1) in groups HFPD+SI and HFPD+CS compared with the control, whereas testicular mRNA and protein levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) in groups HFPD+SI and HFPD+CS significantly increased. The m

  5. Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

    Science.gov (United States)

    Hollander, K S; Tempel Brami, C; Konikoff, F M; Fainaru, M; Leikin-Frenkel, A

    2014-07-01

    Our objective was to test the contribution of dietary enrichment in essential or saturated fatty acids, in normocaloric diets, on the lipid accumulation and insulin resistance in the adult offspring in a C57Bl6/J mice model. Pregnant mothers were fed normocaloric diets containing 6% fat enriched in essential fatty acids (EFA): alpha-linolenic (ALA-18:3, n-3), linoleic (LA-18:2, n-6), or saturated fatty acids (SFA). After a washing-out period with regular diet, the offspring received a high-fat diet before euthanization. Adult mice fed maternal ALA showed lower body weight gain and lower liver fat accumulation, lower HOMA index and lower stearoyl-CoA desaturase (SCD1) activity than those fed maternal SFA. The results observed using this novel model suggest that ALA in maternal diet may have the potential to inhibit insulin resistance in adult offspring.

  6. Effect of a protease inhibitor on the stability of catalase in liver and blood from acatalasemic and normal mice.

    OpenAIRE

    Suzuki, Kazuhiko; Ogata, Masana

    1991-01-01

    Effects of Gabexate mesilate (GM) (([ethyl-4-(6-guanidino hexanoyloxy) benzoate] methane sulfonate)), a protease inhibitor, on the activities of catalase in liver, erythrocytes and reticulocytes from acatalasemic mice were examined. Preincubation without GM at 37 degrees C for 160 min lowered the catalase activities of liver, erythrocytes and reticulocytes from acatalasemic mice, to 24%, 40% and 10% of the initial levels, respectively. But, preincubation with GM at 37 degrees C for 160 min de...

  7. Antibody-mediated allotype suppression in adult mice: the role of antigen, effector isotype and regulatory T cells.

    Science.gov (United States)

    Curling, E M; Dresser, D W

    1984-10-01

    It has been reported (Contemp. Top. Immunobiol. 1974. 3:41) that allotype-specific T suppressor cells can be induced after monoclonal anti-allotype treatment of neonatal (BALB/c X SJL)F1 (Igha/b) mice. Here we show that (BALB/c X CB20)F1 adult-derived spleen cells (SC) are, by contrast, potently suppressed by monoclonal allotype-specific reagents, (when transferred into irradiated BALB/c recipients) in the absence of primary T suppressor cell induction. Such suppression is only induced in activated B cells [exposed to lipopolysaccharide or sheep red blood cells (SRBC)], and is probably dependent on the isotype of the anti-allotype sera administered. For example, two independently produced IgG1 monoclonal reagents raised against the Igh-1b allotype were poorly suppressive or nonsuppressive, whereas an IgG3 and an IgG2a monoclonal antibody induced a 90% suppression of the target allotype in transferred adult SC. It was found that suppression was not due to a depletion of antigen-specific T cell help since: (a) the addition of SRBC-educated T cells did not break suppression and (b) suppressed SC were as good a source of T cell help as normal SC, in the response of virgin or memory B cell (Thy-1-depleted) responses to SRBC in vivo. Suppression was maintained in suppressed cells which had been rechallenged with SRBC after transfer into a second irradiated recipient, but was not induced in normal SC when these were admixed with an equal number from this suppressed SC population. These findings point to a possible mechanism for the regulation of B cell expression, through the formation of an antibody-Ig receptor complex at the surface of the B lymphocyte. After complexing the target cell is either deleted or inactivated. The response to SRBC was reduced or ablated for at least 70 days after treatment with a single dose of anti-allotype serum.

  8. Estabilidade dos potenciais evocados auditivos em indivíduos adultos com audição normal Stability of auditory evoked potentials in adults with normal hearing

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    Carla Gentile Matas

    2011-03-01

    Full Text Available OBJETIVO: Avaliar a estabilidade dos parâmetros dos potenciais evocados auditivos em adultos normais. MÉTODOS: Foram submetidos à avaliação audiológica e eletrofisiológica (potencial evocado auditivo de tronco encefálico - PEATE, potencial evocado auditivo de média latência - PEAML e potencial cognitivo - P300 49 indivíduos normais, de 18 a 40 anos (25 do gênero feminino e 24 do gênero masculino. Realizou-se reavaliação três meses após a avaliação. RESULTADOS: Foram observadas diferenças entre os gêneros na avaliação para as latências das ondas III e V e interpicos I-III e I-V do PEATE e amplitude N2-P3 do P300. Não foram verificadas diferenças significativas para os parâmetros do PEATE, PEAML (latência das ondas Na, Pa e amplitude Na - Pa e P300 (latência da onda P300 entre os resultados obtidos na avaliação e reavaliação. CONCLUSÃO: Exceção feita à amplitude N2-P3, observou-se estabilidade dos parâmetros de PEATE, PEAML e P300 em adultos normais após período de três meses.PURPOSE: To evaluate the stability of parameters of auditory evoked potentials in normal adults. METHODS: Forty-nine normal subjects with ages from 18 to 40 years (25 females and 24 males were submitted to audiological and electrophysiological hearing evaluation (auditory brainstem response - ABR, middle latency response - MLR, and cognitive potential - P300. Subjects were reassessed three months after the initial evaluation. RESULTS: Significant differences were observed between genders regarding the wave latencies III and V and the interpeaks I-III and I-IV of ABR, and the amplitude N2-P3 of the P300. No differences were found between the results of initial and final assessments for the parameters of the ABR, MLR (Na, Pa latencies and Na-Pa amplitude and P300 (P300 latency. CONCLUSION: Except for the N2-P3 amplitude, it was observed stability of the parameters of ABR, MLR and P300 in normal adults after a period of three months.

  9. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations.

    Science.gov (United States)

    Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco; Nielsen, Morten Frost; Kassem, Moustapha; Kousteni, Stavroula

    2016-03-01

    Osteoblasts are emerging regulators of myeloid malignancies since genetic alterations in them, such as constitutive activation of β-catenin, instigate their appearance. The LDL receptor-related protein 5 (LRP5), initially proposed to be a co-receptor for Wnt proteins, in fact favors bone formation by suppressing gut-serotonin synthesis. This function of Lrp5 occurring in the gut is independent of β-catenin activation in osteoblasts. However, it is unknown whether Lrp5 can act directly in osteoblast to influence other functions that require β-catenin signaling, particularly, the deregulation of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5 mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate β-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. Published

  10. Regeneration of pancreatic non-β endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin.

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    Yanqing Zhang

    Full Text Available The non-β endocrine cells in pancreatic islets play an essential counterpart and regulatory role to the insulin-producing β-cells in the regulation of blood-glucose homeostasis. While significant progress has been made towards the understanding of β-cell regeneration in adults, very little is known about the regeneration of the non-β endocrine cells such as glucagon-producing α-cells and somatostatin producing δ-cells. Previous studies have noted the increase of α-cell composition in diabetes patients and in animal models. It is thus our hypothesis that non-β-cells such as α-cells and δ-cells in adults can regenerate, and that the regeneration accelerates in diabetic conditions. To test this hypothesis, we examined islet cell composition in a streptozotocin (STZ-induced diabetes mouse model in detail. Our data showed the number of α-cells in each islet increased following STZ-mediated β-cell destruction, peaked at Day 6, which was about 3 times that of normal islets. In addition, we found δ-cell numbers doubled by Day 6 following STZ treatment. These data suggest α- and δ-cell regeneration occurred rapidly following a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling techniques, we demonstrated α- and δ-cell regeneration involved cell proliferation. Co-staining of the islets with the proliferating cell marker Ki67 showed α- and δ-cells could replicate, suggesting self-duplication played a role in their regeneration. Furthermore, Pdx1(+/Insulin(- cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. This is further confirmed by the detection of Pdx1(+/glucagon(+ cells and Pdx1(+/somatostatin(+ cells following STZ treatment. Taken together, our study demonstrated adult α- and δ-cells could regenerate, and both self-duplication and regeneration from endocrine precursor cells were involved in their regeneration.

  11. Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects

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    Natalya P. Bondar

    2018-01-01

    Full Text Available Stressful events in an early postnatal period have critical implications for the individual’s life and can increase later risk for psychiatric disorders. The aim of this study was to investigate the influence of early-life stress on the social behavior of adult male and female mice. C57Bl/6 mice were exposed to maternal separation (MS, 3 h once a day or handling (HD, 15 min once a day on postnatal day 2 through 14. Adult male and female mice were tested for social behavior in the social interaction test and for individual behavior in the plus-maze and open-field tests. Female mice exposed to maternal separation had increased social behavior and increased anxiety. MS male mice had no changes in social behavior but had significantly disrupted individual behavior, including locomotor and exploratory activity. Handling had positive effects on social behavior in males and females and decreased anxiety in males. Our results support the hypothesis that brief separation of pups from their mothers (handling, which can be considered as moderate stress, may result in future positive changes in behavior. Maternal separation has deleterious effects on individual behavior and significant sex-specific effects on social behavior.

  12. Influence of Botulinumtoxin A on the Expression of Adult MyHC Isoforms in the Masticatory Muscles in Dystrophin-Deficient Mice (Mdx-Mice

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    Ute Ulrike Botzenhart

    2016-01-01

    Full Text Available The most widespread animal model to investigate Duchenne muscular dystrophy is the mdx-mouse. In contrast to humans, phases of muscle degeneration are replaced by regeneration processes; hence there is only a restricted time slot for research. The aim of the study was to investigate if an intramuscular injection of BTX-A is able to break down muscle regeneration and has direct implications on the gene expression of myosin heavy chains in the corresponding treated and untreated muscles. Therefore, paralysis of the right masseter muscle was induced in adult healthy and dystrophic mice by a specific intramuscular injection of BTX-A. After 21 days the mRNA expression and protein content of MyHC isoforms of the right and left masseter, temporal, and the tongue muscle were determined using quantitative RT-PCR and Western blot technique. MyHC-IIa and MyHC-I-mRNA expression significantly increased in the paralyzed masseter muscle of control-mice, whereas MyHC-IIb and MyHC-IIx/d-mRNA were decreased. In dystrophic muscles no effect of BTX-A could be detected at the level of MyHC. This study suggests that BTX-A injection is a suitable method to simulate DMD-pathogenesis in healthy mice but further investigations are necessary to fully analyse the BTX-A effect and to generate sustained muscular atrophy in mdx-mice.

  13. Human paraoxonase and HDL-cholesterol in pakistan patients with acute myocardial infarction and normal healthy adults

    International Nuclear Information System (INIS)

    Iqbal, I.P.; Khan, A.H.; Mehboobali, N.

    2007-01-01

    Human serum paraoxonase is a high density lipoprotein (HDL)-bound enzyme exhibiting antiatherogenic properties. The aim of this study was to investigate any relationship between serum paraoxonase activity and serum levels of HDL-cholesterol in Pakistani patients with acute myocardial infarction (AMI) compared to normal healthy subjects and to examine possible association between serum paraoxonase activity and AMI in Pakistani population. In a case-control study, serum paraoxonase activity and serum levels of HDL-cholesterol and LDL-cholesterol were monitored in 164 Pakistani patients with AMI and 106 normal healthy adults matched for gender, BMI and age within 10 years. Mean serum concentration of HDL-cholesterol and mean serum paraoxonase activity in AMI patients were not significantly different from the corresponding values in normal healthy subjects. Mean serum paraoxonase activity value was significantly lower in normal healthy subjects with low HDL-cholesterol (serum levels < 40mg/dl) compared to the value in those with normal levels of HDL-cholesterol (P=0.04). In AMI patients, paraoxonase activity was lower in subjects with low HDL-cholesterol compared to those with normal levels of HDL-cholesterol, however, the decrease was not statistically significant. Correlation analyses of the data revealed a moderate association of paraoxonase activity with HDL-cholesterol (Pearson's r= 0.225, P<0.01 for AMI patients and r=0.281, P<0.01 for normal healthy controls). Seventy three percent of normal healthy subjects and 65% of AMI patients in this study had low HDL-cholesterol. Low serum paraoxonase activity and high prevalence of low HDL-cholesterol in Pakistani population could be contributing to the high rates of coronary heart disease in this population. (author)

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

    OpenAIRE

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

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until d...

  15. Appropriate slice location to assess maximal cross-sectional area of individual rotator cuff muscles in normal adults and athletes

    International Nuclear Information System (INIS)

    Yanagisawa, Osamu; Dohi, Michiko; Okuwaki, Toru; Tawara, Noriyuki; Takahashi, Hideyuki; Niitsu, Mamoru

    2009-01-01

    We investigated appropriate slice locations for magnetic resonance (MR) imaging evaluation of the maximal cross-sectional area (CSA) of individual rotator cuff (RC) muscles in normal adults and athletes. We used a 1.5-tesla MR system with body-array and spine coils to obtain oblique sagittal T 1 -weighted shoulder images of 29 normal adults (16 men, 13 women); 6 national-level competitive swimmers (4 men, 2 women); 10 collegiate-level female badminton players; and 7 collegiate-level male rowers. We calculated the supraspinatus, infraspinatus, teres minor, and subscapularis CSAs at the 0-1 locations on the scapula (dividing scapula width into 11 locations), 0 representing the medial border of the scapula and 1, the glenoid fossa surface. We evaluated the differences in CSAs at relative locations on the scapula for each muscle in normal adults, swimmers, badminton players, and rowers using a one-way analysis of variance followed by the Tukey test (P<0.05). The supraspinatus CSAs were maximal at 0.7 for all groups. The infraspinatus CSAs were maximal at 0.5 for normal men and women and badminton players, 0.4- and 0.5 locations for swimmers, and 0.4 for rowers. The teres minor CSAs were maximal at 0.9 for all groups except the swimmers (1 location). The subscapularis CSAs were maximal at 0.7 in men, swimmers, and badminton players and 0.6 in women and rowers. The appropriate slice locations for evaluating maximal CSAs are slightly lateral to the center of the scapula for the supraspinatus and subscapularis, at approximately the center of the scapula for the infraspinatus, and near the glenoid fossa for the teres minor. These slice locations should be clinically useful for morphological and/or function-related assessments of shoulder RC muscles. (author)

  16. Association between individual fat depots and cardio-metabolic traits in normal- and overweight children, adolescents and adults.

    Science.gov (United States)

    Hübers, M; Geisler, C; Plachta-Danielzik, S; Müller, M J

    2017-05-08

    To determine age-related associations between fat mass (FM), regional fat depots and cardiometabolic traits in normal- and overweight children, adolescents and adults. Detailed body composition (regional subcutaneous and visceral adipose tissue; SAT, VAT) by whole-body magnetic resonance imaging (MRI), FM and fat-free mass by air-displacement plethysmography, systolic and diastolic blood pressure (SBP, DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL), plasma glucose and plasma insulin were measured in 433 subjects (BMI: 23.6 (21.0-27.7); 151 children and adolescents, aged 6-18 years, 150 young adults, aged 18-30 years and 132 adults, aged 30-60 years). Data were derived from pooled data of the 'Reference Center for Body Composition' in Kiel, Germany. Insulin resistance was determined by the homeostatic model assessment of insulin resistance (HOMA-IR). Partial correlations and multivariate linear regression analyses were used to evaluate the associations between body composition and cardiometabolic traits. A descriptive approach was used to demonstrate age-dependent differences in associations between body fat depots and insulin resistance, independent of BMI. FM, SAT, and VAT increased from childhood to adulthood with low VAT in children and adolescents. When compared to children, TG was higher in adults. HDL and DBP did not differ between age groups. Insulin resistance was highest in male adolescents and female young adults. Associations between body fat depots and cardiometabolic traits were seen after puberty with no associations in pre- and intrapubertal children. When compared to FM, SAT and VAT had the strongest association with insulin resistance in adults. This association was independent of BMI. Associations between individual body fat depots and most cardiometabolic traits became evident after puberty only. The strongest associations were observed between insulin resistance and abdominal fat in adults. The impact of VAT was independent

  17. [Colorimetric investigation of normal tongue and lip colors from 516 healthy adults by visible reflection spectrum].

    Science.gov (United States)

    Zeng, Chang-chun; Yang, Li; Xu, Ying; Liu, Pei-pei; Guo, Shi-jun; Liu, Song-hao

    2011-09-01

    Using the data from normal tongue and lip colors of normal people which were collected by the visible reflection spectrum, we analyzed the colorimetric parameters of tongue and lip colors. In this study, 516 healthy students aging from 19 to 26 from the colleges and universities of Guangdong Province of China were taken as research subjects. After collecting the data of tongue and lip colors of the 516 subjects using visible reflectance spectroscopy, CIE XYZ tristimulus values as defined by the International Commission on Illumination in 1964 were calculated, and the colorimetric parameters of the normal tongue and lip colors were obtained, such as the CIE 1964 chromaticity coordinate, brightness, dominant wavelength and excitation purity. The results of CIE 1964 chromaticity diagram calculated on the visible reflection spectrum showed that the normal tongue color chromaticity coordinate x(10) was 0.341 3±0.008 5 and y(10) was 0.332 6±0.005 1, and the normal lip color chromaticity coordinate x(10) was 0.357 7±0.009 2 and y(10) was 0.338 3±0.005 7; the brightness Y values of the normal tongue color and lip colors were 17.96±3.78 and 19.78±3.72, the dominant wavelength values of the normal tongue color and lip color were (626.3±51.6) nm and (600.4±18.2) nm, and the excitation purity values of the normal tongue color and lip color were 0.083±0.031 and 0.144±0.036, respectively. Application of the visible reflection spectrum is a standard way to collect colorimetric data for inspection of the complexion. The investigation of chromaticity coordinates, brightness, dominant wavelength and excitation purity of the normal tongue and lip colors may offer the basic reference for diagnosing morbid complexion on the tongue and lip colors in traditional Chinese medicine.

  18. Organotypic brain slice cultures of adult transgenic P301S mice--a model for tauopathy studies.

    Directory of Open Access Journals (Sweden)

    Agneta Mewes

    Full Text Available BACKGROUND: Organotypic brain slice cultures represent an excellent compromise between single cell cultures and complete animal studies, in this way replacing and reducing the number of animal experiments. Organotypic brain slices are widely applied to model neuronal development and regeneration as well as neuronal pathology concerning stroke, epilepsy and Alzheimer's disease (AD. AD is characterized by two protein alterations, namely tau hyperphosphorylation and excessive amyloid β deposition, both causing microglia and astrocyte activation. Deposits of hyperphosphorylated tau, called neurofibrillary tangles (NFTs, surrounded by activated glia are modeled in transgenic mice, e.g. the tauopathy model P301S. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explore the benefits and limitations of organotypic brain slice cultures made of mature adult transgenic mice as a potential model system for the multifactorial phenotype of AD. First, neonatal (P1 and adult organotypic brain slice cultures from 7- to 10-month-old transgenic P301S mice have been compared with regard to vitality, which was monitored with the lactate dehydrogenase (LDH- and the MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays over 15 days. Neonatal slices displayed a constant high vitality level, while the vitality of adult slice cultures decreased significantly upon cultivation. Various preparation and cultivation conditions were tested to augment the vitality of adult slices and improvements were achieved with a reduced slice thickness, a mild hypothermic cultivation temperature and a cultivation CO(2 concentration of 5%. Furthermore, we present a substantial immunohistochemical characterization analyzing the morphology of neurons, astrocytes and microglia in comparison to neonatal tissue. CONCLUSION/SIGNIFICANCE: Until now only adolescent animals with a maximum age of two months have been used to prepare organotypic brain slices. The current study

  19. A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation

    DEFF Research Database (Denmark)

    Thudium, Christian S; Moscatelli, Ilana; Flores, Carmen

    2014-01-01

    that osteoclasts are important for regulating osteoblast activity. To illuminate the role of the osteoclast in controlling bone remodeling, we transplanted irradiated skeletally mature 3-month old wild-type mice with hematopoietic stem cells (HSCs) to generate either an osteoclast-rich or osteoclast-poor adult......Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating...... osteopetrosis model. We used fetal liver HSCs from (1) oc/oc mice, (2) RANK KO mice, and (3) compared these to wt control cells. TRAP5b activity, a marker of osteoclast number and size, was increased in the oc/oc recipients, while a significant reduction was seen in the RANK KO recipients. In contrast, the bone...

  20. Foucault, Governmentality, Neoliberalism and Adult Education--Perspective on the Normalization of Social Risks

    Science.gov (United States)

    Kopecký, Martin

    2011-01-01

    The article deals with the relevance of the work of Foucault to critical analysis of the political concept of lifelong learning that currently dominates. This concept relates to the field of adult education and learning. The article makes reference to the relatively late incorporation of Foucault's work within andragogy. It shows the…

  1. False Memory in Adults With ADHD: A Comparison Between Subtypes and Normal Controls.

    Science.gov (United States)

    Soliman, Abdrabo Moghazy; Elfar, Rania Mohamed

    2017-10-01

    To examine the performance on the Deese-Roediger-McDermott task of adults divided into ADHD subtypes and compares their performance to that of healthy controls to examine whether adults with ADHD are more susceptible to the production of false memories under experimental conditions. A total of 128 adults with ADHD (50% females), classified into three Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV-TR) subtypes, were compared with 48 controls. The results indicated that the ADHD participants recalled and recognized fewer studied words than the controls, the ADHD groups produced more false memories than the control group, no differences in either the false positives or the false negatives. The ADHD-combined (ADHD-CT) group recognized significantly more critical words than the control, ADHD-predominantly inattentive (ADHD-IA), and ADHD-predominantly hyperactive-impulsive (ADHD-HI) groups. The ADHD groups recalled and recognized more false positives, were more confident in their false responses, and displayed more knowledge corruption than the controls. The ADHD-CT group recalled and recognized more false positives than the other ADHD groups. The adults with ADHD have more false memories than the controls and that false memory formation varied with the ADHD subtypes.

  2. Toll-like receptor 2 mediates ischemia-reperfusion injury of the small intestine in adult mice.

    Directory of Open Access Journals (Sweden)

    Toshio Watanabe

    Full Text Available Toll-like receptor 2 (TLR2 recognizes conserved molecular patterns associated with both gram-negative and gram-positive bacteria, and detects some endogenous ligands. Previous studies demonstrated that in ischemia-reperfusion (I/R injury of the small intestine, the TLR2-dependent signaling exerted preventive effects on the damage in young mice, but did not have a significant effect in neonatal mice. We investigated the role of TLR2 in adult ischemia-reperfusion injury in the small intestine. Wild-type and TLR2 knockout mice at 16 weeks of age were subjected to intestinal I/R injury. Some wild-type mice received anti-Ly-6G antibodies to deplete circulating neutrophils. In wild-type mice, I/R induced severe small intestinal injury characterized by infiltration by inflammatory cells, disruption of the mucosal epithelium, and mucosal bleeding. Compared to wild-type mice, TLR2 knockout mice exhibited less severe mucosal injury induced by I/R, with a 35%, 33%, and 43% reduction in histological grading score and luminal concentration of hemoglobin, and the numbers of apoptotic epithelial cells, respectively. The I/R increased the activity of myeloperoxidase (MPO, a marker of neutrophil infiltration, and the levels of mRNA expression of tumor necrosis factor-α (TNF-α, intercellular adhesion molecule-1 (ICAM-1, and cyclooxygenase-2 (COX-2 in the small intestine of the wild-type mice by 3.3-, 3.2-, and 13.0-fold, respectively. TLR2 deficiency significantly inhibited the I/R-induced increase in MPO activity and the expression of mRNAs for TNF-α and ICAM-1, but did not affect the expression of COX-2 mRNA. I/R also enhanced TLR2 mRNA expression by 2.9-fold. TLR2 proteins were found to be expressed in the epithelial cells, inflammatory cells, and endothelial cells. Neutrophil depletion prevented intestinal I/R injury in wild-type mice. These findings suggest that TLR2 may mediate I/R injury of the small intestine in adult mice via induction of inflammatory

  3. Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations

    Directory of Open Access Journals (Sweden)

    Timothy J. Bauler

    2011-03-01

    SHP-2 (encoded by PTPN11 is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF and receptor activator of nuclear factor kappa B ligand (RANKL was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.

  4. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

    Science.gov (United States)

    Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

    2014-03-01

    Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

  5. Normal width of the anterior commissure of true vocal cord in Korea adults measured by helical CT

    International Nuclear Information System (INIS)

    Lim, Woo Young; Lim, Dong Hoon; Moon, Jang Il; Ko, Yong Seok; Byeon, Joo Nam; Oh, Jae Hee

    1998-01-01

    To evaluate the mean width of anterior commissure of true vocal cord in Korean adults by measuring its dimension on spiral CT scans. We reviewed the CT scans of 53 Korean adults(age range, 23-73years; mean age 39.2 years;M:F=3D41:12) without laryngeal disorders. Soiral CT scanning was performed around the anterior commissure with 1mm slice thickness and table incrementation for 15 seconds. The anteroposterior width of the anterior commissure was measured on CT scan where the true vocal cord and arytenoid, cricoid and thyroid cartilages were all present. We determined the mean width of the anterior commissure and whether there was a relationship between age and the width of the anterior commissure. The width of the anterior commissure was between 0.9mm and 2.3mm;mean width was 1.60±0.38mm(mean±SD). Using two SDs above the mean would have defined 2.36mm as the upper limit of normal width. Statistically, no significant correlation existed between the age and the width of the anterior commissure(p>0.05). An awareuess of the normal width range of the anterior commissure in Korean adults evaluated by spiral CT enhances the possibility of early detection of invasion of the anterior commissure by glottic cancer.=20

  6. Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling.

    Science.gov (United States)

    Whiddon, Benjamin B; Palmiter, Richard D

    2013-01-30

    Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine-amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch(DTR/+) mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.

  7. Oral candidosis by Candida albicans in normal and xerostomic mice Candidose oral por Candida albicans em camundongos normais e xerostômicos

    Directory of Open Access Journals (Sweden)

    Marilda Aparecida Gonçalves Totti

    2004-09-01

    Full Text Available The aim of this study was to analyze the effect of sialoadenectomy on the development of oral candidosis after one or four inoculations of Candida albicans. Initially, a suspension containing 10(8 cells/ml of C. albicans ATCC 36801 was prepared. Seventy-eight sialoadenectomized mice and a similar amount of mice with normal salivary flow received a single inoculation of C. albicans suspension. Another group with a similar number of mice received 4 inoculations. The control group consisted of 6 sialoadenectomized mice and 6 mice with normal salivary flow that were not inoculated with C. albicans. Candidosis development was studied histologically in the tongue of the animals 1, 2, 3, 5, and 8 days after inoculation and at 15-day intervals up to 165 days. According to the results obtained, it could be concluded that sialoadenectomy and a higher frequency of yeast inoculation influenced the presence and extension of candidosis lesions.O objetivo deste estudo foi analisar o efeito da sialoadenectomia sobre o desenvolvimento da candidose oral após uma ou quatro inoculações de Candida albicans. Inicialmente, uma suspensão contendo 10(8 células/ml de C. albicans ATCC 36801 foi preparada. Setenta e oito camundongos sialoadenectomizados e mesma quantidade de camundongos com fluxo salivar normal receberam uma única inoculação de suspensão de C. albicans. Outro grupo, com o mesmo número de camundongos, recebeu 4 inoculações. O grupo controle consistiu de 6 camundongos sialoadenectomizados e 6 com fluxo salivar normal que não foram inoculados com C. albicans. O desenvolvimento de candidose foi estudado histologicamente na língua dos animais em períodos de 1, 2, 3, 5 e 8 dias após a inoculação e em intervalos de 15 dias até 165 dias. De acordo com os resultados obtidos, conclui-se que a sialoadenectomia e uma maior freqüência de inoculação influenciaram na presença e extensão das lesões de candidose.

  8. Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    International Nuclear Information System (INIS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Shea, Thomas B; Gilman, Vladimir

    2008-01-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE−/− mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or −/−, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE−/− cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE−/− cultures, which may be a reflection of the reduced SAM levels in ApoE−/− mice. The differential impact of SAM on ApoE+/+ and −/− neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis. (communication)

  9. Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

    DEFF Research Database (Denmark)

    Mosconi, Lisa; Rinne, Juha O; Tsui, Wai H

    2013-01-01

    This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40-80-year-old NL received positr...

  10. Severe aortic coarctation in an adult patient with normal brachial blood pressure

    DEFF Research Database (Denmark)

    Leetmaa, Tina H; Nørgaard, Bjarne L; Mølgaard, Henning

    2014-01-01

    The present case shows that a normal brachial blood pressure (BP) does not exclude severe coarctation and should be considered in normotensive patients presenting with a systolic murmur and/or unexplained severe left ventricular hypertrophy. Congenital coarctation of the aorta is a narrowing of t...... originating below the area of coarctation, explaining the equally low BP in both upper extremities....

  11. Normal and obsessional jealousy: a study of a population of young adults.

    Science.gov (United States)

    Marazziti, Donatella; Di Nasso, Elena; Masala, Irene; Baroni, Stefano; Abelli, Marianna; Mengali, Francesco; Mungai, Francesco; Rucci, Paola

    2003-05-01

    Jealousy is a heterogenous emotion ranging from normality to pathology. Several problems still exist in the distinction between normal and pathological jealousy. With the present study, we aimed to contribute to the definition of the boundary between obsessional and normal jealousy by means of a specific self-report questionnaire developed by us. The questionnaire called "Questionnaire on the Affective Relationships" (QAR) and consisting of 30 items, was administered to 400 university students of both sexes and to 14 outpatients affected by obsessive-compulsive disorder (OCD) whose main obsession was jealousy. The total scores and single items were analysed and compared. Two hundred and forty-five, approximately 61% of the questionnaires, were returned. The statistical analyses showed that patients with OCD had higher total scores than healthy subjects; in addition, it was possible to identify an intermediate group of subjects, corresponding to 10% of the total, who were concerned by jealousy thoughts around the partner, but at a lower degree than patients, and that we called "healthy jealous subjects" because they had no other psychopathological trait. Significant differences were also observed for single items in the three groups. Our study showed that 10% of a population of university students, albeit normal, have jealousy thoughts around the partner, as emerged by the specific questionnaire developed by us. This instrument permitted to clearly distinguish these subjects from patients with OCD and healthy subjects with no jealousy concern.

  12. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    Science.gov (United States)

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  13. mPeriod2 Brdm1 and other single Period mutant mice have normal food anticipatory activity.

    Science.gov (United States)

    Pendergast, Julie S; Wendroth, Robert H; Stenner, Rio C; Keil, Charles D; Yamazaki, Shin

    2017-11-14

    Animals anticipate the timing of food availability via the food-entrainable oscillator (FEO). The anatomical location and timekeeping mechanism of the FEO are unknown. Several studies showed the circadian gene, Period 2, is critical for FEO timekeeping. However, other studies concluded that canonical circadian genes are not essential for FEO timekeeping. In this study, we re-examined the effects of the Per2 Brdm1 mutation on food entrainment using methods that have revealed robust food anticipatory activity in other mutant lines. We examined food anticipatory activity, which is the output of the FEO, in single Period mutant mice. Single Per1, Per2, and Per3 mutant mice had robust food anticipatory activity during restricted feeding. In addition, we found that two different lines of Per2 mutant mice (ldc and Brdm1) anticipated restricted food availability. To determine if FEO timekeeping persisted in the absence of the food cue, we assessed activity during fasting. Food anticipatory (wheel-running) activity in all Period mutant mice was also robust during food deprivation. Together, our studies demonstrate that the Period genes are not necessary for the expression of food anticipatory activity.

  14. Elemental concentrations and tracer uptake behavior of manganese, zinc, and selenium in brain of normal mice during development

    International Nuclear Information System (INIS)

    Tarohda, Tohru; Yabushita, Yuko; Kanayama, Yousuke; Amano, Ryohei; Enomoto, Shuichi

    2001-01-01

    Concentrations and uptake behavior of manganese (Mn), zinc (Zn), and selenium (Se) in mouse brain were studied by a multitracer technique, neutron activation analysis and autoradiography. Comparative concentrations on Mn, Zn, and Se and tracer uptake behavior of 54 Mn, 65 Zn, and 75 Se were examined in brains of 1-, 4-, 8-, 21-, and 56-day-old mice, and evaluated in terms of brain concentration (parts per million, ppm) and brain uptake rate (the radioactivity percentage of injected dose per gram of brain, %dose/g), respectively. As a result, the brain concentrations of Mn increased with growth, although those of Se and Zn did not change. On the other hand, the uptakes of the three tracers by brains of 1-day-old mice were much higher than those of older ones. Using radioactive 54 Mn as a single tracer, autoradiography was examined to determine the Mn uptake regional distribution in brains of 1-, 8-, and 21-day-old mice, and a higher regional uptake of Mn by the cerebral cortex, hippocampus, thalamus and hypothalamus in brains of young mice was observed. (author)

  15. Occlusal risk factors associated with temporomandibular disorders in young adults with normal occlusions.

    Science.gov (United States)

    Wang, Chen; Yin, Xinmin

    2012-10-01

    The aim of this study was to characterize occlusal stability in young adults with temporomandibular disorder (TMD). Thirty-one patients (aged 19-31 years) with complete natural dentition and Angle class I occlusion who exhibited TMD were compared with 31 age- and sex-matched healthy control subjects. The occlusal registrations were performed using the T-Scan II occlusal imaging and analysis system. Center of occlusal force, asymmetry index of occlusal force, maximal movement of COF, premature contacts, clusion time, and disclusion time were recorded. Compared with control subjects, TMD subjects had a significantly higher frequency of premature contacts (16/32, 50.0%) and greater bilateral asymmetry in the occlusal force. Furthermore, prolonged clusion time and disclusion time also were observed in TMD subjects. These results suggest that a significant association exists between occlusal stability and TMD in young adults. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. The effects of breeding protocol in C57BL/6J mice on adult offspring behaviour.

    Directory of Open Access Journals (Sweden)

    Claire J Foldi

    Full Text Available Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10-12 days and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH. The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM. Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI of the acoustic startle response. We found that length of sire exposure (LSE had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour.

  17. NEUROPHYSIOLOGICAL STUDY ON THE EFFECT OF ARTIFICIAL FOOD COLOUR AND SWEETENER IN ADULT MALE ALBINO MICE

    International Nuclear Information System (INIS)

    ABDEL-RAHMAN, M.; EL-KHADRAGY, M.F.; ABDEL-AZIZ, R.L.

    2008-01-01

    This study aims to investigate the effect of aspartame (artificial sweetener) and sunset yellow (artificial colour) on monoamines content in different brain areas of the adult male albino mice (cerebellum, brain stem, striatum, hypothalamus and cerebral cortex), and also on testosterone level in serum.The present study showed that the daily intraperitoneal injection of aspartame with dose of 200 mg/kg caused significant increase in monoamines content and testosterone level at most experimental periods. The elevation of monoamines content may be due to increase in phenylalanine concentration which leading to increase the synthesis of monoamines. The elevation of testosterone level may be due to the increment of DA content in hypothalamus which led to increase the release of LHRH. On the other hand, the daily intraperitoneal injection of sunset yellow with a dose of 2.5 mg/kg caused significant decrease in monoamines content and non-significant change in serum testosterone level at most experimental periods. The decrement in monoamines content may be due to the decrease in its uptake by the neurotransmitters or decrease in its synthesis

  18. Distribution and ultrastructure of pigment cells in the skins of normal and albino adult turbot, Scophthalmus Maximus

    Institute of Scientific and Technical Information of China (English)

    GUO Huarong; HUANG Bing; QI Fei; ZHANG Shicui

    2007-01-01

    The distribution and ultrastructure of pigment cells in skins of normal and albino adult turbots were examined with transmission electron microscopy (TEM). Three types of pigment cells of melanophore, iridophore and xanthophore have been recognized in adult turbot skins. The skin color depends mainly on the amount and distribution of melanophore and iridophore, as xanthophore is quite rare. No pigment cells can be found in the epidermis of the skins. In the pigmented ocular skin of the turbot, melanophore and iridophore are usually co-localized in the dermis. This is quite different from the distribution in larvae skin. In albino and white blind skins of adult turbots, however, only iridophore monolayer still exists, while the melanophore monolayer disappears. This cytological evidence explains why the albino adult turbot, unlike its larvae, could never resume its body color no matter what environmental and nutritional conditions were provided. Endocytosis is quite active in the cellular membrane of the iridophore. This might be related to the formation of reflective platelet and stability of the iridophore.

  19. The effects of frequency-encoding gradient upon detectability of the margins and height measurements of normal adult pituitary glands

    International Nuclear Information System (INIS)

    Taketomi, A.; Sato, N.; Aoki, J.; Endo, K.

    2004-01-01

    We investigated the effects of frequency-encoding gradient (FEG) upon detectability and height measurements of the normal adult pituitary gland. We obtained two sets of T1-weighted sagittal images of the pituitary gland from 70 adult subjects without known pituitary dysfunction using 1.5 tesla imagers; one with an inferior-superior FEG, and one with an anterior-posterior FEG. We classified the subjects into three types according to the distribution of fatty marrow in the clivus. Each set of images was assessed for pituitary height on midline sagittal images, and detectability of pituitary margins. Height measurements and detectability scores were evaluated for significant difference between the two FEGs. In subjects with fatty marrow in the clivus, there was significant difference between pituitary height measurements (P<0.005) and pituitary margin detectability (P<0.001). Care should be taken to image the pituitary gland using an anterior-posterior FEG. (orig.)

  20. Neonatal Whisker Trimming Impairs Fear/Anxiety-Related Emotional Systems of the Amygdala and Social Behaviors in Adult Mice.

    Directory of Open Access Journals (Sweden)

    Hitomi Soumiya

    Full Text Available Abnormalities in tactile perception, such as sensory defensiveness, are common features in autism spectrum disorder (ASD. While not a diagnostic criterion for ASD, deficits in tactile perception contribute to the observed lack of social communication skills. However, the influence of tactile perception deficits on the development of social behaviors remains uncertain, as do the effects on neuronal circuits related to the emotional regulation of social interactions. In neonatal rodents, whiskers are the most important tactile apparatus, so bilateral whisker trimming is used as a model of early tactile deprivation. To address the influence of tactile deprivation on adult behavior, we performed bilateral whisker trimming in mice for 10 days after birth (BWT10 mice and examined social behaviors, tactile discrimination, and c-Fos expression, a marker of neural activation, in adults after full whisker regrowth. Adult BWT10 mice exhibited significantly shorter crossable distances in the gap-crossing test than age-matched controls, indicating persistent deficits in whisker-dependent tactile perception. In contrast to controls, BWT10 mice exhibited no preference for the social compartment containing a conspecific in the three-chamber test. Furthermore, the development of amygdala circuitry was severely affected in BWT10 mice. Based on the c-Fos expression pattern, hyperactivity was found in BWT10 amygdala circuits for processing fear/anxiety-related responses to height stress but not in circuits for processing reward stimuli during whisker-dependent cued learning. These results demonstrate that neonatal whisker trimming and concomitant whisker-dependent tactile discrimination impairment severely disturbs the development of amygdala-dependent emotional regulation.

  1. Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

    Science.gov (United States)

    Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

    2014-06-01

    Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

  2. Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

    International Nuclear Information System (INIS)

    Kolesnichenko, T.S.; Gor'kova, T.G.

    1985-01-01

    Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

  3. Volume measurement of thalami in normal Chinese Han nationality adults by the high-resolution MRI

    International Nuclear Information System (INIS)

    Ma Shuai; Chen Nan; Guo Yulin

    2012-01-01

    Objective: To measure the volume of thalamus in 1000 healthy Chinese Han nationality adults, and to analyze the relationship between thalamic volume and age, sex, weight and cerebral volume, to provide reliable data for the construction of database of Chinese adults' digital standard brain. Methods: Totally 1000 healthy Chinese adults of Han nationality aged from 18 to 80 years were recruited.They were divided into 5 groups by age: 18-30, 31-40, 41-50, 51-60 and 61-80 years. Each group included 100 males and 100 females. Brain images were obtained on a 1.5 T MR, and the outline of thalami was drawn with Aquariusws software. Then the thalamic volume was calculated automatically. The volumes of left and right thalamus were compared by paired sample t-test. Thalamic volumes of the same side were compared between males and females by independent sample t-test. And thalamic volumes of different age groups were compared by one-way ANOVA. The relationships between thalamic volume and age, sex, weight and cerebral volume were analyzed respectively. Results: The males' standardized volumes of left and right thalamus of healthy Chinese Han nationality adults were (5776 ± 780), (5655 ± 759) mm 3 , and they were (5464 ±573), (5360 ± 542) mm 3 for female. The males' thalamic volume was more than the females' on the same side (t=2.245, 2.200, P<0.01). The left thalamic volumes of various age groups were (6180 ± 534), (6047 ± 562), (5426 ± 471), (5552 ± 526), (4866 ± 552) mm 3 , respectively, while the right thalamic volumes of the 5 groups were (6069 ± 532), (5895 ± 539), (5357 ± 480), (5396 ± 445),(4791 ± 558)mm 3 , respectively. There were statistically significant difference among the 5 groups (F=165.686, 165.235, P<0.01). The left and right thalamic volume were all negatively correlated with age (r=-0.633, -0.645, P<0.05). Conclusions: With high resolution 1.5 T MR scanner,grey matter and white matter can be depicted clearly and the outline

  4. Induced Ablation of Ghrelin Cells in Adult Mice Does Not Decrease Food Intake, Body Weight, or Response to High Fat Diet

    Science.gov (United States)

    McFarlane, Matthew R.; Brown, Michael S.; Goldstein, Joseph L.; Zhao, Tong-Jin

    2014-01-01

    SUMMARY Injection of the peptide hormone ghrelin stimulates food intake in mice and humans. However, mice born without ghrelin demonstrate no significant loss of appetite. This paradox suggests either that compensation develops in mice born without ghrelin or that ghrelin is not essential for appetite control. To distinguish these possibilities, we generated transgenic mice (Ghrl-DTR) that express the diphtheria toxin receptor in ghrelin-secreting cells. Injection of diphtheria toxin in adulthood ablated ghrelin cells and reduced plasma ghrelin by 80-95%. Ghrelin cell-ablated mice exhibited no loss of appetite or body weight and no resistance to a high fat diet. To stimulate food intake in mice by ghrelin injection, we had to raise plasma levels many-fold above normal. Like germline ghrelin-deficient mice, the ghrelin cell-ablated mice developed profound hypoglycemia when subjected to prolonged calorie restriction, confirming that ghrelin acts to maintain blood glucose under famine conditions. PMID:24836560

  5. Radiation Dose Estimates in Indian Adults in Normal and Pathological Conditions due to 99Tcm-Labelled Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Tyagi, K.; Jain, S.C.; Jain, P.C.

    2001-01-01

    ICRP Publications 53, 62 and 80 give organ dose coefficients and effective doses to ICRP Reference Man and Child from established nuclear medicine procedures. However, an average Indian adult differs significantly from the ICRP Reference Man as regards anatomical, physiological and metabolic characteristics, and is also considered to have different tissue weighting factors (called here risk factors). The masses of total body and most organs are significantly lower for the Indian adult than for his ICRP counterpart (e.g. body mass 52 and 70 kg respectively). Similarly, the risk factors are lower by 20-30% for 8 out of the 13 organs and 30-60% higher for 3 organs. In the present study, available anatomical data of Indians and their risk factors have been utilised to estimate the radiation doses from administration of commonly used 99 Tc m -labelled radiopharmaceuticals under normal and certain pathological conditions. The following pathological conditions have been considered for phosphates/phosphonates - high bone uptake and severely impaired kidney function; IDA - parenchymal liver disease, occlusion of cystic duct, and occlusion of bile duct; DTPA - abnormal renal function; large colloids - early to intermediate diffuse parenchymal liver disease, intermediate to advanced parenchymal liver disease; small colloids - early to intermediate parenchymal liver disease, intermediate to advanced parenchymal liver disease; and MAG3 - abnormal renal function, acute unilateral renal blockage. The estimated 'effective doses' to Indian adults are 14-21% greater than the ICRP value from administration of the same activity of radiopharmaceutical under normal physiological conditions based on anatomical considerations alone, because of the smaller organ masses for the Indian; for some pathological conditions the effective doses are 11-22% more. When tissue risk factors are considered in addition to anatomical considerations, the estimated effective doses are still found to be

  6. Gastrointestinal absorption of plutonium and uranium in fed and fasted adult baboons and mice: application to humans

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Cohen, N.; Ralston, L.G.; Moretti, E.S.; Ayres, L.

    1989-01-01

    Gastrointestinal (GI) absorption values of plutonium and uranium were determined in fed and fasted adult baboons and mice. For both baboons and mice, the GI absorptions of plutonium and uranium were 10 to 20 times higher in 24 h fasted animals than in fed ones. For plutonium, GI absorption values in baboons were almost identical to those in mice for both fed and fasted conditions, and values for fed animals agreed with estimates for humans. For uranium, GI absorption values in fed and fasted baboons were 6 to 7 times higher than those in mice, and agreed well with those fed and fasted humans. For one baboon that was not given its morning meal, plutonium absorption 2 h after the start of the active phase was the same as that in the 24 h fasted animals. In contrast, for baboons that received a morning meal, plutonium absorption did not rise to the value of 24 h fasted baboons even 8 h after the meal. We conclude that GI absorption values for plutonium and uranium in adult baboons are good estimates of the values in humans and that the values for the fasted condition should be used to set standards for oral exposure of persons in the workplace. (author)

  7. Morphological aspects of Schistosoma mansoni adult worms isolated from nourished and undernourished mice: a comparative analysis by confocal laser scanning microscopy

    Directory of Open Access Journals (Sweden)

    Neves Renata Heisler

    2001-01-01

    Full Text Available Malnutrition hampers the course of schistosomiasis mansoni infection just as normal growth of adult worms. A comparative morphometric study on adult specimens (male and female recovered from undernourished (fed with a low protein diet - regional basic diet and nourished (rodent commercial laboratory food, NUVILAB white mice was performed. Tomographic images and morphometric analysis of the oral and ventral suckers, reproductive system and tegument were obtained by means of confocal laser scanning microscopy. Undernourished male specimens presented smaller morphometric values (length and width of the reproductive system (first, third and last testicular lobes and thickness of the tegument than controls. Besides that, it was demonstrated that the dorsal surface of the male worms bears large tubercles unevenly distributed, but kept grouped and flat. At the subtegumental region, vacuolated areas were detected. It was concluded that the inadequate nutritional status of the vertebrate host has a negative influence mainly in the reproductive system and topographical somatic development of male adult Schistosoma mansoni, inducing some alterations on the structure of the parasite.

  8. Hydroxysteroid (17β)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production.

    Science.gov (United States)

    Hakkarainen, Janne; Jokela, Heli; Pakarinen, Pirjo; Heikelä, Hanna; Kätkänaho, Laura; Vandenput, Liesbeth; Ohlsson, Claes; Zhang, Fu-Ping; Poutanen, Matti

    2015-09-01

    Hydroxysteroid (17β)-dehydrogenase type 1 (HSD17B1) catalyzes the conversion of low active 17-ketosteroids, androstenedione (A-dione) and estrone (E1) to highly active 17-hydroxysteroids, testosterone (T) and E2, respectively. In this study, the importance of HSD17B1 in ovarian estrogen production was determined using Hsd17b1 knockout (HSD17B1KO) mice. In these mice, the ovarian HSD17B enzyme activity was markedly reduced, indicating a central role of HSD17B1 in ovarian physiology. The lack of Hsd17b activity resulted in increased ovarian E1:E2 and A-dione:T ratios, but we also observed reduced progesterone concentration in HSD17B1KO ovaries. Accordingly with the altered steroid production, altered expression of Star, Cyp11a1, Lhcgr, Hsd17b7, and especially Cyp17a1 was observed. The ovaries of HSD17B1KO mice presented with all stages of folliculogenesis, while the corpus luteum structure was less defined and number reduced. Surprisingly, bundles of large granular cells of unknown origin appeared in the stroma of the KO ovaries. The HSD17B1KO mice presented with severe subfertility and failed to initiate pseudopregnancy. However, the HSD17B1KO females presented with normal estrous cycle defined by vaginal smears and normal puberty appearance. This study indicates that HSD17B1 is a key enzyme in ovarian steroidogenesis and has a novel function in initiation and stabilization of pregnancy. © FASEB.

  9. A lower dose threshold for the in vivo protective adaptive response to radiation. Tumorigenesis in chronically exposed normal and Trp53 heterozygous C57BL/6 mice

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Burchart, P.; Wyatt, H.

    2008-01-01

    Low doses of ionizing radiation to cells and animals may induce adaptive responses that reduce the risk of cancer. However, there are upper dose thresholds above which these protective adaptive responses do not occur. We have now tested the hypothesis that there are similar lower dose thresholds that must be exceeded in order to induce protective effects in vivo. We examined the effects of low dose/low dose rate fractionated exposures on cancer formation in Trp53 normal or cancer-prone Trp53 heterozygous female C57BL/6 mice. Beginning at 6 weeks of age, mice were exposed 5 days/week to single daily doses (0.33 mGy, 0.7 mGy/h) totaling 48, 97 or 146 mGy over 30, 60 or 90 weeks. The exposures for shorter times (up to 60 weeks) appeared to be below the level necessary to induce overall protective adaptive responses in Trp53 normal mice, and detrimental effects (shortened lifespan, increased frequency) evident for only specific tumor types (B- and T-cell lymphomas), were produced. Only when the exposures were continued for 90 weeks did the dose become sufficient to induce protective adaptive responses, balancing the detrimental effects for these specific cancers, and reducing the risk level back to that of the unexposed animals. Detrimental effects were not seen for other tumor types, and a protective effect was seen for sarcomas after 60 weeks of exposure, which was then lost when the exposure continued for 90 weeks. As previously shown for the upper dose threshold for protection by low doses, the lower dose boundary between protection and harm was influenced by Trp53 functionality. Neither protection nor harm was observed in exposed Trp53 heterozygous mice, indicating that reduced Trp53 function raises the lower dose/dose rate threshold for both detrimental and protective tumorigenic effects. (author)

  10. Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

    OpenAIRE

    Higgins, John P.T.; Wang, Lingli; Kambham, Neeraja; Montgomery, Kelli; Mason, Veronica; Vogelmann, Stefanie U.; Lemley, Kevin V.; Brown, Patrick O.; Brooks, James D.; van de Rijn, Matt

    2004-01-01

    The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied g...

  11. An autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

    International Nuclear Information System (INIS)

    Kasubuchi, Yasuo; Mino, Masahiro; Yoshioka, Hiroshi; Kusunoki, Tomoichi

    1979-01-01

    The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status. (author)

  12. Autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding

    Energy Technology Data Exchange (ETDEWEB)

    Kasubuchi, Y; Mino, M; Yoshioka, H; Kusunoki, T [Kyoto Prefectural Univ. of Medicine (Japan)

    1979-10-01

    The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status.

  13. Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice

    Directory of Open Access Journals (Sweden)

    Kiran Chaudhari

    2014-09-01

    Conclusion: Exercise was the most effective treatment at improving cognitive function in both genotypes and sex, while antioxidants seemed to be effective only in the APOE4. In young adult mice only non-spatial learning and memory were improved. The combination of the two treatments did not yield further improvement in cognition, and there was no antagonistic action of the antioxidant supplementation on the beneficial effects of exercise.

  14. Normal magnetic resonance appearances of the temporomandibular joints in children and young adults aged 2-18 years

    International Nuclear Information System (INIS)

    Angenete, Oskar W.; Augdal, Thomas A.; Jellestad, Stig; Rygg, Marite; Rosendahl, Karen

    2018-01-01

    Knowledge of normal appearances of the temporomandibular joint (TMJ) is paramount when assessing the joint for disease in juvenile idiopathic arthritis. Reliable features defining normal TMJs in children are limited. To establish reliable normal standards for the TMJ at magnetic resonance imaging (MRI). We included children and young adults aged 2-18 years undergoing a head MRI for reasons not believed to affect the TMJs. We assessed TMJ anatomy and contrast enhancement using a high-resolution 3-D T1-weighted sequence. We noted joint fluid and bone marrow oedema based on a T2-weighted sequence. Three experienced radiologists read all examinations twice in consensus and defined intraobserver consensus agreement. We evaluated the TMJs in 101 children and young adults (45 female), mean age 10.7 years (range 2-18 years). The intraobserver consensus agreement for the assessment of anterior condylar inclination in the sagittal/oblique plane was moderate to good (Cohen κ=0.7 for the right side). Cohen κ for intraobserver consensus agreement for condylar shape in the coronal plane on a 0-2 scale was 0.4 for the right and 0.6 for the left. Intraobserver agreement for measurement of joint space height and assessment of bone marrow oedema was poor. There was a statistically significant increase in anterior inclination by age in the sagittal plane on a 0-2 scale (P<0.0001). Eighty percent of the condyles showed a rounded shape in the coronal plane while 20% showed mild flattening. Thirty-five of 36 right TMJs showed contrast enhancement (mild enhancement in 32 joints, moderate in 3 joints). Subjective assessment of the anterior condylar inclination in the sagittal/oblique plane and condylar flattening in the coronal plane can be considered precise features for describing TMJ anatomy in healthy children. There is an increasing anterior inclination by age. Mild contrast enhancement of the TMJs should be considered a normal finding. (orig.)

  15. Adult echocardiographic nomograms: overview, critical review and creation of a software for automatic, fast and easy calculation of normal values.

    Science.gov (United States)

    Cantinotti, Massimiliano; Giordano, Raffaele; Paterni, Marco; Saura, Daniel; Scalese, Marco; Franchi, Eliana; Assanta, Nadia; Koestenberg, Martin; Dulgheru, Raluca; Sugimoto, Tadafumi; Bernard, Anne; Caballero, Luis; Lancellotti, Patrizio

    2017-12-01

    There is a crescent interest on normal adult echocardiographic values and the introduction of new deformation imaging and 3D parameters pose the issue of normative data. A multitude of nomograms has been recently published, however data are often fragmentary, difficult to find, and their strengths/limitations have been never evaluated. (I) to provide a review of current echocardiographic nomograms; (II) to generate a tool for easy and fast access to these data. A literature search was conducted accessing the National Library of Medicine using the keywords: 2D/3D echocardiography, strain, left/right ventricle, atrial, mitral/tricuspid valve, aorta, reference values/nomograms/normal values. Adding the following keywords, the results were further refined: range/intervals, myocardial velocity, strain rate and speckle tracking. Forty one published studies were included. Our study reveals that for several of 2D/3D parameters sufficient normative data exist, however, a few limitations still persist. For some basic parameters (i.e., mitral/tricuspid/pulmonary valves, great vessels) and for 3D valves data are scarce. There is a lack of studies evaluating ethnic differences. Data have been generally expressed as mean values normalised for gender and age instead of computing models incorporating different variables (age/gender/body sizes) to calculate z scores. To summarize results a software ( Echocardio-Normal Values ) who automatically calculate range of normality for a broad range of echocardiographic measurements according to age/gender/weight/height, has been generated. We provide an up-to-date and critical review of strengths/limitation of current adult echocardiographic nomograms. Furthermore we generated a software for automatic, easy and fast access to multiple echocardiographic normative data.

  16. Normal appendix in adults: MDCT findings about the location, thickness and the presence or absence of intraluminal gas

    International Nuclear Information System (INIS)

    Oh, Kyoung Jin; Cho, June Sik; Shin, Kyung Sook; Kim, Ha Young; Lim, Sae Kyung; Ohm, Joon Young; Yoon, Chung Dae; Shin, Byung Seok

    2006-01-01

    We wanted to examine the usefulness of multi-detector CT (MDCT) with multiplanar reformations for evaluating the location, thickness and the presence or absence of intraluminal gas in the normal appendix of adults. From December 2004 to June 2005, we evaluated normal appendices in 427 consecutive adult patients who were scanned with 16-slice MDCT. All these patients had no clinical findings of appendicitis. There were 251 men and 176 women. The age range was 19-84 years (mean age: 55 years). The contrast-enhanced MDCT scans during the portal phase were obtained with 0.75 mm detector collimation and they were reviewed with using the multiplanar reconstruction images (3 mm section thickness). The MDCT images of normal appendices on a PACS monitor were retrospectively analyzed. We analyzed the location, thickness and the presence or absence of intraluminal gas by consensus of two abdominal radiologists. The positions of normal appendices were classified as type I (postileal and medial paracecal), type II (subcecal), type III (retrocecal and retrocolic or laterocolic), type IV (preileal and medical colic) and type V (lower pelvic cavity). The five types of appendiceal locations were as follows: type I (n = 187; 44%), type II (n 78; 18%), type III (n = 92, 22%), type IV (n = 39; 9%) and type V (n = 31; 7%). The appendiceal tips in 29 cases (7%) were unusually located in the right subhepatic space, the small bowel mesentery and the right adnexa. The mean thickness of 427 appendices was 5.8 ± 0.9 mm (range: 3.8-9.2 mm). The appendiceal mean thickness was 5.9 ± 0.9 mm in men and 5.7 ± 0.9 mm in women (ρ < 0.05). 384 (90%) of 427 appendices had intraluminal gas and 43 (10%) had no intraluminal gas, and their mean thickness was 5.9 mm (range: 3.8-9.2 mm) and 5.3 mm (3.8-7.3 mm), respectively (ρ < 0.05). MDCT with multiplanar reformations was useful for evaluating the location, thickness and the presence or absence of intraluminal gas in normal appendix of adults. These

  17. Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers

    International Nuclear Information System (INIS)

    Silva, Mario; Nemec, Stefan F.; Dufresne, Valerie; Occhipinti, Mariaelena; Heidinger, Benedikt H.; Bankier, Alexander A.; Chamberlain, Ryan

    2016-01-01

    Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and Vol Exp/Insp ratio (R = -0.572; p = 0.026). PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. (orig.)

  18. Acute myocardial infarction in a young adult with myocardial bridging and normal coronary arteries

    Directory of Open Access Journals (Sweden)

    Moris Chansky

    2004-09-01

    Full Text Available The authors present a case of a young adult with acute myocardialinfarction, attended at the Emergency Department of HospitalIsraelita Albert Einstein. Acute myocardial infarction caused bymyocardial bridge (intramyocardial tunneled coronary artery is arare clinical entity. The finding of this condition in patients withnormal arteries (non-obstructed vessels is uncommon; it isusually associated with extracardiac triggering factors. The casereported presented an acute myocardial infarction caused by amyocardial bridge as demonstrated in the clinical picture, ECGprogression, enzyme pattern (troponin, CKMB, TGO and LD andventriculography.

  19. Regulation of macrophage accessory cell activity by mycobacteria. I. Ia expression in normal and irradiated mice infected with Mycobacterium mycroti

    International Nuclear Information System (INIS)

    Kaye, P.M.; Feldmann, M.

    1986-01-01

    CBA/Ca mice were infected by either the intravenous or intraperitoneal route with Mycobacterium microti and the subsequent changes in local macrophage populations examined. Following infection, the number of macrophages increased and they showed greater expression of both MHC Class II molecules. This response was not dependent on viability of the mycobacteria, in contrast to reports with other microorganisms such as Listeria. Studies in sublethally irradiated mice indicated that persistent antigen could give rise to a response after a period of host recovery which was radiation dose dependent. This procedure also highlighted differences in the regulation of different murine class II antigens in vivo, as seen by delayed re-expression of I-E antigens. Macrophage accessory cell function, as assessed by an in vitro T cell proliferation assay, correlated with Ia expression after fixation, but not after indomethacin treatment; this highlights the diverse nature of regulatory molecules produced by these cells. (author)

  20. Raman spectroscopy analysis of differences in composition of spent culture media of in vitro cultured preimplantation embryos isolated from normal and fat mice dams.

    Science.gov (United States)

    Fabian, Dušan; Kačmarová, Martina; Kubandová, Janka; Čikoš, Štefan; Koppel, Juraj

    2016-06-01

    The aim of the present study was to compare overall patterns of metabolic activity of in vitro cultured preimplantation embryos isolated from normal and fat mice dams by means of non-invasive profiling of spent culture media using Raman spectroscopy. To produce females with two different types of body condition (normal and fat), a previously established two-generation model was used, based on overfeeding of experimental mice during prenatal and early postnatal development. Embryos were isolated from spontaneously ovulating and naturally fertilized dams at the 2-cell stage of development and cultured to the blastocyst stage in synthetic oviductal medium KSOMaa. Embryos from fat mice (displaying significantly elevated body weight and fat) showed similar developmental capabilities in vitro as embryos isolated from normal control dams (displaying physiological body weight and fat). The results show that alterations in the composition of culture medium caused by the presence of developing mouse preimplantation embryos can be detected using Raman spectroscopy. Metabolic activity of embryos was reflected in evident changes in numerous band intensities in the 1620-1690cm(-1) (amide I) region and in the 1020-1140cm(-1) region of the Raman spectrum for KSOMaa. Moreover, multivariate analysis of spectral data proved that the composition of proteins and other organic compounds in spent samples obtained after the culture of embryos isolated from fat dams was different from that in spent samples obtained after the culture of embryos from control dams. This study demonstrates that metabolic activity of cultured preimplantation embryos might depend on the body condition of their donors. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Effects on normal tissues during radiosensitization of Dalton's Lymphoma by the DNA ligand Hoechst 33342 in Balb/c mice

    International Nuclear Information System (INIS)

    Kalra, Namita; Sampath, Swapna; Adhikari, J.S.; Dwarakanath, B.S.

    2014-01-01

    Hoechst 33342 is a bisbenzimidazole derivative with AT specific minor groove DNA binding ability. Scavenging of free radicals and stabilization of macromolecular structure resulting in reduced induction of DNA damage contributes to radioprotection afforded by the ligand. Their ability to inhibit topoisomerases I and II, which play important roles in damage response pathways including DNA repair has been shown to sensitize tumor cells in vitro and in vivo. Due to its mutagenic and clastogenic potentials, damage to vital normal tissues are a matter of concern in deploying the ligand as adjuvant in radiotherapy. Therefore, we investigated the effects of the ligand in Dalton's Lymphoma (DL) bearing Balb/c mice by studying the local tumor control and animal survival, besides damage to normal tissues like bone marrow, kidney and testis. Hoechst 33342 (10 mg/kg b wt) was administered (i.v.) 1 h before focal irradiation (10 Gy) of the tumor (∼ 500 mm 3 ) grown on the hind leg of the mice. Partial response with a growth delay of 16 days (3 x initial volume) was seen following irradiation, while a complete response (cure; tumor-free survival) was observed in 88% mice following the combined treatment (Hoechst 33342+radiation); ligand alone had no significant effect. Although the ligand induced marginal degree of chromosomal aberrations in the bone marrow, it did not enhance aberrations induced by radiation further. In testes, the proportions of diploid, haploid and hypo-haploid cells as well as resting primary spermatocytes (RPS) were not significantly altered by either. In kidney, Hoechst 33342 alone or in combination with radiation did not cause significant damage to the proximal tubules and glomeruli. These observations suggest that radiosensitization of tumor by the DNA ligand Hoechst 33342 may not be associated with enhanced toxicity to bone marrow as well as proximal normal tissues. (author)

  2. Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [(18)F]-Florbetaben PET Quantitation in Alzheimer's Model Mice.

    Science.gov (United States)

    Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

    2016-01-01

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [(18)F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (R mean = 0.75) was slightly superior to the brainstem (R mean = 0.74) and the cerebellum (R mean = 0.73). Automated

  3. Neural androgen receptors affect the number of surviving new neurones in the adult dentate gyrus of male mice.

    Science.gov (United States)

    Swift-Gallant, A; Duarte-Guterman, P; Hamson, D K; Ibrahim, M; Monks, D A; Galea, L A M

    2018-04-01

    Adult hippocampal neurogenesis occurs in many mammalian species. In rats, the survival of new neurones within the hippocampus is modulated by the action of androgen via the androgen receptor (AR); however, it is not known whether this holds true in mice. Furthermore, the evidence is mixed regarding whether androgens act in neural tissue or via peripheral non-neural targets to promote new neurone survival in the hippocampus. We evaluated whether the action of androgen via AR underlies the survival of new neurones in mice, and investigated whether increasing AR selectively in neural tissue would increase new neurone survival in the hippocampus. We used the cre-loxP system to overexpress AR only in neural tissues (Nestin-AR). These males were compared with wild-type males, as well as control males with 1 of the 2 mutations required for overexpression. Mice were gonadectomised and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU) and for 37 days (following BrdU injection), mice were treated with oil or dihydrotestosterone (DHT). Using immunohistochemistry, proliferation (Ki67) and survival (BrdU) of new neurones were both evaluated in the dorsal and ventral dentate gyrus. Dihydrotestosterone treatment increased the survival of new neurones in the entire hippocampus in wild-type mice and control mice that only have 1 of 2 necessary mutations for transgenic expression. However, DHT treatment did not increase the survival of new neurones in mice that overexpressed AR in neural tissue. Cell proliferation (Ki67) and cell death (pyknotic cells) were not affected by DHT treatment in wild-type or transgenic males. These results suggest that androgens act via neural AR to affect hippocampal neurogenesis by promoting cell survival; however, the relationship between androgen dose and new neurone survival is nonlinear. © 2018 British Society for Neuroendocrinology.

  4. 57Co-bleomycin kinetics in normal and tumour-bearing mice after systemic and local administration

    International Nuclear Information System (INIS)

    Bier, J.; Benders, P.; Bitter, K.; Wenzel, M.

    1979-01-01

    In tumour-free and tumour-bearing mice the body clearance and organ distribution of 57 Co-BLM was measured at different time intervals after i.v., sc, and it. administration of the drug. No significant difference could be demonstrated in body clearance following different doses and routes of application of labelled BLM in tumour-free and tumour-bearing mice. The organ distribution studies showed higher concentrations following iv. compared to sc. or it of 57 Co-BLM: however, the activity in the ipsilateral injection sites was significantly increased after sc. and it. injection. In tumour-bearing mice the activity in the lymph nodes draining injection site was as high as that seen in the draining lymph modes following iv. injection. However, on the contralateral side, the lymph mode concentration was significantly reduced after it injection. These results indicate on the basis of organ distribution of 57 Co-BLM a rational basis for it treatment of malignant tumours. (orig.) [de

  5. Normal kidney size and renal cortical thickness of the Korean adults

    International Nuclear Information System (INIS)

    Chung, Hee Kyung; Hahm, Chang Kok

    1974-01-01

    1. The kidney size and cortical thickness were measured from intravenous pyelograms of healthy Korean adults of 250 males and 250 females. 2. The measured size and cortical thickness of kidney were following figure (mm). 3. The size of kidney of male is a little larger than female both in vertical length and horizontal width. 4. The renal cortical thickness were not significant in differences between male and female, right and left, in each poles. 5. In the study of distribution of length differences between pairs of kidneys in our series, the length of right kidney is larger in 18.6%, and width in 27.2%. 6. Comparative study is carried out measuring the length of first lumbar vertebral bodies including 4 intervertebral spaces. 7. The site of kidney is larger in the group of greater length of vertebral height. 8. The renal cortical thickness have no significant differences in according to the differences of length of vertebral height, in each poles. 9. Comparing with the western authors, the kidney size of the Korean adult is not smaller than western

  6. Gray matter network disruptions and amyloid beta in cognitively normal adults.

    Science.gov (United States)

    Tijms, Betty M; Kate, Mara Ten; Wink, Alle Meije; Visser, Pieter Jelle; Ecay, Mirian; Clerigue, Montserrat; Estanga, Ainara; Garcia Sebastian, Maite; Izagirre, Andrea; Villanua, Jorge; Martinez Lage, Pablo; van der Flier, Wiesje M; Scheltens, Philip; Sanz Arigita, Ernesto; Barkhof, Frederik

    2016-01-01

    Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aβ42 level and for 90 anatomical areas. Associations between continuous Aβ42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aβ42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p levels can be related to gray matter networks disruptions. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Measurements of the normal ventricles and cerebral cisterns of 100 adults with computed tomography

    International Nuclear Information System (INIS)

    Miyamoto, Kyoji

    1979-01-01

    The computed tomographical examinations of 100 patients with normal neurological findings including some volunteers between the ages of 20 to 68 years were evaluated. Measurements of various parts of the ventricular system on the polaroid pictures showed an increase with age and sexual difference. The lateral ventricles were found to be larger in the male in the female. Inverse cella media index, bifrontal cerebroventricular index and bicaudate cerebroventricular index were found to be reliable indicators of ventricular size, when the age and the sex is known. (author)

  8. The adult spinal cord injury without radiographic abnormalities syndrome: magnetic resonance imaging and clinical findings in adults with spinal cord injuries having normal radiographs and computed tomography studies.

    Science.gov (United States)

    Kasimatis, Georgios B; Panagiotopoulos, Elias; Megas, Panagiotis; Matzaroglou, Charalambos; Gliatis, John; Tyllianakis, Minos; Lambiris, Elias

    2008-07-01

    Spinal cord injury without radiographic abnormalities (SCIWORA) is thought to represent mostly a pediatric entity and its incidence in adults is rather underreported. Some authors have also proposed the term spinal cord injury without radiologic evidence of trauma, as more precisely describing the condition of adult SCIWORA in the setting of cervical spondylosis. The purpose of the present study was to evaluate adult patients with cervical spine injuries and radiological-clinical examination discrepancy, and to discuss their characteristics and current management. During a 16-year period, 166 patients with a cervical spine injury were admitted in our institution (Level I trauma center). Upper cervical spine injuries (occiput to C2, 54 patients) were treated mainly by a Halo vest, whereas lower cervical spine injuries (C3-T1, 112 patients) were treated surgically either with an anterior, or posterior procedure, or both. Seven of these 166 patients (4.2%) had a radiologic-clinical mismatch, i.e., they presented with frank spinal cord injury with no signs of trauma, and were included in the study. Magnetic resonance imaging was available for 6 of 7 patients, showing intramedullary signal changes in 5 of 6 patients with varying degrees of compression from the disc and/or the ligamentum flavum, whereas the remaining patient had only traumatic herniation of the intervertebral disc and ligamentum flavum bulging. Follow-up period was 6.4 years on average (1-10 years). This retrospective chart review provides information on adult patients with cervical spinal cord injuries whose radiographs and computed tomography studies were normal. It furthers reinforces the pathologic background of SCIWORA in an adult population, when evaluated by magnetic resonance imaging. Particularly for patients with cervical spondylosis, special attention should be paid with regard to vascular compromise by predisposing factors such as smoking or vascular disease, since they probably contribute in

  9. Effects of Indoor Horseback Riding and Virtual Reality Exercises on the Dynamic Balance Ability of Normal Healthy Adults

    Science.gov (United States)

    Lee, Daehee; Lee, Sangyong; Park, Jungseo

    2014-01-01

    [Purpose] The objective of this study was to determine the effect of indoor horseback riding and virtual reality exercises on the dynamic balance ability of normal adults. [Subjects] This study enrolled 24 normal adults and divided them into two groups: an indoor horseback riding exercise group (IHREG, n = 12) and a virtual reality exercise group (VREG, n = 12). [Methods] IHREG exercised on indoor horseback riding equipment and VREG exercised using the Nintendo Wii Fit three times a week for six weeks. The Biodex Balance System was used to analyze dynamic balance as measured by the overall stability index (OSI), anteroposterior stability index (APSI), and mediolateral stability index (MLSI). [Results] In the within-group comparison, IHREG and VERG both showed significant decreases in the dynamic balance indexes of OSI, APSI, and MLSI after the intervention, but no significant difference was found between the groups. [Conclusion] Both indoor horseback riding and virtual reality exercises were effective at improving the subjects’ dynamic balance ability as measured by OSI, APSI, and MLSI, and can be used as additional exercises for patients with conditions affecting postural control. PMID:25540494

  10. Association between childhood maltreatment and normal adult personality traits: exploration of an understudied field.

    Science.gov (United States)

    Hengartner, Michael P; Cohen, Lisa J; Rodgers, Stephanie; Müller, Mario; Rössler, Wulf; Ajdacic-Gross, Vladeta

    2015-02-01

    We assessed normal personality traits and childhood trauma in approximately 1170 subjects from a general population-based community sample. In bivariate analyses emotional abuse was most pervasively related to personality, showing significant detrimental associations with neuroticism, extraversion, openness, conscientiousness, and agreeableness. Neuroticism was significantly related to emotional abuse and neglect, physical abuse and neglect, and sexual abuse. Emotional abuse was related to neuroticism in men more profoundly than in women (β = 0.095). Adjusting for the covariance between childhood maltreatment variables, neuroticism was mainly related to emotional abuse (β = 0.193), extraversion to emotional neglect (β = -0.259), openness to emotional abuse (β = 0.175), conscientiousness to emotional abuse (β = -0.110), and agreeableness to emotional neglect (β = -0.153). The proportion of variance explained was highest in neuroticism (5.6%) and lowest in openness (1.9%) and conscientiousness (1.8%). These findings help to understand the complex association between childhood maltreatment and both normal and pathological personality.

  11. Salivary habituation to food stimuli in successful weight loss maintainers, obese and normal-weight adults

    Science.gov (United States)

    Bond, DS; Raynor, HA; McCaffery, JM; Wing, RR

    2017-01-01

    Objective Research shows that slower habituation of salivary responses to food stimuli is related to greater energy intake and that obese (Ob) individuals habituate slower than those of normal weight (NW). No study has examined habituation rates in weight loss maintainers (WLMs) who have reduced from obese to normal weight, relative to those who are Ob or NW. Design Salivation to two baseline water trials and 10 lemon-flavored lollipop trials were studied in 14 WLMs, 15 Ob and 18 NW individuals comparable in age, gender and ethnicity. Linear mixed models were used to compare WLMs with Ob and NW groups. Results Salivation in the WLM and NW groups decreased significantly (for both P <0.005) across trials, indicative of habituation. Salivary responses in the Ob group did not habituate (P=0.46). When compared with Ob group, WLMs showed a quicker reduction in salivation (P<0.05). WLM and NW groups did not differ in habituation rate (P=0.49). Conclusions WLMs have habituation rates that are comparable to NW individuals without previous history of obesity, and show quicker habituation than those who are currently obese. These results suggest that physiological responses to food may ‘normalize’ with successful weight loss maintenance. PMID:20010900

  12. Uniparental isodisomy of chromosome 14 in two cases: An abnormal child and a normal adult

    Energy Technology Data Exchange (ETDEWEB)

    Papenhausen, P.R.; Mueller, O.T.; Sutcliffe, M.; Diamond, T.M.; Kousseff, B.G. [Univ. of South Florida College of Medicine, Tampa, FL (United States); Johnson, V.P. [Univ. of South Dakota, Sioux Falls, SD (United States)

    1995-11-20

    Uniparental disomy (UPD) of a number of different chromosomes has been found in association with abnormal phenotypes. A growing body of evidence for an imprinting effect involving chromosome 14 has been accumulating. We report on a case of paternal UPD of chromosome 14 studied in late gestation due to polyhydramnios and a ventral wall hernia. A prenatal karyotype documented a balanced Robertsonian 14:14 translocation. The baby was born prematurely with hairy forehead, retrognathia, mild puckering of the lips and finger contractures. Hypotonia has persisted since birth and at age one year, a tracheostomy for laryngomalacia and gastrostomy for feeding remain necessary. Absence of maternal VNTR polymorphisms and homozygosity of paternal polymorphisms using chromosome 14 specific probes at D14S22 and D14S13 loci indicated paternal uniparental isodisomy (pUPID). Parental chromosomes were normal. We also report on a case of maternal LTPD in a normal patient with a balanced Robertsonian 14:14 translocation and a history of multiple miscarriages. Five previous reports of chromosome 14 UPD suggest that an adverse developmental effect may be more severe whenever the UPD is paternal in origin. This is the second reported patient with paternal UPD and the fifth reported with maternal UPD, and only few phenotypic similarities are apparent. Examination of these chromosome 14 UPD cases of maternal and paternal origin suggests that there are syndromic imprinting effects. 30 refs., 3 figs.

  13. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

    Directory of Open Access Journals (Sweden)

    Susana eMingote

    2016-01-01

    Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

  14. Cognitive function predicts listening effort performance during complex tasks in normally aging adults

    Directory of Open Access Journals (Sweden)

    Jennine Harvey

    2017-01-01

    Full Text Available Purpose: This study examines whether cognitive function, as measured by the subtests of the Woodcock–Johnson III (WCJ-III assessment, predicts listening-effort performance during dual tasks across the adults of varying ages. Materials and Methods: Participants were divided into two groups. Group 1 consisted of 14 listeners (number of females = 11 who were 41–61 years old [mean = 53.18; standard deviation (SD = 5.97]. Group 2 consisted of 15 listeners (number of females = 9 who were 63–81 years old (mean = 72.07; SD = 5.11. Participants were administered the WCJ-III Memory for Words, Auditory Working Memory, Visual Matching, and Decision Speed subtests. All participants were tested in each of the following three dual-task experimental conditions, which were varying in complexity: (1 auditory word recognition + visual processing, (2 auditory working memory (word + visual processing, and (3 auditory working memory (sentence + visual processing in noise. Results: A repeated measures analysis of variance revealed that task complexity significantly affected the performance measures of auditory accuracy, visual accuracy, and processing speed. Linear regression revealed that the cognitive subtests of the WCJ-III test significantly predicted performance across dependent variable measures. Conclusion: Listening effort is significantly affected by task complexity, regardless of age. Performance on the WCJ-III test may predict listening effort in adults and may assist speech-language pathologist (SLPs to understand challenges faced by participants when subjected to noise.

  15. In vitro tests for aerosol deposition II: IVIVCs for different dry powder inhalers in normal adults.

    Science.gov (United States)

    Delvadia, Renishkumar; Hindle, Michael; Longest, P Worth; Byron, Peter R

    2013-06-01

    A new in vitro test method for dry powder inhalers (DPIs) was recently found to be predictive of the published in vivo results for Budelin Novolizer. The present study was intended to assess the method's robustness by evaluating correlations between average drug deposition in vitro and in vivo from five different DPIs. In vitro drug deposition from five marketed DPIs was assessed in a realistic physical airway model of a "medium" sized adult in an experimental setup that allowed deposition to be characterized regionally for carefully selected simulated air flow rate versus time profiles. The DPIs studied were Spiriva(®) HandiHaler(®), Relenza(®) Diskhaler(®), Salbutamol Easyhaler(®), Pulmicort(®) Turbuhaler(®), and Foradil(®) Aerolizer(®). In vitro regional deposition results were compared with those reported in the literature in order to create in vitro-in vivo correlations (IVIVCs) for each inhaler. Mean percent total lung deposition (TLD ± SD) in vitro for Spiriva HandiHaler, Relenza Diskhaler, Salbutamol Easyhaler, Pulmicort Turbuhaler, and Foradil Aerolizer were 17.3 ± 1.2, 22.6 ± 1.1, 29.0 ± 1.1, 28.0 ± 3.0, and 21.7 ± 1.2, respectively. These results showed excellent agreement with reported in vivo values, with absolute prediction errors in TLD of ≤ 2% for all DPIs except Relenza Diskhaler. Similarly, in vitro mouth-throat and device deposition results were stoichiometrically comparable to those reported in vivo for all DPIs except Relenza Diskhaler and Turbuhaler. Inspection of the scintigraphy studies for Relenza Diskhaler and Turbohaler revealed possible problems with powder labeling and result interpretation in their in vivo clinical assessments. A characteristic physical airway model representing a medium-sized adult, when coupled to carefully chosen characteristic inhalation maneuvers used in the clinic, produced results that correlated with regional drug deposition estimates from scintigraphy across a group of different DPIs.

  16. Radioprotective Effect and Follow-up of Melatonin as Antifertility Drug in Male Adult Mice submitted to Whole-Body γ Irradiation

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H.H.; El-Shamy, E.; Sallam, M.H.

    2006-01-01

    Melatonin is universal antioxidant for both man and animals and a substance normally produced in the human body. Radioprotective and follow up of melatonin as anti-fertility drug in whole body γ-irradiated male adult mice were studied. The alterations occurred in reproductive system and biochemical aspects in mice were evaluated. Control group, melatonin treated (received 10 mg/kg body wt for 20 successive days), following up for melatonin treated (2 recovery periods; 60 and 120 days), irradiated (2 Gy-γ-rays), pre-treated (received melatonin before irradiation) and following up for pre-treated (2 recovery periods) groups were designed. Body and testes wt, micronucleus test (MN), chromosomal aberration (CA), seminal plasma melatonin, sperm quality (count, motility and abnormal forms) and hormonal assay in serum (melatonin, testosterone, FSH and prolactin) were recorded for fertility assessment. Oxidative parameters in testis tissue (malonaldehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and nitric oxide (NO)) and biochemical assay (protein and lipid fractions in serum) were investigated for judgment melatonin radioprotective efficacy. Irradiation intensifies the processes of lipo peroxidation and oxidative modification of lipids and proteins with synchronized inhibition of the anti oxidative protection system. Melatonin administration against a background of radiation caused a distinctly expressed antioxidant effect

  17. Seeing the Talker's Face Improves Free Recall of Speech for Young Adults With Normal Hearing but Not Older Adults With Hearing Loss.

    Science.gov (United States)

    Rudner, Mary; Mishra, Sushmit; Stenfelt, Stefan; Lunner, Thomas; Rönnberg, Jerker

    2016-06-01

    Seeing the talker's face improves speech understanding in noise, possibly releasing resources for cognitive processing. We investigated whether it improves free recall of spoken two-digit numbers. Twenty younger adults with normal hearing and 24 older adults with hearing loss listened to and subsequently recalled lists of 13 two-digit numbers, with alternating male and female talkers. Lists were presented in quiet as well as in stationary and speech-like noise at a signal-to-noise ratio giving approximately 90% intelligibility. Amplification compensated for loss of audibility. Seeing the talker's face improved free recall performance for the younger but not the older group. Poorer performance in background noise was contingent on individual differences in working memory capacity. The effect of seeing the talker's face did not differ in quiet and noise. We have argued that the absence of an effect of seeing the talker's face for older adults with hearing loss may be due to modulation of audiovisual integration mechanisms caused by an interaction between task demands and participant characteristics. In particular, we suggest that executive task demands and interindividual executive skills may play a key role in determining the benefit of seeing the talker's face during a speech-based cognitive task.

  18. Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy.

    Science.gov (United States)

    Tyler, Paul M; Servos, Mariah M; de Vries, Romy C; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K

    2017-03-01

    Selinexor (KPT-330) is a first-in-class nuclear transport inhibitor currently in clinical trials as an anticancer agent. To determine how selinexor might affect antitumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T-cell development, a progressive loss of CD8 T cells, and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T-cell development and function. We determined the minimum concentration of selinexor required to block T-cell activation and showed that T-cell-inhibitory effects of selinexor occur at levels above 100 nmol/L, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 4-day drug holiday led to intratumoral IFNγ + , granzyme B + cytotoxic CD8 T cells that were comparable with vehicle-treated mice. Overall, selinexor treatment leads to transient inhibition of T-cell activation, but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T-cell functioning and development of antitumor immunity. Mol Cancer Ther; 16(3); 428-39. ©2017 AACR See related article by Farren et al., p. 417 . ©2017 American Association for Cancer Research.

  19. Clinical dosing regimen of selinexor maintains normal immune homeostasis and T cell effector function in mice: implications for combination with immunotherapy

    Science.gov (United States)

    Tyler, Paul M.; Servos, Mariah M.; de Vries, Romy C.; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K.

    2017-01-01

    Selinexor (KPT-330) is a first in class nuclear transport inhibitor currently in clinical trials as an anti-cancer agent. To determine how selinexor might impact anti-tumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T cell development, a progressive loss of CD8 T cells and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T cell development and function. We determined the minimum concentration of selinexor required to block T cell activation, and showed that T cell inhibitory effects of selinexor occur at levels above 100nM, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 5 day drug holiday led to intratumoral IFNγ+, granzyme B+ cytotoxic CD8 T cells that were comparable to vehicle treated mice. Overall, selinexor treatment leads to transient inhibition of T cell activation but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T cell functioning and development of anti-tumor immunity. PMID:28148714

  20. Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells

    DEFF Research Database (Denmark)

    Welsh, M.; Moffat, L.; Belling, Kirstine Christensen

    2012-01-01

    Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number, but res......Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number......’ subpopulation that had arrested development and only weakly expressed INSL3, luteinizing hormone receptor, and several steroidogenic enzymes. Furthermore, unlike ‘normal’ LCs in PTM-ARKOs, the ‘abnormal’ LCs did not involute as expected in response to exogenous testosterone. Differential function of these LC...... sub-populations is likely to mean that the ‘normal’ LCs work harder to compensate for the ‘abnormal’ LCs to maintain normal serum testosterone. These findings reveal new paracrine mechanisms underlying adult LC development, which can be further investigated using PTM-ARKOs....

  1. Effects of fear of falling and activity restriction on normal and dual task walking in community dwelling older adults.

    Science.gov (United States)

    Donoghue, Orna A; Cronin, Hilary; Savva, George M; O'Regan, Claire; Kenny, Rose Anne

    2013-05-01

    Fear of falling (FOF) is associated with poor physical and psychosocial health and can have debilitating consequences especially when it leads to activity restriction. This study examined whether normal and dual task gait disruptions were independently associated with FOF and activity restriction or if they were fully explained by impaired health status. Data was obtained from The Irish Longitudinal Study on Ageing (TILDA). Community dwelling adults ≥65 years, with a Mini-Mental State Examination score ≥18 and who completed a gait assessment (n=1307) were divided into three groups: no FOF, FOF but no activity restriction (FOF-NAR), FOF with activity restriction (FOF-AR). Physical, psychosocial and cognitive measures were obtained and gait characteristics were assessed using a GAITRite(®) mat during normal and dual task (cognitive) walking. After adjusting for sociodemographics, physical, mental and cognitive health, FOF was associated with reduced gait speed and stride length and increased double support phase and step width in normal and dual task conditions; these changes were most pronounced in those who restrict activities as a result of FOF. These gait changes may be associated with an increased fall risk, however some changes especially increased step width may also reflect positive, compensatory adaptations to FOF. The results also highlight the importance of treating underlying health impairments and preventing the transition from FOF to activity restriction. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. External validation of equations to estimate resting energy expenditure in 14952 adults with overweight and obesity and 1948 adults with normal weight from Italy.

    Science.gov (United States)

    Bedogni, Giorgio; Bertoli, Simona; Leone, Alessandro; De Amicis, Ramona; Lucchetti, Elisa; Agosti, Fiorenza; Marazzi, Nicoletta; Battezzati, Alberto; Sartorio, Alessandro

    2017-11-24

    We cross-validated 28 equations to estimate resting energy expenditure (REE) in a very large sample of adults with overweight or obesity. 14952 Caucasian men and women with overweight or obesity and 1498 with normal weight were studied. REE was measured using indirect calorimetry and estimated using two meta-regression equations and 26 other equations. The correct classification fraction (CCF) was defined as the fraction of subjects whose estimated REE was within 10% of measured REE. The highest CCF was 79%, 80%, 72%, 64%, and 63% in subjects with normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity, respectively. The Henry weight and height and Mifflin equations performed equally well with CCFs of 77% vs. 77% for subjects with normal weight, 80% vs. 80% for those with overweight, 72% vs. 72% for those with class 1 obesity, 64% vs. 63% for those with class 2 obesity, and 61% vs. 60% for those with class 3 obesity. The Sabounchi meta-regression equations offered an improvement over the above equations only for class 3 obesity (63%). The accuracy of REE equations decreases with increasing values of body mass index. The Henry weight & height and Mifflin equations are similarly accurate and the Sabounchi equations offer an improvement only in subjects with class 3 obesity. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. The whole-brain N-acetylaspartate correlates with education in normal adults.

    Science.gov (United States)

    Glodzik, Lidia; Wu, William E; Babb, James S; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U; Gass, Achim; Gonen, Oded

    2012-10-30

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis, 97 middle aged to elderly subjects (51-89 years old, 38% women) underwent brain magnetic resonance imaging and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount by the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject's educational attainment was the sum of his/her years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51-70 years old) participants. In this group, education explained 21% of the variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristics predisposing a subject to higher achievements later in life. We propose that late-life WBNAA may be more affected by other factors acting at midlife and later. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Study on cerebral activation areas during repetition with functional MRI in normal adults

    International Nuclear Information System (INIS)

    Koseki, Yohju

    2009-01-01

    For cerebral activation of speech areas in functional MRI (f-MRI) study, the usefulness of an optical microphone, which made it possible to perform task repetition at real time during scanning, was examined. Subjects were 25 healthy adults (mean age, 27.1±5.6 years), who consisted of 15 right-handed and 10 left-handed or ambidextrous persons. Tasks comprised repetition of monosyllables, non-words, words and sentences. The repetition tasks were covertly performed during scanning of f-MRI by using an optical microphone. In both the right-handed and non-right-handed groups, activations in the left superior temporal gyrus (sensory speech area) were most frequently observed during all of the tasks. In the right-handed group, activations in the left inferior frontal (motor speech area) and superior temporal gyri were significantly more often observed than those in the right inferior frontal and superior temporal gyri. From an assessment of the laterality index (LI), left-side dominant activation was frequently seen in most of the cerebral regions including sensory and motor speech areas, although right-side and bilateral dominant activations were observed in a few cases. In both groups, activations in regions associated with sensory speech were significantly more often seen than those in regions associated with motor speech. The present predominant activations in regions involved in sensory speech indicate that the optical microphone is useful in f-MRI studies using task repetition. (author)

  5. Correlation between the Plasma Insulin and Glucose Concentration in Normal Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jang Kyu; Sung, Ho Kyung; Kim, Jin Eui [Radiological Research Institute, Seoul (Korea, Republic of)

    1971-09-15

    The correlation between the plasma insulin, and glucose concentration was studied in healthy Korean adults consisting of 20 males and 22 females of 16 to 38 years of age. The blood samples of above subjects were obtained through cubital vein at arbitrary times during their usual working hours. Plasma insulin was assayed by means of double antibody system of radioimmunoassay technics, and blood glucose was determined by means of Van Slyke-Folch method. Results were as follows : 1. There were no differences in the blood sugar levels in relation to the plasma insulin concentration either by sex or age. 2. In the case, when the plasma insulin concentration was within 50 mmuU/ml, the correlation between the insulin, and glucose concentration existed, the ratio of which was expressed as; Plasma glucose concentration (mg/dl)=91.9 + 0.08 X Insulin concentration r=0.62. 3. Insulinogenic index was 12.4%, which was somewhat higher than other reports. 4. It is suggested that the correlation between plasma insulin and glucose concentration could be determined at arbitrary times instead of fasting times.

  6. Regional cerebral glucose metabolism is normal in young adults with Down syndrome

    International Nuclear Information System (INIS)

    Schapiro, M.B.; Grady, C.L.; Kumar, A.; Herscovitch, P.; Haxby, J.V.; Moore, A.M.; White, B.; Friedland, R.P.; Rapoport, S.I.

    1990-01-01

    Regional CMRglc (rCMRglc) values were measured with [ 18 F]2-fluoro-2-deoxy-D-glucose ( 18 FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur

  7. Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted poly