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  1. Reparative Dentinogenesis Induced by Mineral Trioxide Aggregate: A Review from the Biological and Physicochemical Points of View

    PubMed Central

    Okiji, Takashi; Yoshiba, Kunihiko

    2009-01-01

    This paper aims to review the biological and physicochemical properties of mineral trioxide aggregate (MTA) with respect to its ability to induce reparative dentinogenesis, which involves complex cellular and molecular events leading to hard-tissue repair by newly differentiated odontoblast-like cells. Compared with that of calcium hydroxide-based materials, MTA is more efficient at inducing reparative dentinogenesis in vivo. The available literature suggests that the action of MTA is attributable to the natural wound healing process of exposed pulps, although MTA can stimulate hard-tissue-forming cells to induce matrix formation and mineralization in vitro. Physicochemical analyses have revealed that MTA not only acts as a “calcium hydroxide-releasing” material, but also interacts with phosphate-containing fluids to form apatite precipitates. MTA also shows better sealing ability and structural stability, but less potent antimicrobial activity compared with that of calcium hydroxide. The clinical outcome of direct pulp capping and pulpotomy with MTA appears quite favorable, although the number of controled prospective studies is still limited. Attempts are being conducted to improve the properties of MTA by the addition of setting accelerators and the development of new calcium silicate-based materials. PMID:20339574

  2. Analysis of the Contribution of Nonresident Progenitor Cells and Hematopoietic Cells to Reparative Dentinogenesis Using Parabiosis Model in Mice

    PubMed Central

    Frozoni, Marcos; Zaia, Alexandre Augusto; Line, Sergio Roberto Peres; Mina, Mina

    2013-01-01

    Introduction The aim of this study was to analyze the contribution of nonresident progenitor/stem cells and hematopoietic cells to reparative dentinogenesis. Methods Parabiosis was established between C57BL/6-TgN(ACTbEGFP)10sb/J transgenic mice (GFP+) and C57BL/6 wild-type mice (GFP−) to ensure blood cross-circulation between animals. Reparative dentinogenesis was stimulated by pulp exposures and capping on the first maxillary molar in the GFP− mice. Histologic sections of injured molars from GFP− mice were analyzed by epifluorescence microscopy to examine the contributions of GFP+ cells (nonresident progenitor cells and hematopoietic cells originating from GFP+ mice) to reparative dentinogenesis. Results GFP+ cells were detected in close association with reparative dentin formed at the site of pulp exposure in the maxillary first molars of the GFP− mice. Conclusions The present study suggests the participation of the nonresident progenitor cells and hematopoietic cells in reparative dentinogenesis. PMID:22892738

  3. Effect of ascorbic acid deficiency on primary and reparative dentinogenesis in non-ascorbate-synthesizing ODS rats.

    PubMed

    Ogawara, M; Aoki, K; Okiji, T; Suda, H

    1997-01-01

    Ascorbic acid is essential to the biosynthesis of collagen, the major organic matrix component of dentine. The ODS rat is a mutant strain of Wistar rat characterized by hereditary lack of L-gulono-gamma-lactone oxidase and thus is unable to synthesize ascorbic acid. ODS rats were given an ascorbic acid-free diet to investigate how ascorbic acid deficiency affects dentine formation in vivo. Histomorphometric analysis on their growing molars and incisors showed a significant reduction in both size and mineral apposition rate of dentine, as revealed by contact microradiography and fluorescent time-marking, respectively. A similar reduction in bone formation was simultaneously demonstrated in the mandible, confirming the previously reported osteopathic effects of ascorbic acid deficiency. When pulp inflammation was induced in lower first molars by making unsealed pulp exposures, specimens from control animals showed continuous deposition of an osteodentine-like tissue in the radicular pulp chamber; this type of mineralized tissue formation was greatly reduced in ascorbic acid-deprived animals. These results indicate that ascorbic acid deficiency hampers dentine formation under both physiological and pathological conditions of the dentine/pulp complex. ODS rats could be useful in investigating in vivo effects of ascorbic acid deficiency on the formation of dentine and other dental mineralized tissues. PMID:9447259

  4. Reparative Curriculum

    ERIC Educational Resources Information Center

    Tarc, Aparna Mishra

    2011-01-01

    Supporting learners' public engagement with traumatic histories of mass human violence can develop and sustain reparative relations across and between strained social collectives. In this article I theorize the intrapersonal and inter-political dynamics of psychical and social reparation through a classroom case of reparative learning. I analyze…

  5. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling.

    PubMed

    Lovelace, Erica S; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard P; Zink, Erika M; Kim, Young-Mo; Kyle, Jennifer E; Webb-Robertson, Bobbie-Jo M; Waters, Katrina M; Metz, Thomas O; Farin, Federico; Oberlies, Nicholas H; Polyak, Stephen J

    2015-08-28

    Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed silymarin suppression of glycolytic, tricarboxylic acid (TCA) cycle, and amino acid metabolism. Anti-inflammatory effects arose with prolonged (i.e., 24 h) silymarin exposure, with suppression of multiple pro-inflammatory mRNAs and signaling pathways including nuclear factor kappa B (NF-κB) and forkhead box O (FOXO). Studies with murine knock out cells revealed that silymarin inhibition of both mTOR and NF-κB was partially AMPK dependent, whereas silymarin inhibition of mTOR required DDIT4. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Thus, natural products activate stress and repair responses that culminate in an anti-inflammatory cellular phenotype. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation. PMID:26186142

  6. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    SciTech Connect

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

    2015-08-28

    Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

  7. Kinetics of reparative DNA replication induced in CBA and C57BL/6 mouse spleen cells by urethane and influenza virus

    SciTech Connect

    Frolov, A.F.; Antonenko, S.V.; Chekova, V.V.; Shcherbinskaya, A.M.; Nadgornaya, N.I.; Zasukhina, G.D.

    1986-09-01

    The authors investigated the reparative replication of DNA, induced by urethane and influenza virus in C57BL/6 and CBA mice which have marked differences in tumor formation. Reparative DNA replication, induced by urethane and influenza virus was investigated by a liquid scintillation method based on measuring incorporation of /sup 3/H-thymidine into the total mass of mouse spleen cells, when replicative DNA synthesis was inhibited by hydroxyurea. The intensity of reparative DNA replication was judged from the value of the stimulation index which is the ratio of the radioactivity in the spleen cells of the experimental animals to the corresponding parameters in cells of intact animals. The phenomenon of the stimulating and inhibitory effects of influenza virus on reparative DNA replication in cells depending on their genotype and sensitivity to virus is established.

  8. Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2.

    PubMed

    Sagomonyants, K; Kalajzic, I; Maye, P; Mina, M

    2015-11-01

    Members of the fibroblast growth factor (FGF) family play essential and important roles in primary and reparative dentinogenesis. Although there appears to be a general agreement on the effects of FGF signaling on the proliferation of pulp cells, there are conflicting results regarding its effects on odontoblast differentiation. We recently examined the effects of continuous exposure of dental pulp cells to FGF2 and showed that the effects of FGF2 on differentiation of progenitor cells into odontoblasts were stage specific and dependent on the stage of cell maturity. The purpose of this study was to gain further insight into cellular and molecular mechanisms regulating the stimulatory effects of FGF2 on odontoblast differentiation. To do so, we examined the effects of early and limited exposure of pulp cells from a series of green fluorescent protein (GFP) reporter transgenic mice that display stage-specific activation of transgenes during odontoblast differentiation to FGF2. Our results showed that early and limited exposure of pulp cells to FGF2 did not have significant effects on the extent of mineralization but induced significant increases in the expression of Dmp1 and Dspp and the number of DMP1-GFP(+) and DSPP-Cerulean(+) odontoblasts. Our results also showed that the stimulatory effects of FGF2 on odontoblast differentiation were mediated through FGFR/MEK/Erk1/2 signaling, increases in Bmp2, and activation of the BMP/BMPR signaling pathway. These observations show that early and limited exposure of pulp cells to FGF2 alone promotes odontoblast differentiation and provides critical insight for applications of FGF2 in dentin regeneration. PMID:26276371

  9. Reading the Reparations Debate

    ERIC Educational Resources Information Center

    Bacon, Jacqueline

    2003-01-01

    This essay examines the ways in which the rhetoric of the reparations debate elucidates the varying accounts of history favored by Americans of different backgrounds, the political and ideological foundations underlying different perspectives on the nature and uses of history, and the norms guiding public deliberation in the contemporary U.S.…

  10. In Vitro Reparative Dentin: a Biochemical and Morphological Study

    PubMed Central

    Teti, G.; Salvatore, V.; Ruggeri, A.; Manzoli, L.; Gesi, M.; Orsini, G.; Falconi, M.

    2013-01-01

    In this study, starting from human dental pulp cells cultured in vitro, we simulated reparative dentinogenesis using a medium supplemented with different odontogenic inductors. The differentiation of dental pulp cells in odontoblast-like cells was evaluated by means of staining, and ultramorphological, biochemical and biomolecular methods. Alizarin red staining showed mineral deposition while transmission electron microscopy revealed a synthesis of extracellular matrix fibers during the differentiation process. Biochemical assays demonstrated that the differentiated phenotype expressed odontoblast markers, such as Dentin Matrix Protein 1 (DMP1) and Dentin Sialoprotein (DSP), as well as type I collagen. Quantitative data regarding the mRNA expression of DMP1, DSP and type I collagen were obtained by Real Time PCR. Immunofluorescence data demonstrated the various localizations of DSP and DMP1 during odontoblast differentiation. Based on our results, we obtained odontoblast-like cells which simulated the reparative dentin processes in order to better investigate the mechanism of odontoblast differentiation, and dentin extracellular matrix deposition and mineralization. PMID:24085272

  11. The neurotrophin receptor p75NTR triggers endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impairment of reparative neovascularization

    PubMed Central

    Caporali, Andrea; Pani, Elisabetta; Horrevoets, Anton J. G.; Kraenkel, Nicolle; Oikawa, Atsuhiko; Sala-Newby, Graciela B.; Meloni, Marco; Cristofaro, Brunella; Graiani, Gallia; Leroyer, Aurelie; Boulanger, Chantal; Herman, Andrew; Spinetti, Gaia; Yoon, Sung Ok; Madeddu, Paolo; Emanueli, Costanza

    2009-01-01

    Diabetes compromises endothelial function and inhibits reparative neovascularization. The neurotrophin receptor p75NTR is scarcely present in healthy endothelial cells (EC), but diabetes induces p75NTR in capillary EC of ischemic limb muscles. Here, we show that forced p75NTR expression impairs survival, proliferation, migration, and adhesion capacities of EC and endothelial progenitor cells (EPC) and inhibits EC tube formation. In EC, p75NTR depresses the VEGF-A/Akt/eNOS/NO pathway and reduces VEGF-A, ITGB1, BIRC5, PTTG1, and VEZF1 mRNA levels. Moreover, both diabetes and p75NTR transfer down-regulate VEGF-A, ITGB1, and VEZF1 in adductor muscles. Forced p75NTR expression by ischemic limb muscles impairs post-ischemic neovascularization and blood flow recovery in normoglycemic mice. Conversely, p75NTR inhibition in diabetic muscles restores proper post-ischemic neovascularization and prevents apoptosis of muscular capillary EC and bone marrow-resident Sca-1+Lin- progenitor cells. Collectively, our data identify the anti-angiogenic action of p75NTR and suggests the therapeutic potential of p75NTR inhibition to combat diabetes-induced microvascular liabilities. PMID:18566344

  12. Tumor necrosis factor alpha is reparative via TNFR2 [corrected] in the hippocampus and via TNFR1 [corrected] in the striatum after virus-induced encephalitis.

    PubMed

    Rodriguez, Moses; Zoecklein, Laurie; Papke, Louisa; Gamez, Jeff; Denic, Aleksandar; Macura, Slobodan; Howe, Charles

    2009-01-01

    Differentiating between injurious and reparative factors facilitates appropriate therapeutic intervention. We evaluated the role of tumor necrosis factor alpha (TNFalpha) in parenchymal brain pathology resolution following virus-induced encephalitis from a picornavirus, Theiler's murine encephalomyelitis virus (TMEV). We infected the following animals with TMEV for 7 to 270 days: B6/129 TNF(-/-) mice (without TNFalpha expression), B6/129 TNFR1(-/-) mice (without TNFalpha receptor 1 expression), and B6/129 TNFR2(-/-) mice (without TNFalpha receptor 2 expression). Normal TNFalpha-expressing controls were TMEV-infected B6, 129/J, B6/129F1 and B6/129F2 mice. Whereas all strains developed inflammation and neuronal injury in the hippocampus and striatum 7 to 21 days postinfection (dpi), the control mice resolved the pathology by 45 to 90 dpi. However, parenchymal hippocampal and striatal injury persisted in B6/129 TNF(-/-) mice following infection. Treating virus-infected mice with active recombinant mouse TNFalpha resulted in less hippocampal and striatal pathology, whereas TNFalpha-neutralizing treatment worsened pathology. T1 "black holes" appeared on MRI during early infection in the hippocampus and striatum in all mice but persisted only in TNF(-/-) mice. TNFR2 [corrected] mediated hippocampal pathology resolution whereas TNFR1 [corrected] mediated striatal healing. These findings indicate the role of TNFalpha in resolution of sublethal hippocampal and striatal injury. PMID:18422761

  13. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice

    PubMed Central

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P. R.

    2016-01-01

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin−Sca-1+cKit+ (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10–12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P < 0.01, n = 8). In db/db mice, mobilization by G-CSF or AMD3100 was either increased or unaffected (P < 0.05, n = 6 to 8). Proliferation, migration, and ischemia-induced mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy. PMID:27188595

  14. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.

    PubMed

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P R

    2016-01-01

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P < 0.01, n = 8). In db/db mice, mobilization by G-CSF or AMD3100 was either increased or unaffected (P < 0.05, n = 6 to 8). Proliferation, migration, and ischemia-induced mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy. PMID:27188595

  15. Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification.

    PubMed

    de La Dure-Molla, Muriel; Philippe Fournier, Benjamin; Berdal, Ariane

    2015-04-01

    Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several post-translational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners. PMID:25118030

  16. Race, Reparations, and Free Expression.

    ERIC Educational Resources Information Center

    Brownstein, Andrew

    2001-01-01

    Describes how a controversial newspaper ad opposing slavery reparations and the subsequent trashing of the student daily have set off a debate at Brown University about the competing values of sensitivity and free expression. (EV)

  17. A Case of Dentinogenesis Imperfecta Treated with Submerged Root Technique

    PubMed Central

    Chandar, Bhanu; Srilakshmi, J.; Khaitan, Tanya; Babu, B. Balaji

    2015-01-01

    Dentinogenesis imperfecta (DGI), an autosomal dominant trait, is one of the most common hereditary disorders affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. Here, we present a case report of a 13-year-old female patient affected with DGI who had undergone prosthetic rehabilitation with submerged root technique. PMID:26501025

  18. Spartathlon, a 246 kilometer foot race: effects of acute inflammation induced by prolonged exercise on circulating progenitor reparative cells.

    PubMed

    Goussetis, Evgenios; Spiropoulos, Antonia; Tsironi, Maria; Skenderi, Katerina; Margeli, Alexandra; Graphakos, Stelios; Baltopoulos, Panayiotis; Papassotiriou, Ioannis

    2009-01-01

    Endothelial progenitor cells (EPCs) and the recently described circulating fibrocytes (CFs) are strongly associated with tissue repair. We investigated the kinetics of both "repair" progenitor cells in healthy athletes who participated in the "Spartahlon" ultradistance foot race (246 km continuous running exercise), which provides a unique model of inducing dramatic systemic inflammatory changes. Peripheral blood mononuclear cells (PBMCs) were isolated from 10 volunteer athletes, who completed successfully the race, before, at the end, and at 48 h post-race. EPCs and CFs were detected as endothelial colony-forming units (CFU-ECs) and as the number of adherent with a spindle-shaped morphology Collagen I(+) cells detected after 6-day culture of PBMCs, respectively. The marked increase of plasma levels of CRP, IL-6, SAA, MCP-1, IL-8, sVCAM-1, sICAM-1, thrombomodulin (sTM) and NT-pro-BNP at the end of race established acute inflammation and tissue injury. EPCs increased by nearly eleven-fold in peripheral blood at the end of the race from 44.5+/-2.5/ml to 494.6+/-27.9/ml and remained increased 428.5+/-31.5/ml at 48 h post-race (p<0.0001). The number of the fibrocytes cultured from PBMCs obtained before, at the end, and 48 h post-race did not reveal any significant difference. These findings indicate that bone marrow responses to acute inflammatory damage, induced by exhausting exercise, with a rapid release of EPCs but not CFs into circulation. Given the ability of EPCs to promote angiogenesis and vascular regeneration, we may suggest that this kind of cell mobilization may serve as a physiologic repair mechanism in acute inflammatory tissue injury. PMID:19233694

  19. The Reparative Motive in Surrogate Mothers.

    ERIC Educational Resources Information Center

    Kanefield, Linda

    1999-01-01

    Explores the motivations of surrogate mothers, focusing on underlying reparative motive--to compensate for or repair an earlier loss or sense of damage. Provides an overview of the typical surrogate's characteristics and personality, discusses the theoretical underpinnings of the reparative motive, and considers the tension between reparation and…

  20. Rationale of the REPARATOR study

    PubMed Central

    Eefting, F.D.; Cramer, M.J.; Stella, P.R.S.; Rensing, B.J.; Doevendans, P.A.

    2006-01-01

    The REPARATOR study is a multicentre clinical trial in which the effect of 80 mg atorvastatin on microvascular (re)perfusion and late ventricular remodelling, and infarct size in patients presenting with an acute ST-elevation myocardial infarction is studied. Primary endpoint is end-systolic volume index at three months measured by quantitative cine magnetic resonance imaging (MRI). Secondary endpoints are cardiac MI (CMR) measurements of global and regional left ventricular function, MRI measurements of infarct size on admission, one week and three months as well as changes between MRI investigations, biochemical markers of infarct size, blush grade, and TIMI frame count. A total of 50 patients will be enrolled. Including three months follow-up, the study will last for six months. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:25696602

  1. Pulp stem cells: implication in reparative dentin formation.

    PubMed

    Dimitrova-Nakov, Sasha; Baudry, Anne; Harichane, Yassine; Kellermann, Odile; Goldberg, Michel

    2014-04-01

    Many dental pulp stem cells are neural crest derivatives essential for lifelong maintenance of tooth functions and homeostasis as well as tooth repair. These cells may be directly implicated in the healing process or indirectly involved in cell-to-cell diffusion of paracrine messages to resident (pulpoblasts) or nonresident cells (migrating mesenchymal cells). The identity of the pulp progenitors and the mechanisms sustaining their regenerative capacity remain largely unknown. Taking advantage of the A4 cell line, a multipotent stem cell derived from the molar pulp of mouse embryo, we investigated the capacity of these pulp-derived precursors to induce in vivo the formation of a reparative dentin-like structure upon implantation within the pulp of a rodent incisor or a first maxillary molar after surgical exposure. One month after the pulp injury alone, a nonmineralized fibrous matrix filled the mesial part of the coronal pulp chamber. Upon A4 cell implantation, a mineralized osteodentin was formed in the implantation site without affecting the structure and vitality of the residual pulp in the central and distal parts of the pulp chamber. These results show that dental pulp stem cells can induce the formation of reparative dentin and therefore constitute a useful tool for pulp therapies. Finally, reparative dentin was also built up when A4 progenitors were performed by alginate beads, suggesting that alginate is a suitable carrier for cell implantation in teeth. PMID:24698687

  2. Osteopontin Is Essential for Type I Collagen Secretion in Reparative Dentin.

    PubMed

    Saito, K; Nakatomi, M; Ida-Yonemochi, H; Ohshima, H

    2016-08-01

    Osteopontin (OPN) is a highly phosphorylated glycoprotein that is a prominent component of the mineralized extracellular matrix of bone. The secretion of OPN by immunocompetent cells plays a role in the differentiation of odontoblast-like cells during pulpal healing following tooth transplantation. This study aimed to clarify the role of OPN during reparative dentinogenesis. A groove-shaped cavity was prepared on the mesial surface of the upper first molars of wild-type (WT) and Opn knockout (KO) mice, and the samples were collected at intervals of 1 to 14 d. The demineralized sections were processed for immunohistochemistry for Ki67, nestin, OPN, dentin sialoprotein (DSP), integrin αvβ3, and type I collagen; in situ hybridization for Opn, col1a1, and dentin sialophosphoprotein (Dspp); and apoptosis assay. For the loss and gain of function experiments, an in vitro culture assay for evaluating dentin-pulp complex regeneration was performed. On day 1 in WT mice, odontoblasts beneath the affected dentin lost nestin immunoreactivity. On day 3, the expression of Opn was recognized at the mesial dental pulp, and OPN was deposited along the predentin-dentin border. Nestin-positive newly differentiated odontoblast-like cells expressed both Dspp and col1a1 and showed positive immunoreactivity for integrin αvβ3, DSP, and type I collagen. Until day 14, reparative dentin formation continued next to the preexisting dentin at the mesial coronal pulp. In contrast, there was no reparative dentin in the Opn KO mice where nestin- and DSP-positive newly differentiated odontoblast-like cells lacked immunoreaction for type I collagen. The in vitro organ culture demonstrated that the administration of recombinant OPN rescued the type I collagen secretion by odontoblast-like cells in the Opn KO mice. The results suggested that the deposition of OPN at the calcification front is essential for the type I collagen secretion by newly differentiated odontoblast-like cells to form

  3. MicroRNA 665 Regulates Dentinogenesis through MicroRNA-Mediated Silencing and Epigenetic Mechanisms.

    PubMed

    Heair, Hannah M; Kemper, Austin G; Roy, Bhaskar; Lopes, Helena B; Rashid, Harunur; Clarke, John C; Afreen, Lubana K; Ferraz, Emanuela P; Kim, Eddy; Javed, Amjad; Beloti, Marcio M; MacDougall, Mary; Hassan, Mohammad Q

    2015-09-01

    Studies of proteins involved in microRNA (miRNA) processing, maturation, and silencing have indicated the importance of miRNAs in skeletogenesis, but the specific miRNAs involved in this process are incompletely defined. Here, we identified miRNA 665 (miR-665) as a potential repressor of odontoblast maturation. Studies with cultured cell lines and primary embryonic cells showed that miR-665 represses the expression of early and late odontoblast marker genes and stage-specific proteases involved in dentin maturation. Notably, miR-665 directly targeted Dlx3 mRNA and decreased Dlx3 expression. Furthermore, RNA-induced silencing complex (RISC) immunoprecipitation and biotin-labeled miR-665 pulldown studies identified Kat6a as another potential target of miR-665. KAT6A interacted physically and functionally with RUNX2, activating tissue-specific promoter activity and prompting odontoblast differentiation. Overexpression of miR-665 reduced the recruitment of KAT6A to Dspp and Dmp1 promoters and prevented KAT6A-induced chromatin remodeling, repressing gene transcription. Taken together, our results provide novel molecular evidence that miR-665 functions in an miRNA-epigenetic regulatory network to control dentinogenesis. PMID:26124283

  4. MicroRNA 665 Regulates Dentinogenesis through MicroRNA-Mediated Silencing and Epigenetic Mechanisms

    PubMed Central

    Heair, Hannah M.; Kemper, Austin G.; Roy, Bhaskar; Lopes, Helena B.; Rashid, Harunur; Clarke, John C.; Afreen, Lubana K.; Ferraz, Emanuela P.; Kim, Eddy; Javed, Amjad; Beloti, Marcio M.; MacDougall, Mary

    2015-01-01

    Studies of proteins involved in microRNA (miRNA) processing, maturation, and silencing have indicated the importance of miRNAs in skeletogenesis, but the specific miRNAs involved in this process are incompletely defined. Here, we identified miRNA 665 (miR-665) as a potential repressor of odontoblast maturation. Studies with cultured cell lines and primary embryonic cells showed that miR-665 represses the expression of early and late odontoblast marker genes and stage-specific proteases involved in dentin maturation. Notably, miR-665 directly targeted Dlx3 mRNA and decreased Dlx3 expression. Furthermore, RNA-induced silencing complex (RISC) immunoprecipitation and biotin-labeled miR-665 pulldown studies identified Kat6a as another potential target of miR-665. KAT6A interacted physically and functionally with RUNX2, activating tissue-specific promoter activity and prompting odontoblast differentiation. Overexpression of miR-665 reduced the recruitment of KAT6A to Dspp and Dmp1 promoters and prevented KAT6A-induced chromatin remodeling, repressing gene transcription. Taken together, our results provide novel molecular evidence that miR-665 functions in an miRNA-epigenetic regulatory network to control dentinogenesis. PMID:26124283

  5. Evidence of two types of odontoblasts during dentinogenesis in elasmobranchs.

    PubMed

    Sasagawa, I

    1995-01-01

    The fine structure of the odontoblasts in the sting rays, Dasyatis akajei, Dasyatidae, and Urolophus aurantiacus, Urolophidae, was examined using light and transmission electron microscopy. In the dentinogenesis stage, the odontoblasts have been classified into two types, that is, dark cells and light cells, based on differences in their fine structure. Many dark odontoblasts found along the predentine displayed well-developed organelles with secretory activity around the nuclei. They contained large amounts of expanded rER, widely distributed Golgi apparatus and secretory granules. In contrast, light odontoblasts showed a relatively clear cytoplasm and extended long processes which passed through the predentine and penetrated into the dentine. They contained large numbers of microtubules in the processes and many mitochondria around the nuclei. It is suggested that the light odontoblasts play an important part in material transport to the dentine and/or act as a sensory organ of the tooth. The dark odontoblasts seem to produce the organic matrix of the dentine and to prepare for mineralization in the dentine. PMID:7554958

  6. 46 CFR 502.253 - Interest in reparation proceedings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 9 2013-10-01 2013-10-01 false Interest in reparation proceedings. 502.253 Section 502.253 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation § 502.253 Interest in reparation proceedings. Except as to applications for refund...

  7. 46 CFR 502.253 - Interest in reparation proceedings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 9 2011-10-01 2011-10-01 false Interest in reparation proceedings. 502.253 Section 502.253 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation § 502.253 Interest in reparation proceedings. Except as to applications for refund...

  8. 46 CFR 502.253 - Interest in reparation proceedings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 9 2014-10-01 2014-10-01 false Interest in reparation proceedings. 502.253 Section 502.253 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation § 502.253 Interest in reparation proceedings. Except as to applications for refund...

  9. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    PubMed Central

    Barron, Martin J; McDonnell, Sinead T; MacKie, Iain; Dixon, Michael J

    2008-01-01

    The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP), suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome), permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a number of options including

  10. [Thrombin--a regulator of reparative processes in wound healing].

    PubMed

    Strukova, S M; Dugina, T N; Chistov, I V; Markvicheva, E A; Kuptsova, S V; Kolokol'chikova, E G; Rumsh, L D; Zubov, V P; Gluza, E

    1998-04-01

    Thrombin, binding to receptors of the protease activated receptor (PAR) family, is involved in wound healing by inducing the reparation processes and regulating the activity of mast cells, which secrete mediators of inflammation. Using thrombin receptor agonist peptide (TRAP-6) for the activation of rat mast cells, effect of several receptors, including PAR-1, on mast cells was demonstrated. It was shown that TRAP increases the concentration of Ca2+ in the cytoplasm of mast cells and regulates cell degranulation, while releasing nitrogen oxide. Thrombin encapsulated in poly(N-vinyl caprolactam)-calcium alginate (PVCL-Ca-Alg) hydrogel films promotes wound healing in rats as demonstrated by the acceleration of fibroblast proliferation and neovascularization. PMID:9612571

  11. Reparative resynchronization in ischemic heart failure: an emerging strategy

    PubMed Central

    Yamada, Satsuki; Terzic, Andre

    2014-01-01

    Cardiac dyssynchrony refers to disparity in cardiac wall motion, a serious consequence of myocardial infarction associated with poor outcome. Infarct-induced scar is refractory to device-based cardiac resynchronization therapy, which relies on viable tissue. Leveraging the prospect of structural and functional regeneration, reparative resynchronization has emerged as a potentially achievable strategy. In proof-of-concept studies, stem-cell therapy eliminates contractile deficit originating from infarcted regions and secures long-term synchronization with tissue repair. Limited clinical experience suggests benefit of cell interventions in acute and chronic ischemic heart disease as adjuvant to standard of care. A regenerative resynchronization option for dyssynchronous heart failure thus merits validation. PMID:24840208

  12. Biomaterials and scaffolds in reparative medicine

    NASA Technical Reports Server (NTRS)

    Chaikof, Elliot L.; Matthew, Howard; Kohn, Joachim; Mikos, Antonios G.; Prestwich, Glenn D.; Yip, Christopher M.; McIntire, L. V. (Principal Investigator)

    2002-01-01

    Most approaches currently pursued or contemplated within the framework of reparative medicine, including cell-based therapies, artificial organs, and engineered living tissues, are dependent on our ability to synthesize or otherwise generate novel materials, fabricate or assemble materials into appropriate 2-D and 3-D forms, and precisely tailor material-related physical and biological properties so as to achieve a desired clinical response. This paper summarizes the scientific and technological opportunities within the fields of biomaterials science and molecular engineering that will likely establish new enabling technologies for cellular and molecular therapies directed at the repair, replacement, or reconstruction of diseased or damaged organs and tissues.

  13. Gross human rights violations and reparation under international law: approaching rehabilitation as a form of reparation

    PubMed Central

    Sveaass, Nora

    2013-01-01

    The strengthening of international criminal law through an increased focus on the right to reparation and rehabilitation for victims of crimes against humanity represents an important challenge to health professionals, particularly to those in the field of trauma research and treatment. A brief outline of some developments in the field of international law and justice for victims of gross human rights violations is presented, with a focus on the right to reparation including the means for rehabilitation. The fulfillment of this right is a complex endeavor which raises many questions. The road to justice and reparation for those whose rights have been brutally violated is long and burdensome. The active presence of trauma-informed health professionals in this process is a priority. Some of the issues raised within the context of states’ obligations to provide and ensure redress and rehabilitation to those subjected to torture and gross human rights violations are discussed, and in particular how rehabilitation can be understood and responded to by health professionals. PMID:23671765

  14. Gross human rights violations and reparation under international law: approaching rehabilitation as a form of reparation.

    PubMed

    Sveaass, Nora

    2013-01-01

    The strengthening of international criminal law through an increased focus on the right to reparation and rehabilitation for victims of crimes against humanity represents an important challenge to health professionals, particularly to those in the field of trauma research and treatment. A brief outline of some developments in the field of international law and justice for victims of gross human rights violations is presented, with a focus on the right to reparation including the means for rehabilitation. The fulfillment of this right is a complex endeavor which raises many questions. The road to justice and reparation for those whose rights have been brutally violated is long and burdensome. The active presence of trauma-informed health professionals in this process is a priority. Some of the issues raised within the context of states' obligations to provide and ensure redress and rehabilitation to those subjected to torture and gross human rights violations are discussed, and in particular how rehabilitation can be understood and responded to by health professionals. PMID:23671765

  15. The therapeutic nature of art in self reparation.

    PubMed

    Hymer, S M

    1983-01-01

    While psychoanalysts have extensively explored the interplay between art and artist, few have examined the functions of art for the patient-participant observer or patient-producer. Art references made by patients during therapy can be reparative to the damaged self. Klein's concept of reparation to the object is expanded upon in order to understand the ways in which the patient makes reparation to his self. This paper focuses on two specific reparative functions (Oxford Dictionary, 1926) that the art source brings to bear on the patient's self: (1) "the restoration or renewal of a thing or part." As the patient reparatively integrates repressed impulses and/or the grandiose self, he comes to experience himself in a renewed way as a whole object who is better able to regulate his self-esteem. (2) "the restoration of a person." Once the patient develops the capacity to maintain a more-or-less stable self and object representation, he may then be ready to reparatively adapt to higher order transformations of self involved in creativity. This paper attempts to demonstrate that the analyst, sensitized to the reparative possibilities inherent in art sources, can therapeutically utilize this material both to facilitate the removal of resistances and to help the patient developmentally attain and maintain a well-regulated, adaptive self. PMID:6192457

  16. Psychological Africanity (Racial Identity) and Its Influence on Support for Reparations

    ERIC Educational Resources Information Center

    Azibo, Daudi Ajani ya

    2008-01-01

    Undergraduates at a historically Black university completed the 1997 N'COBRA Reparations Survey. N'COBRA stands for the National Coalition of Blacks for Reparations in America. Five domains of reparations are covered: education, economic development, personal reparations (i.e., payments to individuals), political prisoners, and African-U.S.…

  17. [Effects of opioid peptide dalargin on reparative processes in wound healing].

    PubMed

    Shekhter, A B; Solov'eva, A I; Spevak, S E; Titov, M I

    1988-10-01

    At intraperitoneal injection and local application of opioid peptide dalargin induces fibroblast proliferation (3-fold increase in the mitotic index) and growth of capillaries, accelerates the maturation of granulation tissue and of scar, epitheliazation of the defect, and considerably reduces the period of healing of skin wound in rats. The stimulating action of dalargin is associated with its effect on the microcirculation system and activation of the macrophage-fibroblast interaction. Possessing the triggering mechanism, the drug induces a cascade of inflammatory-reparative reactions, which reduce the duration of all healing stages. PMID:3191245

  18. Experiment K-310: The effect of spaceflight on osteogenesis and dentinogenesis in the mandibles of rats

    NASA Technical Reports Server (NTRS)

    Simmons, D. J.; Russell, J. E.; Winter, F.; Rosenberg, G. D.; Walker, W. V.

    1981-01-01

    Normal rates of dentinogenesis and osteogenesis in the body of the mandible were observed. The total calcium, inorganic phosphorus and hydroxyproline levels in the jaws and incisors of the flight rats were normal. Gravity density fractionation studies suggested, however, that spaceflight caused a delay in the normal maturation of bone mineral and matrix; normal values were reestablished by 6 days postflight. The teeth were spared. The circadian and ultradian patterns of dentin calcification were normal during spaceflight and recovery periods, but the enamel rhythms displayed a greater amplitude of sulfur concentrations and this abnormal calcium to sulfur ratios only during exposure to zero gravity. The rat mandible and teeth do not suffer the deficits of bone formation common to weight bearing parts of the skeleton during spaceflight. The only derangements detected were in the quality of the matrix and mineral moieties.

  19. 17 CFR 12.407 - Satisfaction of reparation award; enforcement; sanctions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Satisfaction of reparation... Satisfaction of reparation award; enforcement; sanctions. (a) Satisfaction of reparation award—(1) Where... satisfaction of an award (as prescribed in paragraph (a) or (b) of this section) expires, file with...

  20. What's Next?: Japanese American Redress and African American Reparations.

    ERIC Educational Resources Information Center

    Yamamoto, Eric K.

    1999-01-01

    Explores the commitment of Japanese Americans to support other groups seeking redress for historic injustice, and considers the lessons that might be drawn from the process of Japanese American redress. Offers a view of reparations as "repair" rather than compensation. (SLD)

  1. Reparable, high-density microelectronic module provides effective heat sink

    NASA Technical Reports Server (NTRS)

    Carlson, K. J.; Maytone, F. F.

    1967-01-01

    Reparable modular system is used for packaging microelectronic flat packs and miniature discrete components. This three-dimensional compartmented structure incorporates etched phosphor bronze sheets and frames with etched wire conductors. It provides an effective heat sink for electric power dissipation in the absence of convective cooling means.

  2. Bone morphogenetic protein 2-induced human dental pulp cell differentiation involves p38 mitogen-activated protein kinase-activated canonical WNT pathway

    PubMed Central

    Yang, Jing; Ye, Ling; Hui, Tian-Qian; Yang, Dong-Mei; Huang, Ding-Ming; Zhou, Xue-Dong; Mao, Jeremy J; Wang, Cheng-Lin

    2015-01-01

    Both bone morphogenetic protein 2 (BMP2) and the wingless-type MMTV integration site (WNT)/β-catenin signalling pathway play important roles in odontoblast differentiation and dentinogenesis. Cross-talk between BMP2 and WNT/β-catenin in osteoblast differentiation and bone formation has been identified. However, the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely unknown. Here, we demonstrate that BMP2 promotes the differentiation of human dental pulp cells (HDPCs) by activating WNT/β-catenin signalling, which is further mediated by p38 mitogen-activated protein kinase (MAPK) in vitro. BMP2 stimulation upregulated the expression of β-catenin in HDPCs, which was abolished by SB203580 but not by Noggin or LDN193189. Furthermore, BMP2 enhanced cell differentiation, which was not fully inhibited by Noggin or LDN193189. Instead, SB203580 partially blocked BMP2-induced β-catenin expression and cell differentiation. Taken together, these data suggest a possible mechanism by which the elevation of β-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway, which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation. PMID:26047580

  3. Clinical manifestations and dental management of dentinogenesis imperfecta associated with osteogenesis imperfecta: Case report.

    PubMed

    Abukabbos, Halima; Al-Sineedi, Faisal

    2013-10-01

    Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child's growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future. PMID:24371383

  4. Combined Treatment with Laser Sintering and Zirconium: A Case Report of Dentinogenesis Imperfecta

    PubMed Central

    Sahin, Cem; Akgün, Özlem Marti; Basak, Feridun

    2013-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics. PMID:23533828

  5. Clinical manifestations and dental management of dentinogenesis imperfecta associated with osteogenesis imperfecta: Case report

    PubMed Central

    Abukabbos, Halima; Al-Sineedi, Faisal

    2013-01-01

    Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child’s growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future. PMID:24371383

  6. Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III

    SciTech Connect

    MacDougall, M.; Zeichner-David, M.; Davis, A.; Slavkin, H. ); Murray, J. ); Crall, M. )

    1992-01-01

    Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI types II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. The data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

  7. Effects of permafrost microorganisms on skin wound reparation.

    PubMed

    Kalenova, L F; Novikova, M A; Subbotin, A M

    2015-02-01

    Local application of ointment with Bacillus spp. strain MG8 (15,000-20,000 living bacterial cells), isolated from permafrost specimens, on the skin wound of about 60 mm(2) stimulated the reparation processes in experimental mice. A possible mechanism stimulating the regeneration of the damaged tissues under the effect of MG8 could be modulation of the immune system reactivity with more rapid switchover to humoral immunity anti-inflammatory mechanisms aimed at de novo synthesis of protein. PMID:25708330

  8. Reparative giant cell granuloma in a pediatric patient.

    PubMed

    Duarte Ruiz, Blanca; Riba García, Francisco de Asís; Navarro Cuéllar, Carlos; Bucci, Tommaso; Cuesta Gil, Matías; Navarro Vila, Carlos

    2007-08-01

    Reparative giant cell granulomas are benign, infrequent tumors, of non-odontogenic origin, that develop at central or peripheral level. Peripherally located lesions are frequently denominated "giant cell epulis", and never correspond to true neoplasia, but rather to inflammatory reactions secondary to another lesion (hemorrhage, etc.). It should be taken into account, that in general, head and neck tumors of infancy usually demonstrate an atypical biological behaviour. Furthermore, the anatomicopathologic diagnosis is often compromised in this type of lesion. We present the case of a 6-year-old boy, who, three weeks after suffering a slight facial trauma, developed a painless, exophytic swelling of approximately 4 cm, with bleeding on palpation, in the ipsilateral hemimaxilla. The lesion demonstrated rapid, progressive and continuous growth. The facial CT and incisional biopsy confirmed the suspected diagnosis of reparative giant cell granuloma. The patient was surgically treated, carrying out a left marginal maxillectomy associated with the extirpation of the soft-tissue lesion. The resultant defect was reconstructed with a Bichat fat-pad providing the patient with optimal esthetic and functional results. The definitive anatomicopathologic report of the surgical piece is compatible with reparative giant cell granuloma. PMID:17664921

  9. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    NASA Astrophysics Data System (ADS)

    Khodanovich, M. Yu.

    2015-11-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  10. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    SciTech Connect

    Khodanovich, M. Yu.

    2015-11-17

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  11. How Finnish Upper Secondary Students Conceive Transgenerational Responsibility and Historical Reparations: Implications for the History Curriculum

    ERIC Educational Resources Information Center

    Löfström, Jan

    2014-01-01

    The article discusses how Finnish upper secondary school students ponder upon the questions of transgenerational responsibility and historical reparation. These questions have got a prominent place in the history culture in many societies in the last 20 years. The philosophical and political dimensions of reparations for historical injustices have…

  12. If a Tree Falls in the Wilderness: Reparations, Academic Silences, and Social Justice

    ERIC Educational Resources Information Center

    Coates, Rodney D.

    2004-01-01

    The history and dynamics of reparations for African Americans are explored. The lack of current research and writing on the subject in sociology and political sciences journals is contended to be a conspiracy of silence in academia on the subject of restitution for 500 years of oppression. A program of reparations of three kinds is suggested: 1)…

  13. Nuestra culpa: collective guilt and shame as predictors of reparation for historical wrongdoing.

    PubMed

    Brown, Rupert; González, Roberto; Zagefka, Hanna; Manzi, Jorge; Cehajic, Sabina

    2008-01-01

    Three studies examined the hypothesis that collective guilt and shame have different consequences for reparation. In 2 longitudinal studies, the ingroup was nonindigenous Chileans (Study 1: N = 124/120, lag = 8 weeks; Study 2: N = 247/137, lag = 6 months), and the outgroup was Chile's largest indigenous group, the Mapuche. In both studies, it was found that collective guilt predicted reparation attitudes longitudinally. Collective shame had only cross-sectional associations with reparation and no direct longitudinal effects. In Study 2, collective shame moderated the longitudinal effects of collective guilt such that the effects of guilt were stronger for low-shame respondents. In Study 3 (N = 193 nonindigenous Chileans), the cross-sectional relationships among guilt, shame, and reparation attitudes were replicated. The relationship between shame and reparation attitudes was mediated by a desire to improve the ingroup's reputation. PMID:18179319

  14. The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction

    PubMed Central

    Dobaczewski, Marcin; Gonzalez-Quesada, Carlos; Frangogiannis, Nikolaos G

    2009-01-01

    The dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of matrix metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is essential for resolution of inflammation and marks the transition to the proliferative phase. The fibrin-based provisional matrix is lysed and cellular fibronectin is secreted. ED-A fibronectin, mechanical tension and Transforming Growth Factor (TGF)-β are essential for modulation of fibroblasts into myofibroblasts, the main collagen-secreting cells in the wound. The matricellular proteins thrombospondin-1 and -2, osteopontin, tenascin-C, periostin, and secreted protein acidic and rich in cysteine (SPARC) are induced in the infarct regulating cellular interactions and promoting matrix organization. As the infarct matures, matrix cross-linking results in formation of a dense collagen-based scar. At this stage, shielding of fibroblasts from external mechanical tension by the mature matrix network may promote deactivation and cellular quiescence. The components of the extracellular matrix do not passively follow the pathologic alterations of the infarcted heart but critically modulate inflammatory and reparative pathways by transducing signals that affect cell survival, phenotype and gene expression. PMID:19631653

  15. Raising the dead: war, reparation, and the politics of memory.

    PubMed Central

    Summerfield, D.

    1995-01-01

    All societies attach a different range of meanings to war than to natural disasters, and questions of societal recognition, reparation, and justice are generally central. Most modern conflict has been grounded in the use of terror to control and silence whole populations. Those abusing power typically refuse to acknowledge their dead victims, as if they had never existed and were mere wraiths in the memories of those left behind. This denial, and the impunity of those who maintain it, must be challenged if survivors are to make sense of their losses and the social fabric is to mend. For the names and fate of the dead to be properly lodged in the public record of their times also illuminates the costs that may flow from the philosophies and practices of the Western led world order, ones which health workers should be in a position to influence. Images p495-a p496-a p496-b PMID:7647648

  16. 3D visualization and quantification of bone and teeth mineralization for the study of osteo/dentinogenesis in mice models

    NASA Astrophysics Data System (ADS)

    Marchadier, A.; Vidal, C.; Ordureau, S.; Lédée, R.; Léger, C.; Young, M.; Goldberg, M.

    2011-03-01

    Research on bone and teeth mineralization in animal models is critical for understanding human pathologies. Genetically modified mice represent highly valuable models for the study of osteo/dentinogenesis defects and osteoporosis. Current investigations on mice dental and skeletal phenotype use destructive and time consuming methods such as histology and scanning microscopy. Micro-CT imaging is quicker and provides high resolution qualitative phenotypic description. However reliable quantification of mineralization processes in mouse bone and teeth are still lacking. We have established novel CT imaging-based software for accurate qualitative and quantitative analysis of mouse mandibular bone and molars. Data were obtained from mandibles of mice lacking the Fibromodulin gene which is involved in mineralization processes. Mandibles were imaged with a micro-CT originally devoted to industrial applications (Viscom, X8060 NDT). 3D advanced visualization was performed using the VoxBox software (UsefulProgress) with ray casting algorithms. Comparison between control and defective mice mandibles was made by applying the same transfer function for each 3D data, thus allowing to detect shape, colour and density discrepencies. The 2D images of transverse slices of mandible and teeth were similar and even more accurate than those obtained with scanning electron microscopy. Image processing of the molars allowed the 3D reconstruction of the pulp chamber, providing a unique tool for the quantitative evaluation of dentinogenesis. This new method is highly powerful for the study of oro-facial mineralizations defects in mice models, complementary and even competitive to current histological and scanning microscopy appoaches.

  17. [Dynamics of biochemical markers of reparative fibrosis in uncomplicated course of myocardial infarction].

    PubMed

    Kim, L B; Putiatina, A N

    2010-01-01

    Dynamics of biochemical markers of reparative fibrosis in patients with myocardial infarction (MI) with complicated course did not differ from that in the group of patients without complications. Development of complications was associated with elevation of blood serum content of glucosaminoglycans in phase 3 of reparative fibrosis compared with group of patients without complications. This elevation was significant in the group of patients with rhythm disturbances. Statistically significant increase of total urinal oxyproline was found in patients with cardiac aneurism in phase 1 and in patients with cardiogenic shock in phase 3 of reparative fibrosis. These subject allow to speak about participation of reparative fibrosis in development of complications. Complications of myocardial infarction developed in patients aged 58 years and older. PMID:21591385

  18. 17 CFR 12.407 - Satisfaction of reparation award; enforcement; sanctions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... shall remain in effect until the person required to pay the reparation award demonstrates to the... award of post-judgment interest is inadvertently omitted, such interest nevertheless shall run...

  19. Synthetic octacalcium phosphate-enhanced reparative dentine formation via induction of odontoblast differentiation.

    PubMed

    Wang, Xiaogu; Suzawa, Tetsuo; Miyauchi, Tomohiko; Zhao, Baohong; Yasuhara, Rika; Anada, Takahisa; Nakamura, Masanori; Suzuki, Osamu; Kamijo, Ryutaro

    2015-11-01

    Synthetic octacalcium phosphate (OCP) has been suggested to be a useful biomaterial for the regeneration of hard tissues, including bone. However, it remains unknown whether OCP induces dentine formation by dental pulp. We investigated biomineralization of dental pulp exposed to synthetic OCP in vitro and in vivo. When dental pulp was exposed directly to OCP, rapid formation of reparative dentine (RD) was induced and expression of dentine sialoprotein synthesis was observed in dental pulp adjacent to newly synthesized RD. OCP inhibited the proliferation of rat pulp cells and also promoted their odontoblastic differentiation in vitro, as alkaline phosphatase activity, mineralization of pulp cells and the expression level of dentine sialophosphoprotein were enhanced. Direct contact between OCP and pulp cells is required for OCP to exhibit its effects in vitro. The expression level of Runx2, a transcription factor whose downregulation is closely related to odontoblast differentiation, was downregulated in pulp cells cultured with OCP. Structural changes of OCP during culture were determined by Fourier transform infrared spectroscopy. OCP tended to be converted to carbonate hydroxyapatite after incubation with or without pulp cells, which may be analogous to biological apatite crystals. Taken together, our data suggest that synthetic OCP supports RD formation by dental pulp and downregulation of Runx2 may be involved in that stimulatory activity. Furthermore, OCP-apatite conversion is involved in this stimulatory capacity of OCP. PMID:23355511

  20. Performance evaluation of the croissant production line with reparable machines

    NASA Astrophysics Data System (ADS)

    Tsarouhas, Panagiotis H.

    2015-09-01

    In this study, the analytical probability models for an automated serial production system, bufferless that consists of n-machines in series with common transfer mechanism and control system was developed. Both time to failure and time to repair a failure are assumed to follow exponential distribution. Applying those models, the effect of system parameters on system performance in actual croissant production line was studied. The production line consists of six workstations with different numbers of reparable machines in series. Mathematical models of the croissant production line have been developed using Markov process. The strength of this study is in the classification of the whole system in states, representing failures of different machines. Failure and repair data from the actual production environment have been used to estimate reliability and maintainability for each machine, workstation, and the entire line is based on analytical models. The analysis provides a useful insight into the system's behaviour, helps to find design inherent faults and suggests optimal modifications to upgrade the system and improve its performance.

  1. Performance evaluation of the croissant production line with reparable machines

    NASA Astrophysics Data System (ADS)

    Tsarouhas, Panagiotis H.

    2014-09-01

    In this study, the analytical probability models for an automated serial production system, bufferless that consists of n-machines in series with common transfer mechanism and control system was developed. Both time to failure and time to repair a failure are assumed to follow exponential distribution. Applying those models, the effect of system parameters on system performance in actual croissant production line was studied. The production line consists of six workstations with different numbers of reparable machines in series. Mathematical models of the croissant production line have been developed using Markov process. The strength of this study is in the classification of the whole system in states, representing failures of different machines. Failure and repair data from the actual production environment have been used to estimate reliability and maintainability for each machine, workstation, and the entire line is based on analytical models. The analysis provides a useful insight into the system's behaviour, helps to find design inherent faults and suggests optimal modifications to upgrade the system and improve its performance.

  2. [Immunoregulatory role of mesenchymal stem cells in bone reparation processes].

    PubMed

    Zubov, D O

    2008-01-01

    Bone marrow contains mesenchymal stem cells (MSC) including osteoblast progenitor cells. When culturedunder conditions promoting an osteoblastic phenotype,MSC proliferate to form colonies that produce alkaline phosphatase and, subsequently, a mature osteoblastic phenotype. Transplantation of cultured autologous MSC to patients with non-healing bone fractures gives a good result leading to complete bone fracture consolidation. The aim of the study is to determine a quantitative production of IL-1beta, IL-2, IL-4, IL-6, IL-8 and TNF-alpha by cultured uncommitted and committed osteogenic MSC. The results showed that the cytokine profile consisting of IL-1beta, IL-2, IL-4, IL-6, IL-8 and TNF-alpha is secreted by cultured MSC. The secretion of IL-1beta and IL-2 by cultured MSC together with hyper production of IL-6 (up to 276.5 pg/ml, p<0.05) and IL-8 (up to 106.6 ng/ml, p<0.05) by osteoinducted MSC are firstly shown. The immunoregulatory role of transplanted autologous cells in inflammation and own bone reparation processes during posttraumatic bone fracture healing is highlighted. In conclusion, the data obtained allow examining of cultured autologous MSC as effective activators of bone resorption, inflammation and some immunological reactions in the process of altered osteoreparation. PMID:18756772

  3. Reparable Cell Sonoporation in Suspension: Theranostic Potential of Microbubble

    PubMed Central

    Nejad, S. Moosavi; Hosseini, Hamid; Akiyama, Hidenori; Tachibana, Katsuro

    2016-01-01

    The conjunction of low intensity ultrasound and encapsulated microbubbles can alter the permeability of cell membrane, offering a promising theranostic technique for non-invasive gene/drug delivery. Despite its great potential, the biophysical mechanisms of the delivery at the cellular level remains poorly understood. Here, the first direct high-speed micro-photographic images of human lymphoma cell and microbubble interaction dynamics are provided in a completely free suspension environment without any boundary parameter defect. Our real-time images and theoretical analyses prove that the negative divergence side of the microbubble's dipole microstreaming locally pulls the cell membrane, causing transient local protrusion of 2.5 µm in the cell membrane. The linear oscillation of microbubble caused microstreaming well below the inertial cavitation threshold, and imposed 35.3 Pa shear stress on the membrane, promoting an area strain of 0.12%, less than the membrane critical areal strain to cause cell rupture. Positive transfected cells with pEGFP-N1 confirm that the interaction causes membrane poration without cell disruption. The results show that the overstretched cell membrane causes reparable submicron pore formation, providing primary evidence of low amplitude (0.12 MPa at 0.834 MHz) ultrasound sonoporation mechanism. PMID:26941839

  4. Fibronectin is Essential for Reparative Cardiac Progenitor Cell Response Following Myocardial Infarction

    PubMed Central

    Konstandin, Mathias H.; Toko, Haruhiro; Gastelum, Grady M.; Quijada, Pearl; De La Torre, Andrea; Quintana, Mercedes; Collins, Brett; Din, Shabana; Avitabile, Daniele; Völkers, Mirko; Gude, Natalie; Fässler, Reinhard; Sussman, Mark A.

    2013-01-01

    Rationale Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application despite limited mechanistic understanding of the endogenous response following myocardial infarction (MI). Extracellular matrix (ECM) undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair. Objective Demonstrate the significance of Fibronectin (Fn), a component of the ECM, for induction of the endogenous CPC response to MI. Methods and Results This report shows that presence of CPCs correlates with expression of Fn during cardiac development and after MI. In vivo, genetic conditional ablation of Fn blunts CPC response measured 7 days after MI through reduced proliferation and diminished survival. Attenuated vasculogenesis and cardiogenesis during recovery was evident at the end of a 12 week follow-up period. Impaired CPC-dependent reparative remodeling ultimately leads to continuous decline of cardiac function in Fn knockout animals. In vitro, Fn protects and induces proliferation of CPCs via β1-Integrin-FAK-Stat3-Pim1 but Akt-independent mechanism. Conclusion Fn is essential for endogenous CPC expansion and repair needed for stabilization of cardiac function after MI. PMID:23652800

  5. Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury

    PubMed Central

    Sallustio, Fabio; Serino, Grazia; Schena, Francesco Paolo

    2015-01-01

    Abstract Human kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133+/CD24+ cells, with a view to a future application of these cells for the treatment of acute renal injury. PMID:26309808

  6. Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells

    SciTech Connect

    Duncan, Henry F.; Smith, Anthony J.; Fleming, Garry J.P.; Cooper, Paul R.

    2013-06-10

    Application of histone deacetylase inhibitors (HDACi) to cells epigenetically alters their chromatin structure and induces transcriptional and cellular reparative events. This study investigated the application of two HDACi, valproic acid (VPA) and trichostatin A (TSA) on the induction of repair-associated responses in primary dental pulp cell (DPC) cultures. Flow cytometry demonstrated that TSA (100 nM, 400 nM) significantly increased cell viability. Neither HDACi was cytotoxic, although cell growth analysis revealed significant anti-proliferative effects at higher concentrations for VPA (>0.5 mM) and TSA (>50 nM). While high-content-analysis demonstrated that HDACi did not significantly induce caspase-3 or p21 activity, p53-expression was increased by VPA (3 mM, 5 mM) at 48 h. HDACi-exposure induced mineralization per cell dose-dependently to a plateau level (VPA-0.125 mM and TSA-25 nM) with accompanying increases in mineralization/dentinogenic-associated gene expression at 5 days (DMP-1, BMP-2/-4, Nestin) and 10 days (DSPP, BMP-2/-4). Both HDACis, at a range of concentrations, significantly stimulated osteopontin and BMP-2 protein expression at 10 and 14 days further supporting the ability of HDACi to promote differentiation. HDACi exert different effects on primary compared with transformed DPCs and promote mineralization and differentiation events without cytotoxic effects. These novel data now highlight the potential in restorative dentistry for applying low concentrations of HDACi in vital pulp treatment. -- Highlights: • Valproic acid and trichostatin A promoted mineralization in primary pulp cells. • Cell viability, apoptosis, caspase-3, p21 unaltered; p53 increased by valproic acid. • Trichostatin A increased cell viability at 24 h at selected concentrations. • Altered cell toxicity and differentiation between primary and transformed cells. • HDACi-induced the differentiation marker proteins osteopontin and BMP-2.

  7. [Effect of weightlessness on the course of the reparative process in the muscles of the biosatellite Kosmos-2044 rats].

    PubMed

    Il'ina-Kakueva, E I; Burkovskaia, T E

    1991-01-01

    The repair process in the soleus and gastrocnemius muscles of SPF Wistar rats flown for 14 days on the biosatellite Cosmos-2044 was investigated. The muscles were injured 2 days before launch by means of clamp forceps. The exposure inhibited the process but did not impair its phasic development. As a result, the reparative field diminished and took the size of an atrophic muscle; thinner myofibers appeared that originated from the ends of injured atrophic fibers and fibers that underwent splitting. It is postulated that repair inhibition is caused by the same mechanisms that produce muscle atrophy in microgravity. It is suggested that both repair inhibition and muscle atrophy are induced by disorders in the neurotrophic regulation of metabolism due to partial disuse. PMID:8577135

  8. The charisma and deception of reparative therapies: when medical science beds religion.

    PubMed

    Grace, André P

    2008-01-01

    In this article, I examine the history and resurgence of interest in sexual reorientation or reparative therapies. I begin with a critique of the contemporary "ex-gay" movement, interrogating Exodus as the prototype of a politico-religious transformational ministry that works to "cure" homosexuals, and examine how Exodus utilizes ex-gay testimony to deceive harried homosexuals looking for escape from the effects of internalized and cultural homophobia. Next, I investigate how reparative therapies function as orthodox treatments that charismatically meld conservative religious perspectives with medical science to produce a pseudoscience promising to treat homosexuality effectively. In this regard, I assess the ongoing debate regarding gay-affirming versus reparative therapies by first looking at the history of medicalizing homosexuality and then surveying the debate spurred by Robert L. Spitzer's research. I conclude with a consideration of research needed to measure whether efficacious change in sexual orientation is possible. PMID:19064479

  9. 46 CFR Exhibit No. 1 to Subpart O... - Reparation Statement To Be Filed Pursuant to Rule 252

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 9 2011-10-01 2011-10-01 false Reparation Statement To Be Filed Pursuant to Rule 252 No. Exhibit No. 1 to Subpart O of Part 502 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation Pt. 502, Subpt O, Exh. 1 Exhibit No. 1 to Subpart O...

  10. 46 CFR Exhibit No. 1 to Subpart O... - Reparation Statement To Be Filed Pursuant to Rule 252

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Reparation Statement To Be Filed Pursuant to Rule 252 No. Exhibit No. 1 to Subpart O of Part 502 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation Pt. 502, Subpt O, Exh. 1 Exhibit No. 1 to Subpart O...

  11. 46 CFR Exhibit No. 1 to Subpart O... - Reparation Statement To Be Filed Pursuant to Rule 252

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 9 2014-10-01 2014-10-01 false Reparation Statement To Be Filed Pursuant to Rule 252 No. Exhibit No. 1 to Subpart O of Part 502 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation Pt. 502, Subpt O, Exh. 1 Exhibit No. 1 to Subpart O...

  12. 46 CFR Exhibit No. 1 to Subpart O... - Reparation Statement To Be Filed Pursuant to Rule 252

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 9 2013-10-01 2013-10-01 false Reparation Statement To Be Filed Pursuant to Rule 252 No. Exhibit No. 1 to Subpart O of Part 502 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation Pt. 502, Subpt O, Exh. 1 Exhibit No. 1 to Subpart O...

  13. 46 CFR Exhibit No. 1 to Subpart O... - Reparation Statement To Be Filed Pursuant to Rule 252

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 9 2012-10-01 2012-10-01 false Reparation Statement To Be Filed Pursuant to Rule 252 No. Exhibit No. 1 to Subpart O of Part 502 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Reparation Pt. 502, Subpt O, Exh. 1 Exhibit No. 1 to Subpart O...

  14. Transcriptional Repression of the Dspp Gene Leads to Dentinogenesis Imperfecta Phenotype in Col1a1-Trps1 Transgenic Mice

    PubMed Central

    Napierala, Dobrawa; Sun, Yao; Maciejewska, Izabela; Bertin, Terry K; Dawson, Brian; D'Souza, Rena; Qin, Chunlin; Lee, Brendan

    2012-01-01

    Dentinogenesis imperfecta (DGI) is a hereditary defect of dentin, a calcified tissue that is the most abundant component of teeth. Most commonly, DGI is manifested as a part of osteogenesis imperfecta (OI) or the phenotype is restricted to dental findings only. In the latter case, DGI is caused by mutations in the DSPP gene, which codes for dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Although these two proteins together constitute the majority of noncollagenous proteins of the dentin, little is known about their transcriptional regulation. Here we demonstrate that mice overexpressing the Trps1 transcription factor (Col1a1-Trps1 mice) in dentin-producing cells, odontoblasts, present with severe defects of dentin formation that resemble DGI. Combined micro–computed tomography (µCT) and histological analyses revealed tooth fragility due to severe hypomineralization of dentin and a diminished dentin layer with irregular mineralization in Col1a1-Trps1 mice. Biochemical analyses of noncollagenous dentin matrix proteins demonstrated decreased levels of both DSP and DPP proteins in Col1a1-Trps1 mice. On the molecular level, we demonstrated that sustained high levels of Trps1 in odontoblasts lead to dramatic decrease of Dspp expression as a result of direct inhibition of the Dspp promoter by Trps1. During tooth development Trps1 is highly expressed in preodontoblasts, but in mature odontoblasts secreting matrix its expression significantly decreases, which suggests a Trps1 role in odontoblast development. In these studies we identified Trps1 as a potent inhibitor of Dspp expression and the subsequent mineralization of dentin. Thus, we provide novel insights into mechanisms of transcriptional dysregulation that leads to DGI. © 2012 American Society for Bone and Mineral Research. PMID:22508542

  15. 9 CFR 202.103 - Rule 3: Beginning a reparation proceeding.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Rule 3: Beginning a reparation proceeding. 202.103 Section 202.103 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS...) Quantity and quality of the livestock involved; (3) Whether a sale is involved and, if so, the date,...

  16. 9 CFR 202.103 - Rule 3: Beginning a reparation proceeding.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Rule 3: Beginning a reparation proceeding. 202.103 Section 202.103 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS...) Quantity and quality of the livestock involved; (3) Whether a sale is involved and, if so, the date,...

  17. Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E-cadherin via control of Krüppel-like factor 4 (KLF4) during dentinogenesis.

    PubMed

    Lee, Hye-Kyung; Lee, Dong-Seol; Park, Su-Jin; Cho, Kwang-Hee; Bae, Hyun-Sook; Park, Joo-Cheol

    2014-10-10

    Odontoblasts are a type of terminally differentiated matrix-secreting cells. A number of molecular mechanisms are involved in the differentiation of odontoblasts. Several studies demonstrated that Krüppel-like factor 4 (KLF4) promotes odontoblast differentiation via control of dentin sialophosphoprotein (DSPP). Because nuclear factor I-C (NFIC) is also known to control DSPP, we investigated the relationship between NFIC and KLF4 during odontoblast differentiation. Klf4 mRNA expression was significantly decreased in Nfic(-/-) pulp cells compared with wild type cells. In immunohistochemistry assays, dentin matrix protein 1 (Dmp1), and DSP protein expression was barely observed in Nfic(-/-) odontoblasts and dentin matrix. Nfic bound directly to the Klf4 promoter and stimulated Klf4 transcriptional activity, thereby regulating Dmp1 and DSPP expression during odontoblast differentiation. Nfic or Klf4 overexpression promoted mineralized nodule formation in MDPC-23 cells. In addition, Nfic overexpression also decreased Slug luciferase activity but augmented E-cadherin promoter activity via up-regulation of Klf4 in odontoblasts. Our study reveals important signaling pathways during dentinogenesis: the Nfic-Klf4-Dmp1-Dspp and the Nfic-Klf4-E-cadherin pathways in odontoblasts. Our results indicate the important role of NFIC in regulating KLF4 during dentinogenesis. PMID:25138274

  18. A multi-item maintenance center inventory model for low-demand reparable items

    NASA Technical Reports Server (NTRS)

    Schaefer, M. K.

    1983-01-01

    In many military and commercial contexts, complex equipment undergoes scheduled maintenance overhauls at regular intervals during which all failed components are replaced. Failure to have replacements on hand for all failed parts requires emergency measures at premium cost. When reparable parts are highly reliable and expensive, both holding and shortage costs are high. This model determines the reparable parts inventory for a maintenance center under three alternative criteria: (1) maximizing job-completion rate subject to constraint on total holding costs, (2) minimizing total holding costs plus expected job noncompletion costs, and (3) minimizing total holding costs subject to a required minimum job-completion rate. Exact solutions may be obtained using dynamic programming. Approximate solutions, found easily by marginal analysis, have readily computed bounds on possible error. The solution methods for the three formulations are illustrated in a simple example.

  19. 75 FR 3371 - Commission Guidance Concerning the Rules of Practice Relating to Reparations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-21

    ...The Commodity Futures Trading Commission (``Commission'' or ``CFTC'') is issuing this policy statement to clarify and provide guidance to Commission staff and affected parties that Commission Rule 12.1(a), 17 CFR 12.1(a), requires that all rules of practice relating to reparation proceedings under 17 CFR part 12 ``shall be construed liberally so as to secure the just, speedy and inexpensive......

  20. Genomic organization of the human osteopontin gene: Exclusion of the locus from a causative role in the pathogenesis of dentinogenesis imperfecta type II.

    SciTech Connect

    Crosby, A.H.; Edwards, S.J.; Murray, J.C.

    1995-05-01

    Osteopontin (SPP1) is the principal phosphorylated glycoprotein of bone that is also expressed in a limited number of other tissues including dentine. In the current investigation the authors report the genomic organization of the SPP1 gene, which comprises seven exons, six of which contain coding sequence. The splice sites for exon donor and acceptor positions are in close agreement with previously published consensus sequences. Comparison of the human gene with its murine and bovine counterparts revealed a highly homologous organization. A highly informative short tandem repeat polymorphism isolated at the SPP1 locus showed no recombination with the autosomal dominant disorder dentinogenesis imperfecta type II. Nevertheless, sequencing of each exon in individuals affected by this disorder failed to reveal any disease-specific mutations. 25 refs., 2 figs., 2 tabs.

  1. Nondestructive Evaluation (NDE) Results on Sikorsky Aircraft Survivable Affordable Reparable Airframe Program (SARAP) Samples

    NASA Technical Reports Server (NTRS)

    Zalameda, Joseph N.; Anastasi, Robert F.; Madaras, Eric I.

    2004-01-01

    The Survivable, Affordable, Reparable Airframe Program (SARAP) will develop/produce new structural design concepts with lower structural weight, reduced manufacturing complexity and development time, increased readiness, and improved threat protection. These new structural concepts will require advanced field capable inspection technologies to help meet the SARAP structural objectives. In the area of repair, damage assessment using nondestructive inspection (NDI) is critical to identify repair location and size. The purpose of this work is to conduct an assessment of new and emerging NDI methods that can potentially satisfy the SARAP program goals.

  2. Some reflections on Ian McEwan's atonement: enactment, guilt, and reparation.

    PubMed

    Kogan, Ilany

    2014-01-01

    Recognizing that enactments have been discussed in psychoanalysis primarily as occurrences in the treatment setting, the author proposes a new application of the term enactments: that it may pertain to the actions of some individuals in their efforts to cope with bad things that they have done to others. That is, enactment can be a substitute-for-atonement mechanism. The author illustrates this view of enactment through a discussion of Ian McEwan's novel Atonement (2001), and in particular by examining the behavior and motivations of one of its central characters, Briony Tallis. Included are explorations of the relationships between enactment and guilt and between enactment and reparation. PMID:24470364

  3. Regenerative and reparative effects of human chorion-derived stem cell conditioned medium on photo-aged epidermal cells.

    PubMed

    Li, Qiankun; Chen, Yan; Ma, Kui; Zhao, Along; Zhang, Cuiping; Fu, Xiaobing

    2016-04-17

    Epidermal cells are an important regenerative source for skin wound healing. Aged epidermal cells have a low ability to renew themselves and repair skin injury. Ultraviolet (UV) radiation, particularly UVB, can cause photo-aging of the skin by suppressing the viability of human epidermal cells. A chorion-derived stem cell conditioned medium (CDSC-CNM) is thought to have regenerative properties. This study aimed to determine the regenerative effects of CDSC-CNM on UVB-induced photo-aged epidermal cells. Epidermal cells were passaged four times and irradiated with quantitative UVB, and non-irradiated cells served as a control group. Cells were then treated with different concentrations of CDSC-CNM. Compared to the non-irradiated group, the proliferation rates and migration rates of UVB-induced photo-aged epidermal cells significantly decreased (p < 0.05) with increasing intracellular radical oxygen species (ROS) generation and DNA damage. After treatment with CDSC-CNM, photo-aged epidermal cells significantly improved their viability, and their ROS generation and DNA damage decreased. The secretory factors in CDSC-CNM, including epidermal growth factor (EGF), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-8 and the related signaling pathway protein levels, increased compared to the control medium (CM). The potential regenerative and reparative effects of CDSC-CNM indicate that it may be a candidate material for the treatment of prematurely aged skin. The functions of the secretory factors and the mechanisms of CDSC-CNM therapy deserve further attention. PMID:27097375

  4. Effects of human vascular endothelial growth factor on reparative dentin formation

    PubMed Central

    ZHANG, JUAN; LIU, XIA; YU, WEIXIAN; ZHANG, YINGLI; SHI, CE; NI, SHILEI; LIU, QILIN; LI, XIANGWEI; SUN, YINGJIAN; ZHENG, CHANGYU; SUN, HONGCHEN

    2016-01-01

    It is a challenge for dentists to save dental pulp in patients with pulp disease without resorting to root canal therapy. Formation of tertiary dentin to maintain pulp vitality is a key odontoblast response to dental pulp injury. Vascular endothelial growth factor (VEGF) is the most potent angiogenic and vasculogenic factor involved in tertiary dentin formation. It was hypothesized that VEGF may be used to treat pulp diseases such as pulpitis. To explore this hypothesis, the first step was to assess whether VEGF affects dental pulp cells to promote reparative dentin formation. In the current study, an AdCMV-hVEGF vector was constructed to deliver hVEGF into dental pulp cells of exfoliated deciduous teeth (hDPCs) in vitro and dental pulp cells in a rat model in vivo. The collected data clearly demonstrated that hVEGF increased alkaline phosphatase and mineralization by enzymatic activity. RT-qPCR data demonstrated that hVEGF significantly increased the expression levels of genes commonly involved in osteogenesis/odontogenesis. Data from the in vivo assays indicated that hVEGF enhanced pulp cell proliferation and neovascularization, and markedly increased formation of reparative dentin in dental pulp. The in vitro and in vivo data suggest that hVEGF may have potential clinical applications, thus may aid in the development of novel treatment strategies for dental pulpitis. PMID:26647730

  5. The Danieli Inventory of Multigenerational Legacies of Trauma, Part II: Reparative Adaptational Impacts.

    PubMed

    Danieli, Yael; Norris, Fran H; Lindert, Jutta; Paisner, Vera; Kronenberg, Sefi; Engdahl, Brian; Richter, Julia

    2015-05-01

    The impacts of the Holocaust on children of survivors have been widely investigated. However, consensus is limited, and no validated measures have been tailored with or to them. We aimed to develop and validate a scale that measures these specific impacts (Part II of the Danieli Inventory of Multigenerational Legacies of Trauma). We studied 484 adult children of survivors who participated in a cross-sectional web-based survey in English or Hebrew; of these, 191 participated in a clinical interview. Exploratory factor analyses of 58 items to reduce and refine the measure yielded a 36-item scale, Reparative Adaptational Impacts, that had excellent internal consistency (α = .91) and congruence between English and Hebrew versions (φ ≥ .95). Associations between impacts and SCID-based diagnoses of major depressive episode, posttraumatic stress disorder, and generalized anxiety disorder were moderate to strong (ds = 0.48-0.89). Strong associations also emerged between severity of offspring's reparative adaptational impacts and intensity of their parents' posttrauma adaptational styles (Multiple R = .72), with intensity of victim style, especially the mother's, having the strongest effect (β = .31-.33). Having both research and clinical relevance for assessing Holocaust survivors' offspring, future studies might investigate the scale's generalizability to other populations affected by mass trauma. PMID:25985110

  6. Effects of human vascular endothelial growth factor on reparative dentin formation.

    PubMed

    Zhang, Juan; Liu, Xia; Yu, Weixian; Zhang, Yingli; Shi, Ce; Ni, Shilei; Liu, Qilin; Li, Xiangwei; Sun, Yingjian; Zheng, Changyu; Sun, Hongchen

    2016-01-01

    It is a challenge for dentists to save dental pulp in patients with pulp disease without resorting to root canal therapy. Formation of tertiary dentin to maintain pulp vitality is a key odontoblast response to dental pulp injury. Vascular endothelial growth factor (VEGF) is the most potent angiogenic and vasculogenic factor involved in tertiary dentin formation. It was hypothesized that VEGF may be used to treat pulp diseases such as pulpitis. To explore this hypothesis, the first step was to assess whether VEGF affects dental pulp cells to promote reparative dentin formation. In the current study, an AdCMV‑hVEGF vector was constructed to deliver hVEGF into dental pulp cells of exfoliated deciduous teeth (hDPCs) in vitro and dental pulp cells in a rat model in vivo. The collected data clearly demonstrated that hVEGF increased alkaline phosphatase and mineralization by enzymatic activity. RT‑qPCR data demonstrated that hVEGF significantly increased the expression levels of genes commonly involved in osteogenesis/odontogenesis. Data from the in vivo assays indicated that hVEGF enhanced pulp cell proliferation and neovascularization, and markedly increased formation of reparative dentin in dental pulp. The in vitro and in vivo data suggest that hVEGF may have potential clinical applications, thus may aid in the development of novel treatment strategies for dental pulpitis. PMID:26647730

  7. Mapping of the human dentin matrix acidic phosphoprotein gene (DMP1) to the dentinogenesis imperfecta type II critical region at chromosome 4q21

    SciTech Connect

    Aplin, H.M.; Hirst, K.L.; Crosby, A.H.; Dixon, M.J.

    1995-11-20

    Dentinogenesis imperfecta type II (DGI1) is an autosomal dominant disorder of dentin formation, which has been mapped to human chromosome 4q12-q21. The region most likely to contain the DGI1 locus is a 3.2-cM region surrounding the osteopontin (SPP1) locus. Recently, a novel dentin-specific acidic phosphoprotein (dmp1) has been cloned in the rat and mapped to mouse chromosome 5q21. In the current investigation, we have isolated a cosmid containing the human DMP1 gene. The isolation of a short tandem repeat polymorphism at this locus has allowed us to map the DMP1 locus to human chromosome 4q21 and demonstrate that it is tightly linked to DGI1 in two families (Z{sub max} = 11.01, {theta} = 0.001). The creation of a yeast artificial chromosome contig around SPP1 has further allowed us to demonstrate that DMP1 is located within 150 kb of the bone sialoprotein and 490 kb of the SPP1 loci, respectively. DMP1 is therefore a strong candidate for the DGI1 locus. 12 refs., 2 figs., 1 tab.

  8. The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses.

    PubMed

    Bellini, Alberto; Mattoli, Sabrina

    2007-09-01

    Human fibrocytes are mesenchymal progenitors that exhibit mixed morphological and molecular characteristics of hematopoietic stem cells, monocytes and fibroblasts. They likely represent the obligate intermediate stage of differentiation into mature mesenchymal cells of a bone marrow-derived precursor of the monocyte lineage under permissive conditions. On in vitro stimulation with pro-fibrotic cytokines and growth factors, human fibrocytes produce large quantities of extracellular matrix components and further differentiate into cells identical to the contractile myofibroblasts that emerge at the tissue sites during repair processes and in some fibrotic lesions. Studies in various animal models of wound healing or fibrotic diseases have confirmed the ability of fibrocytes to differentiate into mature mesenchymal cells in vivo and have suggested a causal link between fibrocyte accumulation and ongoing tissue fibrogenesis or vascular remodeling in response to tissue damage or hypoxia. Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in human hypertrophic scars, in the skin of patients affected by nephrogenic systemic fibrosis, in human atherosclerotic lesions, and in pulmonary diseases characterized by repeated cycles of inflammation and repair, like asthma. The presence of fibrocyte-like cells has been reported in human chronic pancreatitis and chronic cystitis. Similar cells also populate the stroma surrounding human benign tumors. The available data indicate that human fibrocytes serve as a source of mature mesenchymal cells during reparative processes and in fibrotic disorders or stromal reactions predominantly associated with a persistent inflammatory infiltrate or with the selective recruitment of monocytes induced by ischemic changes and tumor development. A deeper understanding of the mechanisms involved in fibrocyte differentiation in these pathological conditions may lead to the development of novel therapies for

  9. A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

    ERIC Educational Resources Information Center

    Williams, Todd O.

    2012-01-01

    A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

  10. Mother-infant dyadic reparation and individual differences in vagal tone affect 4-month-old infants' social stress regulation.

    PubMed

    Provenzi, Livio; Casini, Erica; de Simone, Paola; Reni, Gianluigi; Borgatti, Renato; Montirosso, Rosario

    2015-12-01

    Infants' social stress regulation (i.e., reactivity and recovery) might be affected by mother-infant dyadic functioning and infants' vagal tone (i.e., respiratory sinus arrhythmia, RSA). This study investigated the role of a specific dyadic functioning feature (i.e., dyadic reparation) and individual differences in vagal tone regulation (i.e., RSA suppression vs. non-suppression) in relation to social stress regulation in 4-month-old infants. A total of 65 mother-infant dyads participated in the face-to-face still-face paradigm. Social stress reactivity and recovery were measured as negative emotionality during Still-Face and Reunion episodes, respectively. RSA was measured during Play, Still-Face, and Reunion episodes. Suppressors had higher dyadic reparation during Play and higher recovery from social stress compared with non-suppressors. Higher reparation during Play was associated with lower reactivity and higher recovery only for suppressors. Findings suggest a joint role of infants' RSA individual differences and dyadic reparation in affecting infants' social stress regulation at 4 months of age. PMID:26247809

  11. Matrix Metalloproteinases and Neurotrauma: Evolving Roles in Injury and Reparative Processes

    PubMed Central

    Zhang, Haoqian; Adwanikar, Hita; Werb, Zena; Noble-Haeusslein, Linda J.

    2010-01-01

    Matrix metalloproteinases (MMPs) are involved in a wide range of proteolytic events in fetal development and normal tissue remodeling as well as wound healing and inflammation. In the CNS, they have been implicated in a variety of neurodegenerative diseases ranging from multiple sclerosis to Alzheimer disease and are integral to stroke-related cell damage. Although studies implicate increased activity of MMPs in pathogenesis in the CNS, there is also a growing literature to support their participation in events that support recovery processes. Here the authors provide a brief overview of MMPs and their regulation, address their complex roles following traumatic injuries to the adult and developing CNS, and consider their time- and context-dependent signatures that influence both injury and reparative processes. PMID:20400713

  12. Evaluation of reparative dentin formation of ProRoot MTA, Biodentine and BioAggregate using micro-CT and immunohistochemistry

    PubMed Central

    Kim, Jia; Song, Young-Sang; Min, Kyung-San; Kim, Sun-Hun; Koh, Jeong-Tae

    2016-01-01

    Objectives The purpose of this study was to assess the ability of two new calcium silicate-based pulp-capping materials (Biodentine and BioAggregate) to induce healing in a rat pulp injury model and to compare them with mineral trioxide aggregate (MTA). Materials and Methods Eighteen rats were anesthetized, cavities were prepared and the pulp was capped with either of ProRoot MTA, Biodentine, or BioAggregate. The specimens were scanned using a high-resolution micro-computed tomography (micro-CT) system and were prepared and evaluated histologically and immunohistochemically using dentin sialoprotein (DSP). Results On micro-CT analysis, the ProRoot MTA and Biodentine groups showed significantly thicker hard tissue formation (p < 0.05). On H&E staining, ProRoot MTA showed complete dentin bridge formation with normal pulpal histology. In the Biodentine and BioAggregate groups, a thick, homogeneous hard tissue barrier was observed. The ProRoot MTA specimens showed strong immunopositive reaction for DSP. Conclusions Our results suggest that calcium silicate-based pulp-capping materials induce favorable effects on reparative processes during vital pulp therapy and that both Biodentine and BioAggregate could be considered as alternatives to ProRoot MTA. PMID:26877988

  13. [The stimulation of reparative regeneration in the treatment of fractures of the extremities with the use of new biotechnologies].

    PubMed

    Sorokin, G V; Borovkov, V N; Eremin, A V; Orlov, A A; Saburina, I N

    2013-01-01

    The paper presents the results of a study of Russian and foreign authors on modern methods of stimulation of reparative regeneration of bone tissue. Highlight general principles for the construction and use of bioplastic materials. An attempt to classify the most famous of biomaterials based on their physico-chemical and biological properties, as well as identified trends in the further development of tissue engineering and its importance in traumatology and orthopedics. PMID:24340626

  14. A New Method to Stabilize C-Kit Expression in Reparative Cardiac Mesenchymal Cells.

    PubMed

    Wysoczynski, Marcin; Dassanayaka, Sujith; Zafir, Ayesha; Ghafghazi, Shahab; Long, Bethany W; Noble, Camille; DeMartino, Angelica M; Brittian, Kenneth R; Bolli, Roberto; Jones, Steven P

    2016-01-01

    Cell therapy improves cardiac function. Few cells have been investigated more extensively or consistently shown to be more effective than c-kit sorted cells; however, c-kit expression is easily lost during passage. Here, our primary goal was to develop an improved method to isolate c-kit(pos) cells and maintain c-kit expression after passaging. Cardiac mesenchymal cells (CMCs) from wild-type mice were selected by polystyrene adherence properties. CMCs adhering within the first hours are referred to as rapidly adherent (RA); CMCs adhering subsequently are dubbed slowly adherent (SA). Both RA and SA CMCs were c-kit sorted. SA CMCs maintained significantly higher c-kit expression than RA cells; SA CMCs also had higher expression endothelial markers. We subsequently tested the relative efficacy of SA vs. RA CMCs in the setting of post-infarct adoptive transfer. Two days after coronary occlusion, vehicle, RA CMCs, or SA CMCs were delivered percutaneously with echocardiographic guidance. SA CMCs, but not RA CMCs, significantly improved cardiac function compared to vehicle treatment. Although the mechanism remains to be elucidated, the more pronounced endothelial phenotype of the SA CMCs coupled with the finding of increased vascular density suggest a potential pro-vasculogenic action. This new method of isolating CMCs better preserves c-kit expression during passage. SA CMCs, but not RA CMCs, were effective in reducing cardiac dysfunction. Although c-kit expression was maintained, it is unclear whether maintenance of c-kit expression per se was responsible for improved function, or whether the differential adherence property itself confers a reparative phenotype independently of c-kit. PMID:27536657

  15. Possible involvement of inflammatory/reparative processes in the development of uterine fibroids.

    PubMed

    Protic, Olga; Toti, Paolo; Islam, Md Soriful; Occhini, Rossella; Giannubilo, Stefano Raffaele; Catherino, William H; Cinti, Saverio; Petraglia, Felice; Ciavattini, Andrea; Castellucci, Mario; Hinz, Boris; Ciarmela, Pasquapina

    2016-05-01

    Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the "usual leiomyoma", characterized by overexpression of ECM proteins, whereas the "cellular type" has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the "usual type". Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the "usual type", we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the "cellular type", stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth. PMID:26613601

  16. A New Method to Stabilize C-Kit Expression in Reparative Cardiac Mesenchymal Cells

    PubMed Central

    Wysoczynski, Marcin; Dassanayaka, Sujith; Zafir, Ayesha; Ghafghazi, Shahab; Long, Bethany W.; Noble, Camille; DeMartino, Angelica M.; Brittian, Kenneth R.; Bolli, Roberto; Jones, Steven P.

    2016-01-01

    Cell therapy improves cardiac function. Few cells have been investigated more extensively or consistently shown to be more effective than c-kit sorted cells; however, c-kit expression is easily lost during passage. Here, our primary goal was to develop an improved method to isolate c-kitpos cells and maintain c-kit expression after passaging. Cardiac mesenchymal cells (CMCs) from wild-type mice were selected by polystyrene adherence properties. CMCs adhering within the first hours are referred to as rapidly adherent (RA); CMCs adhering subsequently are dubbed slowly adherent (SA). Both RA and SA CMCs were c-kit sorted. SA CMCs maintained significantly higher c-kit expression than RA cells; SA CMCs also had higher expression endothelial markers. We subsequently tested the relative efficacy of SA vs. RA CMCs in the setting of post-infarct adoptive transfer. Two days after coronary occlusion, vehicle, RA CMCs, or SA CMCs were delivered percutaneously with echocardiographic guidance. SA CMCs, but not RA CMCs, significantly improved cardiac function compared to vehicle treatment. Although the mechanism remains to be elucidated, the more pronounced endothelial phenotype of the SA CMCs coupled with the finding of increased vascular density suggest a potential pro-vasculogenic action. This new method of isolating CMCs better preserves c-kit expression during passage. SA CMCs, but not RA CMCs, were effective in reducing cardiac dysfunction. Although c-kit expression was maintained, it is unclear whether maintenance of c-kit expression per se was responsible for improved function, or whether the differential adherence property itself confers a reparative phenotype independently of c-kit. PMID:27536657

  17. Reparation in unicellular green algae during chronic exposure to the action of mutagenic factors. II. Restoration of single-stranded DNA breaks following exposure of Chlamydomonas reinchardii to gamma-irradiation

    SciTech Connect

    Sergeeva, S.A.; Ptitsina, S.N.; Shevchenko, V.A.

    1986-12-01

    The restoration of single-stranded breaks in the DNA in different strains of unicellular green algae (chlamydomonads) during chronic exposure to the action of mutagenic factors following ..gamma..-irradiation was investigated. It was shown that the restoration of DNA breaks was most effective in the case of strain M ..gamma../sup mt/sup +//, which is resistant to radiation. Strains, that were sensitive to UV irradiation showed a similar order of DNA break restoration as the wild-type strain. Strain UVS-1 showed a higher level of restoration than the wild-type strain. The data indicated that chlamydomonads have different pathways of reparation, which lead to the restoration of breaks induced by ..gamma..-irradiation and UV-rays.

  18. Genetics Home Reference: dentinogenesis imperfecta

    MedlinePlus

    ... Review. Citation on PubMed Kim JW, Hu JC, Lee JI, Moon SK, Kim YJ, Jang KT, Lee SH, Kim CC, Hahn SH, Simmer JP. Mutational ... on PubMed Kim JW, Nam SH, Jang KT, Lee SH, Kim CC, Hahn SH, Hu JC, Simmer ...

  19. Dentinogenesis and Dentin Sialophosphoprotein (DSPP)

    PubMed Central

    Yamakoshi, Yasuo

    2010-01-01

    Dentin sialophosphoprotein (DSPP) is critical for proper mineralization of tooth dentin, and understanding its structure and function should yield important insights into how dentin biomineralization is controlled. During the recent six years, I have focused on characterizing DSPP-derived proteins isolated from developing porcine teeth. Porcine DSPP is expressed and secreted by odontoblasts and is processed by BMP-1, MMP-20 and MMP-2 into three main parts: dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP). We have learned that DSP is a proteoglycan that forms covalent dimers, DGP is a phosphorylated glycoprotein, and DPP is a highly phosphorylated intrinsically disordered protein that shows extensive length polymorphisms due to the genetic heterogeneity of its coding region. PMID:20157636

  20. [The research of biodegradation of a composite material used in reconstructive and reparative surgery of maxillofacial area].

    PubMed

    Malanchuk, V O; Astapenko, O O; Halatenko, N A; Rozhnova, R A

    2013-09-01

    Dates about the research of biodegradation of epoxy-polyurethane composite material used in reconstructive and reparative surgery of maxillofacial area are reflected in the article. Was founded: 1) notable biodegradation of species from epoxy-polyurethane composition in the term of observation up to 6 months was not founded. That testifies their preservation of physical and mechanical properties. 2) founded, that in species from epoxy-polyurethane composition, which contain levamisole, processes of biodegradation are faster then in species from pure epoxy-polyurethane composition and in species from epoxy-polyurethane composition with hydroxyapatite; 3) material from epoxy-polyurethane composition, which contains levamisole and hydroxyapatite, stays in biological environment in small quantity of petty fragments during the incubation in term of 2 years. So, it biodegrades practically totally. Authors suggest on the basis of achieved information, that the use of epoxy-polyurethane constructions that biodegrade, is pertinently in reconstructive maxillofacial surgery. PMID:25510095

  1. The Peruvian Truth Commission's mental health reparations: empowering survivors of political violence to impact public health policy.

    PubMed

    Laplante, Lisa J; Holguin, Miryam Rivera

    2006-01-01

    The Peruvian Truth and Reconciliation Commission (TRC), formed in 2001, turned national attention toward the serious mental health consequences of the country's 20-year internal armed conflict. The TRC prioritized reparations in mental health, using a legal justification that provided victims-survivors of the war with a rights-based framework for demanding that the public sector attend to their mental health needs. Since the majority of victims-survivors come from historically poor, rural, and marginalized populations and have tended to not exercise their right to health for a variety of social, economic, and cultural reasons, framing mental health in terms of rights helps to empower these people to impact the development of appropriate policies in mental health. The authors suggest that this process contributes directly to improving the mental health of this population. PMID:17265758

  2. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy

    PubMed Central

    Navitskaya, Svetlana; O’Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B.; Busik, Julia V.

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy. PMID:26760976

  3. An In vivo Model for Short-Term Evaluation of the Implantation Effects of Biomolecules or Stem Cells in the Dental Pulp

    PubMed Central

    Lacerda-Pinheiro, Sally; Marchadier, Arnaud; Donãs, Patricio; Septier, Dominique; Benhamou, Laurent; Kellermann, Odile; Goldberg, Michel; Poliard, Anne

    2008-01-01

    The continuously growing rodent incisor is a widely used model to investigate odontogenesis and mineralized tissue formation. This study focused on evaluating the mouse mandibular incisor as an experimental biological tool for analyzing in vivo the capacity of odontoblast-like progenitors or bioactive molecules to contribute to reparative dentinogenesis. We describe here a surgical procedure allowing direct access to the forming part of the incisor dental pulp Amelogenin peptide A+4 adsorbed on agarose beads, or dental pulp progenitor cells were implanted in the pulp following this procedure. After 10 days A+4 induced the formation of an osteodentin occluding almost the totality of the pulp compartment. Implantation of progenitor cells leads to formation of islets of osteodentin-like structures located centrally in the pulp. These pilot studies validate the incisor as an experimental model to test the capacity of progenitor cells or bioactive molecules to induce the formation of reparative dentin. PMID:19088885

  4. Laser-based technique for controlled damage of mesenchymal cell spheroids: a first step in studying reparation in vitro

    PubMed Central

    Ilina, I. V.; Zurina, I. M.; Roskova, A. E.; Gorkun, A. A.; Ovchinnikov, A. V.; Agranat, M. B.; Saburina, I. N.

    2016-01-01

    ABSTRACT Modern techniques of laser microsurgery of cell spheroids were used to develop a new simple reproducible model for studying repair and regeneration in vitro. Nanosecond laser pulses (wavelength 355 nm, frequency 100 Hz, pulse duration 2 ns) were applied to perform a microdissection of the outer and the inner zones of human bone marrow multipotent mesenchymal stromal cells (BM MMSC) spheroids. To achieve effective dissection and preservation of spheroid viability, the energy of laser pulses was optimized and adjusted in the range 7-9 μJ. After microdissection, the edges of the wound surface opened and the angular opening reached a value of more than 180°. The destruction of the initial spheroid structure was observed in the wound area, with surviving cells changing their shape into a round one. Partial restoration of a spheroid form took place in the first six hours. The complete structure restoration accompanying the reparative processes occurred gradually over seven days due to remodelling of surviving cells. PMID:27334698

  5. Laser-based technique for controlled damage of mesenchymal cell spheroids: a first step in studying reparation in vitro.

    PubMed

    Kosheleva, N V; Ilina, I V; Zurina, I M; Roskova, A E; Gorkun, A A; Ovchinnikov, A V; Agranat, M B; Saburina, I N

    2016-01-01

    Modern techniques of laser microsurgery of cell spheroids were used to develop a new simple reproducible model for studying repair and regeneration in vitro Nanosecond laser pulses (wavelength 355 nm, frequency 100 Hz, pulse duration 2 ns) were applied to perform a microdissection of the outer and the inner zones of human bone marrow multipotent mesenchymal stromal cells (BM MMSC) spheroids. To achieve effective dissection and preservation of spheroid viability, the energy of laser pulses was optimized and adjusted in the range 7-9 μJ. After microdissection, the edges of the wound surface opened and the angular opening reached a value of more than 180°. The destruction of the initial spheroid structure was observed in the wound area, with surviving cells changing their shape into a round one. Partial restoration of a spheroid form took place in the first six hours. The complete structure restoration accompanying the reparative processes occurred gradually over seven days due to remodelling of surviving cells. PMID:27334698

  6. [The level of DNA damage and DNA reparation rate in cells of earthworms sampled from natural populations for numerous generations inhabited territories with anthropogenically enhanced levels of radionuclides in soil].

    PubMed

    Kaneva, A V; Belykh, E S; Maystrenko, T A; Shadrin, D M; Pylina, Ya I; Velegzhaninov, I O

    2015-01-01

    Low doses of ionizing radiation and chemical toxic agent effects on biological systems on different organization levels have been studied by numerous researchers. But there is a clear lack of experimental data that allow one to reveal molecular and cellular adaptations of plants and animals from natural populations to adverse effects of environmental factors. The present study was aimed to assess genotoxic effects in earthworms Aporrectodea caliginosa Savigny and Lumbricus rubellus Hoffmeister sampled from the populations that during numerous generations inhabited the territories with a technogeneously enhanced content of natural origin radionuclides and heavy metals in soil. The levels ofthe DNA damage detected with alkaline and neutral versions of Comet-assay in invertebrates from contaminated territories were established not to differ from the spontaneous level found in the animals from the reference population. At the same time the rate of the DNA damage reparation induced in A. caliginosa sampled from the contaminated sites with additional acute γ-irradiation (4 Gy) was found to be considerably higher as compared with earthworms from the reference population. PMID:25962273

  7. Autocrine effects of interleukin-6 mediate acute-phase proinflammatory and tissue-reparative transcriptional responses of canine bladder mucosa.

    PubMed

    Wood, Michael W; Breitschwerdt, Edward B; Gookin, Jody L

    2011-02-01

    During early urinary tract infection (UTI) the interplay between invading bacteria and the urothelium elicits a mucosal response aimed at clearing infection. Unfortunately, the resultant inflammation and associated local tissue injury are responsible for patient symptoms. Interleukin-6 (IL-6), a cytokine released during acute UTI, has both pro- and anti-inflammatory effects on other body systems. Within the urothelium, the IL-6 native-tissue origin, the target cell type(s), and ultimate effect of the cytokine on target cells are largely unknown. In the present study we modeled the UTI IL-6 response ex vivo using canine bladder mucosa mounted in Ussing chambers to determine the inflammatory and reparative role of IL-6. We demonstrated that uropathogenic Escherichia coli infection stimulates the synthesis of IL-6 by all urothelial cell layers, with the urothelial cells alone representing the only site of unequivocal IL-6 receptor expression. Autocrine effects of IL-6 were supported by the activation of urothelial STAT3 signaling and SOCS3 expression. Using exogenous IL-6, a microarray approach, and quantitative reverse transcriptase PCR (q-RT-PCR), 5 target genes (tumor necrosis factor alpha, interleukin-1β, matrix metallopeptidase 2, heparan sulfate d-glucosaminyl 3-O-sulfotransferase 3A1, and hyaluronan synthase 2) that have direct or indirect roles in promoting a proinflammatory state were identified. Two of these genes, heparan sulfate d-glucosaminyl 3-O-sulfotransferase 3A1 and hyaluronan synthase 2, are also potentially important mediators of wound repair via the production of glycosaminoglycan components. These findings suggest that IL-6 secretion during acute UTI may serve a dual biological role by initiating the inflammatory response while also repairing urothelial defenses. PMID:21115724

  8. Autocrine Effects of Interleukin-6 Mediate Acute-Phase Proinflammatory and Tissue-Reparative Transcriptional Responses of Canine Bladder Mucosa▿

    PubMed Central

    Wood, Michael W.; Breitschwerdt, Edward B.; Gookin, Jody L.

    2011-01-01

    During early urinary tract infection (UTI) the interplay between invading bacteria and the urothelium elicits a mucosal response aimed at clearing infection. Unfortunately, the resultant inflammation and associated local tissue injury are responsible for patient symptoms. Interleukin-6 (IL-6), a cytokine released during acute UTI, has both pro- and anti-inflammatory effects on other body systems. Within the urothelium, the IL-6 native-tissue origin, the target cell type(s), and ultimate effect of the cytokine on target cells are largely unknown. In the present study we modeled the UTI IL-6 response ex vivo using canine bladder mucosa mounted in Ussing chambers to determine the inflammatory and reparative role of IL-6. We demonstrated that uropathogenic Escherichia coli infection stimulates the synthesis of IL-6 by all urothelial cell layers, with the urothelial cells alone representing the only site of unequivocal IL-6 receptor expression. Autocrine effects of IL-6 were supported by the activation of urothelial STAT3 signaling and SOCS3 expression. Using exogenous IL-6, a microarray approach, and quantitative reverse transcriptase PCR (q-RT-PCR), 5 target genes (tumor necrosis factor alpha, interleukin-1β, matrix metallopeptidase 2, heparan sulfate d-glucosaminyl 3-O-sulfotransferase 3A1, and hyaluronan synthase 2) that have direct or indirect roles in promoting a proinflammatory state were identified. Two of these genes, heparan sulfate d-glucosaminyl 3-O-sulfotransferase 3A1 and hyaluronan synthase 2, are also potentially important mediators of wound repair via the production of glycosaminoglycan components. These findings suggest that IL-6 secretion during acute UTI may serve a dual biological role by initiating the inflammatory response while also repairing urothelial defenses. PMID:21115724

  9. [Study of reparative DNA synthesis in lymphocytes of persons occupationally exposed to radiation].

    PubMed

    Nikanorova, E A; Ivanov, K Iu; Khaĭmovich, T I; Ptitsina, S N; Shevchenko, V A

    2002-01-01

    The UDS efficiency in lymphocytes of professionals chronically exposed to gamma/neutron radiation, as well as for a control cohort was estimated. A credible reduction of UV-induced UDS (KUV) index as compared to the control was demonstrated. This shows an invalid repair state of blood cells in professionals. As for the control cohort, the decreasing tendency of UDS index with age was found. The correlative analysis of UDS index dependence upon an absorbed dose (based on physical dosimetry data) revealed the trend towards repair index reduction along with a higher total absorbed doze, that is followed by UDS index coming onto a plateau. It was also demonstrated that after a sharp and/or accidental irradiation UDS index reduces as compared to permanent portioned irradiation. It was not observed the influence of smoking upon UDS efficiency in blood lymphocytes neither for control, nor for experimental group. The analysis of vitamin therapy of the both cohorts showed that such therapy raises UDS index of the control (i.e., non-professional) group. Besides, it was found out an additional positive effect of vitamin therapy, i.e. doze leveling in long-term perspective after irradiation. The most expressed KUV/doze correlation was characteristic for professionals, who do not take vitamins and do not smoke. This proves that in blood cells of professionals it is preserved a dependence of repair system invalidity upon the absorbed doze without similar external factors. PMID:12530166

  10. Effects of preventive administration of oxidized dextran on liver injury and reparative regeneration in mice infected with influenza A/H5N1 virus.

    PubMed

    Shkurupy, V A; Potapova, O V; Sharkova, T V; Shestopalov, A M; Troitskii, A V

    2015-02-01

    Intranasal infection of outbred male mice with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus led to high (85%) mortality of animals. Morphological studies of liver specimens showed destructive changes in the parenchyma (93.5% hepatocytes), caused by long persistence of the virus in the liver. The virus persistence was conjugated with activation of cellular immunity, manifesting by an increase in the counts of cells with high expression of proinflammatory cytokines (TNF-α) and lysosomal enzymes (lysozyme, cathepsin D). Injections of oxidized dextran 3 and 1 days before infection reduced mortality and 2-fold attenuated destructive changes in the liver, presumably due to prevention of virus penetration into the target cells, modulation of immune reactions, and stimulation of reparative plastic processes. PMID:25708331

  11. [Reparative Neurogenesis in the Brain and Changes in the Optic Nerve of Adult Trout Oncorhynchus mykiss after Mechanical Damage of the Eye].

    PubMed

    Puschina, E V; Varaksin, A A; Obukhov, D K

    2016-01-01

    Reparative proliferation and neurogenesis in the brain integrative centers after mechanical eye injury in an adult trout Oncorhynchus mykiss have been studied. We have found that proliferation and neurogenesis in proliferative brain regions, the cerebellum, and the optic tectum were significantly enhanced after the eye injury. The cerebellum showed a significant increase in the proliferative activity of the cells of the dorsal proliferative zone and parenchymal cells of the molecular and granular layers. One week after the injury, PCNA-positive radial glia cells have been identified in the tectum. We have found for the first time that the eye trauma resulted in the development of local clusters of undifferentiated cells forming so called neurogenic niches in the tectum and cerebellum. The differentiation of neuronal cells detected by labeling cells with antibodies against the protein HuC/D occurred in the proliferative zones of the telencephalon, the optic tectum, cerebellum, and medulla of a trout within 2 days after the injury. We have shown that the HuC/D expression is higher in the proliferative brain regions than in the definitive neurons of a trout. In addition, we have examined cell proliferation, migration, and apoptosis caused by the eye injury in the contra- and ipsilateral optic nerves and adjacent muscle fibers 2 days after the trauma. The qualitative and quantitative assessment of proliferation and apoptosis in the cells of the optic nerve of a trout has been made using antibodies against PCNA and the TUNEL method. PMID:27149746

  12. Biomimetic fiber mesh scaffolds based on gelatin and hydroxyapatite nano-rods: Designing intrinsic skills to attain bone reparation abilities.

    PubMed

    Sartuqui, Javier; Gravina, A Noel; Rial, Ramón; Benedini, Luciano A; Yahia, L'Hocine; Ruso, Juan M; Messina, Paula V

    2016-09-01

    Intrinsic material skills have a deep effect on the mechanical and biological performance of bone substitutes, as well as on its associated biodegradation properties. In this work we have manipulated the preparation of collagenous derived fiber mesh frameworks to display a specific composition, morphology, open macroporosity, surface roughness and permeability characteristics. Next, the effect of the induced physicochemical attributes on the scaffold's mechanical behavior, bone bonding potential and biodegradability were evaluated. It was found that the scaffold microstructure, their inherent surface roughness, and the compression strength of the gelatin scaffolds can be modulated by the effect of the cross-linking agent and, essentially, by mimicking the nano-scale size of hydroxyapatite in natural bone. A clear effect of bioactive hydroxyapatite nano-rods on the scaffolds skills can be appreciated and it is greater than the effect of the cross-linking agent, offering a huge perspective for the upcoming progress of bone implant technology. PMID:27220014

  13. Chronic reparative changes in medium-sized vessels in a case of primary cutaneous anaplastic large-cell lymphoma with angioinvasive features and cytotoxic phenotype: new histopathological findings in line with indolent clinical behavior.

    PubMed

    Macarenco, Ricardo S; de Oliveira, Deilson Elgui

    2015-05-01

    Angioinvasion/angiodestruction has been reported in a small subset of primary cutaneous anaplastic large-cell lymphomas (PCALCL). Recently, PCALCL with angioinvasive features and cytotoxic phenotype has been characterized as a variant associated with good clinical outcomes despite worrisome histopathologic features. We report a case of PCALCL with angioinvasive features and cytotoxic phenotype associated with reparative changes on the wall of medium-sized vessels involved by the neoplasm, including intimal fibroblastic proliferation and luminal obliteration. This vascular pattern, although previously unreported in PCALCL, is in accordance with the indolent behavior observed in this entity and provides a further link with lymphomatoid papulosis type E. PMID:25365499

  14. Reparative dentistry or restorative dentistry?

    PubMed

    Small, Bruce W

    2008-01-01

    The real definition of restorative dentistry is found in the heart and hands of each individual restorative dentist. His or her training, continuing dental education, mentors, needs (financial and emotional), and style of practice all help to develop a philosophy of dental practice that affects daily restorative decisions. Depending on the factors described above, the decision to repair a tooth or change the environment and restore the tooth to a different shape, size, or color also may change. In recent years, patients' esthetic desires have become more of a factor than they were in previous decades. There are no exact written-tn-stone definitions of restorative dentistry, since the answers are operator-dependent and can vary. This column is meant to be food for thought and perhaps inspire discussion when dentists assemble for meetings or study clubs with the goal of delivering longer-lasting dentistry through a restorative dental practice. PMID:18348367

  15. Experiment K-310: The effect of space flight on ostenogenesis and dentinogenesis in the mandible of rats. Supplement 1: The effects of space flight on alveolar bone modeling and remodeling in the rat mandible

    NASA Technical Reports Server (NTRS)

    Van, P. T.; Vignery, A.; Bacon, R.

    1981-01-01

    The histomorphometric study of alveolar bone, a non-weight-bearing bone submitted mainly to the mechanical stimulations of mastication, showed that space flight decreases the remodeling activity but does not induce a negative balance between resorption and formation. The most dramatic effect of space flight has been observed along the periosteal surface, and especially in areas not covered with masticatory muscles, where bone formation almost stopped completely during the flight period. This bone, having been submitted to the same mechanical forces in the flight animals and the controls, leads to the conclusion that factors other than mechanical loading might be involved in the decreased bone formation during flight.

  16. Evaluation of gamma-Induced Apoptosis in Human Peripheral Blood Lymphocytes

    SciTech Connect

    Baranova, Elena; Boreyko, Alla; Ravnachka, Ivanka; Saveleva, Maria

    2010-01-05

    Several experiments have been performed to study regularities in the induction of apoptotic cells in human lymphocytes by {sup 60}Cogamma-rays at different times after irradiation. Apoptosis induction by {sup 60}Cogamma-rays in human lymphocytes in different cell cycle phases (G{sub 0}, S, G{sub 1}, and G{sub 2}) has been studied. The maximal apoptosis output in lymphocyte cells was observed in the S phase. Modifying effect of replicative and reparative DNA synthesis inhibitors - 1-beta-D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (Hu) - on the kinetics of {sup 60}Cogamma-rays induced apoptosis in human lymphocytes has been studied.

  17. To assess the reparative ability of differentiated mesenchymal stem cells in a rat critical size bone repair defect model using high frequency co-registered photoacoustic/ultrasound imaging and micro computed tomography

    NASA Astrophysics Data System (ADS)

    Zafar, Haroon; Gaynard, Sean; O'Flatharta, Cathal; Doroshenkova, Tatiana; Devine, Declan; Sharif, Faisal; Barry, Frank; Hayes, Jessica; Murphy, Mary; Leahy, Martin J.

    2016-03-01

    Stem cell based treatments hold great potential and promise to address many unmet clinical needs. The importance of non-invasive imaging techniques to monitor transplanted stem cells qualitatively and quantitatively is crucial. The objective of this study was to create a critical size bone defect in the rat femur and then assess the ability of the differentiated mesenchymal stem cells (MSCs) to repair the defect using high frequency co-registered photoacoustic(PA)/ultrasound(US) imaging and micro computed tomography (μCT) over an 8 week period. Combined PA and US imaging was performed using 256 elements, 21 MHz frequency linear-array transducer combined with multichannel collecting system. In vivo 3D PA and US images of the defect bone in the rat femur were acquired after 4 and 8 weeks of the surgery. 3D co-registered structural such as microvasculature and the functional images such as total concentration of haemoglobin (HbT) and the haemoglobin oxygen saturation (sO2) were obtained using PA and US imaging. Bone formation was assessed after 4 and 8 weeks of the surgery by μCT. High frequency linear-array based coregistered PA/US imaging has been found promising in terms of non-invasiveness, sensitivity, adaptability, high spatial and temporal resolution at sufficient depths for the assessment of the reparative ability of MSCs in a rat critical size bone repair defect model.

  18. Topical application of lithium chloride on the pulp induces dentin regeneration.

    PubMed

    Ishimoto, Kazuya; Hayano, Satoru; Yanagita, Takeshi; Kurosaka, Hiroshi; Kawanabe, Noriaki; Itoh, Shinsuke; Ono, Mitsuaki; Kuboki, Takuo; Kamioka, Hiroshi; Yamashiro, Takashi

    2015-01-01

    We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration. PMID:25812134

  19. Topical Application of Lithium Chloride on the Pulp Induces Dentin Regeneration

    PubMed Central

    Ishimoto, Kazuya; Hayano, Satoru; Yanagita, Takeshi; Kurosaka, Hiroshi; Kawanabe, Noriaki; Itoh, Shinsuke; Ono, Mitsuaki; Kuboki, Takuo; Kamioka, Hiroshi; Yamashiro, Takashi

    2015-01-01

    We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration. PMID:25812134

  20. The effects of low-level laser therapy on orthodontically induced root resorption.

    PubMed

    Altan, A Burcu; Bicakci, A Altug; Mutaf, H Ilhan; Ozkut, Mahmut; Inan, V Sevinc

    2015-11-01

    The aim of this study was to evaluate the preventive and/or reparative effects of low-level laser therapy (LLLT) on orthodontically induced inflammatory root resorption (OIIRR) in rats. Thirty rats were divided into four groups (short-term control (SC), short-term laser (SL), long-term control (LC), long-term laser (LL)). In all groups, the left first molar was moved mesially for 11 days. At the end of this period, the rats in groups SC and SL were killed in order to observe the resorption lacunas and to evaluate whether LLLT had any positive effect on root resorption. The groups LC and LL were remained for a healing period of 14 days in order to observe spontaneous repair of the resorption areas and investigate whether LLLT had reparative effects on root resorption. A Ga-Al-As diode laser (Doris, CTL-1106MX, Warsaw, Poland) with a wavelength of 820 nm was used. In SL group, the first molars were irradiated with the dose of 4.8 J/cm2 (50 mW, 12 s, 0.6 J) on every other day during force application. In LL group, the irradiation period was started on the day of appliance removal and the first molars were irradiated with the dose of 4.8 J/cm2 on every other day for the next 14 days. LLLT significantly increased the number of osteoblasts and fibroblasts, and inflammatory response in SL group in comparison with SC group (P = .001). The amount of resorption did not represent any difference between the two groups (P = .16). In LL group, LLLT significantly increased the number of fibroblasts and decreased the amount of resorption in comparison with LC group (P = .001; P = .02). Both parameters indicating the reparative and the resorptive processes were found to be increased by LLLT applied during orthodontic force load. LLLT applied after termination of the orthodontic force significantly alleyed resorption and enhanced/accelerated the healing of OIIRR. LLLT has significant reparative effects on OIIRR while it is not possible to say that it definitely has a

  1. Reparative inflammation takes charge of tissue regeneration.

    PubMed

    Karin, Michael; Clevers, Hans

    2016-01-21

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an evolutionarily important process. Recent insights have shed light on the cellular and molecular processes through which conventional inflammatory cytokines and Wnt factors control mammalian tissue repair and regeneration. This is particularly important for regeneration in the gastrointestinal system, especially for intestine and liver tissues in which aberrant and deregulated repair results in severe pathologies. PMID:26791721

  2. The reparability of contemporary composite resins

    PubMed Central

    Spyrou, Maria; Koliniotou-Koumpia, Eugenia; Kouros, Pantelis; Koulaouzidou, Elisabeth; Dionysopoulos, Pavlos

    2014-01-01

    Objective: The objective was to investigate the way that various surface treatments could influence the bond strength of the repair of methacrylate (MC) and silorane (SIL) composites. Materials and Methods: A total of 160 MC and SIL cylindrical specimens were polymerized and aged in artificial saliva solution for 7 days. Depending on the following surface treatment (diamond bur or air abrasion), and the conditioning procedure (orthophosphoric acid or sodium hypochlorite), 16 groups were formed and repaired either with MC, either with SIL composite. Repaired specimens were subjected to an additional aging procedure in artificial saliva for 7 days, followed by thermo-cycling and then stressed in shear at a rate of 0.5 mm/min until failure. Failure patterns were analyzed using stereomicroscope and scanning electron microscopy. Results: MC composite showed statistically significant higher bond strength both as a base or repair material than SIL (P < 0.001). Statistically significant differences were not observed, when grinding and conditioning procedures was compared. Pretest failures were observed when aged MC-based composite was repaired with SIL-based. Conclusions: Type of composite seems to be the main factor influencing the bond strength of the repair. MC-based composite showed better repairability than SIL composite. Optimum repair conditions should include knowledge of the composite's composition. PMID:25202216

  3. Depletion of Hepatic Macrophages Aggravates Liver Lesions Induced in Rats by Thioacetamide (TAA).

    PubMed

    Golbar, Hossain M; Izawa, Takeshi; Wijesundera, Kavindra K; Bondoc, Alexandra; Tennakoon, Anusha H; Kuwamura, Mitsuru; Yamate, Jyoji

    2016-02-01

    Hepatic macrophages play crucial roles in hepatotoxicity. We investigated immunophenotypes of macrophages in liver injury induced in rats by thioacetamide (TAA; 300 mg/kg, intraperitoneal) after hepatic macrophage depletion; hepatic macrophages were depleted by liposomal clodronate (CLD; 10 ml/kg, i.v.) one day before TAA injection. Samples were obtained on post-TAA injection days 0, 1, 2, 3, 5, and 7. TAA injection induced coagulation necrosis of hepatocytes on days 1 through 3 and subsequent reparative fibrosis on days 5 and 7 in the centrilobular area, accompanied by increased numbers of M1 macrophages (expressing cluster of differentiation [CD]68 and major histocompatibility complex class II) and M2 macrophages (expressing CD163 and CD204) mainly on days 1 through 3. TAA + CLD treatment markedly decreased the numbers of M1 and M2 macrophages mainly on days 1 through 3; CD163(+) Kupffer cells were most sensitive to CLD depletion. In TAA + CLD-treated rats, interestingly, coagulation necrosis of hepatocytes was prolonged with more increased levels of hepatic enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase) to TAA-treated rats; reparative fibrosis was incomplete and replaced by dystrophic calcification in the injured area, indicating the aggravated damage. Furthermore, in TAA + CLD-treated rats, inflammatory factors (monocyte chemoattractant protein [MCP]-1, interferon-γ, tumor necrosis factor-α, and interleukin-10) and fibrosis-related factors (transforming growth factor-β1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1) were decreased at messenger RNA levels, indicating abnormal macrophage functions. It was clearly demonstrated that hepatic macrophages have important roles in tissue damage and remodeling in hepatotoxicity. PMID:26957569

  4. Zebrafish fin regeneration after cryoinjury-induced tissue damage

    PubMed Central

    Chassot, Bérénice; Pury, David

    2016-01-01

    ABSTRACT Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump. PMID:27215324

  5. Zebrafish fin regeneration after cryoinjury-induced tissue damage.

    PubMed

    Chassot, Bérénice; Pury, David; Jaźwińska, Anna

    2016-01-01

    Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump. PMID:27215324

  6. High pH-Sensitive TRPA1 Activation in Odontoblasts Regulates Mineralization.

    PubMed

    Kimura, M; Sase, T; Higashikawa, A; Sato, M; Sato, T; Tazaki, M; Shibukawa, Y

    2016-08-01

    Calcium hydroxide and mineral trioxide aggregate are widely used for indirect and direct pulp capping and root canal filling. Their dissociation into Ca(2+) and OH(-) in dental pulp creates an alkaline environment, which activates reparative/reactionary dentinogenesis. However, the mechanisms by which odontoblasts detect the pH of the extracellular environment remain unclear. We examined the alkali-sensitive intracellular Ca(2+) signaling pathway in rat odontoblasts. In the presence or absence of extracellular Ca(2+), application of alkaline solution increased intracellular Ca(2+) concentration, or [Ca(2+)]i Alkaline solution-induced [Ca(2+)]i increases depended on extracellular pH (8.5 to 10.5) in both the absence and the presence of extracellular Ca(2+) The amplitude was smaller in the absence than in the presence of extracellular Ca(2+) Each increase in [Ca(2+)]i, activated by pH 7.5, 8.5, or 9.5, depended on extracellular Ca(2+) concentration; the equilibrium binding constant for extracellular Ca(2+) concentration decreased as extracellular pH increased (1.04 mM at pH 7.5 to 0.11 mM at pH 9.5). Repeated applications of alkaline solution did not have a desensitizing effect on alkali-induced [Ca(2+)]i increases and inward currents. In the presence of extracellular Ca(2+), alkaline solution-induced [Ca(2+)]i increases were suppressed by application of an antagonist of transient receptor potential ankyrin subfamily member 1 (TRPA1) channels. Ca(2+) exclusion efficiency during alkaline solution-induced [Ca(2+)]i increases was reduced by a Na(+)-Ca(2+) exchanger antagonist. Alizarin red and von Kossa staining revealed increased mineralization levels under repeated high pH stimulation, whereas the TRPA1 antagonist strongly reduced this effect. These findings indicate that alkaline stimuli-such as the alkaline environment inside dental pulp treated with calcium hydroxide or mineral trioxide aggregate-activate Ca(2+) mobilization via Ca(2+) influx mediated by TRPA1

  7. Modelization of DNA fragmentation induced in human fibroblasts by Fe-56 ions

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Belli, M.; Campa, A.; Esposito, G.; Friedland, W.; Ottolenghi, A.; Paretzke, H.

    DNA double-strand breaks DSB are widely recognized as cellular critical lesions in the pathways leading from initial energy deposition by radiation to the formation of relevant biological endpoints such as gene mutations chromosome aberrations and cell death Chromatin conformation and radiation track structure are expected to have a strong influence on the spatial modulation of DSB induction at the scale of the nucleosome i e 100 base pairs bp and of the low-level chromatin fiber organization i e 1 kbp At larger scales the DNA fragmentation pattern induced by sparsely ionizing radiation approaches a scenario resulting from a random distribution of DSB However the pattern induced by high-LET irradiation can lead to deviation from randomness also at these scales This feature can have important biological consequences since spatial correlation of DSB is thought to affect their reparability Therefore studies on fragment size distributions induced by radiations of various qualities can help to link the physical characteristics of radiation with the cellular endpoints This is an important issue for understanding the main mechanisms of cell damage induced by HZE particles In this work we have compared the pattern of DNA fragmentation in the range 1-5700 kbp induced in human fibroblasts by gamma -rays with that induced by high-energy Fe-ions which have biological significance for radiation protection issues during long term astronauts travels The study has taken into account the comparison of the experimental fragmentation spectra

  8. Prompt repair of hydrogen peroxide-induced DNA lesions prevents catastrophic chromosomal fragmentation.

    PubMed

    Mahaseth, Tulip; Kuzminov, Andrei

    2016-05-01

    Iron-dependent oxidative DNA damage in vivo by hydrogen peroxide (H2O2, HP) induces copious single-strand(ss)-breaks and base modifications. HP also causes infrequent double-strand DNA breaks, whose relationship to the cell killing is unclear. Since hydrogen peroxide only fragments chromosomes in growing cells, these double-strand breaks were thought to represent replication forks collapsed at direct or excision ss-breaks and to be fully reparable. We have recently reported that hydrogen peroxide kills Escherichia coli by inducing catastrophic chromosome fragmentation, while cyanide (CN) potentiates both the killing and fragmentation. Remarkably, the extreme density of CN+HP-induced chromosomal double-strand breaks makes involvement of replication forks unlikely. Here we show that this massive fragmentation is further amplified by inactivation of ss-break repair or base-excision repair, suggesting that unrepaired primary DNA lesions are directly converted into double-strand breaks. Indeed, blocking DNA replication lowers CN+HP-induced fragmentation only ∼2-fold, without affecting the survival. Once cyanide is removed, recombinational repair in E. coli can mend several double-strand breaks, but cannot mend ∼100 breaks spread over the entire chromosome. Therefore, double-strand breaks induced by oxidative damage happen at the sites of unrepaired primary one-strand DNA lesions, are independent of replication and are highly lethal, supporting the model of clustered ss-breaks at the sites of stable DNA-iron complexes. PMID:27078578

  9. Mechanisms and Functional Significance of Stroke-Induced Neurogenesis

    PubMed Central

    Marlier, Quentin; Verteneuil, Sebastien; Vandenbosch, Renaud; Malgrange, Brigitte

    2015-01-01

    Stroke affects one in every six people worldwide, and is the leading cause of adult disability. After stroke, some limited spontaneous recovery occurs, the mechanisms of which remain largely unknown. Multiple, parallel approaches are being investigated to develop neuroprotective, reparative and regenerative strategies for the treatment of stroke. For years, clinical studies have tried to use exogenous cell therapy as a means of brain repair, with varying success. Since the rediscovery of adult neurogenesis and the identification of adult neural stem cells in the late nineties, one promising field of investigation is focused upon triggering and stimulating this self-repair system to replace the neurons lost following brain injury. For instance, it is has been demonstrated that the adult brain has the capacity to produce large numbers of new neurons in response to stroke. The purpose of this review is to provide an updated overview of stroke-induced adult neurogenesis, from a cellular and molecular perspective, to its impact on brain repair and functional recovery. PMID:26696816

  10. Mechanisms and Functional Significance of Stroke-Induced Neurogenesis.

    PubMed

    Marlier, Quentin; Verteneuil, Sebastien; Vandenbosch, Renaud; Malgrange, Brigitte

    2015-01-01

    Stroke affects one in every six people worldwide, and is the leading cause of adult disability. After stroke, some limited spontaneous recovery occurs, the mechanisms of which remain largely unknown. Multiple, parallel approaches are being investigated to develop neuroprotective, reparative and regenerative strategies for the treatment of stroke. For years, clinical studies have tried to use exogenous cell therapy as a means of brain repair, with varying success. Since the rediscovery of adult neurogenesis and the identification of adult neural stem cells in the late nineties, one promising field of investigation is focused upon triggering and stimulating this self-repair system to replace the neurons lost following brain injury. For instance, it is has been demonstrated that the adult brain has the capacity to produce large numbers of new neurons in response to stroke. The purpose of this review is to provide an updated overview of stroke-induced adult neurogenesis, from a cellular and molecular perspective, to its impact on brain repair and functional recovery. PMID:26696816

  11. The physical basis of ventilator-induced lung injury

    PubMed Central

    Plataki, Maria; Hubmayr, Rolf D

    2010-01-01

    Although mechanical ventilation (MV) is a life-saving intervention for patients with acute respiratory distress syndrome (ARDS), it can aggravate or cause lung injury, known as ventilator-induced lung injury (VILI). The biophysical characteristics of heterogeneously injured ARDS lungs increase the parenchymal stress associated with breathing, which is further aggravated by MV. Cells, in particular those lining the capillaries, airways and alveoli, transform this strain into chemical signals (mechanotransduction). The interaction of reparative and injurious mechanotransductive pathways leads to VILI. Several attempts have been made to identify clinical surrogate measures of lung stress/strain (e.g., density changes in chest computed tomography, lower and upper inflection points of the pressure–volume curve, plateau pressure and inflammatory cytokine levels) that could be used to titrate MV. However, uncertainty about the topographical distribution of stress relative to that of the susceptibility of the cells and tissues to injury makes the existence of a single ‘global’ stress/strain injury threshold doubtful. PMID:20524920

  12. Induced Abortion

    MedlinePlus

    ... Induced Abortion Patient Education FAQs Induced Abortion Patient Education Pamphlets - Spanish Induced Abortion FAQ043, May 2015 PDF Format Induced ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  13. Substance P induces M2-type macrophages after spinal cord injury.

    PubMed

    Jiang, Mei H; Chung, Eunkyung; Chi, Guang F; Ahn, Woosung; Lim, Ji E; Hong, Hyun S; Kim, Dae W; Choi, Hyeongwon; Kim, Jiyoung; Son, Youngsook

    2012-09-12

    The potential benefits or the tissue-damaging effects of inflammatory response after central nervous system injuries have long been disputed. Recent studies have noted that substance P (SP), a neuropeptide, plays an important role in the wound-healing process by recruiting bone marrow stem cells to the injured tissue. In this study, we examined whether SP can enhance recovery from spinal cord injury (SCI) in Sprague-Dawley rats through its known function of stem cell mobilization and/or through the modulation of inflammation. We examined proinflammatory and anti-inflammatory cytokines and markers for macrophage subtypes. SP treatment modulated the SCI microenvironment toward a more anti-inflammatory and reparative one by inducing interleukin-10 and M2 macrophages and suppressing inducible nitric oxide synthase and tumor necrosis factor-α. This modulation was achieved at 1 day much earlier than SP-stimulated bone marrow stem cells' mobilization. Early intervention of the devastating inflammatory response by SP treatment caused the lesion cavity to become filled with robust axonal outgrowth that overlaid the M2 macrophages at 2 weeks--all of which culminated in tissue sparing and improvement in functional recovery from the SCI. SP is therefore a potential anti-inflammatory modulator for the treatment of injury-induced inflammatory central nervous system disorders. PMID:22825006

  14. Mobilization of endogenous bone marrow-derived stem cells in a thioacetamide-induced mouse model of liver fibrosis.

    PubMed

    El-Akabawy, Gehan; El-Mehi, Abeer

    2015-06-01

    The clinical significance of enhancing endogenous circulating haematopoietic stem cells is becoming increasingly recognized, and the augmentation of circulating stem cells using granulocyte-colony stimulating factor (G-CSF) has led to promising preclinical and clinical results for several liver fibrotic conditions. However, this approach is largely limited by cost and the infeasibility of maintaining long-term administration. Preclinical studies have reported that StemEnhance, a mild haematopoietic stem cell mobilizer, promotes cardiac muscle regeneration and remedies the manifestation of diabetes. However, the effectiveness of StemEnhance in ameliorating liver cirrhosis has not been studied. This study is the first to evaluate the beneficial effect of StemEnhance administration in a thioacetamide-induced mouse model of liver fibrosis. StemEnhance augmented the number of peripheral CD34-positive cells, reduced hepatic fibrosis, improved histopathological changes, and induced endogenous liver proliferation. In addition, VEGF expression was up-regulated, while TNF-α expression was down-regulated in thioacetamide-induced fibrotic livers after StemEnhance intake. These data suggest that StemEnhance may be useful as a potential therapeutic candidate for liver fibrosis by inducing reparative effects via mobilization of haematopoietic stem cells. PMID:25857836

  15. MEPE-Derived ASARM Peptide Inhibits Odontogenic Differentiation of Dental Pulp Stem Cells and Impairs Mineralization in Tooth Models of X-Linked Hypophosphatemia

    PubMed Central

    Khaddam, Mayssam; Naji, Jiar; Coyac, Benjamin R.; Baroukh, Brigitte; Letourneur, Franck; Lesieur, Julie; Decup, Franck; Le Denmat, Dominique; Nicoletti, Antonino; Poliard, Anne; Rowe, Peter S.; Huet, Eric; Vital, Sibylle Opsahl; Linglart, Agnès; McKee, Marc D.; Chaussain, Catherine

    2013-01-01

    Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) cause X-linked familial hypophosphatemic rickets (XLH), a disorder having severe bone and tooth dentin mineralization defects. The absence of functional PHEX leads to abnormal accumulation of ASARM (acidic serine- and aspartate-rich motif) peptide − a substrate for PHEX and a strong inhibitor of mineralization − derived from MEPE (matrix extracellular phosphoglycoprotein) and other matrix proteins. MEPE-derived ASARM peptide accumulates in tooth dentin of XLH patients where it may impair dentinogenesis. Here, we investigated the effects of ASARM peptides in vitro and in vivo on odontoblast differentiation and matrix mineralization. Dental pulp stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into a 3D collagen scaffold, and induced towards odontogenic differentiation. Cultures were treated with synthetic ASARM peptides (phosphorylated and nonphosphorylated) derived from the human MEPE sequence. Phosphorylated ASARM peptide inhibited SHED differentiation in vitro, with no mineralized nodule formation, decreased odontoblast marker expression, and upregulated MEPE expression. Phosphorylated ASARM peptide implanted in a rat molar pulp injury model impaired reparative dentin formation and mineralization, with increased MEPE immunohistochemical staining. In conclusion, using complementary models to study tooth dentin defects observed in XLH, we demonstrate that the MEPE-derived ASARM peptide inhibits both odontogenic differentiation and matrix mineralization, while increasing MEPE expression. These results contribute to a partial mechanistic explanation of XLH pathogenesis: direct inhibition of mineralization by ASARM peptide leads to the mineralization defects in XLH teeth. This process appears to be positively reinforced by the increased MEPE expression induced by ASARM. The MEPE-ASARM system can therefore be considered as a potential therapeutic

  16. Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.

    PubMed

    Dong, Yanjun; Pan, Jenny S; Zhang, Liping

    2013-01-01

    Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex) suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production. PMID:23516508

  17. Myostatin Suppression of Akirin1 Mediates Glucocorticoid-Induced Satellite Cell Dysfunction

    PubMed Central

    Dong, Yanjun; Pan, Jenny S.; Zhang, Liping

    2013-01-01

    Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex) suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production. PMID:23516508

  18. Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits.

    PubMed

    Ouédraogo, Moustapha; Lamien-Sanou, Assita; Ramdé, Norbert; Ouédraogo, Aimé S; Ouédraogo, Moussa; Zongo, Salifou P; Goumbri, Olga; Duez, Pierre; Guissou, Pierre I

    2013-03-01

    Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. The nephroprotective effect of aqueous-ethanolic extract of Moringa oleifera leaves (150 and 300 mg/kg) was evaluated against gentamicin-induced (80 mg/kg) renal injury in rabbits. Serum urea and creatinine levels were evaluated as the markers of renal nephrotoxicity. At the end of the experiment, the kidneys of rabbits were excised for histological examinations and determination of lipid peroxidation levels. Serum urea and creatinine levels were reduced in the M. oleifera (150 and 300 mg/kg) plus gentamicin treated groups. On histological examinations, kidney of intoxicated rabbits groups which received M. oleifera extract showed reparative tendencies. A highly significant (p < 0.01) elevation was observed in lipid peroxidation (LPO) level in the kidneys of gentamicin-intoxicated rabbits whereas combined treatment of M. oleifera and gentamicin group showed a highly significant (p < 0.01) depletion in LPO. The present study indicates that aqueous-ethanolic extract of M. oleifera leaves attenuates renal injury in rabbits treated with gentamicin, possibly by inhibiting lipid peroxidation. PMID:22197459

  19. Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption.

    PubMed

    Xu, H; Snider, T N; Wimer, H F; Yamada, S S; Yang, T; Holmbeck, K; Foster, B L

    2016-01-01

    Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP(-/-)) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data indicate that MT1-MMP activity in the dental mesenchyme, and not in epithelial-derived HERS, is essential for proper tooth root formation and eruption. In summary, our studies point to an indispensable role for MT1-MMP-mediated matrix remodeling in tooth eruption through effects on bone formation, soft tissue remodeling and organization of the follicle/PDL region. PMID:26780723

  20. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    PubMed

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. PMID:24345734

  1. Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats

    PubMed Central

    Fujita, Shunsuke; Ushio, Soichiro; Ozawa, Nana; Masuguchi, Ken; Kawashiri, Takehiro; Oishi, Ryozo; Egashira, Nobuaki

    2015-01-01

    Background Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells. Methods Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves. Results Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice. Conclusion These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes. PMID:26536615

  2. Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

    PubMed Central

    2010-01-01

    Background Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ≤5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy. PMID:20925932

  3. MMP2-cleavage of DMP1 generates a bioactive peptide promoting differentiation of dental pulp stem/progenitor cell.

    PubMed

    Chaussain, Catherine; Eapen, Asha Sarah; Huet, Eric; Floris, Caroline; Ravindran, Sriram; Hao, Jianjun; Menashi, Suzanne; George, Anne

    2009-01-01

    Dentin Matrix Protein 1 (DMP1) plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2) is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain) domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N- and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP) and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury. PMID:19908197

  4. MMP2-CLEAVAGE OF DMP1 GENERATES A BIOACTIVE PEPTIDE PROMOTING DIFFERENTIATION OF DENTAL PULP STEM/PROGENITOR CELLS

    PubMed Central

    Chaussain, Catherine; Eapen, Asha Sarah; Huet, Eric; Floris, Caroline; Ravindran, Sriram; Hao, Jianjun; Menashi, Suzanne; George, Anne

    2011-01-01

    Dentin Matrix Protein 1 (DMP1) plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2) is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain) domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N- and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP) and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury. PMID:19908197

  5. Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart

    PubMed Central

    Ylä-Herttuala, Seppo; Betsholtz, Christer; Andrae, Johanna

    2016-01-01

    Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells in vertebrate development. To what extent PDGFs also exert beneficial homeostatic or reparative roles in adult organs, as opposed to adverse fibrogenic responses in pathology, are unclear. PDGF signaling plays critical roles during heart development, during which forced overexpression of PDGFs induces detrimental cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct myocardial repair. Different PDGFs may exert different effects mediated through the two PDGF receptors (PDGFRα and PDGFRβ) in different cell types. Here, we assessed responses induced by five known PDGF isoforms in the adult mouse heart in the context of adenovirus vector-mediated inflammation. Our results show that different PDGFs have different, in some cases even opposing, effects. Strikingly, whereas the major PDGFRα agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFRα-positive fibroblasts, PDGFRβ agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirus-induced inflammation and produced a small and dense scar (PDGF-D). These results provide evidence for PDGF isoform-specific inflammation-modulating functions that may have therapeutic implications. They also illustrate a surprising complexity in the PDGF-mediated pathophysiological responses. PMID:27513343

  6. Queer Reparations: Dialogue and the Queer Past of Schooling

    ERIC Educational Resources Information Center

    Marshall, Daniel

    2014-01-01

    This article reflects on historical homophobia within educational practice and administration as an effort to consider how we might promote dialogue around the queer past of schooling. Along the way, it provides some discussion of the significance of archival knowledge in helping us to develop an understanding of the past while also providing…

  7. Juneteenth, Black Texans and the Case of Reparations

    ERIC Educational Resources Information Center

    Jeffries, Judson L.

    2004-01-01

    The history of Juneteenth, slavery, and deferred freedom is filled with heroes, plots, and interesting twists. For many of African descent, Juneteenth is a day to commemorate the official ending of American slavery. Slavery did not end with the issuance of the Emancipation Proclamation. Not until June 19, 1865 was slavery abolished--two and a half…

  8. Bringing Culture in: Community Responses to Apology, Reconciliation, and Reparations

    ERIC Educational Resources Information Center

    Miller, Bruce Granville

    2006-01-01

    In this paper, the author describes historic Coast Salish ritual practices and the concepts regarding wrongdoing and redemption that underlie them. He draws out the implications, particularly the associated dangers, derived from these existing rituals for ritual work conducted by outsiders engaging Coast Salish peoples. Finally, he considers the…

  9. Vascular Ageing and Exercise: Focus on Cellular Reparative Processes

    PubMed Central

    Ross, Mark D.; Malone, Eva; Florida-James, Geraint

    2016-01-01

    Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with “vascular ageing” and are often accompanied by a reduced ability for the body to repair vascular damage, termed “reendothelialization.” Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this “vascular ageing” process. PMID:26697131

  10. "Transformational Ministry" and "Reparative Therapy": Transformative Learning Gone Awry.

    ERIC Educational Resources Information Center

    Grace, Andre P.

    North Americans' fear and preoccupation with safety and security as a result of the September 11 attacks is similar to that felt by gays and lesbians in daily life. Queer persons are not part of the Christian family, according to Jerry Falwell and other rightist Christian fundamentalists, including those involved in transformative ministry and…

  11. Magnetic responsive hydroxyapatite composite scaffolds construction for bone defect reparation

    PubMed Central

    Zeng, Xiao Bo; Hu, Hao; Xie, Li Qin; Lan, Fang; Jiang, Wen; Wu, Yao; Gu, Zhong Wei

    2012-01-01

    Introduction In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. A type of magnetic scaffold composed of magnetic nanoparticles (MNPs) and hydroxyapatite (HA) for bone repair has been developed by our research group. Aim and methods In this study, to investigate the influence of the MNP content (in the scaffolds) on the cell behaviors and the interactions between the magnetic scaffold and the exterior magnetic field, a series of MNP-HA magnetic scaffolds with different MNP contents (from 0.2% to 2%) were fabricated by immersing HA scaffold into MNP colloid. ROS 17/2.8 and MC3T3-E1 cells were cultured on the scaffolds in vitro, with and without an exterior magnetic field, respectively. The cell adhesion, proliferation and differentiation were evaluated via scanning electron microscopy; confocal laser scanning microscopy; and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase, and bone gla protein activity tests. Results The results demonstrated the positive influence of the magnetic scaffolds on cell adhesion, proliferation, and differentiation. Further, a higher amount of MNPs on the magnetic scaffolds led to more significant stimulation. Conclusion The magnetic scaffold can respond to the exterior magnetic field and engender some synergistic effect to intensify the stimulating effect of a magnetic field to the proliferation and differentiation of cells. PMID:22848165

  12. Fibroblast growth factor-23 induces cellular senescence in human mesenchymal stem cells from skeletal muscle.

    PubMed

    Sato, Chisato; Iso, Yoshitaka; Mizukami, Takuya; Otabe, Koji; Sasai, Masahiro; Kurata, Masaaki; Sanbe, Takeyuki; Sekiya, Ichiro; Miyazaki, Akira; Suzuki, Hiroshi

    2016-02-12

    Although muscle wasting and/or degeneration are prevalent in patients with chronic kidney disease, it remains unknown whether FGF-23 influences muscle homeostasis and regeneration. Mesenchymal stem cells (MSCs) in skeletal muscle are distinct from satellite cells and have a known association with muscle degeneration. In this study we sought to investigate the effects of FGF-23 on MSCs isolated from human skeletal muscle in vitro. The MSCs expressed FGF receptors (1 through 4) and angiotensin-II type 1 receptor, but no traces of the Klotho gene were detected. MSCs and satellite cells were treated with FGF-23 and angiotensin-II for 48 h. Treatment with FGF-23 significantly decreased the number of MSCs compared to controls, while treatment with angiotensin-II did not. FGF-23 and angiotensin-II both left the cell counts of the satellite cells unchanged. The FGF-23-treated MSCs exhibited the senescent phenotype, as judged by senescence-associated β-galactosidase assay, cell morphology, and increased expression of p53 and p21 in western blot analysis. FGF-23 also significantly altered the gene expression of oxidative stress regulators in the cells. In conclusion, FGF-23 induced premature senescence in MSCs from skeletal muscle via the p53/p21/oxidative-stress pathway. The interaction between the MSCs and FGF-23 may play a key role in the impaired muscle reparative mechanisms of chronic kidney disease. PMID:26797283

  13. Mesenchymal stem cells alleviate experimental asthma by inducing polarization of alveolar macrophages.

    PubMed

    Song, Xiaolian; Xie, Shuanshuan; Lu, Kun; Wang, Changhui

    2015-04-01

    The reparative and immunoregulatory properties of mesenchymal stromal cells (MSCs) have made them attractive candidates for cellular therapy. However, the underlying mechanism of the effects of transplanted MSCs on allergic asthma remains elusive. Here, we show that administration of MSCs isolated from human bone marrow provoked a pronounced polarization in alveolar macrophages to M2 subtypes, rather than induced an increase in the total macrophage number, and efficiently inhibited hallmark features of asthma, including airway hyperresponsiveness and eosinophilic accumulation. Moreover, transforming growth factor beta (TGF-β) signaling pathway appeared to mediate the effects of MSCs on macrophage polarization and subsequently the inhibition of hallmark features of asthma. Inhibition of TGF-β signaling was sufficient to inhibit the macrophage polarization in response to MSCs and consequently reserved the inhibitory effects of macrophage polarization on hallmark features of asthma. Collectively, our data demonstrate that human MSCs have immunosuppressive activity on asthma, which is mediated by TGF-β-signaling-dependent alveolar macrophage polarization. PMID:24958014

  14. Transplantation of human induced cerebellar granular-like cells improves motor functions in a novel mouse model of cerebellar ataxia

    PubMed Central

    Zhu, Tongming; Tang, Hailiang; Shen, Yiwen; Tang, Qisheng; Chen, Luping; Wang, Zhifu; Zhou, Ping; Xu, Feng; Zhu, Jianhong

    2016-01-01

    Stem cell-based reparative approaches have been applied to cerebellum-related disorders during the last two decades. Direct lineage reprogramming of human fibroblasts into functional granular neurons holds great promise for biomedical applications such as cerebellum regeneration and cellbased disease modeling. In the present study, we showed that a combination of Ascl1, Sox2 and OCT4, in a culture subsequently treated with secreted factors (BMP4, Wnt3a and FGF8b), was capable of converting human fibroblasts from the scalp tissue of patients with traumatic brain injury (TBI) into functional human induced cerebellar granular-like cells (hiCGCs). Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells to human cerebellum granular cells. Our strategy improved the efficiency for hiCGCs induction, which gave the highest conversion efficiency 12.30±0.88%, and Ath1+/Tuj1+ double positive cells to 5.56±0.80%. We transplanted hiCGCs into the cerebellum of NmycTRE/TRE: tTS mice, a novel mouse model of cerebellar ataxia, and demonstrated that the hiCGCs were able to survive, migrate, proliferate and promote mild functional recovery after been grafted into cerebellum. PMID:27158363

  15. Enhanced Lithium-Induced Brain Recovery Following Cranial Irradiation Is Not Impeded by Inflammation

    PubMed Central

    Malaterre, Jordane; McPherson, Cameron S.; Denoyer, Delphine; Lai, Emily; Hagekyriakou, Jim; Lightowler, Sally; Shudo, Koishi; Ernst, Matthias; Ashley, David M.; Short, Jennifer L.; Wheeler, Greg

    2012-01-01

    Radiation-induced brain injury occurs in many patients receiving cranial radiation therapy, and these deleterious effects are most profound in younger patients. Impaired neurocognitive functions in both humans and rodents are associated with inflammation, demyelination, and neural stem cell dysfunction. Here we evaluated the utility of lithium and a synthetic retinoid receptor agonist in reducing damage in a model of brain-focused irradiation in juvenile mice. We found that lithium stimulated brain progenitor cell proliferation and differentiation following cranial irradiation while also preventing oligodendrocyte loss in the dentate gyrus of juvenile mice. In response to inflammation induced by radiation, which may have encumbered the optimal reparative action of lithium, we used the anti-inflammatory synthetic retinoid Am80 that is in clinical use in the treatment of acute promyelocytic leukemia. Although Am80 reduced the number of cyclooxygenase-2-positive microglial cells following radiation treatment, it did not enhance lithium-induced neurogenesis recovery, and this alone was not significantly different from the effect of lithium on this proinflammatory response. Similarly, lithium was superior to Am80 in supporting the restoration of new doublecortin-positive neurons following irradiation. These data suggest that lithium is superior in its restorative effects to blocking inflammation alone, at least in the case of Am80. Because lithium has been in routine clinical practice for 60 years, these preclinical studies indicate that this drug might be beneficial in reducing post-therapy late effects in patients receiving cranial radiotherapy and that blocking inflammation in this context may not be as advantageous as previously suggested. PMID:23197851

  16. Enhanced lithium-induced brain recovery following cranial irradiation is not impeded by inflammation.

    PubMed

    Malaterre, Jordane; McPherson, Cameron S; Denoyer, Delphine; Lai, Emily; Hagekyriakou, Jim; Lightowler, Sally; Shudo, Koishi; Ernst, Matthias; Ashley, David M; Short, Jennifer L; Wheeler, Greg; Ramsay, Robert G

    2012-06-01

    Radiation-induced brain injury occurs in many patients receiving cranial radiation therapy, and these deleterious effects are most profound in younger patients. Impaired neurocognitive functions in both humans and rodents are associated with inflammation, demyelination, and neural stem cell dysfunction. Here we evaluated the utility of lithium and a synthetic retinoid receptor agonist in reducing damage in a model of brain-focused irradiation in juvenile mice. We found that lithium stimulated brain progenitor cell proliferation and differentiation following cranial irradiation while also preventing oligodendrocyte loss in the dentate gyrus of juvenile mice. In response to inflammation induced by radiation, which may have encumbered the optimal reparative action of lithium, we used the anti-inflammatory synthetic retinoid Am80 that is in clinical use in the treatment of acute promyelocytic leukemia. Although Am80 reduced the number of cyclooxygenase-2-positive microglial cells following radiation treatment, it did not enhance lithium-induced neurogenesis recovery, and this alone was not significantly different from the effect of lithium on this proinflammatory response. Similarly, lithium was superior to Am80 in supporting the restoration of new doublecortin-positive neurons following irradiation. These data suggest that lithium is superior in its restorative effects to blocking inflammation alone, at least in the case of Am80. Because lithium has been in routine clinical practice for 60 years, these preclinical studies indicate that this drug might be beneficial in reducing post-therapy late effects in patients receiving cranial radiotherapy and that blocking inflammation in this context may not be as advantageous as previously suggested. PMID:23197851

  17. Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats.

    PubMed

    Brandenberger, Christina; Hotchkiss, Jon A; Krieger, Shannon M; Pottenger, Lynn H; Harkema, Jack R

    2015-11-01

    This study investigated the time- and concentration-dependent effects of inhaled ethylene on eosinophilic rhinitis and nasal epithelial remodeling in Fisher 344 rats exposed to 0, 10, 50, 300, or 10,000 ppm ethylene, 6 h/day, 5 days/week for up to 4 weeks. Morphometric quantitation of eosinophilic inflammation and mucous cell metaplasia/hyperplasia (MCM) and nasal mucosal gene expression were evaluated at anatomic sites previously shown to undergo ethylene-induced epithelial remodeling. Serum levels of total IgE, IgG1 and IgG2a were measured to determine if ethylene exposure increased the expression of Th2-associated (IgE and IgG1) relative to Th1-associated (IgG2a) antibody isotypes. Rats exposed to 0 or 10,000 ppm for 1, 3, 5, 10, or 20 days were analyzed to assess the temporal pattern of ethylene-induced alterations in nasal epithelial cell proliferation, morphology and gene expression. Rats exposed to 0, 10, 50, 300, and 10,000 ppm ethylene for 20 days were analyzed to assess concentration-dependent effects on lesion development. Additional rats exposed 4 weeks to 0, 300, or 10,000 ppm ethylene were held for 13 weeks post-exposure to examine the persistence of ethylene-induced mucosal alterations. The data indicate that cell death and reparative cell proliferation were not a part of the pathogenesis of ethylene-induced nasal lesions. Enhanced gene expression of Th2 cytokines (e.g., IL-5, IL-13) and chitinase (YM1/2) in the nasal mucosa was much greater than that of Th1 cytokines (e.g., IFNγ) after ethylene exposure. A significant increase in MCM was measured after 5 days of exposure to 10,000 ppm ethylene and after 20 days of exposure 10 ppm ethylene. Ethylene-induced MCM was reversible after cessation of exposure. No increase in total serum IgE, IgG1 or IgG2a was measured in any ethylene-exposed group. These data do not support involvement of an immune-mediated allergic mechanism in the pathogenesis of ethylene-induced nasal lesions in rats. Repeated

  18. Hepatoprotective effect of the aqueous extract of Simarouba amara Aublet (Simaroubaceae) stem bark against carbon tetrachloride (CCl4)-induced hepatic damage in rats.

    PubMed

    Maranhão, Hélida M L; Vasconcelos, Carlos F B; Rolim, Larissa A; Neto, Pedro J Rolim; Neto, Jacinto da C Silva; Filho, Reginaldo C da Silva; Fernandes, Mariana P; Costa-Silva, João H; Araújo, Alice V; Wanderley, Almir G

    2014-01-01

    Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle-corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver. PMID:25365298

  19. Inducing labor

    MedlinePlus

    ... surrounds your baby in the womb. It contains membranes or layers of tissue. One method of inducing ... break the bag of waters" or rupture the membranes. Your health care provider will do a pelvic ...

  20. AUTOTAXIN DOWNREGULATES LPS – INDUCED MICROGLIA ACTIVATION AND PRO-INFLAMMATORY CYTOKINES PRODUCTION

    PubMed Central

    Awada, Rana; Saulnier-Blache, Jean Sébastien; Grès, Sandra; Bourdon, Emmanuel; Rondeau, Philippe; Parimisetty, Avinash; Orihuela, Ruben; Harry, G. Jean; d’Hellencourt, Christian Lefebvre

    2014-01-01

    Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death and survival. We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A+) microglia were treated with LPS. Tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1 and B7.2) were determined by flow cytometry. ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFα and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1 and B7.2 expressions were reduced in A+ cells. Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation. PMID:25053164

  1. Chronic administration of galanin attenuates the TNBS-induced colitis in rats.

    PubMed

    Talero, E; Sánchez-Fidalgo, S; Calvo, J R; Motilva, V

    2007-06-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder considered as a consequence of an aberrant response of the immune system to luminal antigens. Numerous groups of agents are being evaluated as novel therapeutic approaches for its treatment; in this way, different peptides have emerged as potential candidates. Galanin is an active neuropeptide distributed in the central and periphery nervous systems although it has been also described having important autocrine and paracrine regulatory capacities with interesting inflammatory and immune properties. In this line, we have observed that galanin treatment has a significant preventive effect in the experimental trinitrobenzensulfonic acid (TNBS) acute model of inflammatory colitis. The aim of the present study was to investigate intensively the role played by the peptide in the evolution of the inflammatory pathology associated to IBD. Galanin (5 and 10 microg/kg/day) was administered i.p., daily, starting 24 h after TNBS instillation, and continuing for 14 and 21 days. The lesions were blindly scored according to macroscopic and histological analyses and quantified as ulcer index. The results demonstrated that chronic administration of galanin improved the colon injury than the TNBS induced. The study by Western-blotting of the expression of nitric oxide inducible enzyme (iNOS), as well as the total nitrite production (NO) assayed by Griess-reaction, showed significant reduction associated with peptide administration. The number of mast cells was also identified in histological preparations stained with toluidine blue and the results showed that samples from galanin treatment, mostly at 21 days, had increased the number of these cells and many of them had a degranulated feature. In conclusion, chronic administration of galanin is able to exert a beneficial effect in the animal model of IBD assayed improving the reparative process. Participation of nitric oxide pathways and mucosal mast cells

  2. Brm Inhibits the Proliferative Response of Keratinocytes and Corneal Epithelial Cells to Ultraviolet Radiation-Induced Damage

    PubMed Central

    Hassan, Nur Mohammad Monsur; Painter, Nicole; Howlett, C. Rolfe; Farrell, Andrew W.; Di Girolamo, Nick; Lyons, J. Guy; Halliday, Gary M.

    2014-01-01

    Ultraviolet radiation (UV) from sunlight is the primary cause of skin and ocular neoplasia. Brahma (BRM) is part of the SWI/SNF chromatin remodeling complex. It provides energy for rearrangement of chromatin structure. Previously we have found that human skin tumours have a hotspot mutation in BRM and that protein levels are substantially reduced. Brm−/− mice have enhanced susceptibility to photocarcinogenesis. In these experiments, Brm−/− mice, with both or a single Trp53 allele were exposed to UV for 2 or 25 weeks. In wild type mice the central cornea and stroma became atrophic with increasing time of exposure while the peripheral regions became hyperplastic, presumably as a reparative process. Brm−/−, Trp53+/−, and particularly the Brm−/− Trp53+/− mice had an exaggerated hyperplastic regeneration response in the corneal epithelium and stroma so that the central epithelial atrophy or stromal loss was reduced. UV induced hyperplasia of the epidermis and corneal epithelium, with an increase in the number of dividing cells as determined by Ki-67 expression. This response was considerably greater in both the Brm−/− Trp53+/+ and Brm−/− Trp53+/− mice indicating that Brm protects from UV-induced enhancement of cell division, even with loss of one Trp53 allele. Cell division was disorganized in Brm−/− mice. Rather than being restricted to the basement membrane region, dividing cells were also present in the suprabasal regions of both tissues. Brm appears to be a tumour suppressor gene that protects from skin and ocular photocarcinogenesis. These studies indicate that Brm protects from UV-induced hyperplastic growth in both cutaneous and corneal keratinocytes, which may contribute to the ability of Brm to protect from photocarcinogenesis. PMID:25254962

  3. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice.

    PubMed

    Zhu, Ying-Gang; Feng, Xiao-Mei; Abbott, Jason; Fang, Xiao-Hui; Hao, Qi; Monsel, Antoine; Qu, Jie-Ming; Matthay, Michael A; Lee, Jae W

    2014-01-01

    We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia coli endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. coli endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. coli endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus. PMID:23939814

  4. Concise Review: Modeling Multiple Sclerosis With Stem Cell Biological Platforms: Toward Functional Validation of Cellular and Molecular Phenotypes in Inflammation-Induced Neurodegeneration

    PubMed Central

    Orack, Joshua C.; Deleidi, Michela; Pitt, David; Mahajan, Kedar; Nicholas, Jacqueline A.; Boster, Aaron L.; Racke, Michael K.; Comabella, Manuel; Watanabe, Fumihiro

    2015-01-01

    In recent years, tremendous progress has been made in identifying novel mechanisms and new medications that regulate immune cell function in multiple sclerosis (MS). However, a significant unmet need is the identification of the mechanisms underlying neurodegeneration, because patients continue to manifest brain atrophy and disability despite current therapies. Neural and mesenchymal stem cells have received considerable attention as therapeutic candidates to ameliorate the disease in preclinical and phase I clinical trials. More recently, progress in somatic cell reprogramming and induced pluripotent stem cell technology has allowed the generation of human “diseased” neurons in a patient-specific setting and has provided a unique biological tool that can be used to understand the cellular and molecular mechanisms of neurodegeneration. In the present review, we discuss the application and challenges of these technologies, including the generation of neurons, oligodendrocytes, and oligodendrocyte progenitor cells (OPCs) from patients and novel stem cell and OPC cellular arrays, in the discovery of new mechanistic insights and the future development of MS reparative therapies. PMID:25593207

  5. Interaction between spring temperature-photoperiod and experimentally induced transient cold shock influencing proliferative activity in the brain of an adult terrestrial heterothermic vertebrate, Rana bergeri (Günther, 1986).

    PubMed

    Chimenti, Claudio; Margotta, Vito

    2015-01-01

    The seasonal thermal cycle and correlated variations in photoperiod exert antithetical influences on the proliferation of the reserve brain stem cells, which are mostly ependymal and subependymal, of adult earth-dwelling heterothermic vertebrates upon deprivation of an encephalic area. Also, an induced sudden, transient thermal stress preceding surgical cerebral maiming increases or depresses the proliferation of these stand-by cells, depending on the season. In particular, the concomitance of spring temperature and photoperiod with a cold stimulus increases proliferation. To re-evaluate these findings, normal adults of Rana bergeri were exposed to a cold shock in spring time. The outlined patterns, as revealed by immunocytochemical detection of a proliferation-linked antigen, showed that those conditions affect only the forebrain, where immunoreactivity was identifiable in quiescent cells mostly located in peculiar telencephalic ependymal sites, known as zonae germinativae dorsales and ventrales, while the regions lying behind had no substantial proliferative response. These results may be due to the absence of further proliferative stimuli (surgical stress, cerebral ablation), so that only the stand-by cells in the encephalic areas more rich in such cells are activated to proliferate. The findings are in line with the subordinate position of Anurans as compared with Urodeles, which are the most gifted with spontaneous and experimentally induced reparative and regenerative capacity among vertebrates. PMID:27086439

  6. Exercise-Induced Bronchoconstriction

    MedlinePlus

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  7. The nitroreductase system of inducible targeted ablation facilitates cell-specific regenerative studies in zebrafish.

    PubMed

    White, David T; Mumm, Jeff S

    2013-08-15

    At the turn of the 20th century, classical regenerative biology--the study of organismal/tissue/limb regeneration in animals such as crayfish, snails, and planaria--garnered much attention. However, scientific luminaries such as Thomas Hunt Morgan eventually turned to other fields after concluding that inquiries into regenerative mechanisms were largely intractable beyond observational intrigues. The field of regeneration has enjoyed a resurgence in research activity at the turn of the 21st century, in large part due to "the promise" of cultured stem cells regarding reparative therapeutic approaches. Additionally, genomics-based methods that allow sophisticated genetic/molecular manipulations to be carried out in nearly any species have extended organismal regenerative biology well beyond observational limits. Throughout its history, complex paradigms such as limb regeneration--involving multiple tissue/cell types, thus, potentially multiple stem cell subtypes--have predominated the regenerative biology field. Conversely, cellular regeneration--the replacement of specific cell types--has been studied from only a few perspectives (predominantly muscle and mechanosensory hair cells). Yet, many of the degenerative diseases that regenerative biology hopes to address involve the loss of individual cell types; thus, a primary emphasis of the embryonic/induced stem cell field is defining culture conditions which promote cell-specific differentiation. Here we will discuss recent methodological approaches that promote the study of cell-specific regeneration. Such paradigms can reveal how the differentiation of specific cell types and regenerative potential of discrete stem cell niches are regulated. In particular, we will focus on how the nitroreductase (NTR) system of inducible targeted cell ablation facilitates: (1) large-scale genetic and chemical screens for identifying factors that regulate regeneration and (2) in vivo time-lapse imaging experiments aimed at

  8. Drug-induced hypoglycemia

    MedlinePlus

    ... medlineplus.gov/ency/article/000310.htm Drug-induced hypoglycemia To use the sharing features on this page, please enable JavaScript. Drug-induced hypoglycemia is low blood sugar that results from medication. ...

  9. Genetic compensation of high dose radiation-induced damage in an anhydrobiotic insect

    NASA Astrophysics Data System (ADS)

    Gusev, Oleg; Nakahara, Yuichi; Sakashita, Tetsuya; Kikawada, Takahiro; Okuda, Takashi

    Anhydrobiotic larvae of African chironomid Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. The tolerance against various extreme environments exhibited by that insect might be due to being almost completely desiccated replacing water with trehalose, a state where little or no chemical reactions occur. From 2005 dried larvae of this insect are being used in a number of space experiments, both inside and outside of ISS as a model organism for estimation the limits of higher organisms' resistance to space environment stresses and long-term storage of the alive anhydrobiotic organisms during continues spaceflight. We have shown previously that both hydrated and dried larvae of Polypedilum vanderplanki have very higher tolerance against both highand low-linear energy transfer (LET), surviving after 7000Gy irradiation. It was suggested that the larvae would have effective DNA-reparation system in addition to artificial protection provided by glass-stage without water. In the present study we conducted analysis of stress-related gene expression in the larvae after 70-2000 Gy irradiations. Both DNA damage level and activity of DNA-reparation, anti-apoptotic and protein-damage related genes were analyzed. Direct visualization of DNA damage in the larvae fat body cells using Comet Assay showed that fragmented by radiation DNA is re-arranged within 76-98 hours after exposure. We found that massive overexpression of hsp and anti-oxidant genes occur in larvae entering anhydrobiosis , and provides refolding of proteins after rehydration. In the irradiated larvae overexpression of DNA-reparation enzymes anti-apoptotic genes was confirmed, suggesting that survival after high-dose irradiation is a result of combination of highly effective blocking of entering the apoptosis after severe DNA damage and DNA reparation.

  10. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

    PubMed Central

    Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

  11. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    PubMed

    Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

  12. Flow-induced vibration

    SciTech Connect

    Blevins, R.D.

    1990-01-01

    This book reports on dimensional analysis; ideal fluid models; vortex-induced vibration; galloping and flutter; instability of tube and cylinder arrays; vibrations induced by oscillating flow; vibration induced by turbulence and sound; damping of structures; sound induced by vortex shedding; vibrations of a pipe containing a fluid flow; indices. It covers the analysis of the vibrations of structures exposed to fluid flows; explores applications for offshore platforms and piping; wind-induced vibration of buildings, bridges, and towers; and acoustic and mechanical vibration of heat exchangers, power lines, and process ducting.

  13. Cavitation-resistant inducer

    DOEpatents

    Dunn, Charlton; Subbaraman, Maria R.

    1989-01-01

    An improvement in an inducer for a pump wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs.

  14. Cavitation-resistant inducer

    DOEpatents

    Dunn, C.; Subbaraman, M.R.

    1989-06-13

    An improvement in an inducer for a pump is disclosed wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs. 11 figs.

  15. Activation and suppression of cellular immunity during reparative liver regeneration in mice

    SciTech Connect

    Rakhmilevich, A.L.; Sidorenko, O.N.

    1986-10-01

    The authors study the effect of partial hepatectomy (PHE) on the functional activity of various lymphocyte populations in vitro and in vivo, namely its effect on proliferative, effector and killer activity. A mixture of 50 microliters of reacting spleen cells and 100 microliters of stimulating spleen cells from mice, irradiated in a dose of 2000 rads, was incubated as described. /sup 3/H-thymidine was added to the medium before the end of incubation. The radioactivity of the samples was measured in a beta-spectrometer. Activity of immune and normal killer cells was determined in the membrane-toxic test with /sup 3/H-uridine. Depression of killer activity and of the graft versus host reaction after PHE is evidently due to the action of suppressor cells as is shown by the example of lowering of the helper function in mixed lymphocyte culture.

  16. Before the Threshold: Destruction, Reparation and Creativity in Relation to the Depressive Position

    ERIC Educational Resources Information Center

    Edwards, Judith

    2005-01-01

    In this paper, the author revisits the classic idea formulated by Hanna Segal that creativity takes place from a depressive position impulse to repair previous destruction wrought on internal parental objects. The author proposes that in the light of psychoanalytic work with deprived and borderline children, there may need to be a rider to this…

  17. Adipose-derived Mesenchymal Stem Cells and Their Reparative Potential in Ischemic Heart Disease.

    PubMed

    Badimon, Lina; Oñate, Blanca; Vilahur, Gemma

    2015-07-01

    Adipose tissue has long been considered an energy storage and endocrine organ; however, in recent decades, this tissue has also been considered an abundant source of mesenchymal cells. Adipose-derived stem cells are easily obtained, show a strong capacity for ex vivo expansion and differentiation to other cell types, release a large variety of angiogenic factors, and have immunomodulatory properties. Thus, adipose tissue is currently the focus of considerable interest in the field of regenerative medicine. In the context of coronary heart disease, numerous experimental studies have supported the safety and efficacy of adipose-derived stem cells in the setting of myocardial infarction. These results have encouraged the clinical use of these stem cells, possibly prematurely. Indeed, the presence of cardiovascular risk factors, such as hypertension, coronary disease, diabetes mellitus, and obesity, alter and reduce the functionality of adipose-derived stem cells, putting in doubt the efficacy of their autologous implantation. In the present article, white adipose tissue is described, the stem cells found in this tissue are characterized, and the use of these cells is discussed according to the preclinical and clinical trials performed so far. PMID:26028258

  18. Compatibilite deformationnelle des betons autoplacants pour des utilisations dans les reparations des infrastructures routieres

    NASA Astrophysics Data System (ADS)

    Ghezal, Aicha Fadela

    Concrete structures repairs in Civil Engineering by using a thin bonded overlay is common practice. However the repaired structures are often victim of premature deterioration of the new repair material due to the appearance of restrained shrinkage cracks. In this context, the main objective of this thesis is to identify, through the experimental program called Phase I the principal parameters that significantly influence the creep potential of the evaluated mixtures. Once these parameters identified, the experimental entitled Phase II is conducted under conditions simulating repairs, and emphasis was placed on restrained shrinkage using instrumented ring test. Article 1 summarized the laboratory investigation undertaken to evaluate the potential of flexural creep behavior of several SCC. The results show clearly that the flexural creep potential of SCC varies widely depending on the nature of HRWR in use. In general, the use of naphthalene sulfonate leads to higher creep by comparison to polycarboxylate. It has been shown also that even when belonging to the same A.S.T.M. classification (polycarboxylic family) the magnitude of flexural creep varies also widely depending on the properties of polycarboxylic chemicals admixture. Based on the identified parameters in phase I, namely PNS superplasticizers type and PC2, with two ternary blended cements with fly ash (BTCFA) and slag (BTCS), the second experimental program was undertaken and summarized in articles 2 and 3. As presented in article 2, the results indicate that optimized SCCs produced with blended ternary cement with fly ash (BTCFA) developed at earlier age lower compressive and splitting-tensile strengths than the corresponding SCCs with blended cement with slag (BTCS). Test results also indicated that the drying shrinkage of SCCs based on BTCFA is higher than the corresponding SCCs proportioned with BTCS and attributed in part to higher total pores volume measured at 120 days on SCC BTCFA. The restrained shrinkage of SCC summarized in article 3 show that the resistance of SCC to shrinkage cracks was quite different depending on the nature of HRWR and the binder type in use. The cracking age increases in mixtures proportioned with PC-HRWR comparatively to PNS-HRWR. The SCC mixtures based on blended ternary cement containing Class F fly ash show shorter cracking age than the corresponding SCCs proportioned with ternary blended cement containing slag. Moreover, a data analysis of current research shows that the ratio of tensile strength to free shrinkage and modulus of elasticity, referred as index of dimensional compatibility, is a promising assessment of cracking resistant performance. In this way, only the free shrinkage test (ASTM C157) and basic mechanical properties are required to assess cracking of candidate concrete mixture designs.

  19. Lessons From Reparative Therapy Applied to Post-Abortion Grief Counseling.

    PubMed

    Panozzo, Dwight

    2016-06-01

    There is evidence from the legislative, judicial, and counseling sectors that the sun is setting on therapies designed to change sexual orientation. Despite this evidence, there is also evidence that similar pseudoscientific interventions continue to be used in at least one other area-post-abortion counseling. The key factor shared by both interventions is their dependence on unvalidated explanations of behavior. In the case of changing the expression of sexual orientation, the harm at the personal and communal levels is clear. In the case of post-abortion counseling, the harm is hypothesized, and the reasons why a communal response is lacking in the post-abortion community are described. Steps clinicians can take to alleviate the probable harm caused by the use of unvalidated/unvalidatable interventions, with a particular emphasis on identifying and expunging culturally derived and oppressive interventions currently used, are delineated as clinical and social justice activities to reduce human suffering. PMID:26513482

  20. Experimental study of reparative regeneration processes in the wound treated with bioactive dressings.

    PubMed

    Chekmareva, I A

    2002-02-01

    Quantitative and structural functional analysis of granulation tissue cells during treatment with protein-polysaccharide dressing Collahit F was carried out. The preparation effectively cleansed the wound from detritus, prevented secondary infection due to stimulation of the functional activity of macrophages and due to the effect of its antiseptic component (furagin), and stimulated proliferative activity of fibroblasts and granulation tissue microvessels on day 5 of treatment, thus promoting repair processes in the wound. PMID:12428293

  1. A slow release calcium delivery system for the study of reparative dentine formation.

    PubMed

    Hunter, A R; Kirk, E E; Robinson, D H; Kardos, T B

    1998-06-01

    Several liquid, semi-solid and solid delivery systems were formulated and tested to devise a method of reproducibly administering accurate micro-doses of calcium into a 700 microns diameter cavity in a rat maxillary incisor tooth, in the absence of hydroxyl ions. Development of this delivery system was necessary to facilitate studies of the mechanisms of pulpal repair and odontoblast differentiation. The principal requirements for the delivery system were that it should be easily administered into a small pulp exposure in the rat incisor and that a greater than 1000-fold range in calcium ion concentrations could be incorporated and delivered for a period of 2-3 days, preferably in an acidic environment to minimize the effect of non-specific nucleation under alkaline conditions. Poly- (ethylene) glycol microspheres were found to be an ideal vehicle. Under the in vitro dissolution conditions used, complete release of all calcium salts occurred within 12-15 hours, except for the very water-insoluble calcium stearate. It was anticipated that the release of calcium ions would be significantly more prolonged in vivo because of the physical constraints of the prepared cavity as well as the restricted access to fluid flow. PMID:9863419

  2. Synergetic effects of ciliary neurotrophic factor and olfactory ensheathing cells on optic nerve reparation (complete translation)

    PubMed Central

    Yin, Dan-ping; Chen, Qing-ying; Liu, Lin

    2016-01-01

    At present, there is no effective treatment for the repair of the optic nerve after injury, or improvement of its microenvironment for regeneration. Intravitreally injected ciliary neurotrophic factor (CNTF) and olfactory ensheathing cells (OECs) promote the long-distance regrowth of severed optic nerve fibers after intracranial injury. Here, we examined the efficacy of these techniques alone and in combination, in a rat model of optic nerve injury. We injected condensed OEC suspension at the site of injury, or CNTF into the vitreous body, or both simultaneously. Retrograde tracing techniques showed that 4 weeks postoperatively, the number of surviving retinal ganglion cells and their axonal density in the optic nerve were greater in rats subjected to OEC injection only than in those receiving CNTF injection only. Furthermore, combined OEC + CNTF injection achieved better results than either monotherapy. These findings confirm that OECs are better than CNTF at protecting injured neurons in the eye, but that combined OEC and CNTF therapy is notably more effective than either treatment alone. PMID:27482233

  3. [Characteristics of the reparative regeneration of fins in the polypterid fish (Polypteridae, Actinopterygii)].

    PubMed

    Nikiforova, A I; Golichenkov, V A

    2012-01-01

    Epimorphic regeneration of fins was studied in different ray-finned fishes (Actinopterygii), but species representing the phylogenetically basal lineages of the taxon have remained outside the attention of researchers. Information on the regenerative abilities of these groups is important both for understanding the evolutionary origins of the epimorphic regeneration phenomenon and for assessing the universality of regenerative potencies in Actinopterygii. Addressing this problem, we studied for the first time fin regeneration in two members of the archaic family Polypteridae: the ropefish (Erpetoichthys calabaricus) and the Senegal bichir (Polypterus senegalus). Along with the ability to regenerate the bony rays of fins, widespread among Actinopterygii, polypterids show the ability to effectively regenerate the endoskeleton and musculature of their fins. This unusual feature allows us to suggest polypterids as new model organisms for the study of the mechanisms of vertebrate limb regeneration. PMID:22650079

  4. Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson's disease.

    PubMed

    Muñoz-Manchado, Ana B; Villadiego, Javier; Suárez-Luna, Nela; Bermejo-Navas, Alfonso; Garrido-Gil, Pablo; Labandeira-García, José L; Echevarría, Miriam; López-Barneo, José; Toledo-Aral, Juan J

    2013-03-01

    Intrastriatal transplantation of dopaminergic carotid body (CB) cells ameliorates parkinsonism in animal models and, with less efficacy, in Parkinson's disease patients. CB-based cell therapy was initially proposed because of its high dopamine content. However, later studies suggested that its beneficial effect might be due to a trophic action exerted on nigrostriatal neurons. Compatible with this concept are the high levels of neurotrophic factors encountered in CB cells. To test experimentally this idea, unilateral striatal transplants were performed with a sham graft in the contralateral striatum, as a robust internal control. Thereafter, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6, -tetrahydropyridine was injected during 3 months. CB grafts protected from degeneration ipsilateral nigral dopaminergic neurons projecting to the transplant in a dose-dependent manner regarding size and glial cell line-derived neurotrophic factor expression. Grafts performed at different times after the onset of the neurotoxic treatment demonstrated with histological and behavioral methods protection and repair of the nigrostriatal pathway by CB transplants. This study provides a mechanistic explanation for the action of CB transplants on parkinsonian models. It should also help to improve cell therapy approaches to Parkinson's disease. PMID:22743091

  5. Integrated imaging of hepatic tumors in childhood. Part II. Benign lesions (congenital, reparative, and inflammatory)

    SciTech Connect

    Miller, J.H.; Greenspan, B.S.

    1985-01-01

    The authors have encountered benign liver masses as frequently as malignant lesions in children with hepatomegaly. Lesions studied included abscesses, cavernous hemangioma/hemangioendothelioma, adenoma of glycogen storage disease, choledochal cysts, focal nodular hyperplasia, cystic hepatoblastoma, and hamartoma. An intergrated imaging protocol involving ultrasound, computed tomography, and scintigraphy proved to be more helpful than any one modality in establishing the benign or malignant nature of a hepatic neoplasm and the type of tumor, which is of particular importance when surgical exploration and/or biopsy is contraindicated.

  6. 9 CFR 202.103 - Rule 3: Beginning a reparation proceeding.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... by the Agency, or may be a formal document, or may be a letter, mailgram, or telegram. It may be..., telegrams, invoices, manifests, accounts of sales, and special contracts or agreements, and checks...

  7. 9 CFR 202.103 - Rule 3: Beginning a reparation proceeding.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... by the Agency, or may be a formal document, or may be a letter, mailgram, or telegram. It may be..., telegrams, invoices, manifests, accounts of sales, and special contracts or agreements, and checks...

  8. 9 CFR 202.103 - Rule 3: Beginning a reparation proceeding.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... by the Agency, or may be a formal document, or may be a letter, mailgram, or telegram. It may be..., telegrams, invoices, manifests, accounts of sales, and special contracts or agreements, and checks...

  9. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review.

    PubMed

    Freitag, Julien; Bates, Dan; Boyd, Richard; Shah, Kiran; Barnard, Adele; Huguenin, Leesa; Tenen, Abi

    2016-01-01

    Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition. PMID:27229856

  10. Reparation by Proxy: Experiences of Working with Pregnant Teenagers and Adolescent Mothers

    ERIC Educational Resources Information Center

    Hurley, Anne

    2010-01-01

    This paper describes brief work with pregnant teenagers, adolescent mothers, their infants and their wider families, a group who would not ordinarily seek treatment in child and adolescent mental health services. The work takes place in a community context in London and includes a home visiting service for young people unable to attend…

  11. Life Writing Lite: Judy Garland and Reparative Rhetorics of Celebrity Life Writing

    ERIC Educational Resources Information Center

    Janangelo, Joseph

    2010-01-01

    This essay offers a rhetorical reading of entertainer Judy Garland's early life writing projects. The author focuses on two open letters Garland published in 1950, in which she talks to the public and press to let them know "the truth" ("Open") about her life and how much her audience means to her. As a troubled celebrity, Garland had for years…

  12. Reparable Harm: Assessing and Addressing Disparities Faced by Boys and Men of Color in California. Monograph

    ERIC Educational Resources Information Center

    Davis, Lois M.; Kilburn, M. Rebecca; Schultz, Dana J.

    2009-01-01

    The study identifies some of the greatest disparities for boys and men of color relative to their white counterparts across specific socioeconomic, health, safety, and school readiness indicators in California and provides information about different strategies for reducing the disparities--including effective programs, practices, and…

  13. The effect of blood contamination on dislocation resistance of different endodontic reparative materials.

    PubMed

    Üstün, Yakup; Topçuoğlu, Hüseyin S; Akpek, Firdevs; Aslan, Tuğrul

    2015-09-01

    This study evaluated the retention characteristics of ProRoot mineral trioxide aggregate (MTA), RetroMTA, Supra MTA, and Biodentine biomaterials used to repair furcation perforations contaminated with blood. Furcal perforations measuring 1.3 mm in diameter and 2 mm in height were created in 96 mandibular first molar teeth, which were then randomly divided into the following two groups (n = 48): contaminated (+) or non-contaminated (-) with blood. The groups were subdivided into four groups (n = 12) according to the material used (ProRoot MTA, RetroMTA, Supra MTA, and Biodentine) to seal the perforations. The samples were allowed to set for 14 days and were then subjected to push-out testing. The results were analyzed using ANOVA, and the failure modes were examined using a surgical microscope. ProRoot MTA (+/-) and RetroMTA (+/-) exhibited superior bond strength values; in addition, there were no significant differences among these groups (P > 0.05). Biodentine (+) showed intermediate values that were sometimes statistically similar to the ProRoot MTA (+/-) and RetroMTA (+/-) groups (P > 0.05) and, at other times, the Biodentine (-) and Supra MTA (+/-) groups (P > 0.05). The lowest bond strength values were shown by the Biodentine (-) and Supra MTA groups (P > 0.05). "Adhesive failure mode" was the most frequently observed type for all tested materials. Blood contamination did not affect the dislocation resistance of materials. PMID:26369481

  14. An application of embryonic skin cells to repair diabetic skin wound: a wound reparation trail.

    PubMed

    Qian, De Jian; Guo, Xiang Kai; Duan, Hui Chuan; Han, Zhi Hua; Meng, Fei; Liu, Ju; Wang, Yan

    2014-12-01

    Cell therapy has shown its power to promote diabetic chronic wound healing. However, problems of scar formation and loss of appendages have not yet been solved. Our study aims to explore the potential of using embryonic skin cells (ESkCs) to repair diabetic wounds. Circular wound was created on the back of the diabetic mice, and ESkCs stained with CM-DIL were transplanted into the wound. Wound area was recorded at the day 4, 7, 11, and 14 after transplantation. The tissue samples were obtained at week 1, 2, and 3, and the tissue sections were stained by transforming growth factor β1 (TGF-β1), TGF-β3, vascular endothelial growth factor (VEGF), and CD31. The new skin formed on the wound of the diabetic mice with ESkC treatment at week 1 but not on the wounds of the non-treatment group. The histological scores of diabetic group with ESkC treatment were significantly better than the non-treatment group (P < 0.05). The fluorescence examination of CM-DIL and CD31 staining indicated that the ESkCs participated in the tissue regeneration, hair follicles formation, and angiogenesis. The expression of TGF-β1 and VEGF in ESkC-treated groups was noticeable in week 1 but disappeared in week 2. TGF-β3 was not expressed at week 1 but expressed markedly around hair follicles in week 2 in ESkC-treated groups. Our study demonstrated that ESkCs are capable of developing new skin with appendage restoration to repair the diabetic wounds. PMID:25030484

  15. Induced pluripotency with endogenous and inducible genes

    SciTech Connect

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-10-15

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER{sup TAM}) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols.

  16. Space Station Induced Monitoring

    NASA Technical Reports Server (NTRS)

    Spann, James F. (Editor); Torr, Marsha R. (Editor)

    1988-01-01

    This report contains the results of a conference convened May 10-11, 1988, to review plans for monitoring the Space Station induced environment, to recommend primary components of an induced environment monitoring package, and to make recommendations pertaining to suggested modifications of the Space Station External Contamination Control Requirements Document JSC 30426. The contents of this report are divided as Follows: Monitoring Induced Environment - Space Station Work Packages Requirements, Neutral Environment, Photon Emission Environment, Particulate Environment, Surface Deposition/Contamination; and Contamination Control Requirements.

  17. Mania Induced by Opipramol

    PubMed Central

    Firoz, Kazhungil; Khaleel, Asfia; Rajmohan, V; Kumar, Manoj; Raghuram, TM

    2015-01-01

    Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania. PMID:25722522

  18. Mania induced by opipramol.

    PubMed

    Firoz, Kazhungil; Khaleel, Asfia; Rajmohan, V; Kumar, Manoj; Raghuram, Tm

    2015-01-01

    Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania. PMID:25722522

  19. Noise-Induced Hearing Loss

    MedlinePlus

    ... Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is noise-induced hearing ... additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound in our environment, ...

  20. Vitiligo, drug induced (image)

    MedlinePlus

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains ...

  1. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  2. Gasoline-induced mucositis

    SciTech Connect

    Hoffman, D.L.; Swanson, B.Z. Jr.; Lutins, N.D.

    1980-02-01

    Gasoline-induced mucositis may become more common because of fuel shortages or increased fuel cost. Dentists should, therefore, consider this oral irritant in the differential diagnosis of oral lesions.

  3. Thrombocytopenia - drug induced

    MedlinePlus

    ... and a seizure medicine called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  4. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  5. Exercise-induced asthma

    MedlinePlus

    Wheezing - exercise-induced; Reactive airway disease - exercise ... Having asthma symptoms when you exercise does not mean you cannot or should not exercise. But be aware of your EIA triggers. Cold or dry air may ...

  6. Vitiligo, drug induced (image)

    MedlinePlus

    ... drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally occurs as a result of medications, as is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains the normal skin texture.

  7. Drug-induced nightmares.

    PubMed

    2000-12-01

    (1) A wide variety of drugs have been implicated in nightmares, often on inadequate evidence. (2) Recurrent nightmares can be induced by many drugs, and not only agents with psychotropic or neurological effects. PMID:11475499

  8. Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

    NASA Astrophysics Data System (ADS)

    Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

    2011-03-01

    In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

  9. Ethionamide-induced Pellagra.

    PubMed

    Gupta, Yashashree; Shah, Ira

    2015-08-01

    Pellagra is a disorder characterized by dermatitis, diarrhea, dementia and eventually death, resulting from a deficiency of niacin or its precursor tryptophan. Ethionamide (a second-line antituberculosis agent)-induced pellagra is rarely encountered in clinical practice. Prompt diagnosis and treatment with nicotinamide can prevent life-threatening complications. To date, only three cases have been reported. We report a 13-year-old girl presenting with ethionamide-induced pellagra that resolved after the administration of niacin. PMID:25828829

  10. Isoniazid-induced alopecia

    PubMed Central

    Gupta, K. B.; Kumar, V.; Vishvkarma, S.; Shandily, R.

    2011-01-01

    Isoniazid is a safe and very effective antituberculosis drug. Antimitotic agents routinely cause alopecia. Drug-induced alopecia is usually reversible upon withdrawal of the drug. Isoniazid, thiacetazone and ethionamide are the antituberculosis drugs which have been associated with alopecia. Isoniazid-induced alopecia was observed in one case and confirmed by the finding that hair growth resumed when drug removed from the regimen. PMID:21654989

  11. Induced polarization response of microbial induced sulfideprecipitation

    SciTech Connect

    Ntarlagiannis, Dimitrios; Williams, Kenneth Hurst; Slater, Lee; Hubbard, Susan

    2004-06-04

    A laboratory scale experiment was conducted to examine the use of induced polarization and electrical conductivity to monitor microbial induced sulfide precipitation under anaerobic conditions in sand filled columns. Three columns were fabricated; one for electrical measurements, one for geochemical sampling and a third non-inoculated column was used as a control. A continual upward flow of nutrients and metals in solution was established in each column. Desulfovibrio vulgaris microbes were injected into the middle of the geochemical and electrical columns. Iron and zinc sulfides precipitated along a microbial action front as a result of sulfate reduction due by Desulfovibrio vulgaris. The precipitation front initially developed near the microbial injection location, and subsequently migrated towards the nutrient inlet, as a result of chemotaxis by Desulfovibrio vulgaris. Sampling during and subsequent to the experiment revealed spatiotemporal changes in the biogeochemical measurements associated with microbial sulfate reduction. Conductivity measurements were insensitive to all biogeochemical changes occurred within the column. Changes in the IP response (of up to 14 mrad)were observed to coincide in place and in time with the active microbe respiration/sulfide precipitation front as determined from geochemical sampling. The IP response is correlated with the lactate concentration gradient, an indirect measurement of microbial metabolism, suggesting the potential of IP as a method for monitoring microbial respiration/activity. Post experimental destructive sample analysis and SEM imaging verified the geochemical results and supported our hypothesis that microbe induced sulfide precipitation is directly detectable using electrical methods. Although the processes not fully understood, the IP response appears to be sensitive to this anaerobic microbial precipitation, suggesting a possible novel application for the IP method.

  12. Relationships among magnetic resonance imaging, histological findings, and IGF-I in steroid-induced osteonecrosis of the femoral head in rabbits* §

    PubMed Central

    Chen, Xing-can; Weng, Jian; Chen, Xue-qun; Du, Ji-zeng; Zhu, Miao-ping; Pan, Yong-qing; Liu, Miao

    2008-01-01

    Objective: To study the relationships among magnetic resonance imaging (MRI), histological findings, and insulin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits. Methods: Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I. Results: At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific “line-like sign”. The MRI findings of all femora in Group B were normal. Conclusion: MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies. PMID:18837481

  13. Drug-induced panniculitides.

    PubMed

    Borroni, G; Torti, S; D'Ospina, R M; Pezzini, C

    2014-04-01

    A substantial number of all panniculitides fails to recognize a specific etiology, and that is true also for a relatively frequent type of panniculitis, such as erythema nodosum (EN). Between the recognized causative factors of panniculitides, infectious, physical agents, autoimmune mechanisms and neoplastic disorders are well known. On the contrary, the role of drugs as inducers of panniculitides is marginally considered, and their report limited to anecdotal observations, often without due histopathological support. Since the clinical and histopathological features of drug-induced panniculitides are indistinguishable from those caused by other agents, the causative relationship may be demonstrated by the history of previous drug intake and by clinical improvement after drug discontinuation. We reviewed the currently reported descriptions of drug-induced panniculitis, including a few exemplificative original observations. EN results as the most frequently reported drug-induced panniculitis. Among the causative drugs of EN a variety of medications, with disparate, or even opposite, mechanisms of action are reported, thus limiting the understanding of the pathogenesis. Common causative drugs include oral contraceptives, nonsteroidal anti-inflammatory drugs, antiobiotics and leukotriene-modifying agents. Unfortunately, in several cases, the diagnosis of drug-induced EN is done on clinical findings alone. In those cases, the lack of histopathological support does not allow to define a precise clinicopathological correlation on etiologic grounds. Drug-induced lobular and mixed panniculitides, including eosinophilic panniculitis, are even more rarely described. Reported causative agents are glatiramer acetate, interferon beta and heparin (at sites of injections), and systemic steroids, tyrosine kinase inhibitors and BRAF with subcutaneous fat involvement at distance. In view of the recent introduction of new classes of drugs, attention should be paid to disclose their

  14. [Intravenous Sedation and Repeated "the Same Day General Anesthesia" for a School-age Boy with Dandy-Walker Syndrome and Dentinogenesis].

    PubMed

    Hitosugi, Takashi; Tsukamoto, Masanori; Fujiwara, Shigeki; Yokoyama, Takeshi

    2016-03-01

    Dandy-Walker syndrome (DWS) is characterized by perfect or partial defect of the cerebellum vermis and cystic dilatation of the posterior fossa communicating with the fourth ventricle. Common clinical signs are mental retardation, cerebellar ataxia, and those of increased intracranial pressure (ICP). Associated congenital anomalies are craniofacial, cardiac, renal, and skeletal abnormalities. We experienced a case of intravenous sedation and six times of "the same day" general anesthesia for a school-aged boy (10-13 years old) with DWS and hypodentinogenesis. The patient underwent an examination and dental treatments. We had to pay attention to airway management tracheal tube selection and control of ICP. In addition, we should prevent tooth injuries through mishaps during tracheal intubations, since all-tooth-hypoplasia with fragile dental crowns was strongly suggested in this case. Detailed postoperative care is also required for general anesthesia afflicted with DWS. PMID:27097514

  15. Crystalglobulin-Induced Nephropathy

    PubMed Central

    Gupta, Vinay; El Ters, Mireille; Kashani, Kianoush; Leung, Nelson

    2015-01-01

    Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy. PMID:25190731

  16. Radiation-induced gliomas

    PubMed Central

    Prasad, Gautam; Haas-Kogan, Daphne A.

    2013-01-01

    Radiation-induced gliomas represent a relatively rare but well-characterized entity in the neuro-oncologic literature. Extensive retrospective cohort data in pediatric populations after therapeutic intracranial radiation show a clearly increased risk in glioma incidence that is both patient age- and radiation dose/volume-dependent. Data in adults are more limited but show heightened risk in certain groups exposed to radiation. In both populations, there is no evidence linking increased risk associated with routine exposure to diagnostic radiation. At the molecular level, recent studies have found distinct genetic differences between radiation-induced gliomas and their spontaneously-occurring counterparts. Clinically, there is understandable reluctance on the part of clinicians to re-treat patients due to concern for cumulative neurotoxicity. However, available data suggest that aggressive intervention can lead to improved outcomes in patients with radiation-induced gliomas. PMID:19831840

  17. Gravitationally induced quantum transitions

    NASA Astrophysics Data System (ADS)

    Landry, A.; Paranjape, M. B.

    2016-06-01

    In this paper, we calculate the probability for resonantly inducing transitions in quantum states due to time-dependent gravitational perturbations. Contrary to common wisdom, the probability of inducing transitions is not infinitesimally small. We consider a system of ultracold neutrons, which are organized according to the energy levels of the Schrödinger equation in the presence of the Earth's gravitational field. Transitions between energy levels are induced by an oscillating driving force of frequency ω . The driving force is created by oscillating a macroscopic mass in the neighborhood of the system of neutrons. The neutron lifetime is approximately 880 sec while the probability of transitions increases as t2. Hence, the optimal strategy is to drive the system for two lifetimes. The transition amplitude then is of the order of 1.06 ×10-5, and hence with a million ultracold neutrons, one should be able to observe transitions.

  18. Bacteriocin Inducer Peptides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  19. Irradiation-Induced Nanostructures

    SciTech Connect

    Birtcher, R.C.; Ewing, R.C.; Matzke, Hj.; Meldrum, A.; Newcomer, P.P.; Wang, L.M.; Wang, S.X.; Weber, W.J.

    1999-08-09

    This paper summarizes the results of the studies of the irradiation-induced formation of nanostructures, where the injected interstitials from the source of irradiation are not major components of the nanophase. This phenomena has been observed by in situ transmission electron microscopy (TEM) in a number of intermetallic compounds and ceramics during high-energy electron or ion irradiations when the ions completely penetrate through the specimen. Beginning with single crystals, electron or ion irradiation in a certain temperature range may result in nanostructures composed of amorphous domains and nanocrystals with either the original composition and crystal structure or new nanophases formed by decomposition of the target material. The phenomenon has also been observed in natural materials which have suffered irradiation from the decay of constituent radioactive elements and in nuclear reactor fuels which have been irradiated by fission neutrons and other fission products. The mechanisms involved in the process of this nanophase formation are discussed in terms of the evolution of displacement cascades, radiation-induced defect accumulation, radiation-induced segregation and phase decomposition, as well as the competition between irradiation-induced amorphization and recrystallization.

  20. Shrouded inducer pump

    DOEpatents

    Meng, Sen Y.

    1989-01-01

    An improvement in a pump including a shrouded inducer, the improvement comprising first and second sealing means 32,36 which cooperate with a first vortex cell 38 and a series of secondary vortex cells 40 to remove any tangential velocity components from the recirculation flow.

  1. Drug-induced hyperkalemia.

    PubMed

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia. PMID:25047526

  2. Methacholine induced headache.

    PubMed Central

    Carratala, C.; Gea, J. G.; Aguar, M. C.; Grau, S.; Espadaler-Medina, J. M.; Broquetas, J. M.

    1995-01-01

    A lung function technician developed episodes of headache, probably related to the use of methacholine. The headache disappeared with breathing 100% oxygen. Cholinergic agents are known to induce headaches but the mechanism remains unclear. Vascular factors could be implicated. PMID:7660351

  3. Methacholine induced headache.

    PubMed

    Carratala, C; Gea, J G; Aguar, M C; Grau, S; Espadaler-Medina, J M; Broquetas, J M

    1995-03-01

    A lung function technician developed episodes of headache, probably related to the use of methacholine. The headache disappeared with breathing 100% oxygen. Cholinergic agents are known to induce headaches but the mechanism remains unclear. Vascular factors could be implicated. PMID:7660351

  4. DRUG INDUCED CHOLESTASIS

    PubMed Central

    Padda, Manmeet S.; Sanchez, Mayra; Akhtar, Abbasi J.; Boyer, James L.

    2011-01-01

    Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug induced cholestasis. This review summarizes their variable clinical presentations, examines the, role of transport proteins in hepatic drug clearance and toxicity and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management. PMID:21480339

  5. Does formaldehyde induce aneuploidy?

    PubMed

    Speit, Günter; Kühner, Stefanie; Linsenmeyer, Regina; Schütz, Petra

    2011-11-01

    Formaldehyde (FA) was tested for a potential aneugenic activity in mammalian cells. We employed tests to discriminate between aneugenic and clastogenic effects in accordance with international guidelines for genotoxicity testing. The cytokinesis-block micronucleus test (CBMNT) in combination with fluorescence in situ hybridisation (FISH) with a pan-centromeric probe was performed with cultured human lymphocytes and the human A549 lung cell line. FA induced micronuclei (MN) in binuclear cells of both cell types under standard in vitro test conditions following the OECD guideline 487. FISH analysis revealed that the vast majority of induced MN were centromere negative, thus indicating a clastogenic effect. A similar result was obtained for MN induced by γ-irradiation, whereas the typical aneugens colcemid (COL) and vincristine (VCR) predominantly induced centromere-positive MN. Furthermore, COL and VCR clearly enhanced the MN frequency in mononuclear lymphocytes in the CBMNT, whereas such an effect was not observed for γ-irradiation and FA. In experiments with the Chinese hamster V79 cell line, the aneugens COL and VCR clearly increased the frequency of tetraploid second division metaphases, whereas FA did not cause such an effect. Altogether, our results confirm the clastogenicity of FA in cultured mammalian cells but exclude a significant aneugenic activity. PMID:21804075

  6. Ethionamide-induced gynecomastia

    PubMed Central

    Dixit, Ramakant; George, Jacob; Sharma, Arun K.; chhabra, Naveen; Jangir, Suresh K.; Mishra, Vikas

    2012-01-01

    Gynecomastia is very rare during antituberculosis chemotherapy. We describe a 38-year-old male patient who developed a painful gynecomastia following second-line drug therapy for multidrug-resistant pulmonary tuberculosis. Gynecomastia disappeared after stopping the ethionamide. A published literature on antituberculosis-induced gynecomastia is also briefly discussed. PMID:22629101

  7. Schedule-Induced Stereotypy.

    ERIC Educational Resources Information Center

    Emerson, Eric; Howard, Denise

    1992-01-01

    The phenomena of the induction and entrainment of adjunctive behaviors was investigated in 8 people (ages 5-51) with severe or profound mental retardation who exhibited stereotypic behaviors. Seven of the eight demonstrated evidence of schedule-induced stereotypic behavior, whereas five also showed evidence of the entrainment of these behaviors by…

  8. Geomagnetism and Induced Voltage

    ERIC Educational Resources Information Center

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it is…

  9. Effects of Induced Astigmatism.

    ERIC Educational Resources Information Center

    Schubert, Delwyn G.; Walton, Howard N.

    1968-01-01

    The relationship of astigmatism to reading and the possible detrimental effects it might have on reading were investigated. The greatest incidence of astigmatism was for the with-the-rule type ranging from .50 to 1.00 diopter. This type of astigmatism was induced in 35 seniors from the Los Angeles College of Optometry by placing cylindrical lenses…

  10. Injection-induced earthquakes.

    PubMed

    Ellsworth, William L

    2013-07-12

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard. PMID:23846903

  11. Hypoxia-Inducible Hydrogels

    PubMed Central

    Park, Kyung Min; Gerecht, Sharon

    2014-01-01

    Oxygen is vital for the existence of all multicellular organisms, acting as a signaling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during development, regeneration, and cancer. Here we report a novel hypoxia-inducible (HI) hydrogel composed of gelatin and ferulic acid that can form hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen levels and gradients within the hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro via hypoxia-inducible factors activation of matrix metalloproteinases and promote rapid neovascularization from the host tissue during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from fundamental studies of developmental, regenerative and disease processes through the engineering of healthy and diseased tissue models towards the treatment of hypoxia-regulated disorders. PMID:24909742

  12. Drug-induced Photosensitivity.

    PubMed

    Zuba, Ewelina Bogumiła; Koronowska, Sandra; Osmola-Mańkowska, Agnieszka; Jenerowicz, Dorota

    2016-04-01

    Ultraviolet radiation is considered the main environmental physical hazard to the skin. It is responsible for photoaging, sunburns, carcinogenesis, and photodermatoses, including drug-induced photosensitivity. Drug-induced photosensitivity is an abnormal skin reaction either to sunlight or to artificial light. Drugs may be a cause of photoallergic, phototoxic, and photoaggravated dermatitis. There are numerous medications that can be implicated in these types of reactions. Recently, non-steroidal anti-inflammatory drugs have been shown to be a common cause of photosensitivity. As both systemic and topical medications may promote photosensitive reactions, it is important to take into consideration the potential risk of occurrence such reactions, especially in people chronically exposed to ultraviolet radiation. PMID:27149132

  13. Exercise-induced purpura.

    PubMed

    Ramelet, Albert-Adrien

    2004-01-01

    Exercise-induced purpura (EIP) occurs on the lower legs after unusual or major muscular activity, as in marathon runners or as after long walks, especially in the mountains in hot weather. In leisure walkers, patients are otherwise healthy females. There is no relation with chronic venous disorder. Erythematous, urticarial or purpuric plaques arise on the lower leg, usually sparing the skin compressed by socks. Symptoms include itch, pain and a burning sensation. Histopathology demonstrates leukocytoclastic vasculitis. The lesions fade after some days, with frequent relapses at further muscular exercises and may be prevented in some cases by compression, intake of venoactive drugs and local application of steroids. EIP is not uncommon, even if very few descriptions have yet been published. It appears to be consecutive to venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation, after a prolonged and unusual exercise, such as running or walking in hot weather. PMID:15178910

  14. Tulipalin A induced phytotoxicity

    PubMed Central

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-01-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure. PMID:25024947

  15. Tulipalin A induced phytotoxicity.

    PubMed

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-04-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure. PMID:25024947

  16. Asthma induced by enkephalin.

    PubMed Central

    Leslie, R D; Bellamy, D; Pyke, D A

    1980-01-01

    A total of 291 diabetics were studied to see whether an asthmatic reaction was associated with facial flushing induced by chlorpropamide and alcohol. Of these patients, 191 reported facial flushing, of whom 12 reported breathlessness as well. Of these 12, five also described wheezing, and respiratory function tests showed them to have asthma. Three of these five patients underwent further tests, which showed that the asthmatic reaction could be prevented by giving disodium cromoglycate and the specific opiate antagonist naloxone. One patient developed wheezing when given an enkephalin analogue with opiate-like activity. Asthma induced by chlorpropamide and alcohol was concluded to be mediated by endogenous peptides with opiate-like activity such as enkephalin. PMID:7357255

  17. Anesthetic-induced anaphylaxis.

    PubMed

    Norred, Carol L

    2012-04-01

    The purpose of this course is to update nurse anesthetists about anesthetic-induced anaphylaxis. This course discusses the pathophysiologic process of anaphylaxis with descriptions of the allergic immune response and the mediators and mechanisms of mast cell activation. The preoperative identification of patients at high risk and the assessment of potential anesthetic triggers of a hypersensitivity and/or allergic reaction are prudent strategies to minimize the risk of anaphylaxis. Other practices recommended for clinicians include suggestions for anesthetic management to decrease threat of an allergic response in high-risk patients. Furthermore, the identification of the severity grade of hypersensitivity reactions and the appropriate treatment of perioperative anaphylaxis is discussed. In addition, postoperative and follow-up interventions, including testing for patients who have had an anesthetic-induced hypersensitivity reaction, are considered. PMID:22586882

  18. Sepsis-induced Cardiomyopathy

    PubMed Central

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  19. Fluoroscopy-induced radionecrosis.

    PubMed

    Tchanque-Fossuo, Catherine N; Kamangar, Faranak; Ho, Baran; Chang, Shurong; Dahle, Sara E; Schulman, Joshua M; Isseroff, R Rivkah

    2016-01-01

    Complications from radiation exposure during fluoroscopic guidance of cardiac catheterization may occur. With repeated procedures, the risk for cutaneous injuries increases. Herein, we describe a 59-year-old man with extensive coronary artery disease, who had undergone multiple revascularization procedures and developed a non-healing ulcer on his left inferior scapula. The patient's medical history, physical exam findings, and histopathology gave clues to a case of radiation-induced dermatitis and necrosis. PMID:27617939

  20. Radiation-induced schwannomas

    SciTech Connect

    Rubinstein, A.B.; Reichenthal, E.; Borohov, H.

    1989-06-01

    The histopathology and clinical course of three patients with schwannomas of the brain and high cervical cord after therapeutic irradiation for intracranial malignancy and for ringworm of the scalp are described. Earlier reports in the literature indicated that radiation of the scalp may induce tumors in the head and neck. It is therefore suggested that therapeutic irradiation in these instances was a causative factor in the genesis of these tumors.

  1. Levetiracetam-induced pancytopenia.

    PubMed

    Alzahrani, Talal; Kay, Dana; Alqahtani, Saeed A; Makke, Yamane; Lesky, Linda; Koubeissi, Mohamad Z

    2015-01-01

    Pancytopenia is a rare side effect of levetiracetam (LEV) that is associated with severe morbidity that requires hospitalization. Here, we report a patient with a right temporoparietal tumor who underwent a temporal craniotomy with resection of the mass and was started on LEV for seizure prophylaxis per the neurosurgery local protocol. The patient developed LEV-induced pancytopenia, which was successfully managed by discontinuation of this medication. Our report aims to increase awareness of this rare cause of pancytopenia among clinicians. PMID:26744695

  2. Radiation-induced osteochondromas

    SciTech Connect

    Libshitz, H.I.; Cohen, M.A.

    1982-03-01

    Radiation-induced osteochondromas, either single or multiple, occur more commonly than is generally recognized. The incidence following irradiation for childhood malignancy is approximately 12%. Any open epiphysis is vulnerable. Age at irradiation, time of appearance following therapy, dose and type of radiation, and clinical course in 14 cases are dicussed. Due to growth of the lesion and/or pain, 3 tumors were excised. None revealed malignant degeneration.

  3. [Induced autotetraploid grape mutants].

    PubMed

    Kuliev, V M

    2011-01-01

    The methods of experimental mitotic and meiotic polyploidy in grapes are represented in the article. Results of cytological, histo-anatomical, biomorphological researches of induced autotetraploids are shown. Genetic characteristics, parameters of generative organs, quantitative and structural genome changes were studied. Comparative quantitative changes in the content of chloroplast and mitochondrion DNAs and RNAs in diploids and autotetraploids were defined. Also are shown. The biology-economic evaluation of autotetraploids on comparison with the initial grape variety is represented. PMID:21774401

  4. Polarization induced doped transistor

    DOEpatents

    Xing, Huili; Jena, Debdeep; Nomoto, Kazuki; Song, Bo; Zhu, Mingda; Hu, Zongyang

    2016-06-07

    A nitride-based field effect transistor (FET) comprises a compositionally graded and polarization induced doped p-layer underlying at least one gate contact and a compositionally graded and doped n-channel underlying a source contact. The n-channel is converted from the p-layer to the n-channel by ion implantation, a buffer underlies the doped p-layer and the n-channel, and a drain underlies the buffer.

  5. Remotely induced atmospheric lasing

    SciTech Connect

    Sprangle, Phillip; Penano, Joseph; Gordon, Daniel; Hafizi, Bahman; Scully, Marlan

    2011-05-23

    We propose and analyze a remote atmospheric lasing configuration which utilizes a combination of an ultrashort pulse laser to form a plasma filament (seed electrons) by tunneling ionization and a heater pulse which thermalizes the seed electrons. Electrons collisionally excite nitrogen molecules and induce lasing in the ultraviolet. The lasing gain is sufficiently high to reach saturation within the length of the plasma filament. A remotely generated ultraviolet source may have applications for standoff detection of biological and chemical agents.

  6. Valproate Induced Hyperammonemic Delirium

    PubMed Central

    Muraleedharan, Anupama; Gangadhar, Reneega; Das, Soumitra

    2015-01-01

    Sodium valproate induced hyperammonaemic delirium with normal liver function tests is a relatively uncommon adverse effect. It may be mistaken for psychosis or worsening of mania leading to wrong diagnosis and improper management. Plasma ammonia levels should be monitored in all patients developing altered mental status after receiving valproate therapy. This is a case series of hyperammonaemic delirium due to valproate reported to the Department of Pharmacology from Department of Psychiatry over a period of one year. PMID:26816916

  7. Sildenafil induced priapism.

    PubMed

    Aoyagi, T; Hayakawa, K; Miyaji, K; Ishikawa, H; Hata, M

    1999-11-01

    A 53 year-old Japanese man was referred to our hospital for persistent priapism, which had been induced by 200 mg (usual dose 25-50 mg) of sildenafil citrate (Viagra) three days earlier. He had a history of erectile dysfunction and had undergone penile injection therapy elsewhere; however, he had not used injection therapy this time. He obtained sildenafil personally without a doctor's prescription. He had not taken any other drugs that affect the metabolism of sildenafil, nor did he have any medical complications that might induce priapism. Since needle aspiration and irrigation were ineffective as first line therapy, surgical treatment was indicated to relieve the condition; a incision of tunica albuginea of both corpora cavernosa was made, and vigorous irrigation of saline washed out the blood clots. This is the first case report of priapism induced by sildenafil. Although this drug can be obtained through private commerce, it should be used under professional guidance as its abuse may lead to severe morbidity. PMID:11933312

  8. Ethanol-induced analgesia

    SciTech Connect

    Pohorecky, L.A.; Shah, P.

    1987-09-07

    The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to produce non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.

  9. Allergen-induced asthma

    PubMed Central

    Cockcroft, Donald W

    2014-01-01

    It was only in the late 19th century that specific allergens, pollen, animal antigens and, later, house dust mite, were identified to cause upper and lower airway disease. Early allergen challenge studies, crudely monitored before measurement of forced expiratory volume in 1 s became widespread in the 1950s, focused on the immediate effects but noted in passing prolonged and/or recurrent asthma symptoms. The late asthmatic response, recurrent bronchoconstriction after spontaneous resolution of the early responses occurring 3 h to 8 h or more postchallenge, has been identified and well characterized over the past 50 years. The associated allergen-induced airway hyper-responsiveness (1977) and allergen-induced airway inflammation (1985) indicate that these late sequelae are important in the mechanism of allergen-induced asthma. Allergens are now recognized to be the most important cause of asthma. A standardized allergen inhalation challenge model has been developed and is proving to be a valuable research tool in the investigation of asthma pathophysiology and of potential new pharmacological agents for the treatment of asthma. PMID:24791256

  10. Glucocorticoid-induced osteoporosis

    PubMed Central

    Briot, Karine; Roux, Christian

    2015-01-01

    Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the first cause in young people. Bone loss and increased rate of fractures occur early after the initiation of corticosteroid therapy, and are then related to dosage and treatment duration. The increase in fracture risk is not fully assessed by bone mineral density measurements, as it is also related to alteration of bone quality and increased risk of falls. In patients with rheumatoid arthritis, a treat-to-target strategy focusing on low disease activity including through the use of low dose of prednisone, is a key determinant of bone loss prevention. Bone loss magnitude is variable and there is no clearly identified predictor of the individual risk of fracture. Prevention or treatment of osteoporosis should be considered in all patients who receive prednisone. Bisphosphonates and the anabolic agent parathyroid hormone (1–34) have shown their efficacy in the treatment of corticosteroid-induced osteoporosis. Recent international guidelines are available and should guide management of corticosteroid-induced osteoporosis, which remains under-diagnosed and under-treated. Duration of antiosteoporotic treatment should be discussed at the individual level, depending on the subject's characteristics and on the underlying inflammation evolution. PMID:26509049