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Sample records for pulp inflammation increases

  1. TOOTH PULP INFLAMMATION INCREASES BDNF EXPRESSION IN RODENT TRIGEMINAL GANGLION NEURONS

    PubMed Central

    Tarsa, Leila; Bałkowiec-Iskra, Ewa; Kratochvil, F. James; Jenkins, Victoria K.; McLean, Anne; Brown, Alexandra; Smith, Julie Ann; Baumgartner, J. Craig; Balkowiec, Agnieszka

    2010-01-01

    Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or TRPV1, revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice compared to rats. Thus, mouse TG provides a

  2. Is Pulp Inflammation a Prerequisite for Pulp Healing and Regeneration?

    PubMed Central

    Goldberg, Michel; Njeh, Akram; Uzunoglu, Emel

    2015-01-01

    The importance of inflammation has been underestimated in pulpal healing, and in the past, it has been considered only as an undesirable effect. Associated with moderate inflammation, necrosis includes pyroptosis, apoptosis, and nemosis. There are now evidences that inflammation is a prerequisite for pulp healing, with series of events ahead of regeneration. Immunocompetent cells are recruited in the apical part. They slide along the root and migrate toward the crown. Due to the high alkalinity of the capping agent, pulp cells display mild inflammation, proliferate, and increase in number and size and initiate mineralization. Pulp fibroblasts become odontoblast-like cells producing type I collagen, alkaline phosphatase, and SPARC/osteonectin. Molecules of the SIBLING family, matrix metalloproteinases, and vascular and nerve mediators are also implicated in the formation of a reparative dentinal bridge, osteo/orthodentin closing the pulp exposure. Beneath a calciotraumatic line, a thin layer identified as reactionary dentin underlines the periphery of the pulp chamber. Inflammatory and/or noninflammatory processes contribute to produce a reparative dentinal bridge closing the pulp exposure, with minute canaliculi and large tunnel defects. Depending on the form and severity of the inflammatory and noninflammatory processes, and according to the capping agent, pulp reactions are induced specifically. PMID:26538825

  3. Tooth pulp inflammation increases brain-derived neurotrophic factor expression in rodent trigeminal ganglion neurons.

    PubMed

    Tarsa, L; Bałkowiec-Iskra, E; Kratochvil, F J; Jenkins, V K; McLean, A; Brown, A L; Smith, J A; Baumgartner, J C; Balkowiec, A

    2010-06-01

    Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or transient receptor potential vanilloid type 1 (TRPV1), revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice

  4. Scaffolds to Control Inflammation and Facilitate Dental Pulp Regeneration

    PubMed Central

    Colombo, John S.; Moore, Amanda N.; Hartgerink, Jeffrey D.; D’Souza, Rena N.

    2014-01-01

    In dentistry, the maintenance of a vital dental pulp is of paramount importance, as teeth devitalized by root canal treatment may become more brittle and prone to structural failure over time. Advanced carious lesions can irreversibly damage the dental pulp by propagating a sustained inflammatory response throughout the tissue. While the inflammatory response initially drives tissue repair, sustained inflammation has an enormously destructive effect on the vital pulp, eventually leading to total necrosis of the tissue and necessitating its removal. The implications of tooth devitalization have driven significant interest in the development of bioactive materials that facilitate the regeneration of damaged pulp tissues by harnessing the capacity of the dental pulp for self-repair. In considering the process by which pulpitis drives tissue destruction, it is clear that an important step in supporting the regeneration of pulpal tissues is the attenuation of inflammation. Macrophages, key mediators of the immune response, may play a critical role in the resolution of pulpitis due to their ability to switch to a pro-resolution phenotype. This process can be driven by the resolvins, a family of molecules derived from fatty acids that show great promise as therapeutic agents. In this review, we outline the importance of preserving the capacity of the dental pulp to self-repair through the rapid attenuation of inflammation. Potential treatment modalities, such as shifting macrophages to a pro-resolving phenotype with resolvins are described, and a range of materials known to support the regeneration of dental pulp are presented. PMID:24698696

  5. Scaffolds to control inflammation and facilitate dental pulp regeneration.

    PubMed

    Colombo, John S; Moore, Amanda N; Hartgerink, Jeffrey D; D'Souza, Rena N

    2014-04-01

    In dentistry, the maintenance of a vital dental pulp is of paramount importance because teeth devitalized by root canal treatment may become more brittle and prone to structural failure over time. Advanced carious lesions can irreversibly damage the dental pulp by propagating a sustained inflammatory response throughout the tissue. Although the inflammatory response initially drives tissue repair, sustained inflammation has an enormously destructive effect on the vital pulp, eventually leading to total necrosis of the tissue and necessitating its removal. The implications of tooth devitalization have driven significant interest in the development of bioactive materials that facilitate the regeneration of damaged pulp tissues by harnessing the capacity of the dental pulp for self-repair. In considering the process by which pulpitis drives tissue destruction, it is clear that an important step in supporting the regeneration of pulpal tissues is the attenuation of inflammation. Macrophages, key mediators of the immune response, may play a critical role in the resolution of pulpitis because of their ability to switch to a proresolution phenotype. This process can be driven by the resolvins, a family of molecules derived from fatty acids that show great promise as therapeutic agents. In this review, we outline the importance of preserving the capacity of the dental pulp to self-repair through the rapid attenuation of inflammation. Potential treatment modalities, such as shifting macrophages to a proresolving phenotype with resolvins are described, and a range of materials known to support the regeneration of dental pulp are presented. PMID:24698696

  6. Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury

    PubMed Central

    Li, Ji-Guo; Lin, Jia-Ji; Wang, Zhao-Ling; Cai, Wen-Ke; Wang, Pei-Na; Jia, Qian; Zhang, An-Sheng; Wu, Gao-Yi; Zhu, Guo-Xiong; Ni, Long-Xing

    2015-01-01

    Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-ĸB signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-ĸB signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1β, IL-18 and TNF-α in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-ĸB, TNF-α and IL-1β in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-ĸB signaling as well as IL-1β and TNF-α production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-ĸB signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that

  7. Expression of Vesicular Glutamate Transporters VGLUT1 and VGLUT2 in the Rat Dental Pulp and Trigeminal Ganglion following Inflammation

    PubMed Central

    Hong, Jae Hyun; Kim, Yun Sook; Choi, So Young; Kim, Tae Heon; Cho, Yi Sul; Bae, Yong Chul

    2014-01-01

    Background There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund’s adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis. Results The density of VGLUT2− immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group. Conclusions These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation. PMID:25290694

  8. Viruses in pulp and periapical inflammation: a review.

    PubMed

    Hernández Vigueras, Scarlette; Donoso Zúñiga, Manuel; Jané-Salas, Enric; Salazar Navarrete, Luis; Segura-Egea, Juan José; Velasco-Ortega, Eugenio; López-López, José

    2016-05-01

    The presence of viruses in endodontic disease has been studied in the last decade. Their presence is associated with periapical radiolucency and with clinical findings, such as pain. The aim of this review is to analyze the scientific evidence currently published about viruses in pulp and periapical inflammation, and its possible clinical implications. A literature review was carried out using the Medline/Pubmed database. The search was performed, in English and Spanish, using the following keyword combinations: virus AND endodontic; virus AND periapical; virus AND pulpitis; herpesvirus AND periapical; papillomavirus AND periapical. We subsequently selected the most relevant studies, which complied with the search criterion. A total of 21 articles were included, of which 18 detected the present of viruses in the samples. In 3 of the studies, viral presence was not found in the samples studied. The Epstein-Barr virus was found in about 41 % of cases compared to controls, in which it was present in about 2 %. The main association between viruses and endodontic pathosis is between Cytomegalovirus and Epstein-Barr virus; these are found in 114 of the 406 samples of different endodontic pathosis. Some evidence supports that the Epstein-Barr virus is present in a significant number of endodontic diseases, without exact knowledge of their action in these diseases. PMID:25796386

  9. Sensory Neuropeptides and Endogenous Opioids Expression in Human Dental Pulp with Asymptomatic Inflammation: In Vivo Study

    PubMed Central

    Chavarria-Bolaños, Daniel; Flores-Reyes, Hector; Lombana-Sanchez, Nelson; Cerda-Cristerna, Bernardino; Pozos-Guillen, Amaury

    2015-01-01

    Purpose. This study quantified the expression of substance P (SP), calcitonin gene-related peptide (CGRP), β-endorphins (β-End), and methionine-enkephalin (Met-Enk) in human dental pulp following orthodontic intrusion. Methods. Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons) were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg), which would undergo controlled intrusive force for seven days, and the control group (CTRg), which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA). Results. All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg. Conclusions. SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain. PMID:26538838

  10. Chronic Inflammation and Angiogenic Signaling Axis Impairs Differentiation of Dental-Pulp Stem Cells

    PubMed Central

    Boyle, Michael; Chun, Crystal; Strojny, Chelsee; Narayanan, Raghuvaran; Bartholomew, Amelia; Sundivakkam, Premanand; Alapati, Satish

    2014-01-01

    Dental-pulp tissue is often exposed to inflammatory injury. Sequested growth factors or angiogenic signaling proteins that are released following inflammatory injury play a pivotal role in the formation of reparative dentin. While limited or moderate angiogenesis may be helpful for dental pulp maintenance, the induction of significant level of angiogenesis is probably highly detrimental. Hitherto, several studies have addressed the effects of proinflammatory stimuli on the survival and differentiation of dental-pulp stem cells (DPSC), in vitro. However, the mechanisms communal to the inflammatory and angiogenic signaling involved in DPSC survival and differentiation remain unknown. Our studies observed that short-term exposure to TNF-α (6 and 12 hours [hrs]) induced apoptosis with an upregulation of VEGF expression and NF-κB signaling. However, long-term (chronic) exposure (14 days) to TNF-α resulted in an increased proliferation with a concomitant shortening of the telomere length. Interestingly, DPSC pretreated with Nemo binding domain (NBD) peptide (a cell permeable NF-κB inhibitor) significantly ameliorated TNF-α- and/or VEGF-induced proliferation and the shortening of telomere length. NBD peptide pretreatment significantly improved TNF-α-induced downregulation of proteins essential for differentiation, such as bone morphogenic proteins (BMP)-1 & 2, BMP receptor isoforms-1&2, trasnforming growth factor (TGF), osteoactivin and osteocalcin. Additionally, inhibition of NF-κB signaling markedly increased the mineralization potential, a process abrogated by chronic exposure to TNF-α. Thus, our studies demonstrated that chronic inflammation mediates telomere shortening via NF-κB signaling in human DPSC. Resultant chromosomal instability leads to an emergence of increased proliferation of DPSC, while negatively regulating the differentiation of DPSC, in vitro. PMID:25427002

  11. Kallikrein Promotes Inflammation in Human Dental Pulp Cells Via Protease-Activated Receptor-1.

    PubMed

    Hayama, Tomomi; Kamio, Naoto; Okabe, Tatsu; Muromachi, Koichiro; Matsushima, Kiyoshi

    2016-07-01

    Plasma kallikrein (KLKB1), a serine protease, cleaves high-molecular weight kininogen to produce bradykinin, a potent vasodilator and pro-inflammatory peptide. In addition, KLKB1 activates plasminogen and other leukocyte and blood coagulation factors and processes pro-enkephalin, prorenin, and C3. KLKB1 has also been shown to cleave protease-activated receptors in vascular smooth muscle cells to regulate the expression of epidermal growth factor receptor. In this study, we investigated KLKB1-dependent inflammation and activation of protease-activated receptor-1 in human dental pulp cells. These cells responded to KLKB1 stimulation by increasing intracellular Ca(2+) , upregulating cyclooxygenase-2, and secreting prostaglandin E2 . Remarkably, SCH79797, an antagonist of protease-activated receptor-1, blocked these effects. Thus, these data indicate that KLKB1 induces inflammatory reactions in human dental tissues via protease-activated receptor 1. J. Cell. Biochem. 117: 1522-1528, 2016. © 2015 Wiley Periodicals, Inc. PMID:26566265

  12. Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation

    PubMed Central

    2013-01-01

    Background The purpose of the present study is to evaluate the mechanisms underlying tongue-referred pain associated with tooth pulp inflammation. Method Using mechanical and temperature stimulation following dental surgery, we have demonstrated that dental inflammation and hyperalgesia correlates with increased immunohistochemical staining of neurons for TLR4 and HSP70. Results Mechanical or heat hyperalgesia significantly enhanced in the ipsilateral tongue at 1 to 9 days after complete Freund’s adjuvant (CFA) application to the left lower molar tooth pulp compared with that of sham-treated or vehicle-applied rats. The number of fluorogold (FG)-labeled TLR4-immunoreactive (IR) cells was significantly larger in CFA-applied rats compared with sham-treated or vehicle-applied rats to the molar tooth. The number of heat shock protein (Hsp) 70-IR neurons in trigeminal ganglion (TG) was significantly increased on day 3 after CFA application compared with sham-treated or vehicle-applied rats to the molar tooth. About 9.2% of TG neurons were labeled with DiI applied to the molar tooth and FG injected into the tongue, and 15.4% of TG neurons were labeled with FG injected into the tongue and Alexa-labeled Hsp70-IR applied to the tooth. Three days after Hsp70 or lipopolysaccharide (LPS) application to the tooth in naive rats, mechanical or heat hyperalgesia was significantly enhanced compared with that of saline-applied rats. Following successive LPS-RS, an antagonist of TLR4, administration to the TG for 3 days, the enhanced mechanical or heat hyperalgesia was significantly reversed compared with that of saline-injected rats. Noxious mechanical responses of TG neurons innervating the tongue were significantly higher in CFA-applied rats compare with sham rats to the tooth. Hsp70 mRNA levels of the tooth pulp and TG were not different between CFA-applied rats and sham rats. Conclusions The present findings indicate that Hsp70 transported from the tooth pulp to TG neurons

  13. Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice.

    PubMed

    Pivoraitė, Ugnė; Jarmalavičiūtė, Akvilė; Tunaitis, Virginijus; Ramanauskaitė, Giedrė; Vaitkuvienė, Aida; Kašėta, Vytautas; Biziulevičienė, Genė; Venalis, Algirdas; Pivoriūnas, Augustas

    2015-10-01

    The primary goal of this study was to examine the effects of human dental pulp stem cell-derived exosomes on the carrageenan-induced acute inflammation in mice. Exosomes were purified by differential ultracentrifugation from the supernatants of stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) cultivated in serum-free medium. At 1 h post-carrageenan injection, exosomes derived from supernatants of 2 × 10(6) SHEDs were administered by intraplantar injection to BALB/c mice; 30 mg/kg of prednisolone and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively. Edema was measured at 6, 24, and 48 h after carrageenan injection. For the in vivo imaging experiments, AngioSPARK750, Cat B 750 FAST, and MMPSense 750 FAST were administered into the mouse tail vein 2 h post-carrageenan injection. Fluorescence images were acquired at 6, 24, and 48 h after edema induction by IVIS Spectrum in vivo imaging system. Exosomes significantly reduced the carrageenan-induced edema at all the time points studied (by 39.5, 41.6, and 25.6% at 6, 24, and 48 h after injection, respectively), to similar levels seen with the positive control (prednisolone). In vivo imaging experiments revealed that, both exosomes and prednisolone suppress activities of cathepsin B and matrix metalloproteinases (MMPs) at the site of carrageenan-induced acute inflammation, showing more prominent effects of prednisolone at the early stages, while exosomes exerted their suppressive effects gradually and at later time points. Our study demonstrates for the first time that exosomes derived from human dental pulp stem cells suppress carrageenan-induced acute inflammation in mice. PMID:25903966

  14. Role of matrix metalloproteinases in dental caries, pulp and periapical inflammation: An overview.

    PubMed

    Jain, Atul; Bahuguna, Rachana

    2015-01-01

    Matrix metalloproteinases (MMPs) are a group of more than 25 secreted and membrane bound enzymes that represent class of enzymes responsible for degradation of pericellular substrates. They have been isolated from dentine, odontoblasts, pulp and periapical tissue. They play an important role in dentine matrix formation, modulating caries progression and secondary dentine formation. Earlier microbial proteolytic enzymes were believed to be responsible for degradation of dentine organic matrix, but lately the accumulated body of evidence suggests that MMPs have an important role in the process. During normal tissue modelling, differentiation during development, in modulating the cell behaviour, maintaining homeostasis and in numerous extracellular pathologic conditions, MMPs tends to be an equally important participant. Odontoblasts secrete some of the essential MMPs for both physiologic and pathologic conditions. MMPs also appear to be a participant in the process of reversible and irreversible pulpitis. Although they tend to have low expression and activity in adult tissues but at the onset of any destructive pathologic process, their production shoots up. They appear to have a significant presence during times of inflammation in the periapical region as well. We take a look at the various factors and evidence pointing towards the role of MMPs in the progression of caries, pulpal and periapical inflammation. PMID:26605147

  15. Role of matrix metalloproteinases in dental caries, pulp and periapical inflammation: An overview

    PubMed Central

    Jain, Atul; Bahuguna, Rachana

    2015-01-01

    Matrix metalloproteinases (MMPs) are a group of more than 25 secreted and membrane bound enzymes that represent class of enzymes responsible for degradation of pericellular substrates. They have been isolated from dentine, odontoblasts, pulp and periapical tissue. They play an important role in dentine matrix formation, modulating caries progression and secondary dentine formation. Earlier microbial proteolytic enzymes were believed to be responsible for degradation of dentine organic matrix, but lately the accumulated body of evidence suggests that MMPs have an important role in the process. During normal tissue modelling, differentiation during development, in modulating the cell behaviour, maintaining homeostasis and in numerous extracellular pathologic conditions, MMPs tends to be an equally important participant. Odontoblasts secrete some of the essential MMPs for both physiologic and pathologic conditions. MMPs also appear to be a participant in the process of reversible and irreversible pulpitis. Although they tend to have low expression and activity in adult tissues but at the onset of any destructive pathologic process, their production shoots up. They appear to have a significant presence during times of inflammation in the periapical region as well. We take a look at the various factors and evidence pointing towards the role of MMPs in the progression of caries, pulpal and periapical inflammation. PMID:26605147

  16. Effect of miR-146a/bFGF/PEG-PEI Nanoparticles on Inflammation Response and Tissue Regeneration of Human Dental Pulp Cells

    PubMed Central

    Liu, Lu; Shu, Shan; Cheung, Gary Shunpan; Wei, Xi

    2016-01-01

    Introduction. Inflammation in dental pulp cells (DPCs) initiated by Lipopolysaccharide (LPS) results in dental pulp necrosis. So far, whether there is a common system regulating inflammation response and tissue regeneration remains unknown. miR-146a is closely related to inflammation. Basic fibroblast growth factor (bFGF) is an important regulator for differentiation. Methods. To explore the effect of miR-146a/bFGF on inflammation and tissue regeneration, polyethylene glycol-polyethyleneimine (PEG-PEI) was synthesized, and physical characteristics were analyzed by dynamic light scattering and gel retardation analysis. Cell absorption, transfection efficiency, and cytotoxicity were assessed. Alginate gel was combined with miR-146a/PEG-PEI nanoparticles and bFGF. Drug release ratio was measured by ultraviolet spectrophotography. Proliferation and odontogenic differentiation of DPCs with 1 μg/mL LPS treatment were determined. Results. PEG-PEI prepared at N/P 2 showed complete gel retardation and smallest particle size and zeta potential. Transfection efficiency of PEG-PEI was higher than lipo2000. Cell viability decreased as N/P ratio increased. Drug release rate amounted to 70% at the first 12 h and then maintained slow release afterwards. Proliferation and differentiation decreased in DPCs with LPS treatment, whereas they increased in miR-146a/bFGF gel group. Conclusions. PEG-PEI is a promising vector for gene therapy. miR-146a and bFGF play critical roles in inflammation response and tissue regeneration of DPCs. PMID:27057540

  17. Effect of miR-146a/bFGF/PEG-PEI Nanoparticles on Inflammation Response and Tissue Regeneration of Human Dental Pulp Cells.

    PubMed

    Liu, Lu; Shu, Shan; Cheung, Gary Shunpan; Wei, Xi

    2016-01-01

    Introduction. Inflammation in dental pulp cells (DPCs) initiated by Lipopolysaccharide (LPS) results in dental pulp necrosis. So far, whether there is a common system regulating inflammation response and tissue regeneration remains unknown. miR-146a is closely related to inflammation. Basic fibroblast growth factor (bFGF) is an important regulator for differentiation. Methods. To explore the effect of miR-146a/bFGF on inflammation and tissue regeneration, polyethylene glycol-polyethyleneimine (PEG-PEI) was synthesized, and physical characteristics were analyzed by dynamic light scattering and gel retardation analysis. Cell absorption, transfection efficiency, and cytotoxicity were assessed. Alginate gel was combined with miR-146a/PEG-PEI nanoparticles and bFGF. Drug release ratio was measured by ultraviolet spectrophotography. Proliferation and odontogenic differentiation of DPCs with 1 μg/mL LPS treatment were determined. Results. PEG-PEI prepared at N/P 2 showed complete gel retardation and smallest particle size and zeta potential. Transfection efficiency of PEG-PEI was higher than lipo2000. Cell viability decreased as N/P ratio increased. Drug release rate amounted to 70% at the first 12 h and then maintained slow release afterwards. Proliferation and differentiation decreased in DPCs with LPS treatment, whereas they increased in miR-146a/bFGF gel group. Conclusions. PEG-PEI is a promising vector for gene therapy. miR-146a and bFGF play critical roles in inflammation response and tissue regeneration of DPCs. PMID:27057540

  18. Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

    PubMed Central

    Tancharoen, Salunya; Tengrungsun, Tassanee; Suddhasthira, Theeralaksna; Kikuchi, Kiyoshi; Vechvongvan, Nuttavun; Maruyama, Ikuro

    2014-01-01

    High mobility group box 1 (HMGB1), a nonhistone DNA-binding protein, is released into the extracellular space and promotes inflammation. HMGB1 binds to related cell signaling transduction receptors, including receptor for advanced glycation end products (RAGE), which actively participate in vascular and inflammatory diseases. The aim of this study was to examine whether RAGE and HMGB1 are involved in the pathogenesis of pulpitis and investigate the effect of Prevotella intermedia (P. intermedia) lipopolysaccharide (LPS) on RAGE and HMGB1 expression in odontoblast-like cells (OLC-1). RAGE and HMGB1 expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Upregulated expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1 immunoreactivity was seen in stromal pulp fibroblasts-like cells in human pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-κB activation. These findings suggest that RAGE and HMGB1 play an important role in the pulpal immune response to oral bacterial infection. PMID:25114379

  19. EFFECT OF BETAMETHASONE ON THE PULP AFTER TOPICAL APPLICATION TO THE DENTIN OF RAT TEETH: VASCULAR ASPECTS OF THE INFLAMMATION

    PubMed Central

    Fachin, Elaine Vianna Freitas; Scarparo, Roberta Kochenborger; Pezzi, Ana Paula Weissheimer; Luisi, Simone Bonato; Sant'ana, Manoel

    2009-01-01

    Objective: This study investigated the pulpal effect of topically applied betamethasone to the dentin of rat molars in the vascular phase of inflammation. Material and Methods: Deep cavities were prepared on the occlusal face of the maxillary right and left 1st molars with non-refrigerated inverted-cone steel burs at low speed. Three groups were formed: Group I was composed of right 1st molars; Group II was composed of left 1st molars that received the application of a drop of betamethasone on dentin surface for 5 min; and Group III (control) was composed of right 2nd molars that received no cavity preparation or betamethasone application. Changes in the vascular characteristics of the pulp tissue were checked by calculating the pulp vascular area in relation to its total area and the number of blood vessels per unit area. Data were subjected to ANOVA and Tukey's test (α=0.05). Results: Group I presented a significantly larger number of vessels (p<0.05) than Group II. Regarding the vascular/total area ratio (%), Group I presented statistically significantly higher values (p=0.01) than Groups II and III. Conclusion: Betamethasone applied on the dentin of rat teeth proved to reduce the vascular phase of pulp inflammation regarding vessel diameter and number of blood vessels. PMID:19668994

  20. Possibilities for increasing the power generation with biomass in pulp and paper mills

    SciTech Connect

    Nousianinen, I.K.

    1995-11-01

    Even today the share of wood derived fuels in the Finnish energy supply is significant and it is higher than in any other industrialized western country. The energy content of wood derived fuels used in 1993 was equivalent to 4.36 million toe. The wood raw material used in pulp and paper mills is harvested by log-length method, in which the trees are delimbed and bucked to timber assortments at the stump prior to subsequent transport to the road side. The long-distance transport to the mills is performed by truck-trailers. Debarking takes place in debarking drums, after which the bark-free stemwood is chipped to clean chips for pulping. The bark is removed from any drum, shredded, mechanically dried and conveyed to the power plant for energy production. In order to increase the amount of wood fuel in proportion to raw wood material various integrated harvesting methods are being developed. On the other hand, the pulp and paper mills are seen as a significant potential sector for increasing the use of wood fuel in energy production. Forest management in Finland is characterized by two or three selective thinnings during rotation period. Integrated harvesting methods can be applied to the first thinnings and to the spruce-dominant regeneration fellings. The annual potential of wood fuel production with integrated harvesting methods is in the first thinnings 0.9-1.2 million toe and in the spruce-dominant regeneration fellings 0.6-0.8 million toe. The increased amount of wood fuel allows mills either to decrease the amount of purchased fuel or with new power plant technologies the amount of purchased power. In the typical pulp and paper mills the energy content of additional wood fuel produced with integrated harvesting methods can be 50-60 MW. By pressurized gasification of bark and additional wood fuel, by integrated methods and from other mills, the power generation can be increased with 70-90 MW.

  1. Innovative endodontic therapy for anti-inflammatory direct pulp capping of permanent teeth with a mature apex

    PubMed Central

    Komabayashi, Takashi; Zhu, Qiang

    2010-01-01

    Direct pulp capping is a treatment of an exposed vital pulp with a dental material to facilitate the formation of reparative dentin and maintenance of vital pulp. It has been studied as an alternate way to avoid vital pulp extirpation. However, the success rate of pulp capping is much lower than that of vital pulp extirpation. Therefore, direct pulp capping is currently considered controversial by many clinicians. To increase success rate, a critical need exists to develop new biologically-based therapeutics that reduce pulp inflammation, promote the continued formation of new dentin-pulp complex, and restore vitality by stimulating the regrowth of pulpal tissue. Bioengineered anti-inflammatory direct pulp capping materials, together with adhesive materials for leakage prevention, have great potential to improve the condition of the existing pulp from an inflamed to a non-inflamed status and lead to a high rate of long-term success. PMID:20416524

  2. Pulp-temperature increases after selective ablation of caries by KTP:NdYAG laser

    NASA Astrophysics Data System (ADS)

    Nammour, S.; Kowalyk, Kenneth; Valici, Ch.; Guillaume, Patrick

    1997-05-01

    The aim of this investigation is to define optimal parameters of KTP laser irradiation during caries removal. 12 decayed human teeth, recently extracted were used. Their rot canals were prepared for insertion of a thermocouple probe into the pulp chamber. The demineralized tissues have been colored by Acid Red 52 before proceeding to different conditions of irradiation. Pulpal temperature increases were found under the following parameters with 15 seconds continuous lasing: 400mw, 0.10 m sec pulse width, PRR pulp temperature to get back to its baseline.

  3. Effects of Tamarindus indica fruit pulp extract on abundance of HepG2 cell lysate proteins and their possible consequential impact on metabolism and inflammation.

    PubMed

    Chong, Ursula R W; Abdul-Rahman, Puteri S; Abdul-Aziz, Azlina; Hashim, Onn H; Mat-Junit, Sarni

    2013-01-01

    The fruit pulp extract of Tamarindus indica has been reported for its antioxidant and hypolipidemic properties. In this study, the methanol extract of T. indica fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate proteins. Cell lysate was extracted from HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp. Approximately 2500 spots were resolved using two-dimensional gel electrophoresis and the abundance of 20 cellular proteins was found to be significantly reduced. Among the proteins of reduced abundance, fourteen, including six proteins involved in metabolism (including ethanolamine phosphate cytidylyltransferase), four mitochondrial proteins (including prohibitin and respiratory chain proteins), and four proteins involved in translation and splicing, were positively identified by mass spectrometry and database search. The identified HepG2 altered abundance proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA) software, are suggestive of the effects of T. indica fruit pulp extract on metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the methanol fruit pulp extract of T. indica was shown to cause reduced abundance of HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative phosphorylation, protein synthesis, and cellular metabolism. PMID:24455694

  4. Effects of Tamarindus indica Fruit Pulp Extract on Abundance of HepG2 Cell Lysate Proteins and Their Possible Consequential Impact on Metabolism and Inflammation

    PubMed Central

    Chong, Ursula R. W.; Abdul-Rahman, Puteri S.; Abdul-Aziz, Azlina; Hashim, Onn H.; Mat-Junit, Sarni

    2013-01-01

    The fruit pulp extract of Tamarindus indica has been reported for its antioxidant and hypolipidemic properties. In this study, the methanol extract of T. indica fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate proteins. Cell lysate was extracted from HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp. Approximately 2500 spots were resolved using two-dimensional gel electrophoresis and the abundance of 20 cellular proteins was found to be significantly reduced. Among the proteins of reduced abundance, fourteen, including six proteins involved in metabolism (including ethanolamine phosphate cytidylyltransferase), four mitochondrial proteins (including prohibitin and respiratory chain proteins), and four proteins involved in translation and splicing, were positively identified by mass spectrometry and database search. The identified HepG2 altered abundance proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA) software, are suggestive of the effects of T. indica fruit pulp extract on metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the methanol fruit pulp extract of T. indica was shown to cause reduced abundance of HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative phosphorylation, protein synthesis, and cellular metabolism. PMID:24455694

  5. Carbon Tetrachloride Increases the Pro-inflammatory Cytokines Levels in Different Brain Areas of Wistar Rats: The Protective Effect of Acai Frozen Pulp.

    PubMed

    de Souza Machado, Fernanda; Marinho, Jéssica Pereira; Abujamra, Ana Lúcia; Dani, Caroline; Quincozes-Santos, André; Funchal, Cláudia

    2015-09-01

    Acai offers health benefits associated with its high antioxidante capacity, phytochemical composition, nutritional and sensory value. Therefore, the objective of this study was to evaluate the protective effect of acai frozen pulp on carbon tetrachloride (CCl4)-induced damage via modulation of anti- and pro-inflammatory cytokines in rat brain tissue. The rats were treated via oral (gavage) daily with water or acai frozen pulp for 14 days at a dose of 7 μL/g. On the 15th day, the animals in each group received a single intraperitoneal injection of CCl4 in a dose of 3.0 mL/kg or the same volume of mineral oil. After 4 h, the animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were dissected and homogenated to evaluate the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 18 (IL-18), interleukin 6 (IL-6) and interleukin 10 (IL-10). Data were statistically analyzed by analysis of variance followed by the Tukey post hoc test. It was observed that CCl4 increased TNF-α, IL-1β and IL-18 levels in all brain tissues, and that acai frozen pulp was able to prevent this increase. IL-6 and IL-10 brain tissue levels remained unchanged during all treatments. CCl4 experimental model was suitable to investigate brain tissue anti and pro-inflammatory cytokines. Acai frozen pulp prevented an increase in IL-1β, IL-18 and TNF-α, while IL-6 and IL-10 levels remained unchanged. The precise pathway by which inflammation contribute to hepatic encephalopathy, as well as to how this pathway can be modulated, is still under investigation. PMID:26283513

  6. Resveratrol Increases Osteoblast Differentiation In Vitro Independently of Inflammation.

    PubMed

    Ornstrup, Marie Juul; Harsløf, Torben; Sørensen, Lotte; Stenkjær, Liselotte; Langdahl, Bente Lomholt; Pedersen, Steen Bønløkke

    2016-08-01

    Low-grade inflammation negatively affects bone. Resveratrol is a natural compound proven to possess both anti-inflammatory and bone protective properties. However, it is uncertain if the bone effects are mediated though anti-inflammatory effects. Firstly, we investigated if resveratrol affects proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Secondly, we investigated if inflammation negatively affects proliferation and differentiation, and if resveratrol counteracts this through anti-inflammatory effects. Mesenchymal stem cells were obtained from bone marrow aspiration in 13 healthy individuals and cultured towards the osteoblast cell lineage. The cells were stimulated with resveratrol, lipopolysaccharide (LPS), LPS + resveratrol, or vehicle (control) for 21 days. Compared to control, resveratrol decreased cell number by 35 % (p < 0.05) and induced differentiation (a 3-fold increase in alkaline phosphatase (p < 0.002), while P1NP and OPG showed similar trends). LPS induced inflammation with a 44-fold increase in interleukin-6 (p < 0.05) and an extremely prominent increase in interleukin-8 production (p < 0.05) relative to control. In addition, LPS increased cell count (p < 0.05) and decreased differentiation (a reduction in P1NP production (p < 0.02)). Co-stimulation with LPS + resveratrol did not reduce interleukin-6 or interleukin-8, but nonetheless, cell count was reduced (p < 0.05) and alkaline phosphatase, P1NP, and OPG increased (p < 0.05 for all). Thus, resveratrol stimulates osteoblast differentiation independently of inflammation. PMID:27000750

  7. Increased levels of inosine in a mouse model of inflammation

    PubMed Central

    Prestwich, Erin G; Mangerich, Aswin; Pang, Bo; McFaline, Jose L; Lonkar, Pallavi; Sullivan, Matthew R; Trudel, Laura J; Taghizedeh, Koli; Dedon, Peter C

    2013-01-01

    One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To determine the most biologically deleterious chemistries of inflammation, we previously assessed products across the spectrum of DNA damage arising in inflamed tissues in the SJL mouse model nitric oxide over-production (Pang et al., Carcinogenesis 28: 1807–1813, 2007). Among the anticipated DNA damage chemistries, we observed significant changes only in lipid peroxidation-derived etheno adducts. We have now developed an isotope-dilution, liquid chromatography-coupled, tandem quadrupole mass spectrometric method to quantify representative species across the spectrum of RNA damage products predicted to arise at sites of inflammation, including nucleobase deamination (xanthosine, inosine), oxidation (8-oxoguanosine), and alkylation (1,N6-etheno-adenosine). Application of the method to liver, spleen, and kidney from the SJL mouse model revealed generally higher levels of oxidative background RNA damage than was observed in DNA in control mice. However, compared to control mice, RcsX treatment to induce nitric oxide overproduction resulted in significant increases only in inosine and only in the spleen. Further, the nitric oxide synthase inhibitor, N-methylarginine, did not significantly affect the levels of inosine in control and RcsX-treated mice. The differences between DNA and RNA damage in the same animal model of inflammation point to possible influences from DNA repair, RcsX-induced alterations in adenosine deaminase activity, and differential accessibility of DNA and RNA to reactive oxygen and nitrogen species as determinants of nucleic acid damage during inflammation. PMID:23506120

  8. Pulp temperature increase during photo-activated disinfection (PAD) of periodontal pockets: an in vitro study.

    PubMed

    El Yazami, H; Zeinoun, Toni; Bou Saba, S; Lamard, L; Peremans, A; Limme, M; Geerts, S; Lamy, M; Nammour, S

    2010-09-01

    The capacity of photo-sensitizers, used in combination with laser light to kill micro-organisms has been demonstrated in different studies. Photo-activated disinfection (PAD) has been introduced in periodontology as an aid for disinfection of periodontal pockets. The aim of this study is to verify the harm for dental vitality of the use of PAD in periodontal pockets. Root canals of 24 freshly extracted human teeth where prepared using profiles up to a size of ISO #50 and filled with thermo-conductor paste. A silicon-based false gum was made in which a periodontal pocket was created and filled with photo-sensitizer phenothiazine chloride (phenothiazine-5-ium, 3.7-bis (dimethylamino)-, chloride). The external root surface was irradiated during 60 s with a 660-nm diode laser (output power: 20 mW; power density: 0.090 W/cm(2); Energy density: 5.46 J/cm(2)) using a periodontal tip with a diameter of 1 mm and a length of 7 mm. Temperatures were recorded inside the root canal using a thermocouple. Measurements were recorded every second, starting at 10 s before lasering, during the irradiation and were continued for 150 s after the end of irradiation, and six measurements were done per tooth. An average temperature increase of 0.48 +/- 0.11 degrees C was recorded. Our results demonstrated that pulp temperature increase was lower than 3 degrees C, which is considered to be harmless for pulp injury. Regarding pulp temperature increase, the use of PAD for disinfection of periodontal pockets can be considered as a safe procedure for dental vitality. PMID:19529881

  9. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    SciTech Connect

    Zhang, Xufang; Jiang, Hongwei; Gong, Qimei; Fan, Chen; Huang, Yihua; Ling, Junqi

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  10. Increased CD40+ fibrocytes in patients with idiopathic orbital inflammation

    PubMed Central

    Lee, Brian J; Atkins, Stephen; Ginter, Anna; Elner, Victor M; Nelson, Christine C; Douglas, Raymond S

    2014-01-01

    Objective To investigate the phenotypic and functional characteristics of peripheral and tissue-infiltrating stem cells, called fibrocytes in patients with idiopathic orbital inflammation (IOI). Methods Seven patients with IOI were studied. In the three patients requiring orbital biopsy, fibrocytes were identified in orbital tissue from patients with IOI compared to healthy controls using immunohistochemistry. Fibrocytes from the peripheral blood of all seven patients and controls were quantified and phenotyped by flow cytometry and immunofluorescence for expression of CD34, alpha smooth muscle actin, CD40 and Collagen 1. Quantitation of CD40-mediated IL-6 production was measured using ELISA. Results Orbital biopsy specimens from patients with IOI demonstrate tissue infiltration by fibrocytes (n=3). Fibrocytes are present in the peripheral blood of IOI patients (n= 7) but are scarce in healthy donors (n=19). Fibrocytes from IOI patients express substantial levels of CD40 and ligation of CD40 increases IL-6 expression. Conclusions Fibrocytes are present in the peripheral blood and orbital tissues of patients with IOI and constitutively express CD40 and express IL-6 in response to ligation. This site-specific predilection of CD34+ fibrocytes to sites of orbital inflammation and fibrosis may suggest a role in IOI. Moreover CD40-mediated activation cytokine production may contribute to the proinflammatory and profibrotic features of IOI and may provide a mechanism for future targeted therapy. PMID:25098443

  11. The 82-plex plasma protein signature that predicts increasing inflammation

    PubMed Central

    Tepel, Martin; Beck, Hans C.; Tan, Qihua; Borst, Christoffer; Rasmussen, Lars M.

    2015-01-01

    The objective of the study was to define the specific plasma protein signature that predicts the increase of the inflammation marker C-reactive protein from index day to next-day using proteome analysis and novel bioinformatics tools. We performed a prospective study of 91 incident kidney transplant recipients and quantified 359 plasma proteins simultaneously using nano-Liquid-Chromatography-Tandem Mass-Spectrometry in individual samples and plasma C-reactive protein on the index day and the next day. Next-day C-reactive protein increased in 59 patients whereas it decreased in 32 patients. The prediction model selected and validated 82 plasma proteins which determined increased next-day C-reactive protein (area under receiver-operator-characteristics curve, 0.772; 95% confidence interval, 0.669 to 0.876; P < 0.0001). Multivariable logistic regression showed that 82-plex protein signature (P < 0.001) was associated with observed increased next-day C-reactive protein. The 82-plex protein signature outperformed routine clinical procedures. The category-free net reclassification index improved with 82-plex plasma protein signature (total net reclassification index, 88.3%). Using the 82-plex plasma protein signature increased net reclassification index with a clinical meaningful 10% increase of risk mainly by the improvement of reclassification of subjects in the event group. An 82-plex plasma protein signature predicts an increase of the inflammatory marker C-reactive protein. PMID:26445912

  12. Increased alveolar soluble annexin V promotes lung inflammation and fibrosis.

    PubMed

    Buckley, Susan; Shi, Wei; Xu, Wei; Frey, Mark R; Moats, Rex; Pardo, Annie; Selman, Moises; Warburton, David

    2015-11-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF. Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF. Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators. PMID:26160872

  13. Experimental model to measure the increase of dental pulp temperature in vivo during laser application

    NASA Astrophysics Data System (ADS)

    Nicola, Ester M. D.; Junqueira, Silvio L. M.; Busato, Mara S.

    1994-09-01

    Carbon dioxide laser has been used in dental surgery. The existence of healthy teeth, which have pulp vitality needing to be preserved, is observed in a great number of cases. In this work we describe an experimental model which provides the measurement of temperature in pulp chamber `in vivo,' during oral surgeries in which the CO2 laser beam is applied to gingival tissue. The problems met during the search for the best way to place the thermal probe regarding the diameter and depth of pulp chamber and the thickness of the tissue layer formed by gum and maxillary bone are discussed. We use a thermocouple placed in the pulp chamber of superior canine teeth in dogs. After that, the probe was also placed between gum and dental root. Since the temperature at gingival surface was known, it was easy to determine the rise in temperature at pulp chamber and also to observe the thermal gradient from gum to tissue to bone, thus avoiding pulp damage during laser applications.

  14. Intra-pulp temperature increase of equine cheek teeth during treatment with motorized grinding systems: influence of grinding head position and rotational speed

    PubMed Central

    2014-01-01

    Background In equine practice, teeth corrections by means of motorized grinding systems are standard procedure. The heat resulting from that treatment may cause irreparable damage to the dental pulp. It has been shown that a 5.5°C temperature rise may cause severe destruction in pulp cells. Hence, the capability to continuously form secondary dentine is lost, and may lead, due to equine-typical occlusal tooth abrasion, to an opening of the pulp cavity. To obtain reliable data on the intra-pulp increase in temperature during corrective treatments, equine cheek teeth (CT) were modified in a way (occlusal surface smoothed, apical parts detached, pulp horns standardized) that had been qualified in own former published studies. All parameters influencing the grinding process were standardized (force applied, initial temperatures, dimensions of pulp horns, positioning of grinding disk, rotational speed). During grinding experiments, imitating real dental treatments, the time span for an intra-pulp temperature increase of 5.5°C was determined. Results The minimum time recorded for an intra-pulp temperature increase of 5.5°C was 38 s in mandibular CT (buccal grinding, 12,000 rpm) and 70 s in maxillary CT (flat occlusal grinding, 12,000 rpm). The data obtained showed that doubling the rotational speed of the disk results in halving the time span after which the critical intra-pulp temperature increase in maxillary CT is reached. For mandibular CT, the time span even drops by two thirds. Conclusion The use of standardized hypsodont CT enabled comparative studies of intra-pulp heating during the grinding of occlusal tooth surfaces using different tools and techniques. The anatomical structure of the natural vital hypsodont tooth must be kept in mind, so that the findings of this study do not create a deceptive sense of security with regard to the time-dependent heating of the native pulp. PMID:24559121

  15. Nav1.7 expression is increased in painful human dental pulp

    PubMed Central

    Luo, Songjiang; Perry, Griffin M; Levinson, S Rock; Henry, Michael A

    2008-01-01

    Background Animal studies and a few human studies have shown a change in sodium channel (NaCh) expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1) Nav1.7, N52 and PGP9.5, and 2) Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier), and myelin basic protein (MBP), and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache. PMID:18426592

  16. Placental inflammation is not increased in inflammatory bowel disease

    PubMed Central

    Taleban, Sasha; Gundogan, Fusun; Chien, Edward K.; Degli-Esposti, Silvia; Saha, Sumona

    2015-01-01

    Background Women with inflammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental inflammation than non-IBD controls. Methods Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5 Crohn’s disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory response. The history and birth outcomes of all IBD subjects were reviewed and matched to 26 non-IBD controls by gestational age at delivery. Results Of women with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of the IBD patients had mild-moderate disease flares during pregnancy. Five (36%) patients required corticosteroids, 2 (14%) were maintained on an immunomodulator, and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their pregnancy. Chorioamnionitis was the only identified placental pathology present in the placentas reviewed, occurring less frequently in cases compared to controls (7% vs. 27%, P=0.32). Conclusions Placental inflammatory activation does not appear to be responsible for the increase in adverse birth outcome in women with IBD. Further studies are necessary to validate these findings in IBD to explain poor birth outcomes. PMID:26423206

  17. Aspartate aminotransferase activity in human healthy and inflamed dental pulps.

    PubMed

    Spoto, G; Fioroni, M; Rubini, C; Tripodi, D; Perinetti, G; Piattelli, A

    2001-06-01

    Aspartate aminotransferase (AST) seems to be an important mediator of inflammatory processes. Its role in the progression and detection of inflammatory periodontal disease has been increasingly recognized in recent years. In the present study AST activity was analyzed in normal healthy human dental pulps, in reversible pulpitis, and in irreversible pulpitis. Enzymatic AST activity showed that the control values for the healthy pulps were 4.8 +/- 0.7 units/mg of pulp tissue. In reversible pulpitis specimens the AST activity increased to 7.98 +/- 2.1 units/mg of pulp tissue. In irreversible pulpitis specimens the values decreased to 2.28 +/- 1.7 units/mg of pulp tissue. Differences between the groups (control versus reversible pulpitis and reversible pulpitis versus irreversible pulpitis) were statistically significant (p = 0.0015). These results could point to a role of AST in the early events that lead to development of pulpal inflammation. PMID:11487132

  18. Increasing the lignin yield of the Alkaline Polyol Pulping process by treating black liquor with laccases of Myceliophthora thermophila.

    PubMed

    Engel, Norman; Hundt, Martin; Schapals, Tino

    2016-03-01

    The Alkaline Polyol Pulping process separates cellulose from lignocellulosic biomass by dissolving lignin to a great extent. Due to the pulping conditions the dissolved lignin depolymerises and only 75% can be precipitated. To increase this amount, a 24 h reaction of laccases of Myceliophthora thermophila with lignin dissolved in black liquor of the AlkaPolP process was investigated. The influence of pH, temperature, enzyme concentration and partial oxygen pressure was examined in a batch stirred tank reactor using a Box-Behnken factorial design. Due to the enzymatic reaction the lignin polymerises which results in an enhanced lignin precipitation. The addition of a mediator improves the polymerisation but decreases the amount of precipitable lignin. The influence of the parameters on precipitation yield and molecular mass can sufficiently be described with a second-order model and optimum conditions can be assessed. FT-IR spectra of the obtained lignins revealed that its typical phenolic structure is preserved. PMID:26722808

  19. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells.

    PubMed

    Zhang, Xufang; Jiang, Hongwei; Gong, Qimei; Fan, Chen; Huang, Yihua; Ling, Junqi

    2014-08-01

    High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration. PMID:25019990

  20. Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review

    PubMed Central

    Colman, Ruben J.

    2016-01-01

    Background/Aims Ulcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed. We performed a systematic review and meta-analysis to explore the relationship between histologic inflammation and risk for neoplasia among available observational studies. Methods Three databases (EMBASE, MEDLINE and the Cochrane Library) were systematically searched. Studies were included if they included UC patients who underwent colonoscopic assessment and when histologic inflammation and colorectal neoplasia were both reported. Colorectal neoplasia rates were compared. Quantitative meta-analysis was attempted. Results Four of 1,422 records found were eligible. Results from 2 case-control studies reported a 3.5-fold increased risk for colorectal neoplasia associated with a single point increase in histologic inflammation. This result was further corroborated by one cohort study that demonstrated increased hazard ratios. The second cohort study reported outcomes for patients with normal gross endoscopy, but had increased histological inflammation when neoplasia was assessed. Finally, this study reported increased risk for neoplastic progression by histological inflammation among patients who were normal by gross endoscopic evaluation. Quantitative meta-analysis was unsuccessful due to heterogeneity between study measures. Conclusions There is strong evidence that histologic inflammation among patients with UC increases the risk of colorectal neoplasia. The depth and nature of assessment of additional clinical variables was varied and may have resulted in greater outcome discrepancy. Additional study related to mechanisms of inflammation-related neoplasia and therapeutic modification is needed.

  1. Can Pulp Fibroblasts Kill Cariogenic Bacteria? Role of Complement Activation.

    PubMed

    Jeanneau, C; Rufas, P; Rombouts, C; Giraud, T; Dejou, J; About, I

    2015-12-01

    Complement system activation has been shown to be involved in inflammation and regeneration processes that can be observed within the dental pulp after moderate carious decay. Studies simulating carious injuries in vitro have shown that when human pulp fibroblasts are stimulated by lipoteichoic acid (LTA), they synthetize all complement components. Complement activation leads to the formation of the membrane attack complex (MAC), which is known for its bacterial lytic effect. This work was designed to find out whether human pulp fibroblasts can kill Streptococcus mutans and Streptococcus sanguinis via complement activation. First, histological staining of carious tooth sections showed that the presence of S. mutans correlated with an intense MAC staining. Next, to simulate bacterial infection in vitro, human pulp fibroblasts were incubated in serum-free medium with LTA. Quantification by an enzymatic assay showed a significant increase of MAC formation on bacteria grown in this LTA-conditioned medium. To determine whether the MAC produced by pulp fibroblasts was functional, bacteria sensitivity to LTA-conditioned medium was evaluated using agar well diffusion assay and succinyl dehydrogenase (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide [MTT]) assay. Both assays showed that S. mutans and S. sanguinis were sensitive to LTA-conditioned medium. Finally, to evaluate whether MAC formation on cariogenic bacteria, by pulp fibroblasts, can be directly induced by the presence of these bacteria, a specific coculture model of human pulp fibroblasts and bacteria was developed. Immunofluorescence revealed an intense MAC labeling on bacteria after direct contact with pulp fibroblasts. The observed MAC formation and its lethal effects were significantly reduced when CD59, an inhibitor of MAC formation, was added. Our findings demonstrate that the MAC produced by LTA-stimulated pulp fibroblasts is functional and can kill S. mutans and S. sanguinis. Taken together

  2. Increased synthesis and release of endothelin-1 during the initial phase of airway inflammation.

    PubMed

    Finsnes, F; Christensen, G; Lyberg, T; Sejersted, O M; Skjønsberg, O H

    1998-11-01

    Recently, we have shown a substantial increase in the endothelin-1 (ET-1) concentration in bronchoalveolar fluid (BALF) during an experimental eosinophilic airway inflammation. Moreover, we observed a significant inhibition of the inflammatory response after treatment with an endothelin receptor antagonist. This indicates that ET-1 may have proinflammatory properties and play a key role in eosinophilic inflammations, such as bronchial asthma. Accordingly, we hypothesized that the synthesis and release of ET-1 precedes the inflammatory response, and that the bronchial epithelium is the site of ET-1 synthesis in the lungs. An eosinophilic airway inflammation was induced by intratracheal Sephadex instillation in rats, and the animals were evaluated after 15 min, 30 min, 1, 2, 3, 6, 12, and 48 h. The ET-1 mRNA synthesis, assessed by Northern and slot blot analyses, was significantly increased 15 min after Sephadex challenge, peaking at 30 min with a 4.7-fold increase, before any signs of inflammation in the BALF could be observed. The increased synthesis was mainly located to the bronchial epithelium and macrophages at sites of inflammation as determined by in situ hybridization. A significant increase in tissue ET-1 was observed 3 h after provocation, and the recruitment of eosinophils followed a substantial release of ET-1 peptide in BALF peaking at 24 h with a 13-fold increase. Therefore, the rapid ET-1 mRNA synthesis and the considerable increase in the level of ET-1 indicate that this peptide plays an important role in the initiation of an eosinophilic airway inflammation. PMID:9817714

  3. Autonomic Nervous System Dysfunction and Inflammation Contribute to the Increased Cardiovascular Mortality Risk Associated With Depression

    PubMed Central

    Kop, Willem J.; Stein, Phyllis K.; Tracy, Russell P.; Barzilay, Joshua I.; Schulz, Richard; Gottdiener, John S.

    2011-01-01

    Objective To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression. Methods Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 ± 4.6 years; 59.1% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA1) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates. Results Depression was associated with ANS dysfunction (DFA1, p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95% confidence interval, 1.23–2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95% confidence interval, 1.05–2.83) when adjusting for independent HRV and inflammation predictors (DFA1, heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7% (p < .001). Conclusion Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures. PMID:20639389

  4. Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

    PubMed Central

    de Punder, Karin; Pruimboom, Leo

    2015-01-01

    Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here, we hypothesize that stresses (defined as homeostatic disturbances) can induce low-grade inflammation by increasing the availability of water, sodium, and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases. PMID:26029209

  5. P-selectin increases angiotensin II-induced cardiac inflammation and fibrosis via platelet activation

    PubMed Central

    LIU, GAIZHEN; LIANG, BIN; SONG, XIAOSU; BAI, RUI; QIN, WEIWEI; SUN, XU; LU, YAN; BIAN, YUNFEI; XIAO, CHUANSHI

    2016-01-01

    Platelet activation is important in hypertension-induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P-selectin recruits leukocytes to sites of inflammation, the role of P-selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet-derived P-selectin promotes hypertensive cardiac inflammation and fibrosis. P-selectin knockout (P-sel KO) mice and wild-type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross-transplanted with platelets originating from either WT or P-sel KO mice. P-selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P-sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P-sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α-smooth muscle actin and transforming growth factor β1 (TGF-β1) expression levels were decreased in the P-sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P-sel KO mice, the number of Mac-2 (galectin-3)- and TGF-β1-positive cells was increased in mice that received WT platelets compared with those that received P-sel KO platelets, and the mRNA expression levels of collagen I and TGF-β1 were also increased. The results from the present study suggest that activated platelets secrete P-selectin to promote cardiac inflammation and fibrosis in Ang II-induced hypertension. PMID:27121797

  6. P‑selectin increases angiotensin II‑induced cardiac inflammation and fibrosis via platelet activation.

    PubMed

    Liu, Gaizhen; Liang, Bin; Song, Xiaosu; Bai, Rui; Qin, Weiwei; Sun, Xu; Lu, Yan; Bian, Yunfei; Xiao, Chuanshi

    2016-06-01

    Platelet activation is important in hypertension‑induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P‑selectin recruits leukocytes to sites of inflammation, the role of P‑selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet‑derived P‑selectin promotes hypertensive cardiac inflammation and fibrosis. P‑selectin knockout (P‑sel KO) mice and wild‑type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross‑transplanted with platelets originating from either WT or P‑sel KO mice. P‑selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P‑sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P‑sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α‑smooth muscle actin and transforming growth factor β1 (TGF‑β1) expression levels were decreased in the P‑sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P‑sel KO mice, the number of Mac‑2 (galectin‑3)‑ and TGF‑β1‑positive cells was increased in mice that received WT platelets compared with those that received P‑sel KO platelets, and the mRNA expression levels of collagen I and TGF‑β1 were also increased. The results from the present study suggest that activated platelets secrete P‑selectin to promote cardiac inflammation and fibrosis in Ang II‑induced hypertension. PMID:27121797

  7. Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice.

    PubMed

    Michel, Tatiana; Thérésine, Maud; Poli, Aurélie; Domingues, Olivia; Ammerlaan, Wim; Brons, Nicolaas H C; Hentges, François; Zimmer, Jacques

    2011-06-01

    Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN(-/-)) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN(-/-) mice. The bronchial inflammatory response of OVA-sensitized NTN(-/-) mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN(-/-) mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN(-/-) mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN(-/-) mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma. PMID:21508262

  8. A Review on Vital Pulp Therapy in Primary Teeth

    PubMed Central

    Parisay, Iman; Ghoddusi, Jamileh; Forghani, Maryam

    2015-01-01

    Maintaining deciduous teeth in function until their natural exfoliation is absolutely necessary. Vital pulp therapy (VPT) is a way of saving deciduous teeth. The most important factors in success of VPT are the early diagnosis of pulp and periradicular status, preservation of the pulp vitality and proper vascularization of the pulp. Development of new biomaterials with suitable biocompatibility and seal has changed the attitudes towards preserving the reversible pulp in cariously exposed teeth. Before exposure and irreversible involvement of the pulp, indirect pulp capping (IPC) is the treatment of choice, but after the spread of inflammation within the pulp chamber and establishment of irreversible pulpitis, removal of inflamed pulp tissue is recommended. In this review, new concepts in preservation of the healthy pulp tissue in deciduous teeth and induction of the reparative dentin formation with new biomaterials instead of devitalization and the consequent destruction of vital tissues are discussed. PMID:25598803

  9. A review on vital pulp therapy in primary teeth.

    PubMed

    Parisay, Iman; Ghoddusi, Jamileh; Forghani, Maryam

    2015-01-01

    Maintaining deciduous teeth in function until their natural exfoliation is absolutely necessary. Vital pulp therapy (VPT) is a way of saving deciduous teeth. The most important factors in success of VPT are the early diagnosis of pulp and periradicular status, preservation of the pulp vitality and proper vascularization of the pulp. Development of new biomaterials with suitable biocompatibility and seal has changed the attitudes towards preserving the reversible pulp in cariously exposed teeth. Before exposure and irreversible involvement of the pulp, indirect pulp capping (IPC) is the treatment of choice, but after the spread of inflammation within the pulp chamber and establishment of irreversible pulpitis, removal of inflamed pulp tissue is recommended. In this review, new concepts in preservation of the healthy pulp tissue in deciduous teeth and induction of the reparative dentin formation with new biomaterials instead of devitalization and the consequent destruction of vital tissues are discussed. PMID:25598803

  10. Non-infected hemodialysis catheters are associated with increased inflammation compared to arteriovenous fistulas.

    PubMed

    Goldstein, Stuart L; Ikizler, T Alp; Zappitelli, Michael; Silverstein, Douglas M; Ayus, Juan C

    2009-11-01

    Although hemodialysis catheters predispose to infection which, in turn, causes inflammation, we studied whether they induce inflammation independent of infection. We compared the level of the inflammatory marker C-reactive protein (CRP) in maintenance hemodialysis patients, comparing those dialyzed using a non-infected catheter to those using arteriovenous fistulas. All incident patients had catheters and fistula placement at dialysis initiation. In 35 patients the fistulas matured, the catheters were removed and the patients were evaluated at 6 months (catheter-fistula). These results were compared to 15 patients in whom the fistula did not mature and catheter use persisted for 6 months (catheter-catheter). There was a significant 82% reduction in the CRP level in the catheter-fistula group but a 16% increase in the catheter-catheter group at 6 months. The changes in CRP did not differ by gender, diabetes status, or by race, and was not correlated with a change in phosphorus, age, or urea reduction ratio at 1 month following hemodialysis initiation. Decreased CRP was associated with increased hemoglobin and albumin. Patients with persistent fistula use from dialysis initiation through 6 months had consistently low CRP levels over that time period. Our study shows that catheters might contribute to increased inflammation independent of infection, and supports avoidance of catheters and a timely conversion to fistulas with catheter removal. PMID:19675528

  11. Glutaminase Increases in Rat Dorsal Root Ganglion Neurons after Unilateral Adjuvant-Induced Hind Paw Inflammation

    PubMed Central

    Hoffman, E. Matthew; Zhang, Zijia; Schechter, Ruben; Miller, Kenneth E.

    2016-01-01

    Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir) with quantitative image analysis of L4 dorsal root ganglion (DRG) neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA) compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm2), presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy. PMID:26771651

  12. The Epidermal Growth Factor Receptor Increases Cytokine Production and Cutaneous Inflammation in Response to Ultraviolet Irradiation

    PubMed Central

    El-Abaseri, Taghrid Bahig; Repertinger, Susan K.; Hansen, Laura A.

    2013-01-01

    The epidermal growth factor receptor (EGFR) is activated in cutaneous keratinocytes upon ultraviolet (UV) exposure and has been implicated in ultraviolet-(UV-)induced inflammation and skin tumorigenesis. Egfr mutant mice and EGFR inhibitors were used to investigate the hypothesis that EGFR activation augments inflammation following UV irradiation. Topical treatment of mouse skin with the EGFR inhibitor AG1478 before UV exposure suppressed UV-induced erythema, edema, mast cell infiltration, and neutrophil infiltration. Genetic ablation of Egfr and EGFR inhibition by AG1478 also suppressed the increase in the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-1α, KC (murine IL-8), and cyclooxygenase-2 (COX-2) after UV exposure of cultured keratinocytes. Finally, genetic ablation of inhibition of EGFR in cultured keratinocytes decreased p38 activation after UV, while inhibition of p38 kinase reduced COX-2 expression after UV. These data demonstrate that EGFR regulates multiple aspects of UV-induced inflammation and suggest activation of p38 kinase leading to increased COX-2 and cytokine expression as one mechanism through which it acts. PMID:23878744

  13. Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

    PubMed Central

    Piepenbrink, Michael S.; Samuel, Memorie; Zheng, Bo; Carter, Brittany; Fucile, Christopher; Bunce, Catherine; Kiebala, Michelle; Khan, Atif A.; Thakar, Juilee; Maggirwar, Sanjay B.; Morse, Diane; Rosenberg, Alexander F.; Haughey, Norman J.; Valenti, William; Keefer, Michael C.; Kobie, James J.

    2016-01-01

    Background Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. Methods and Findings A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. Conclusions These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing

  14. Ovariectomy in mature mice does not increase food intake, but increases adiposity and adipose tissue inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause, characterized by reduced estrogen (E2), is associated with increased adiposity and metabolic pathology. Molecular mechanisms underlying this association between low E2 status and metabolic disease are not fully elucidated. When mice are fed a high fat diet (HFD) to induce obesity and diab...

  15. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    SciTech Connect

    Tada, Hiroyuki; Nemoto, Eiji; Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi

    2010-04-16

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.

  16. Glucocorticoids increase excitotoxic injury and inflammation in the hippocampus of adult male rats

    PubMed Central

    Sorrells, Shawn F.; Munhoz, Carolina D.; Manley, Nathan C.; Yen, Sandra; Sapolsky, Robert M.

    2014-01-01

    Background/Aims Stress exacerbates neuron loss in many CNS injuries via the actions of adrenal glucocorticoid (GC) hormones. For some injuries, this GC-endangerment of neurons is accompanied by greater immune cell activation in the CNS, a surprising outcome given the potent immunosuppressive properties of GCs. Methods To determine whether the effects of GCs on inflammation contribute to neuron death or result from it, we tested whether non-steroidal anti-inflammatory drugs could protect neurons from GCs during kainic acid excitotoxicity in adrenalectomized male rats. We next measured GC effects on (i) chemokine production (CCL2, CINC-1), (ii) signals that suppress immune activation (CX3CL1, CD22, CD200, and TGF-b), and (iii) NF-kB activity. Results Concurrent treatment with minocycline but not indomethacin prevented GC-endangerment. GCs did not substantially affect CCL2, CINC-1, or baseline NF-kB activity, but they did suppress CX3CL1, CX3CR1, and CD22 expression in the hippocampus, factors that normally restrain inflammatory responses. Conclusions These findings demonstrate that cellular inflammation is not necessarily suppressed by GCs in the injured hippocampus; instead, GCs may worsen hippocampal neuron death, at least in part, by increasing the neurotoxicity of CNS inflammation. PMID:25228100

  17. Increased saturated fatty acids in obesity alter resolution of inflammation in part by stimulating prostaglandin production.

    PubMed

    Hellmann, Jason; Zhang, Michael J; Tang, Yunan; Rane, Madhavi; Bhatnagar, Aruni; Spite, Matthew

    2013-08-01

    Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry-based lipidomics approach, we found that in db/db mice, PGE2/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals. PMID:23785121

  18. ASIC3 deficiency increases inflammation but decreases pain behavior in arthritis

    PubMed Central

    Sluka, Kathleen A.; Rasmussen, Lynn A.; Edgar, Meghan M.; O’Donnell, James M.; Walder, RoxanneY.; Kolker, Sandra J.; Boyle, David L; Firestein, Gary S.

    2013-01-01

    Objective Through its location on nociceptors, acid sensing ion channel 3 (ASIC3) is activated by decreases in pH and plays a significant role in musculoskeletal pain. We recently showed that decreases in pH activate ASIC3 located on fibroblast-like synoviocytes (FLS). Since FLS are key cells in the inflammatory process we tested if ASIC3-deficient mice with arthritis have altered inflammation and pain relative to controls. Methods Arthritis was induced by injection of a cocktail of anti-type II collagen antibodies induced collagen antibodyarthritis (CAIA). Inflammation and pain parameters in ASIC3−/− and ASIC3+/+ mice were assessed. Disease severity was measured with clinical arthritis scores, joint diameters, histological analysis of joints, and qPCR for synovial gene expression. Pain behaviors were measured by examining withdrawal thresholds of the joint and paw and by measuring physical activity levels in mice. Cell death was assessed with a Live/Dead assay in FLS in response to decreases in pH. Results Surprisingly, ASIC3−/− mice with CAIA demonstrated significantly increased joint inflammation, joint destruction and expression of IL-6, MMP-3 and MMP-13 in joint tissue compared to ASIC3+/+ mice. ASIC3+/+ FLS show enhanced cell death when exposed to pH 6.0 in the presence of interleukin-1β that is abolished in ASIC3−/− FLS. Despite enhanced disease severity, ASIC3−/− mice do not develop mechanical hypersensitivity of the paw and show greater levels of physical activity. Conclusion These data are consistent with the hypothesis that ASIC3 plays a protective role in inflammatory arthritis conditions by limiting inflammation through enhanced synoviocyte cell death to reduce disease severity and produce pain to reduce joint use. PMID:23335302

  19. A novel glass ionomer cement containing MgCO(3 )apatite induced the increased proliferation and differentiation of human pulp cells in vitro.

    PubMed

    Laiteerapong, Arunee; Lochaiwatana, Yossakit; Hirata, Isao; Okazaki, Masayuki; Mori, Kenta; Murakami, Shinya; Poolthong, Suchit

    2012-01-01

    This study aimed to investigate the in vitro biological response of human dental pulp cells to glass ionomer cement (GIC, Fuji IX GP(®)) containing 2.5% magnesium carbonate apatite (MgCO(3)Ap). MgCO(3)Ap was synthesized by wet method and characterized using FT-IR, XPS, and SEM. Fuji IX GP(®) served as a control. Test and control cements were prepared by encapsulated mixing the powder with Fuji IX-liquid (P/L=3.6:1). Eluates from cements extracted by 1 mL culture medium were collected at day 1, 7 and 14, and used for WST-1 proliferation assay. For ALPase activity, cells were maintained with cements in transwells, harvested and enzyme activity was measured at day 1, 4, 7, 14, and 21. We found a higher cell proliferation and increased ALPase activity by pulp cells in the test group compared to the control. This suggests the potential of GIC containing this novel biological apatite as a restorative material for pulp-dentin regeneration. PMID:23037840

  20. Thiamylal sodium increased inflammation and the proliferation of vascular smooth muscle cells

    PubMed Central

    Hoka, Sumio

    2016-01-01

    Background Thiamylal sodium is a common anesthetic barbiturate prepared in alkaline solution for clinical use. There is no previously reported study on the effects of barbiturates on the inflammation and proliferation of vascular smooth muscle cells (VSMCs). Here, we examined the effects of clinical-grade thiamylal sodium solution (TSS) on the inflammation and proliferation of rat VSMCs. Methods Expression levels of interleukin (IL)-1α, IL-1β, IL-6, and toll-like receptors in rat VSMCs were detected by quantitative reverse transcription-polymerase chain reaction and microarray analyses. The production of IL-6 by cultured VSMCs or ex vivo-cultured rat aortic segments was detected in supernatants by enzyme-linked immunosorbent assay. VSMC proliferation and viability were determined by the water-soluble tetrazolium-1 assay and trypan blue staining, respectively. Results TSS increased expression of IL-1α, IL-6, and TLR4 in VSMCs in a dose-dependent manner, and reduced IL-1β expression. Ex vivo TSS stimulation of rat aorta also increased IL-6. Low concentrations of TSS enhanced VSMC proliferation, while high concentrations reduced both cell proliferation and viability. Expression of IL-1 receptor antagonist, which regulates cell proliferation, was not increased by TSS stimulation. Exposure of cells to the TSS additive, sodium carbonate, resulted in significant upregulation of IL-1α and IL-6 mRNA levels, to a greater extent than TSS. Conclusions TSS-induced proinflammatory cytokine production by VSMCs is caused by sodium carbonate. However, pure thiamylal sodium has an anti-inflammatory effect in VSMCs. TSS exposure to VSMCs may promote vascular inflammation, leading to the progression of atherosclerosis or in-stent restenosis, resulting in vessel bypass graft failure. PMID:27274372

  1. Sickle cell disease increases high mobility group box 1: a novel mechanism of inflammation

    PubMed Central

    Xu, Hao; Wandersee, Nancy J.; Guo, YiHe; Jones, Deron W.; Holzhauer, Sandra L.; Hanson, Madelyn S.; Machogu, Evans; Brousseau, David C.; Hogg, Neil; Densmore, John C.; Kaul, Sushma; Hillery, Cheryl A.

    2014-01-01

    High mobility group box 1 (HMGB1) is a chromatin-binding protein that maintains DNA structure. On cellular activation or injury, HMGB1 is released from activated immune cells or necrotic tissues and acts as a damage-associated molecular pattern to activate Toll-like receptor 4 (TLR4). Little is known concerning HMGB1 release and TLR4 activity and their role in the pathology of inflammation of sickle cell disease (SCD). Circulating HMGB1 levels were increased in both humans and mice with SCD compared with controls. Furthermore, sickle plasma increased HMGB1-dependent TLR4 activity compared with control plasma. HMGB1 levels were further increased during acute sickling events (vasoocclusive crises in humans or hypoxia/reoxygenation injury in mice). Anti-HMGB1 neutralizing antibodies reduced the majority of sickle plasma-induced TLR4 activity both in vitro and in vivo. These findings show that HMGB1 is the major TLR4 ligand in SCD and likely plays a critical role in SCD-mediated inflammation. PMID:25339362

  2. Mineral Trioxide Aggregate and Portland Cement for Direct Pulp Capping in Dog: A Histopathological Evaluation

    PubMed Central

    Bidar, Maryam; Naghavi, Neda; Mohtasham, Nooshin; Sheik-Nezami, Mahshid; Fallahrastegar, Amir; Afkhami, Farzaneh; Attaran Mashhadi, Negin; Nargesi, Iman

    2014-01-01

    Background and aims. Mineral trioxide aggregate and calcium hydroxide are considered the gold standard pulp-capping materials. Recently, Portland cement has been introduced with properties similar to those of mineral trioxide aggregate. Histopathological effects of direct pulp capping using mineral trioxide aggregate and Portland cements on dog dental pulp tissue were evaluated in the present study. Materials and methods. This histopatological study was carried out on 64 dog premolars. First, the pulp was exposed with a sterile bur. Then, the exposed pulp was capped with white or gray mineral trioxide aggregates and white or gray Portland cements in each quadrant and sealed with glass-ionomer. The specimens were evaluated under a light microscope after 6 months. Statistical analysis was carried out using Kruskal-Wallis test. Statistical significance was defined at α=5%. Results. There was no acute inflammation in any of the specimens. Chronic inflammation in white and gray mineral trioxide aggregates and white and gray Portland cements was reported to be 45.5%, 27.3%, 57.1% and 34.1%, respectively. Although the differences were not statistically significant, severe inflammation was observed mostly adjacent to white mineral trioxide aggregate. The largest extent of increased vascularization (45%) and the least increase in fibrous tissue were observed adjacent to white mineral trioxide aggregate, with no significant differences. In addition, the least calcified tissue formed adjacent to white mineral trioxide aggregate, although the difference was not significant. Conclusion. The materials used in this study were equally effective as pulp protection materials following direct pulp capping in dog teeth. PMID:25346831

  3. Erythropoietin Exacerbates Inflammation and Increases the Mortality of Histoplasma capsulatum-Infected Mice

    PubMed Central

    Locachevic, Gisele Aparecida; Pereira, Priscilla Aparecida Tartari; Secatto, Adriana; Fontanari, Caroline; Galvão, Alyne Fávero; Prado, Morgana Kelly Borges; Zoccal, Karina Furlani; Petta, Tânia; Moraes, Luiz Alberto Beraldo; Ramos, Simone Gusmão; de Castro, Fabíola Attie; Sorgi, Carlos Artério; Faccioli, Lúcia Helena

    2015-01-01

    Erythropoietin (EPO) is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc). Considering that little is known about EPO's role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80+/CD80+ and F4/80+/CD86+ cells to the bronchoalveolar space, induced higher production of IFN-γ, IL-6, MIP-1α, MCP-1, and LTB4, reduced PGE2 concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection. PMID:26538835

  4. Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea.

    PubMed

    Emin, Memet; Wang, Gang; Castagna, Francesco; Rodriguez-Lopez, Josanna; Wahab, Romina; Wang, Jing; Adams, Tessa; Wei, Ying; Jelic, Sanja

    2016-01-01

    Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during transient cessation of breathing, triples the risk for cardiovascular diseases. We used a phage display peptide library as an unbiased approach to investigate whether IH, which is specific to OSA, activates endothelial cells (ECs) in a distinctive manner. The target of a differentially bound peptide on ECs collected from OSA patients was identified as CD59, a major complement inhibitor that protects ECs from the membrane attack complex (MAC). A decreased proportion of CD59 is located on the EC surface in OSA patients compared with controls, suggesting reduced protection against complement attack. In vitro, IH promoted endothelial inflammation predominantly via augmented internalization of CD59 and consequent MAC deposition. Increased internalization of endothelial CD59 in IH appeared to be cholesterol-dependent and was reversed by statins in a CD59-dependent manner. These studies suggest that reduced complement inhibition may mediate endothelial inflammation and increase vascular risk in OSA patients. PMID:26738794

  5. Erythropoietin Exacerbates Inflammation and Increases the Mortality of Histoplasma capsulatum-Infected Mice.

    PubMed

    Locachevic, Gisele Aparecida; Pereira, Priscilla Aparecida Tartari; Secatto, Adriana; Fontanari, Caroline; Galvão, Alyne Fávero; Prado, Morgana Kelly Borges; Zoccal, Karina Furlani; Petta, Tânia; Moraes, Luiz Alberto Beraldo; Ramos, Simone Gusmão; de Castro, Fabíola Attie; Sorgi, Carlos Artério; Faccioli, Lúcia Helena

    2015-01-01

    Erythropoietin (EPO) is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc). Considering that little is known about EPO's role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80(+)/CD80(+) and F4/80(+)/CD86(+) cells to the bronchoalveolar space, induced higher production of IFN-γ, IL-6, MIP-1α, MCP-1, and LTB4, reduced PGE2 concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection. PMID:26538835

  6. Lunasin alleviates allergic airway inflammation while increases antigen-specific Tregs.

    PubMed

    Yang, Xiaowei; Zhu, Jingjing; Tung, Chun-Yu; Gardiner, Gail; Wang, Qun; Chang, Hua-Chen; Zhou, Baohua

    2015-01-01

    Lunasin is a naturally occurring peptide isolated from soybeans and has been explored in cancer treatment. Lunasin inhibits NF-κB activation and thus pro-inflammatory cytokine and mediator production in macrophages. In this study we demonstrate that lunasin can effectively suppress allergic airway inflammation in two murine models of asthma. In an OVA+Alum sensitization model, intranasal lunasin treatment at the time of OVA challenges significantly reduced total cells counts in bronchoalveolar lavage (BAL) fluid and eosinophilia, peribronchiolar inflammatory infiltration, goblet cell metaplasia and airway IL-4 production. In an OVA+LPS intranasal sensitization model, lunasin treatment either at the time of sensitization or challenge has similar effects in suppress allergic airway inflammation including significantly reduced total cell and eosinophil counts in BAL fluid, inflammatory gene Fizz1 expression in the lung, and IL-4 production by OVA re-stimulated cells from mediastinal lymph nodes. We further show that intranasal instillation of OVA+lunasin significantly increases OVA-specific regulatory T cell (Treg) accumulation in the lung comparing to OVA only treatment. Taken together, our results suggest lunasin as an anti-inflammatory agent can be potentially used in asthma therapy or as an adjuvant to enhance the induction of antigen-specific Tregs and thus boost the efficacy of allergy immunotherapy. PMID:25646897

  7. Lunasin Alleviates Allergic Airway Inflammation while Increases Antigen-Specific Tregs

    PubMed Central

    Yang, Xiaowei; Zhu, Jingjing; Tung, Chun-Yu; Gardiner, Gail; Wang, Qun; Chang, Hua-Chen; Zhou, Baohua

    2015-01-01

    Lunasin is a naturally occurring peptide isolated from soybeans and has been explored in cancer treatment. Lunasin inhibits NF-κB activation and thus pro-inflammatory cytokine and mediator production in macrophages. In this study we demonstrate that lunasin can effectively suppress allergic airway inflammation in two murine models of asthma. In an OVA+Alum sensitization model, intranasal lunasin treatment at the time of OVA challenges significantly reduced total cells counts in bronchoalveolar lavage (BAL) fluid and eosinophilia, peribronchiolar inflammatory infiltration, goblet cell metaplasia and airway IL-4 production. In an OVA+LPS intranasal sensitization model, lunasin treatment either at the time of sensitization or challenge has similar effects in suppress allergic airway inflammation including significantly reduced total cell and eosinophil counts in BAL fluid, inflammatory gene Fizz1 expression in the lung, and IL-4 production by OVA re-stimulated cells from mediastinal lymph nodes. We further show that intranasal instillation of OVA+lunasin significantly increases OVA-specific regulatory T cell (Treg) accumulation in the lung comparing to OVA only treatment. Taken together, our results suggest lunasin as an anti-inflammatory agent can be potentially used in asthma therapy or as an adjuvant to enhance the induction of antigen-specific Tregs and thus boost the efficacy of allergy immunotherapy. PMID:25646897

  8. The Metabolic Syndrome and Inflammation: 
Role of Insulin Resistance and Increased Adiposity

    PubMed Central

    Farooq, Wajiha; Farwa, Umme; Khan, Faisal Rashid

    2015-01-01

    Objectives We sought to determine the role of obesity and insulin resistance (IR) in the pathogenesis of inflammation in metabolic syndrome (MetS). Methods Our study included 100 patients with MetS and 100 age and gender matched control patients who attended a tertiary care laboratory in Rawalpindi, Pakistan. Anthropometric data was obtained including height and weight to calculate body mass index. A record of patient’s blood pressure (BP), waist circumference (WC) and hip circumference (HC) was made. Biochemical analysis included measurements of fasting glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), insulin, and high-sensitivity C reactive protein (hsCRP). IR was determined by the homeostasis mode assessment insulin resistance (HOMA-IR) method. Results The levels of hs-CRP were found to be elevated in all patients with MetS where it correlated significantly with all its components including measures of obesity, fasting insulin and glucose levels, IR, TG and HDL-c. However, on linear regression analysis only WC, fasting insulin, and HOMA-IR remained significantly correlated with hs-CRP. Conclusion MetS is a condition characterized by chronic low-grade inflammation, which arises because of increased abdominal adiposity and IR. Large multicenter studies are needed to gain insight into its pathogenesis and derive treatment strategies. PMID:25960834

  9. Loss of neutral ceramidase increases inflammation in a mouse model of inflammatory bowel disease

    PubMed Central

    Snider, Ashley J.; Wu, Bill X.; Jenkins, Russell W.; Sticca, Jonathan A.; Kawamori, Toshihiko; Hannun, Yusuf A.; Obeid, Lina M.

    2012-01-01

    Sphingolipids are emerging as important mediators of immune and inflammatory responses. We have previously demonstrated that sphingosine-1-phosphate (S1P) and its synthetic enzyme sphingosine kinase-1 (SK1) play an important role in inflammatory bowel disease. S1P generation is dependent on SK phosphorylation of sphingosine. Generation of sphingosine results only from the breakdown of ceramide by ceramidases (CDase). In this study, we set out to determine the role of neutral CDase (nCDase) in S1P generation and inflammatory bowel disease. To this end, we established nCDase expression is increased in patients with ulcerative colitis. Using the dextran sulfate sodium (DSS)-induced colitis model, we determined nCDase activity increased in colon epithelium, but not submucosa, in wild-type (WT) mice. Following DSS, ceramide levels were elevated in colon epithelium from WT and nCDase−/− mice, while S1P levels were significantly elevated only in the epithelium of nCDase−/− mice. Similarly, cyclooxygenase-2 (Cox-2) levels were significantly elevated only in the epithelium of nCDase−/− mice. Neutral CDase−/− mice also exhibited higher endotoxin levels in circulation, as well as higher circulating levels of S1P. This increase in S1P in nCDase−/− mice was accompanied by a marked leukocytosis, most notably circulating neutrophils and lymphocytes. Taken together these data demonstrate that loss of nCDase results in an unexpected increase in S1P generation in inflammation, and suggests that nCDase may actually protect against inflammation. PMID:22940715

  10. Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis

    PubMed Central

    Lied, Gülen Arslan; Milde, Anne Marita; Nylund, Kim; Mujic, Maja; Grimstad, Tore; Hausken, Trygve; Gilja, Odd Helge

    2012-01-01

    Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS) in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS). Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha) and fecal samples (HemoFEC occult blood) were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS-induced colitis was able to be visualized by transabdominal sonography. Moreover, ultrasound findings, occult blood sampling, and histological findings supported each other, indicating that ultrasonography can be used to assess inflammation in a rat experimental model. PMID:23055765

  11. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice.

    PubMed

    McCabe, Laura R; Irwin, Regina; Schaefer, Laura; Britton, Robert A

    2013-08-01

    Osteoporosis can result from intestinal inflammation, as is seen with inflammatory bowel disease. Probiotics, microorganisms that provide a health benefit to the host when ingested in adequate amounts, can have anti-inflammatory properties and are currently being examined to treat inflammatory bowel disease. Here, we examined if treating healthy male mice with Lactobacillus reuteri ATCC PTA 6475 (a candidate probiotic with anti-TNFα activity) could affect intestinal TNFα levels and enhance bone density. Adult male mice were given L. reuteri 6475 orally by gavage for 3×/week for 4 weeks. Examination of jejunal and ileal RNA profiles indicates that L. reuteri suppressed basal TNFα mRNA levels in the jejunum and ileum in male mice, but surprisingly not in female mice. Next, we examined bone responses. Micro-computed tomography demonstrated that L. reuteri 6475 treatment increased male trabecular bone parameters (mineral density, bone volume fraction, trabecular number, and trabecular thickness) in the distal femur metaphyseal region as well as in the lumbar vertebrae. Cortical bone parameters were unaffected. Dynamic and static histomorphometry and serum remodeling parameters indicate that L. reuteri ingestion increases osteoblast serum markers and dynamic measures of bone formation in male mice. In contrast to male mice, L. reuteri had no effect on bone parameters in female mice. Taken together our studies indicate that femoral and vertebral bone formation increases in response to oral probiotic use, leading to increased trabecular bone volume in male mice. PMID:23389860

  12. Antioxidant Protects against Increases in Low Molecular Weight Hyaluronan and Inflammation in Asphyxiated Newborn Pigs Resuscitated with 100% Oxygen

    PubMed Central

    Akgul, Yucel; Ramgopal, Mrithyunjay; Mija, Dan S.; Cheong, Naeun; Longoria, Christopher; Mahendroo, Mala; Nakstad, Britt; Saugstad, Ola D.; Savani, Rashmin C.

    2012-01-01

    Background Newborn resuscitation with 100% oxygen is associated with oxidative-nitrative stresses and inflammation. The mechanisms are unclear. Hyaluronan (HA) is fragmented to low molecular weight (LMW) by oxidative-nitrative stresses and can promote inflammation. We examined the effects of 100% oxygen resuscitation and treatment with the antioxidant, N-acetylcysteine (NAC), on lung 3-nitrotyrosine (3-NT), LMW HA, inflammation, TNFα and IL1ß in a newborn pig model of resuscitation. Methods & Principal Findings Newborn pigs (n = 40) were subjected to severe asphyxia, followed by 30 min ventilation with either 21% or 100% oxygen, and were observed for the subsequent 150 minutes in 21% oxygen. One 100% oxygen group was treated with NAC. Serum, bronchoalveolar lavage (BAL), lung sections, and lung tissue were obtained. Asphyxia resulted in profound hypoxia, hypercarbia and metabolic acidosis. In controls, HA staining was in airway subepithelial matrix and no 3-NT staining was seen. At the end of asphyxia, lavage HA decreased, whereas serum HA increased. At 150 minutes after resuscitation, exposure to 100% oxygen was associated with significantly higher BAL HA, increased 3NT staining, and increased fragmentation of lung HA. Lung neutrophil and macrophage contents, and serum TNFα and IL1ß were higher in animals with LMW than those with HMW HA in the lung. Treatment of 100% oxygen animals with NAC blocked nitrative stress, preserved HMW HA, and decreased inflammation. In vitro, peroxynitrite was able to fragment HA, and macrophages stimulated with LMW HA increased TNFα and IL1ß expression. Conclusions & Significance Compared to 21%, resuscitation with 100% oxygen resulted in increased peroxynitrite, fragmentation of HA, inflammation, as well as TNFα and IL1ß expression. Antioxidant treatment prevented the expression of peroxynitrite, the degradation of HA, and also blocked increases in inflammation and inflammatory cytokines. These findings provide insight

  13. Increasing Fatty Acid Oxidation Remodels the Hypothalamic Neurometabolome to Mitigate Stress and Inflammation

    PubMed Central

    McFadden, Joseph W.; Aja, Susan; Li, Qun; Bandaru, Veera V. R.; Kim, Eun-Kyoung; Haughey, Norman J.; Kuhajda, Francis P.; Ronnett, Gabriele V.

    2014-01-01

    Modification of hypothalamic fatty acid (FA) metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO) from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1) and fatty acid oxidation (FAOx), exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK) in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS), and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism. PMID:25541737

  14. Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.

    PubMed

    Gao, Xiao-Ming; Moore, Xiao-Lei; Liu, Yang; Wang, Xin-Yu; Han, Li-Ping; Su, Yidan; Tsai, Alan; Xu, Qi; Zhang, Ming; Lambert, Gavin W; Kiriazis, Helen; Gao, Wei; Dart, Anthony M; Du, Xiao-Jun

    2016-07-01

    Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation. PMID:27129192

  15. Rapamycin increases neuronal survival, reduces inflammation and astrocyte proliferation after spinal cord injury.

    PubMed

    Goldshmit, Yona; Kanner, Sivan; Zacs, Maria; Frisca, Frisca; Pinto, Alexander R; Currie, Peter D; Pinkas-Kramarski, Ronit

    2015-09-01

    Spinal cord injury (SCI) frequently leads to a permanent functional impairment as a result of the initial injury followed by secondary injury mechanism, which is characterised by increased inflammation, glial scarring and neuronal cell death. Finding drugs that may reduce inflammatory cell invasion and activation to reduce glial scarring and increase neuronal survival is of major importance for improving the outcome after SCI. In the present study, we examined the effect of rapamycin, an mTORC1 inhibitor and an inducer of autophagy, on recovery from spinal cord injury. Autophagy, a process that facilitates the degradation of cytoplasmic proteins, is also important for maintenance of neuronal homeostasis and plays a major role in neurodegeneration after neurotrauma. We examined rapamycin effects on the inflammatory response, glial scar formation, neuronal survival and regeneration in vivo using spinal cord hemisection model in mice, and in vitro using primary cortical neurons and human astrocytes. We show that a single injection of rapamycin, inhibited p62/SQSTM1, a marker of autophagy, inhibited mTORC1 downstream effector p70S6K, reduced macrophage/neutrophil infiltration into the lesion site, microglia activation and secretion of TNFα. Rapamycin inhibited astrocyte proliferation and reduced the number of GFAP expressing cells at the lesion site. Finally, it increased neuronal survival and axonogenesis towards the lesion site. Our study shows that rapamycin treatment increased significantly p-Akt levels at the lesion site following SCI. Similarly, rapamycin treatment of neurons and astrocytes induced p-Akt elevation under stress conditions. Together, these findings indicate that rapamycin is a promising candidate for treatment of acute SCI condition and may be a useful therapeutic agent. PMID:25936601

  16. Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice

    PubMed Central

    Weldy, Chad S.; White, Collin C.; Wilkerson, Hui-Wen; Larson, Timothy V.; Stewart, James A.; Gill, Sean E.; Parks, William C.; Kavanagh, Terrance J.

    2012-01-01

    Context Inhalation of ambient fine particulate matter (PM2.5) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM2.5 in urban settings is diesel exhaust particulate (DEP), and DEP-induced lung inflammation is likely a critical event mediating many of its adverse health effects. Oxidative stress has been proposed to be an important factor in PM2.5-induced lung inflammation, and the balance between pro- and antioxidants is an important regulator of this inflammation. An important intracellular antioxidant is the tripeptide thiol glutathione (GSH). Glutamate cysteine ligase (GCL) carries out the first step in GSH synthesis. In humans, relatively common genetic polymorphisms in both the catalytic (Gclc) and modifier (Gclm) subunits of GCL have been associated with increased risk for lung and cardiovascular diseases. Objective This study was aimed to determine the effects of Gclm expression on lung inflammation following DEP exposure in mice. Materials and methods We exposed Gclm wild type, heterozygous, and null mice to DEP via intranasal instillation and assessed lung inflammation as determined by neutrophils and inflammatory cytokines in lung lavage, inflammatory cytokine mRNA levels in lung tissue, as well as total lung GSH, Gclc, and Gclm protein levels. Results The Gclm heterozygosity was associated with a significant increase in DEP-induced lung inflammation when compared to that of wild type mice. Discussion and conclusion This finding indicates that GSH synthesis can mediate DEP-induced lung inflammation and suggests that polymorphisms in Gclm may be an important factor in determining adverse health outcomes in humans following inhalation of PM2.5. PMID:21967497

  17. Increased inflammation in sanctuary sites may explain viral blips in HIV infection

    DOE PAGESBeta

    Piovoso, Michael J.; Cardozo, E. Fabian; Zurakowski, Ryan

    2016-05-18

    Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in allmore » compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days–1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.« less

  18. Increased inflammation in sanctuary sites may explain viral blips in HIV infection.

    PubMed

    Cardozo, E Fabian; Piovoso, Michael J; Zurakowski, Ryan

    2016-08-01

    Combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days(-1). Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments. PMID:27444025

  19. Cell- and isoform-specific increases in arginase expression in acute silica-induced pulmonary inflammation.

    PubMed

    Poljakovic, Mirjana; Porter, Dale W; Millecchia, Lyndell; Kepka-Lenhart, Diane; Beighley, Christopher; Wolfarth, Michael G; Castranova, Vincent; Morris, Sidney M

    2007-01-15

    Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase were elucidated in lungs of Sprague-Dawley rats 24 h following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time polymerase chain reaction (PCR), and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced two- and three-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100 g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no inducible nitric oxide synthase (iNOS) immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica. PMID:17365572

  20. Cell- and Isoform-specific Increases in Arginase Expression in Acute Silica-induced Pulmonary Inflammation

    PubMed Central

    Poljakovic, Mirjana; Porter, Dale W.; Millecchia, Lyndell; Kepka-Lenhart, Diane; Beighley, Christopher; Wolfarth, Michael G.; Castranova, Vincent; Morris, Sidney M.

    2009-01-01

    Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase was elucidated in lungs of Sprague-Dawley rats 24 hr following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time PCR, and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced 2- and 3-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no iNOS immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica. PMID:17365572

  1. Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment.

    PubMed

    Delpech, Jean-Christophe; Thomazeau, Aurore; Madore, Charlotte; Bosch-Bouju, Clementine; Larrieu, Thomas; Lacabanne, Chloe; Remus-Borel, Julie; Aubert, Agnès; Joffre, Corinne; Nadjar, Agnès; Layé, Sophie

    2015-11-01

    Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment. PMID:25948102

  2. POZONE technology to bleach pulp

    SciTech Connect

    Wang, H.; Shi, Y.; Le, L.; Wang, S.M.; Wei, J.; Chang, S.G.

    1997-09-01

    Currently, there has been a move in the pulp and paper industry to reduce or eliminate chlorine-based bleaching due to environmental concerns. The POZONE process, a chemical means of ozone production, has been used to bleach wood pulp. The brightness, Kappa number, and viscosity of wood pulp subjected to POZONE treatment have been determined. Brightness increases of up to 44 points and Kappa number decreases of as much as 22 points have been achieved. Promise for effective industrial application has been demonstrated.

  3. Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart

    PubMed Central

    Sattari, Saeed; Dryden, William F; Eliot, Lise A; Jamali, Fakhreddin

    2003-01-01

    Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism. The effect of interferon-induced acute inflammation on the pharmacokinetics and electrocardiogram of verapamil (20 mg kg−1, p.o.) and nifedipine (0.1 mg kg−1, i.v.) was studied in Sprague–Dawley rats. The effect of both acute and chronic inflammation on radioligand binding to cardiac L-type calcium channels was also investigated. Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected. As has been reported for humans, the increased verapamil concentration coincided with a reduction in the degree to which PR interval is prolonged by the drug. The effect of nifedipine on PR interval was also reduced by inflammation. Maximum binding of 3H-nitrendipine to cardiac cell membrane was significantly reduced from 63.2±2.5 fmol mg−1 protein in controls to 46.4±2.0 in acute inflammation and from 66.8±2.2 fmol mg−1 protein in controls to 42.2±2.0 in chronic inflammation. Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml−1 of rat tissue necrosis factor-α did not influence the binding indices to the calcium channels. Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels. PMID:12839868

  4. Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion.

    PubMed

    Gorin, Caroline; Rochefort, Gael Y; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Muller, Laurent; Chaussain, Catherine; Germain, Stéphane

    2016-03-01

    Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. PMID:26798059

  5. Potential of hot water extraction of birch wood to produce high-purity dissolving pulp after alkaline pulping.

    PubMed

    Borrega, Marc; Tolonen, Lasse K; Bardot, Fanny; Testova, Lidia; Sixta, Herbert

    2013-05-01

    The potential of hot water extraction of birch wood to produce highly purified dissolving pulp in a subsequent soda-anthraquinone pulping process was evaluated. After intermediate extraction intensities, pulps with low xylan content (3-5%) and high cellulose yield were successfully produced. Increasing extraction intensity further decreased the xylan content in pulp. However, below a xylan content of 3%, the cellulose yield dramatically decreased. This is believed to be due to cleavage of glycosidic bonds in cellulose during severe hot water extractions, followed by peeling reactions during alkaline pulping. Addition of sodium borohydride as well as increased anthraquinone concentration in the pulping liquor increased the cellulose yield, but had no clear effects on pulp purity and viscosity. The low intrinsic viscosity of pulps produced after severe extraction intensities and soda-anthraquinone pulping corresponded to the viscosity at the leveling-off degree of polymerization, suggesting that nearly all amorphous cellulose had been degraded. PMID:23260272

  6. Gallbladder inflammation is associated with increase in mucin expression and pigmented stone formation.

    PubMed

    Vilkin, Alexander; Nudelman, Israel; Morgenstern, Sara; Geller, Alex; Bar Dayan, Yosefa; Levi, Zohar; Rodionov, Galina; Hardy, Britta; Konikoff, Fred; Gobbic, Diana; Niv, Yaron

    2007-07-01

    Mucin is a high molecular weight glycoprotein that plays an important role in protecting the gallbladder epithelium from the detergent effect of bile. However, it also participates in gallstone formation. There is little information about a possible relationship between gallbladder inflammation and mucin expression or gallbladder stones' characteristics. The aims of this study were to investigate stone characteristics and patterns of mucin expression in the gallbladder epithelium and bile of gallstone patients, in relation to inflammation. Gallbladder bile and tissue samples from 21 patients were obtained at surgery. Mucin content was evaluated by gel filtration on a Sepharose CL-4B column. Dot blot for bile mucin apoproteins and immunohistochemistry staining for gallbladder mucosal mucin apoproteins were performed with antibodies to MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score (0-3) was used for assessment of antigen expression and the level of inflammation. Gallstone cholesterol content was determined in 16 patients. MUC 5AC and MUC 5B were demonstrated in 95.4 and 100% of gallbladder bile samples, respectively. Immunohistochemistry staining with antibodies to MUC 2, MUC 3, MUC 5AC, MUC 5B and MUC 6 were positive in 0, 100, 85.7, 100 and 95.4% of the gallbladder mucosal samples, respectively. Pigmented brown stones were associated with a higher level of gallbladder inflammation. Mucin species expressed in gallbladder epithelium are MUC3, MUC5AC, MUC5B and MUC6. MUC5AC and MUC5B are secreted into bile. Inflammation of the gallbladder is accompanied by a higher level of MUC5AC expression and is associated with pigmented brown stones. PMID:17385041

  7. Increased GIP signaling induces adipose inflammation via a HIF-1α-dependent pathway and impairs insulin sensitivity in mice.

    PubMed

    Chen, Shu; Okahara, Fumiaki; Osaki, Noriko; Shimotoyodome, Akira

    2015-03-01

    Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone secreted in response to dietary fat and glucose. The blood GIP level is elevated in obesity and diabetes. GIP stimulates proinflammatory gene expression and impairs insulin sensitivity in cultured adipocytes. In obesity, hypoxia within adipose tissue can induce inflammation. The aims of this study were 1) to examine the proinflammatory effect of increased GIP signaling in adipose tissues in vivo and 2) to clarify the association between GIP and hypoxic signaling in adipose tissue inflammation. We administered GIP intraperitoneally to misty (lean) and db/db (obese) mice and examined adipose tissue inflammation and insulin sensitivity. We also examined the effects of GIP and hypoxia on expression of the GIP receptor (GIPR) gene and proinflammatory genes in 3T3-L1 adipocytes. GIP administration increased monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration into adipose tissue and increased blood glucose in db/db mice. GIPR and hypoxia-inducible factor-1α (HIF-1α) expressions were positively correlated in the adipose tissue in mice. GIPR expression increased dramatically in differentiated adipocytes. GIP treatment of adipocytes increased MCP-1 and interleukin-6 (IL-6) production. Adipocytes cultured either with RAW 264 macrophages or under hypoxia expressed more GIPR and HIF-1α, and GIP treatment increased gene expression of plasminogen activator inhibitor 1 and IL-6. HIF-1α gene silencing diminished both macrophage- and hypoxia-induced GIPR expression and GIP-induced IL-6 expression in adipocytes. Thus, increased GIP signaling plays a significant role in adipose tissue inflammation and thereby insulin resistance in obese mice, and HIF-1α may contribute to this process. PMID:25537494

  8. Effects of inflammation on pharmacokinetics/pharmacodynamics: increasing recognition of its contribution to variability in response.

    PubMed

    Schmith, V D; Foss, J F

    2008-06-01

    Inflammation is an interesting phenomenon that crosses many disciplines as part of the host response to disease, whether it is the acute response to an infectious, traumatic, or surgical event or the more chronic responses to systemic disease such as malignancy, rheumatoid arthritis, asthma, inflammatory bowel disease, or diabetes. The impact of inflammatory states on the variability in drug response should be an integral part of research conducted across disciplines within clinical pharmacology. PMID:18488052

  9. Inflammation, Endothelial Dysfunction and Increased Left Ventricular Mass in Chronic Kidney Disease (CKD) Patients: A Longitudinal Study

    PubMed Central

    Dounousi, Evangelia; Jager, Kitty J.; Papagianni, Aikaterini; Pappas, Konstantinos; Siamopoulos, Kostas C.; Zoccali, Carmine; Tsakiris, Dimitrios

    2015-01-01

    Introduction Within this longitudinal study we investigated the association of inflammation markers C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) and endothelial dysfunction markers intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with left ventricular mass indexed for height2·71 (LVMI) in hypertensive predialysis CKD patients. Material and Methods From 2004 to 2005, 182 incident consecutive adult patients from the outpatient CKD clinics of two hospitals in Greece with CKD and hypertension or using antihypertensive medication, were included. Of these, 107 patients underwent CRP (mg/l) and LVMI (g/height2·71) measurements annually for three years. Results In the longitudinal analyses, using linear mixed modeling, a higher IL-6 (ß = 1.9 (95%ci:0.38;3.5), inflammation score based on CRP, IL-6 and TNF-α (ß = 5.0 (95%ci:0.72; 9.4) and VCAM-1 (ß = 0.01 (95%ci:0.005;0.02) were associated with higher LVMI. These models were adjusted for age, gender and primary renal disease, and for confounders that on top changed the beta with ≥10%, i.e. diuretic use (for IL-6 and inflammation score). Conclusion The results suggest that in predialysis CKD patients, inflammation as well as endothelial dysfunction may play an important role towards the increase in LVMI. PMID:26398099

  10. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  11. Pulpitis increases the proportion of atypical nodes of Ranvier in human dental pulp axons without a change in Nav1.6 sodium channel expression.

    PubMed

    Luo, S; Perry, G M; Levinson, S R; Henry, M A

    2010-09-15

    Studies show a change in sodium channel (NaCh) expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth to study NaCh expression and here examine the expression of the major NaCh isoform located at nodes of Ranvier, Na(v)1.6, in normal and painful samples. Pulpal sections were double-labeled with human-specific Na(v)1.6 antibody and caspr antibody (paranodal protein to identify nodes). Confocal microscopy was used to obtain a z-series of optically-sectioned images of axon bundles surrounded by inflammatory cells in painful samples and of similar regions within the coronal pulp of normal samples. Nodes contained within these images were classified as typical or atypical as based on caspr staining relationships, and NIH ImageJ software was used to quantify the size and immunofluorescence staining intensity of Na(v)1.6 accumulations at these nodal sites. Results show no significant difference in the size or immunofluorescence staining intensity of Na(v)1.6 nodal accumulations located at either typical or atypical nodal sites (heminodes and split nodes) within axons in normal samples when compared to painful samples (n=9/each group). In contrast, there was a highly significant decrease in the proportion of typical nodal sites and an increase in atypical nodal sites in painful samples when compared to normal samples. The unchanged expression of Na(v)1.6 contrasts to our previous finding that showed an increased expression of Na(v)1.7 at both typical and atypical nodal sites within painful samples. Together, these findings suggest there is not a simple replacement of one isoform with another, but rather an increased co-expression of multiple isoforms at both intact and remodeling/demyelinating (atypical) nodal sites within the painful dental pulp. The resultant heterogeneous population of isoforms may produce unique axonal excitability properties that could contribute to spontaneous pain

  12. Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes

    PubMed Central

    Tjeerdema, Nathanja; Georgiadi, Anastasia; Jonker, Jacqueline T; van Glabbeek, Marjolijn; Dehnavi, Reza Alizadeh; Tamsma, Jouke T; Smit, Johannes W A; Kersten, Sander; Rensen, Patrick C N

    2014-01-01

    Background Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages. Objective To assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). Design We studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS−I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro. Results As compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS−I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS−I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages. Conclusions Plasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli. PMID:25512873

  13. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor

    PubMed Central

    Malmhäll, Carina; Rådinger, Madeleine; Ramos-Ramirez, Patricia; Lu, You; Deák, Tünde; Semitekolou, Maria; Gaga, Mina; Sjöstrand, Margareta; Lötvall, Jan; Bossios, Apostolos

    2016-01-01

    Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. Methods A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Results Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Conclusion Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation. PMID:27513955

  14. Dental Pulp Defence and Repair Mechanisms in Dental Caries

    PubMed Central

    Farges, Jean-Christophe; Alliot-Licht, Brigitte; Renard, Emmanuelle; Ducret, Maxime; Gaudin, Alexis; Smith, Anthony J.; Cooper, Paul R.

    2015-01-01

    Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical and in vitro experimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteria in vivo. PMID:26538821

  15. Fyn Deficiency Promotes a Preferential Increase in Subcutaneous Adipose Tissue Mass and Decreased Visceral Adipose Tissue Inflammation

    PubMed Central

    Lee, Ting-Wen A.; Kwon, Hyokjoon; Zong, Haihong; Yamada, Eijiro; Vatish, Manu; Pessin, Jeffrey E.; Bastie, Claire C.

    2013-01-01

    Previous studies have demonstrated that Fyn knockout (FynKO) mice on a standard chow diet display increased glucose clearance and whole-body insulin sensitivity associated with decreased adiposity resulting from increased fatty acid use and energy expenditure. Surprisingly, however, despite a similar extent of adipose tissue (AT) mass accumulation on a high-fat diet, the FynKO mice remained fully glucose tolerant and insulin sensitive. Physiologic analyses demonstrated that the FynKO mice had a combination of skewed AT expansion into the subcutaneous compartment rather than to the visceral depot, reduced AT inflammation associated with reduced T-cell and macrophage infiltration, and increased proportion of anti-inflammatory M2 macrophages. These data demonstrate that Fyn is an important regulator of whole-body integrative metabolism that coordinates AT expansion, inflammation, and insulin sensitivity in states of nutrient excess. These data further suggest that inhibition of Fyn function may provide a novel target to prevent AT inflammation, insulin resistance, and the dyslipidemia components of the metabolic syndrome. PMID:23321073

  16. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking.

    PubMed

    Maggioli, E; McArthur, S; Mauro, C; Kieswich, J; Kusters, D H M; Reutelingsperger, C P M; Yaqoob, M; Solito, E

    2016-01-01

    Sex differences have been widely reported in neuroinflammatory disorders, focusing on the contributory role of estrogen. The microvascular endothelium of the brain is a critical component of the blood-brain barrier (BBB) and it is recognized as a major interface for communication between the periphery and the brain. As such, the cerebral capillary endothelium represents an important target for the peripheral estrogen neuroprotective functions, leading us to hypothesize that estrogen can limit BBB breakdown following the onset of peripheral inflammation. Comparison of male and female murine responses to peripheral LPS challenge revealed a short-term inflammation-induced deficit in BBB integrity in males that was not apparent in young females, but was notable in older, reproductively senescent females. Importantly, ovariectomy and hence estrogen loss recapitulated an aged phenotype in young females, which was reversible upon estradiol replacement. Using a well-established model of human cerebrovascular endothelial cells we investigated the effects of estradiol upon key barrier features, namely paracellular permeability, transendothelial electrical resistance, tight junction integrity and lymphocyte transmigration under basal and inflammatory conditions, modeled by treatment with TNFα and IFNγ. In all cases estradiol prevented inflammation-induced defects in barrier function, action mediated in large part through up-regulation of the central coordinator of tight junction integrity, annexin A1. The key role of this protein was then further confirmed in studies of human or murine annexin A1 genetic ablation models. Together, our data provide novel mechanisms for the protective effects of estrogen, and enhance our understanding of the beneficial role it plays in neurovascular/neuroimmune disease. PMID:26321046

  17. Root maturation and dentin–pulp response to enamel matrix derivative in pulpotomized permanent teeth

    PubMed Central

    Darwish, Sherif S; Abd El Meguid, Shadia H; Wahba, Nadia A; Mohamed, Ahmed A-R; Chrzanowski, Wojciech

    2014-01-01

    The success of pulpotomy of young permanent teeth depends on the proper selection of dressing materials. This study aimed to evaluate the histological and histomorphometric response of dentin–pulp complex to the enamel matrix derivative (Emdogain® gel) compared to that of calcium hydroxide when used as a pulp dressing in immature young permanent dogs’ teeth. Dentin-like tissues bridging the full width of the coronal pulp at the interface between the injured and healthy pulp tissues were seen after 1 month in both groups. With time, the dentin bridge increased in thickness for calcium hydroxide but disintegrated and fully disappeared for Emdogain-treated group. Progressive inflammation and total pulp degeneration were only evident with Emdogain-treated group. The root apices of Emdogain-treated teeth became matured and closed by cementum that attached to new alveolar bone by a well-oriented periodontal ligament. In young permanent dentition, Emdogain could be a good candidate for periodontium but not dentino–pulpal complex regeneration. PMID:24551447

  18. Root maturation and dentin-pulp response to enamel matrix derivative in pulpotomized permanent teeth.

    PubMed

    Darwish, Sherif S; Abd El Meguid, Shadia H; Wahba, Nadia A; Mohamed, Ahmed A-R; Chrzanowski, Wojciech; Abou Neel, Ensanya A

    2014-01-01

    The success of pulpotomy of young permanent teeth depends on the proper selection of dressing materials. This study aimed to evaluate the histological and histomorphometric response of dentin-pulp complex to the enamel matrix derivative (Emdogain(®) gel) compared to that of calcium hydroxide when used as a pulp dressing in immature young permanent dogs' teeth. Dentin-like tissues bridging the full width of the coronal pulp at the interface between the injured and healthy pulp tissues were seen after 1 month in both groups. With time, the dentin bridge increased in thickness for calcium hydroxide but disintegrated and fully disappeared for Emdogain-treated group. Progressive inflammation and total pulp degeneration were only evident with Emdogain-treated group. The root apices of Emdogain-treated teeth became matured and closed by cementum that attached to new alveolar bone by a well-oriented periodontal ligament. In young permanent dentition, Emdogain could be a good candidate for periodontium but not dentino-pulpal complex regeneration. PMID:24551447

  19. Dicarbonyl stress in the absence of hyperglycemia increases endothelial inflammation and atherogenesis similar to that observed in diabetes.

    PubMed

    Tikellis, Chris; Pickering, Raelene J; Tsorotes, Despina; Huet, Olivier; Cooper, Mark E; Jandeleit-Dahm, Karin; Thomas, Merlin C

    2014-11-01

    The deleterious effects of high glucose levels and enhanced metabolic flux on the vasculature are thought to be mediated by the generation of toxic metabolites, including reactive dicarbonyls like methylglyoxal (MG). In this article, we demonstrate that increasing plasma MG to levels observed in diabetic mice either using an exogenous source (1% in drinking water) or generated following inhibition, its primary clearance enzyme, glyoxalase-1 (with 50 mg/kg IP bromobenzyl-glutathione cyclopentyl diester every second day), was able to increase vascular adhesion and augment atherogenesis in euglycemic apolipoprotein E knockout mice to a similar magnitude as that observed in hyperglycemic mice with diabetes. The effects of MG appear partly mediated by activation of the receptor for advanced glycation end products (RAGE), as deletion of RAGE was able to reduce inflammation and atherogenesis associated with MG exposure. However, RAGE deletion did not completely prevent inflammation or vascular damage, possibly because the induction of mitochondrial oxidative stress by dicarbonyls also contributes to inflammation and atherogenesis. Such data would suggest that a synergistic combination of RAGE antagonism and antioxidants may offer the greatest utility for the prevention and management of diabetic vascular complications. PMID:24812427

  20. 12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels

    PubMed Central

    Hajek, Amanda R.; Lindley, Alexa R.; Favoreto, Silvio; Carter, Roderick; Schleimer, Robert P.; Kuperman, Douglas A.

    2009-01-01

    Background Induction of 15-lipoxygenase-1 (15-LO-1) has been observed in the airways of subjects with asthma, although its physiologic role in the airways has remained largely undefined. Objectives We sought to test the hypothesis that the mouse 15-LO-1 ortholog 12/15-LO contributes to the development of allergic airways inflammation. Methods Two models were used to evaluate wild-type and 12/15-LO–deficient mice. The systemic model involved intraperitoneal injections of allergen, and the mucosal model involved allergen exposures occurring exclusively in the airways. The systemic and mucosal-specific contributions of 12/15-LO to allergic sensitization and airways inflammation were determined by comparing the results obtained in the 2 models. Results In the mucosal model 12/15-LO knockout mice were protected from the development of allergic sensitization and airways inflammation, as evidenced by circulating levels of allergen-specific IgE, IgG1, and IgG2a; the profile of inflammatory cells in bronchoalveolar lavage fluid; and the expression of cytokines and mediators in lung tissue. In the systemic model 12/15-LO knockout mice were not protected. This suggested the presence of a lung-restricted protective role for 12/15-LO deficiency that was potentially accounted for by increased activation of mucosal B cells and increased production of the known mucosal-specific protective mediator secretory IgA. Conclusions Induction of 15-LO-1 in asthma might contribute to allergic sensitization and airways inflammation, potentially by causing suppression of secretory IgA. PMID:18692885

  1. Increased Apoptosis of Inflamed Odontoblasts Is Associated with CD47 Loss.

    PubMed

    Wang, H S; Pei, F; Chen, Z; Zhang, L

    2016-06-01

    Survival of odontoblasts during infection and inflammation determines prognosis of the dental pulp. CD47 is a "self"-label surface marker on viable cells. The aim of the present study is to investigate the interaction between CD47, autophagy, and apoptosis in inflamed human dental pulp and lipopolysaccharide (LPS)-treated mDPC6T cells. We identified activation of autophagy and apoptosis in the odontoblasts due to inflammation of the human dental pulp. Furthermore, downregulation of CD47 correlated with increased autophagy and apoptosis in dental pulp of the patients afflicted with either caries and/or pulpitis. We also detected colocalization of CD47 and LC3 in the inflamed odontoblasts. In addition, functional study indicated that loss of CD47 activates autophagy and increases apoptosis, indicating that CD47 plays a key role in the LPS-induced autophagy and apoptosis of odontoblasts. PMID:26912219

  2. Refining of Polysulfide Pulps

    NASA Astrophysics Data System (ADS)

    Copur, Yalcin

    This study compares the modified kraft process, polysulfide pulping, one of the methods to obtain higher pulp yield, with conventional kraft method. More specifically, the study focuses on the refining effects of polysulfide pulp, which is an area with limited literature. Physical, mechanical and chemical properties of kraft and polysulfide pulps (4% elemental sulfur addition to cooking digester) cooked under the same conditions were studied as regards to their behavior under various PFI refining (0, 3000, 6000, 9000 revs.). Polysulfide (PS) pulping, compared to the kraft method, resulted in higher pulp yield and higher pulp kappa number. Polysulfide also gave pulp having higher tensile and burst index. However, the strength of polysulfide pulp, tear index at a constant tensile index, was found to be 15% lower as compared to the kraft pulp. Refining studies showed that moisture holding ability of chemical pulps mostly depends on the chemical nature of the pulp. Refining effects such as fibrillation and fine content did not have a significant effect on the hygroscopic behavior of chemical pulp.

  3. Increasing Regulatory T Cells With Interleukin-2 and Interleukin-2 Antibody Complexes Attenuates Lung Inflammation and Heart Failure Progression.

    PubMed

    Wang, Huan; Hou, Lei; Kwak, Dongmin; Fassett, John; Xu, Xin; Chen, Angela; Chen, Wei; Blazar, Bruce R; Xu, Yawei; Hall, Jennifer L; Ge, Jun-Bo; Bache, Robert J; Chen, Yingjie

    2016-07-01

    Congestive heart failure (CHF) is associated with an increase of leukocyte infiltration, proinflammatory cytokines, and fibrosis in the heart and lung. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) suppress inflammatory responses in various clinical conditions. We postulated that expansion of Tregs attenuates CHF progression by reducing cardiac and lung inflammation. We investigated the effects of interleukin-2 (IL-2) plus IL-2 monoclonal antibody clone JES6-1 complexes (IL2/JES6-1) on induction of Tregs, transverse aortic constriction-induced cardiac and lung inflammation, and CHF progression in mice. We demonstrated that end-stage CHF caused a massive increase of lung macrophages and T cells, as well as relatively mild left ventricular (LV) leukocyte infiltration. Administration of IL2/JES6-1 caused an ≈6-fold increase of Tregs within CD4(+) T cells in the spleen, lung, and heart of mice. IL2/JES6-1 treatment of mice with existing transverse aortic constriction-induced LV failure markedly reduced lung and right ventricular weight and improved LV ejection fraction and LV end-diastolic pressure. Mechanistically, IL2/JES6-1 treatment significantly increased Tregs; suppressed CD4(+) T-cell accumulation; dramatically attenuated leukocyte infiltration, including decreasing CD45(+) cells, macrophages, CD8(+) T cells, and effector memory CD8(+); and reduced proinflammatory cytokine expressions and fibrosis in the lung of mice. Furthermore, IL2/JES6-1 administered before transverse aortic constriction attenuated the development of LV hypertrophy and dysfunction in mice. Our data indicate that increasing Tregs through administration of IL2/JES6-1 effectively attenuates pulmonary inflammation, right ventricular hypertrophy, and further LV dysfunction in mice with existing LV failure, suggesting that strategies to properly expand Tregs may be useful in reducing CHF progression. PMID:27160197

  4. Changes are in Store for Pulping Technology

    ERIC Educational Resources Information Center

    Environmental Science and Technology, 1975

    1975-01-01

    The pulp and paper industry are being forced by economic considerations and air pollution regulations to consider alternatives to the use of sulfur systems, be they kraft, acid or neutral sulfite. To meet environmental requirements and combat erosion of profits, modernized non-sulfur pulping methods will increasingly appear on the scene. (BT)

  5. Increase in Sialylation and Branching in the Mouse Serum N-glycome Correlates with Inflammation and Ovarian Tumour Progression

    PubMed Central

    Saldova, Radka; Piccard, Helene; Pérez-Garay, Marta; Harvey, David J.; Struwe, Weston B.; Galligan, Marie C.; Berghmans, Nele; Madden, Stephen F.; Peracaula, Rosa; Opdenakker, Ghislain; Rudd, Pauline M.

    2013-01-01

    Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in late stage, often as the result of the unavailability of sufficiently sensitive biomarkers for early detection, tumour progression and tumour-associated inflammation. Glycosylation is the most common posttranslational modification of proteins; it is altered in cancer and therefore is a potential source of biomarkers. We investigated the quantitative and qualitative effects of anti-inflammatory (acetylsalicylic acid) and pro-inflammatory (thioglycolate and chlorite-oxidized oxyamylose) drugs on glycosylation in mouse cancer serum. A significant increase in sialylation and branching of glycans in mice treated with an inflammation-inducing compound was observed. Moreover, the increases in sialylation correlated with increased tumour sizes. Increases in sialylation and branching were consistent with increased expression of sialyltransferases and the branching enzyme MGAT5. Because the sialyltransferases are highly conserved among species, the described changes in the ovarian cancer mouse model are relevant to humans and serum N-glycome analysis for monitoring disease treatment and progression might be a useful biomarker. PMID:24023608

  6. Defatted avocado pulp reduces body weight and total hepatic fat but increases plasma cholesterol in male rats fed diets with cholesterol.

    PubMed

    Naveh, Einat; Werman, Moshe J; Sabo, Edmond; Neeman, Ishak

    2002-07-01

    The potential use of avocado as a fiber source was evaluated. The total dietary fiber content of fresh avocado fruit of the Ettinger variety was 5.2 g/100 g. Approximately 75% was insoluble, and 25% soluble. The water-holding capacity of dry defatted avocado pulp was similar to that of cellulose, and trypsin inhibitors were not detected. The dietary and metabolic consequences of the avocado pulp were studied in male rats fed normal and hypercholesterolemic diets. Rats consumed semipurified diets containing either avocado pulp as the dietary fiber source or cellulose (control) with or without 10 g/kg cholesterol and 5 g/kg cholic acid. Food consumption and body weight gain were lower in rats fed avocado compared with those fed cellulose. Relative cecum weight was higher in avocado-fed rats. Plasma and hepatic cholesterol levels did not differ in rats fed diets without cholesterol, but plasma cholesterol was greater in avocado-fed than in cellulose-fed rats that consumed cholesterol. Regardless of dietary cholesterol, hepatic total fat levels, as evaluated histologically, but not directly, were lower in avocado-fed rats. These data suggest the presence of an appetite depressant in avocado and that avocado pulp interferes with hepatic fat metabolism. PMID:12097685

  7. Vital Pulp Therapy—Current Progress of Dental Pulp Regeneration and Revascularization

    PubMed Central

    Zhang, Weibo; Yelick, Pamela C.

    2010-01-01

    Pulp vitality is extremely important for the tooth viability, since it provides nutrition and acts as biosensor to detect pathogenic stimuli. In the dental clinic, most dental pulp infections are irreversible due to its anatomical position and organization. It is difficult for the body to eliminate the infection, which subsequently persists and worsens. The widely used strategy currently in the clinic is to partly or fully remove the contaminated pulp tissue, and fill and seal the void space with synthetic material. Over time, the pulpless tooth, now lacking proper blood supply and nervous system, becomes more vulnerable to injury. Recently, potential for successful pulp regeneration and revascularization therapies is increasing due to accumulated knowledge of stem cells, especially dental pulp stem cells. This paper will review current progress and feasible strategies for dental pulp regeneration and revascularization. PMID:20454445

  8. Carrageenan-Induced Colonic Inflammation Is Reduced in Bcl10 Null Mice and Increased in IL-10-Deficient Mice

    PubMed Central

    Bhattacharyya, Sumit; Xue, Liquan; Devkota, Suzanne; Chang, Eugene; Morris, Stephan; Tobacman, Joanne K.

    2013-01-01

    The common food additive carrageenan is a known activator of inflammation in mammalian tissues and stimulates both the canonical and noncanonical pathways of NF-κB activation. Exposure to low concentrations of carrageenan (10 μg/mL in the water supply) has produced glucose intolerance, insulin resistance, and impaired insulin signaling in C57BL/6 mice. B-cell leukemia/lymphoma 10 (Bcl10) is a mediator of inflammatory signals from Toll-like receptor (TLR) 4 in myeloid and epithelial cells. Since the TLR4 signaling pathway is activated in diabetes and by carrageenan, we addressed systemic and intestinal inflammatory responses following carrageenan exposure in Bcl10 wild type, heterozygous, and null mice. Fecal calprotectin and circulating keratinocyte chemokine (KC), nuclear RelA and RelB, phospho(Thr559)-NF-κB-inducing kinase (NIK), and phospho(Ser36)-IκBα in the colonic epithelial cells were significantly less (P < 0.001) in the carrageenan-treated Bcl10 null mice than in controls. IL-10-deficient mice exposed to carrageenan in a germ-free environment showed an increase in activation of the canonical pathway of NF-κB (RelA) activation, but without increase in RelB or phospho-Bcl10, and exogenous IL-10 inhibited only the canonical pathway of NF-κB activation in cultured colonic cells. These findings demonstrate a Bcl10 requirement for maximum development of carrageenan-induced inflammation and lack of complete suppression by IL-10 of carrageenan-induced inflammation. PMID:23766559

  9. Short Term Exercise Induces PGC-1α, Ameliorates Inflammation and Increases Mitochondrial Membrane Proteins but Fails to Increase Respiratory Enzymes in Aging Diabetic Hearts

    PubMed Central

    Botta, Amy; Laher, Ismail; Beam, Julianne; DeCoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L.; Ghosh, Sanjoy

    2013-01-01

    PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age. PMID:23936397

  10. PET-Scan Shows Peripherally Increased Neurokinin 1 Receptor Availability in Chronic Tennis Elbow: Visualizing Neurogenic Inflammation?

    PubMed Central

    Peterson, Magnus; Svärdsudd, Kurt; Appel, Lieuwe; Engler, Henry; Aarnio, Mikko; Gordh, Torsten; Långström, Bengt; Sörensen, Jens

    2013-01-01

    In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET) with the NK1 specific radioligand [11C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow. Trial Registration ClinicalTrials.gov NCT00888225 http://clinicaltrials.gov/ PMID:24155873

  11. LPS induces pulp progenitor cell recruitment via complement activation.

    PubMed

    Chmilewsky, F; Jeanneau, C; Laurent, P; About, I

    2015-01-01

    Complement system, a major component of the natural immunity, has been recently identified as an important mediator of the dentin-pulp regeneration process through STRO-1 pulp cell recruitment by the C5a active fragment. Moreover, it has been shown recently that under stimulation with lipoteichoic acid, a complex component of the Gram-positive bacteria cell wall, human pulp fibroblasts are able to synthesize all proteins required for complement activation. However, Gram-negative bacteria, which are also involved in tooth decay, are known as powerful activators of complement system and inflammation. Here, we investigated the role of Gram-negative bacteria-induced complement activation on the pulp progenitor cell recruitment using lipopolysaccharide (LPS), a major component of all Gram-negative bacteria. Our results show that incubating pulp fibroblasts with LPS induced membrane attack complex formation and C5a release in serum-free fibroblast cultures. The produced C5a binds to the pulp progenitor cells' membrane and induces their migration toward the LPS stimulation chamber, as revealed by the dynamic transwell migration assays. The inhibition of this migration by the C5aR-specific antagonist W54011 indicates that the pulp progenitor migration is mediated by the interaction between C5a and C5aR. Our findings demonstrate, for the first time, a direct interaction between the recruitment of progenitor pulp cells and the activation of complement system generated by pulp fibroblast stimulation with LPS. PMID:25359783

  12. CHBPR: SINGLE NUCLEOTIDE POLYMORPHISMS OF THE DOPAMINE D2 RECEPTOR INCREASE INFLAMMATION AND FIBROSIS IN HUMAN RENAL PROXIMAL TUBULE CELLS

    PubMed Central

    Jiang, Xiaoliang; Konkalmatt, Prasad; Yang, Yu; Gildea, John; Jones, John E.; Cuevas, Santiago; Felder, Robin A.; Jose, Pedro A.; Armando, Ines

    2014-01-01

    The dopamine D2 receptor (D2R) negatively regulates inflammation in mouse renal proximal tubule cells (RPTCs) and lack or downregulation of the receptor in mice increases the vulnerability to renal inflammation independent of blood pressure. Some common single nucleotide polymorphisms (SNPs; rs 6276, 6277, and 1800497) in the human (h) DRD2 gene are associated with decreased D2R expression and function, as well as high blood pressure. We tested the hypothesis that human RPTCs expressing these SNPs have increased expression of inflammatory and injury markers. We studied immortalized hRPTCs carrying D2R SNPs and compared them with cells carrying no D2R SNPs. RPTCs with D2R SNPs had decreased D2R expression and function. The expressions of the pro-inflammatory TNFα and the pro-fibrotic TGFβ1 and its signaling targets Smad3 and Snail1 were increased in hRPTC with D2R SNPs. These cells also showed induction of epithelial mesenchymal transition and production of extracellular matrix proteins, assessed by increased vimentin, fibronectin -1, and Col 1a. To test the specificity of these D2R SNP effects, hRPTC with D2R SNPs were transfected with a plasmid encoding wild-type DRD2. D2R expression was increased and those of TGFβ1, Smad3, Snail1, vimentin, fibronecti-1 and Col 1a were decreased in hRPTC with D2R SNPs transfected with wild-type DRD2 compared to hRPTC-D2R SNP transfected with empty vector. These data support the hypothesis that D2R function has protective effects in human RPTCs and suggest that carriers of these SNPs may be prone to chronic renal disease and high blood pressure. PMID:24379187

  13. Kupffer cells-dependent inflammation in the injured liver increases recruitment of mesenchymal stem cells in aging mice

    PubMed Central

    Zong, Chen; Lai, Fobao; Zhu, Pengxi; Liu, Yu; Jiang, Jinghua; Yang, Yang; Gao, Lu; Ye, Fei; Zhao, Qiudong; Li, Rong; Han, Zhipeng; Wei, Lixin

    2016-01-01

    Mesenchymal stem cells (MSCs) repair tissue injury and may be used to treat immune associated diseases. In carbon tetrachloride (CCl4)-induced liver injury murine model, we administered MSCs. When MSCs were transmitted to young and old mice with liver injury, more MSCs were recruited in old mice. In old mice, inflammation, characterized by TNF-α and IL-6, was increased due to hyper-activation and hyper-function of Kupffer cells. Blocking Kupffer cells decreased MSCs migration in old mice. In vitro, Kupffer cells isolated from old mice secreted more inflammatory cytokines and chemokines. Thus, hyper-activation of Kupffer cells in old mice increased recruitment of MSCs after their therapeutic administration. PMID:26716516

  14. Selenium Deficiency-Induced Inflammation and Increased Expression of Regulating Inflammatory Cytokines in the Chicken Gastrointestinal Tract.

    PubMed

    Gao, Xuejiao; Zhang, Ziwei; Xing, Houjuan; Yu, Jiao; Zhang, Naisheng; Xu, Shiwen

    2016-09-01

    Selenium (Se), a nutritionally essential trace element, plays an important role in various aspects of health for a wide range of species, including birds. Se deficiency inhibits the growth of immune organs and decreases immune function, leading to many inflammatory diseases. The present study determined the effects and mechanism of dietary Se deficiency on gastrointestinal tract tissue inflammation. The histopathological changes showed that Se deficiency induced inflammatory lesions in the gastrointestinal tract tissues (glandular stomach, gizzard, duodenum, small intestine, and rectum). The expression levels of PTGE (prostagland E synthase), COX-2 (cyclooxygenase-2), TNF-α (tumor necrosis factor α), and NF-κB (nuclear transfer factor κB) in the gastrointestinal tract tissues (glandular stomach, gizzard, duodenum, small intestine, and rectum) were determined by qPCR on days 15, 25, 35, 45, and 55, respectively. The results showed that Se deficiency induced high expression levels of PTGE, COX-2, TNF-α, and NF-κB in the gastrointestinal tract tissues. The effects were more obvious in the duodenum and small intestine than those in the glandular stomach, gizzard, and rectum. In addition, the expression levels of these proteins in the gastrointestinal tract tissue increased in a time-dependent manner with Se deficiency feeding time. Furthermore, Se deficiency induced the production of pro-inflammatory factors, thus aggravating inflammatory lesions in the gastrointestinal tract. The effect of Se deficiency on inflammation and other gastrointestinal tract diseases should be further studied. PMID:26899319

  15. The distinct distributions of immunocompetent cells in rat dentin pulp after pulpotomy.

    PubMed

    Zhang, Min; Kokabu, Shoichiro; Nakatomi, Chihiro; Sugiyama, Goro; Matsuo, Kou; Jimi, Eijiro

    2015-04-01

    Pulpotomy involves the removal of the coronal portion of pulp, including the diseased tissue, with the intent of maintaining the vitality of the remaining pulpal tissue via a therapeutic dressing. Once odontoblasts suffer injuries, the differentiation of mesenchymal cells is induced from the precursor cell population in the dental pulp, and these cells are recruited to the injured site to differentiate into odontoblasts. However, the involvement of immunocompetent cells during pulpal regeneration remains unclear. Thus, the purpose of this study was to investigate the properties of macrophages that infiltrated wound healing sites in rats between 1 and 28 days after pulpotomy (dap). During the inflammatory phase, ED1(+) (CD68(+) ) macrophages significantly increased throughout root pulp, especially apical to the demarcation zone, and this population persisted until 3 dap before decreasing gradually until 28 dap. OX6(+) macrophages expressing class II MHC also increased in the apical pulp at 1 dap and declined thereafter. However, OX6(+) cells appeared prior to dentin bridge formation at 3 dap and appeared again apical to the dentin bridge during the healing stage at 14 dap. The shift from ED1(+) cells in the inflammation phase to OX6(+) cells during dentin bridge formation might contribute to wound healing. PMID:25371095

  16. Frontal Fibrosing Alopecia and Increased Scalp Sweating: Is Neurogenic Inflammation the Common Link?

    PubMed Central

    Harries, Matthew J.; Wong, Sharon; Farrant, Paul

    2016-01-01

    Frontal fibrosing alopecia (FFA) is an uncommon scarring hair loss disorder that is characterized by a band-like recession of the frontal hair line with eyebrow hair loss. We present a series of patients with FFA and increased sweating predominantly localized to the scalp, and potential explanations for this association are discussed. We hypothesize that the reported increase in sweating seen in our patients may be in part related to the inflammatory process occurring locally within the skin, either inducing a local axonal sweating reflex or through direct modulation of sweat gland secretion by neuropeptides. PMID:27386462

  17. Deficiency in Serine Protease Inhibitor Neuroserpin Exacerbates Ischemic Brain Injury by Increased Postischemic Inflammation

    PubMed Central

    Ludewig, Peter; Bernreuther, Christian; Krasemann, Susanne; Arunachalam, Priyadharshini; Gerloff, Christian; Glatzel, Markus; Magnus, Tim

    2013-01-01

    The only approved pharmacological treatment for ischemic stroke is intravenous administration of plasminogen activator (tPA) to re-canalize the occluded cerebral vessel. Not only reperfusion but also tPA itself can induce an inflammatory response. Microglia are the innate immune cells of the central nervous system and the first immune cells to become activated in stroke. Neuroserpin, an endogenous inhibitor of tPA, is up-regulated following cerebral ischemia. To examine neuroserpin-dependent mechanisms of neuroprotection in stroke, we studied neuroserpin deficient (Ns−/−) mice in an animal model of temporal focal ischemic stroke. Infarct size and neurological outcome were worse in neuroserpin deficient mice even though the fibrinolytic activity in the ischemic brain was increased. The increased infarct size was paralleled by a selective increase in proinflammatory microglia activation in Ns−/− mice. Our results show excessive microglial activation in Ns−/− mice mediated by an increased activity of tPA. This activation results in a worse outcome further underscoring the potential detrimental proinflammatory effects of tPA. PMID:23658802

  18. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function

    PubMed Central

    Izumoto-Akita, Takako; Tsunekawa, Shin; Yamamoto, Akihito; Uenishi, Eita; Ishikawa, Kota; Ogata, Hidetada; Iida, Atsushi; Ikeniwa, Makoto; Hosokawa, Kaori; Niwa, Yasuhiro; Maekawa, Ryuya; Yamauchi, Yuichiro; Seino, Yusuke; Hamada, Yoji; Hibi, Hideharu; Arima, Hiroshi; Ueda, Minoru; Oiso, Yutaka

    2015-01-01

    Objective Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival. Research design and methods Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. Results Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. Conclusions These findings suggest that SHED-CM provides direct protection and encourages the propagation of

  19. Chronic psoriatic skin inflammation leads to increased monocyte adhesion and aggregation

    PubMed Central

    Golden, Jackelyn B.; Groft, Sarah G.; Squeri, Michael V.; Debanne, Sara M.; Ward, Nicole L.; McCormick, Thomas S.; Cooper, Kevin D.

    2015-01-01

    Psoriasis patients exhibit an increased risk of death by cardiovascular disease (CVD) and have elevated levels of circulating intermediate (CD14++CD16+) monocytes. This elevation could represent evidence of monocyte dysfunction in psoriasis patients at risk of CVD, as increases in circulating CD14++CD16+ monocytes are predictive of myocardial infarction and death. An elevation in the CD14++CD16+ cell population has been previously reported in patients with psoriatic disease, which has been confirmed in the cohort of our human psoriasis patients. CD16 expression was induced in CD14++CD16neg classical monocytes following plastic adhesion, which also elicited enhanced β2 but not β1 integrin surface expression, suggesting increased adhesive capacity. Indeed, we found that psoriasis patients have increased monocyte aggregation among circulating PBMCs which is recapitulated in the KC-Tie2 murine model of psoriasis. Visualization of human monocyte aggregates using imaging cytometry revealed that classical CD14++CD16neg monocytes are the predominant cell type participating in these aggregate pairs. Many of these pairs also included CD16+ monocytes, which could account for apparent elevations of intermediate monocytes. Additionally, intermediate monocytes and monocyte aggregates were the predominant cell type to adhere to TNF-α and IL-17A-stimulated dermal endothelium. Ingenuity Pathway Analysis (IPA) demonstrated that monocyte aggregates have a distinct transcriptional profile from singlet monocytes and monocytes following plastic adhesion, suggesting that circulating monocyte responses to aggregation are not fully accounted for by homotypic adhesion, and that further factors influence their functionality. PMID:26223654

  20. Chitosan coating of copper nanoparticles reduces in vitro toxicity and increases inflammation in the lung

    NASA Astrophysics Data System (ADS)

    Worthington, Kristan L. S.; Adamcakova-Dodd, Andrea; Wongrakpanich, Amaraporn; Mudunkotuwa, Imali A.; Mapuskar, Kranti A.; Joshi, Vijaya B.; Guymon, C. Allan; Spitz, Douglas R.; Grassian, Vicki H.; Thorne, Peter S.; Salem, Aliasger K.

    2013-10-01

    Despite their potential for a variety of applications, copper nanoparticles induce very strong inflammatory responses and cellular toxicity following aerosolized delivery. Coating metallic nanoparticles with polysaccharides, such as biocompatible and antimicrobial chitosan, has the potential to reduce this toxicity. In this study, copper nanoparticles were coated with chitosan using a newly developed and facile method. The presence of coating was confirmed using x-ray photoelectron spectroscopy, rhodamine tagging of chitosan followed by confocal fluorescence imaging of coated particles and observed increases in particle size and zeta potential. Further physical and chemical characteristics were evaluated using dissolution and x-ray diffraction studies. The chitosan coating was shown to significantly reduce the toxicity of copper nanoparticles after 24 and 52 h and the generation of reactive oxygen species as assayed by DHE oxidation after 24 h in vitro. Conversely, inflammatory response, measured using the number of white blood cells, total protein, and cytokines/chemokines in the bronchoalveolar fluid of mice exposed to chitosan coated versus uncoated copper nanoparticles, was shown to increase, as was the concentration of copper ions. These results suggest that coating metal nanoparticles with mucoadhesive polysaccharides (e.g. chitosan) could increase their potential for use in controlled release of copper ions to cells, but will result in a higher inflammatory response if administered via the lung.

  1. Black ginger extract increases physical fitness performance and muscular endurance by improving inflammation and energy metabolism.

    PubMed

    Toda, Kazuya; Hitoe, Shoketsu; Takeda, Shogo; Shimoda, Hiroshi

    2016-05-01

    We previously reported that polymethoxyflavones (PMFs) in black ginger (Kaempferia parviflora) extract (KPE) increased energy production by activating AMP-activated protein kinase (AMPK) in C2C12 myoblasts. We herein evaluated the effects of KPE on physical fitness performance and muscular endurance in mice. Male mice were orally administered KPE for 4 weeks, and then forced swimming test, open-field test, inclined plane test, and wire hanging test were performed. KPE significantly increased the swimming time, motility after swimming, and grip strength. IL-6 and TNF-α mRNA expression levels were decreased in the soleus muscle, whereas peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and glycogen synthase mRNA expression levels, mitochondrial number, and glycogen content were increased. These results were in agreement with those obtained for KPE and PMFs in C2C12. Therefore, the activation of AMPK by PMFs may be one of the mechanisms by which KPE improves physical fitness performance and muscular endurance. PMID:27441286

  2. Pulp and paper mills

    SciTech Connect

    Not Available

    1980-10-14

    The various hazards present in the many steps used in the production of products from pulp and paper mills were reviewed and discussed. The biological effects of 43 chemical, physical and dust hazards were detailed in the report. Dust hazards included exposures to wood dust, mold and bagasse dusts and fibrogenic dusts. Physical hazards included high heat and humidity, and noise. Raw materials and chemical intermediates discussed included calcium-oxide (1305788), magnesium-oxide (1309484), pulping liquors, sodium-hydroxide (1310732), sulfate, sulfites, sulfides, sulfur (7704349) and sulfuric-acid (7664939). Pulp bleaching agents were discussed along with papermaking additives, contaminants and/or byproducts, and pulping or combustion effluents. Sampling and analytical techniques for physical and chemical hazards were discussed. Engineering controls for hazards in pulp and paper mills were reviewed. OSHA regulations governing pulp and paper mills were evaluated.

  3. Inadequate Processing of Decellularized Dermal Matrix Reduces Cell Viability In Vitro and Increases Apoptosis and Acute Inflammation In Vivo

    PubMed Central

    Morris, Aaron H.; Chang, Julie; Kyriakides, Themis R.

    2016-01-01

    Abstract Decellularized tissue scaffolds are commonly used in the clinic because they can be used as substitutes for more traditional biomaterials, while imparting additional physiological effects. Nevertheless, reports of complications associated with their use are widespread and poorly understood. This study probes possible causes of these complications by examining cell viability and apoptosis in response to eluents from decellularized dermis. Using multiple sources of decellularized dermis, this study shows that typical decellularized scaffolds (prepared with commonly used laboratory techniques, as well as purchased from commercial sources) contain soluble components that are cytotoxic and that these components can be removed by extensive washes in cell culture media. In addition, this study demonstrates that these observed in vitro phenotypes correlate with increased apoptosis and acute inflammation when implanted subcutaneously in mice. PMID:27500014

  4. BMP-7 Treatment Increases M2 Macrophage Differentiation and Reduces Inflammation and Plaque Formation in Apo E-/- Mice

    PubMed Central

    Singla, Dinender K.; Singla, Reetu; Wang, Jing

    2016-01-01

    Inflammation plays a fundamental role in the inception and development of atherosclerosis (ATH). Mechanisms of inflammation include the infiltration of monocytes into the injured area and subsequent differentiation into either pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages. We have previously published data suggesting bone morphogenetic protein-7 (BMP-7) enhances M2 macrophage differentiation and anti-inflammatory cytokine secretion in vitro. In this regard, we hypothesized BMP-7 would inhibit plaque formation in an animal model of ATH through monocytic plasticity mediation. ATH was generated in male and female Apo E-/- mice via partial left carotid artery (PLCA) ligation and mice were divided into 3 groups: Sham, PLCA, and PLCA+BMP-7 (200ug/kg; i.v.). Our data suggest that BMP-7 inhibits plaque formation and increases arterial systolic velocity. Furthermore, we report inhibition of monocyte infiltration and a decrease in associated pro-inflammatory cytokines (MCP-1, TNF-α, and IL-6) in the PLCA+BMP-7 mice. In contrast, our data suggest a significant (p<0.05) increase in M2 macrophage populations with consequential enhanced anti-inflammatory cytokine (IL-1RA, IL-10, and Arginase 1) expression following BMP-7 treatment. We have also observed that mechanisms promoting monocyte into M2 macrophage differentiation by BMP-7 involve the upregulation and activation of the BMP-7 receptor (BMP-7RII). In conclusion, we report that BMP-7 has the potential to mediate cellular plasticity and mitigate the inflammatory immune response, which results in decreased plaque formation and improved blood velocity. PMID:26824441

  5. BMP-7 Treatment Increases M2 Macrophage Differentiation and Reduces Inflammation and Plaque Formation in Apo E-/- Mice.

    PubMed

    Singla, Dinender K; Singla, Reetu; Wang, Jing

    2016-01-01

    Inflammation plays a fundamental role in the inception and development of atherosclerosis (ATH). Mechanisms of inflammation include the infiltration of monocytes into the injured area and subsequent differentiation into either pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages. We have previously published data suggesting bone morphogenetic protein-7 (BMP-7) enhances M2 macrophage differentiation and anti-inflammatory cytokine secretion in vitro. In this regard, we hypothesized BMP-7 would inhibit plaque formation in an animal model of ATH through monocytic plasticity mediation. ATH was generated in male and female Apo E(-/-) mice via partial left carotid artery (PLCA) ligation and mice were divided into 3 groups: Sham, PLCA, and PLCA+BMP-7 (200 ug/kg; i.v.). Our data suggest that BMP-7 inhibits plaque formation and increases arterial systolic velocity. Furthermore, we report inhibition of monocyte infiltration and a decrease in associated pro-inflammatory cytokines (MCP-1, TNF-α, and IL-6) in the PLCA+BMP-7 mice. In contrast, our data suggest a significant (p<0.05) increase in M2 macrophage populations with consequential enhanced anti-inflammatory cytokine (IL-1RA, IL-10, and Arginase 1) expression following BMP-7 treatment. We have also observed that mechanisms promoting monocyte into M2 macrophage differentiation by BMP-7 involve the upregulation and activation of the BMP-7 receptor (BMP-7RII). In conclusion, we report that BMP-7 has the potential to mediate cellular plasticity and mitigate the inflammatory immune response, which results in decreased plaque formation and improved blood velocity. PMID:26824441

  6. Increased risk of cardiovascular disease in premenopausal female ragpickers of Eastern India: involvement of inflammation, oxidative stress, and platelet hyperactivity.

    PubMed

    Mondal, Nandan Kumar; Roychoudhury, Sanghita; Mukherjee, Sayali; Siddique, Shabana; Banerjee, Madhuchanda; Slaughter, Mark S; Lahiri, Twisha; Ray, Manas Ranjan

    2016-08-01

    Millions of poor people in the developing world still thrive on ragpicking. In the present study, we have examined whether ragpicking is associated with increased risk of cardiovascular disease. For this, we have enrolled 112 premenopausal female ragpickers (median age 30 years) and 98 age-matched housemaids as control from Kolkata, Eastern India. Venous blood was drawn for routine hematology; flow cytometry was used to measure generation of reactive oxygen species (ROS) by leukocytes, surface expression of CD62P (P-selectin) in platelets and CD11b in leukocytes. Collagen-induced platelet aggregation was evaluated by aggregometer, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Soluble P-selectin (sP-sel) and CD40L (sCD40L), neutrophil-activating protein-2 (NAP-2), platelet and plasma serotonin, oxidized low-density lipoprotein (oxLDL), and anticardiolipin antibodies (aCL) in plasma were measured by ELISA. Compared with control, the ragpickers had significantly higher prevalence of hypertension and prehypertension, and hypertension was positively associated with ragpicking. The ragpickers also had higher levels of inflammation (elevated NAP-2), oxidative stress (elevated ROS generation with depleted SOD) with oxLDL, platelet activation and aggregability, soluble CD40 ligand, with altered serotonin level (rose in plasma but depleted in platelet). A greater percentage of ragpickers had elevated serum level of aCL of the IgG and IgM isotypes than the controls. The results suggest that the occupation of ragpicking increases the risk of cardiovascular diseases in premenopausal women of Eastern India via inflammation, oxidative stress, platelet hyperactivity, and hypertension. PMID:27421852

  7. Inflammation induced by increased frequency of intermittent hypoxia is attenuated by tempol administration.

    PubMed

    Zhang, J; Zheng, L; Cao, J; Chen, B; Jin, D

    2015-12-01

    The levels of serum inflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in heart tissues in response to different frequencies of intermittent hypoxia (IH) and the antioxidant tempol were evaluated. Wistar rats (64 males, 200-220 g) were randomly divided into 6 experimental groups and 2 control groups. Four groups were exposed to IH 10, 20, 30, or 40 times/h. The other 2 experimental groups were challenged with IH (30 times/h) plus tempol, either beginning on day 0 (IH30T0) or on day 29 (IH30T29). After 6 weeks of challenge, serum levels of tumor necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1, and interleukin-10 were measured, and western blot analysis was used to detect NF-κB p65 and HIF-1α in myocardial tissues. Serum levels of TNF-α and ICAM-1 and myocardial expression of NF-κB p65 and HIF-1α were all significantly higher in IH rats than in controls (P<0.001). Increased IH frequency resulted in more significant changes. Administration of tempol in IH rats significantly reduced levels of TNF-α, ICAM-1, NF-κB and HIF-1α compared with the non-tempol-treated group (F=16.936, P<0.001). IH induced an inflammatory response in a frequency-dependent manner. Additionally, HIF-1α and NF-κB were increased following IH administration. Importantly, tempol treatment attenuated this effect. PMID:26397969

  8. Inflammation induced by increased frequency of intermittent hypoxia is attenuated by tempol administration

    PubMed Central

    Zhang, J.; Zheng, L.; Cao, J.; Chen, B.; Jin, D.

    2015-01-01

    The levels of serum inflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in heart tissues in response to different frequencies of intermittent hypoxia (IH) and the antioxidant tempol were evaluated. Wistar rats (64 males, 200-220 g) were randomly divided into 6 experimental groups and 2 control groups. Four groups were exposed to IH 10, 20, 30, or 40 times/h. The other 2 experimental groups were challenged with IH (30 times/h) plus tempol, either beginning on day 0 (IH30T0) or on day 29 (IH30T29). After 6 weeks of challenge, serum levels of tumor necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1, and interleukin-10 were measured, and western blot analysis was used to detect NF-κB p65 and HIF-1α in myocardial tissues. Serum levels of TNF-α and ICAM-1 and myocardial expression of NF-κB p65 and HIF-1α were all significantly higher in IH rats than in controls (P<0.001). Increased IH frequency resulted in more significant changes. Administration of tempol in IH rats significantly reduced levels of TNF-α, ICAM-1, NF-κB and HIF-1α compared with the non-tempol-treated group (F=16.936, P<0.001). IH induced an inflammatory response in a frequency-dependent manner. Additionally, HIF-1α and NF-κB were increased following IH administration. Importantly, tempol treatment attenuated this effect. PMID:26397969

  9. Acid-Sensitive Sheddable PEGylated PLGA Nanoparticles Increase the Delivery of TNF-α siRNA in Chronic Inflammation Sites.

    PubMed

    Aldayel, Abdulaziz M; Naguib, Youssef W; O'Mary, Hannah L; Li, Xu; Niu, Mengmeng; Ruwona, Tinashe B; Cui, Zhengrong

    2016-01-01

    There has been growing interest in utilizing small interfering RNA (siRNA) specific to pro-inflammatory cytokines, such as tumor necrosis factor-α ( TNF-α), in chronic inflammation therapy. However, delivery systems that can increase the distribution of the siRNA in chronic inflammation sites after intravenous administration are needed. Herein we report that innovative functionalization of the surface of siRNA-incorporated poly (lactic-co-glycolic) acid (PLGA) nanoparticles significantly increases the delivery of the siRNA in the chronic inflammation sites in a mouse model. The TNF-α siRNA incorporated PLGA nanoparticles were prepared by the standard double emulsion method, but using stearoyl-hydrazone-polyethylene glycol 2000, a unique acid-sensitive surface active agent, as the emulsifying agent, which renders (i) the nanoparticles PEGylated and (ii) the PEGylation sheddable in low pH environment such as that in chronic inflammation sites. In a mouse model of lipopolysaccharide-induced chronic inflammation, the acid-sensitive sheddable PEGylated PLGA nanoparticles showed significantly higher accumulation or distribution in chronic inflammation sites than PLGA nanoparticles prepared with an acid-insensitive emulsifying agent (i.e., stearoyl-amide-polyethylene glycol 2000) and significantly increased the distribution of the TNF-α siRNA incorporated into the nanoparticles in inflamed mouse foot. PMID:27434685

  10. Novel neuroprotective mechanisms of memantine: increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation.

    PubMed

    Wu, Hung-Ming; Tzeng, Nian-Sheng; Qian, Li; Wei, Sung-Jen; Hu, Xiaoming; Chen, Shih-Heng; Rawls, Scott M; Flood, Patrick; Hong, Jau-Shyong; Lu, Ru-Band

    2009-09-01

    Memantine shows clinically relevant efficacy in patients with Alzheimer's disease and Parkinson's disease. Most in vivo and in vitro studies attribute the neuroprotective effects of memantine to the blockade of N-methyl-D-aspartate (NMDA) receptor on neurons. However, it cannot be excluded that mechanisms other than NMDA receptor blockade may contribute to the neuroprotective effects of this compound. To address this question, primary midbrain neuron-glia cultures and reconstituted cultures were used, and lipopolysaccharide (LPS), an endotoxin from bacteria, was used to produce inflammation-mediated dopaminergic (DA) neuronal death. Here, we show that memantine exerted both potent neurotrophic and neuroprotective effects on DA neurons in rat neuron-glia cultures. The neurotrophic effect of memantine was glia dependent, as memantine failed to show any positive effect on DA neurons in neuron-enriched cultures. More specifically, it seems to be that astroglia, not microglia, are the source of the memantine-elicited neurotrophic effects through the increased production of glial cell line-derived neurotrophic factor (GDNF). Mechanistic studies showed that GDNF upregulation was associated with histone hyperacetylation by inhibiting the cellular histone deacetylase activity. In addition, memantine also displays neuroprotective effects against LPS-induced DA neuronal damage through its inhibition of microglia activation showed by both OX-42 immunostaining and reduction of pro-inflammatory factor production, such as extracellular superoxide anion, intracellular reactive oxygen species, nitric oxide, prostaglandin E(2), and tumor necrosis factor-alpha. These results suggest that the neuroprotective effects of memantine shown in our cell culture studies are mediated in part through alternative novel mechanisms by reducing microglia-associated inflammation and by stimulating neurotrophic factor release from astroglia. PMID:19536110

  11. Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause promotes central obesity, adipose tissue (AT) inflammation and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages (M's), T-cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation an...

  12. Increased surfactant protein D fails to improve bacterial clearance and inflammation in serpinB1-/- mice.

    PubMed

    Stolley, J Michael; Gong, Dapeng; Farley, Kalamo; Zhao, Picheng; Cooley, Jessica; Crouch, Erika C; Benarafa, Charaf; Remold-O'Donnell, Eileen

    2012-12-01

    Previously, we described the protective role of the neutrophil serine protease inhibitor serpinB1 in preventing early mortality of Pseudomonas aeruginosa lung infection by fostering bacterial clearance and limiting inflammatory cytokines and proteolytic damage. Surfactant protein D (SP-D), which maintains the antiinflammatory pulmonary environment and mediates bacterial removal, was degraded in infected serpinB1-deficient mice. Based on the hypothesis that increased SP-D would rescue or mitigate the pathological effects of serpinB1 deletion, we generated two serpinB1(-/-) lines overexpressing lung-specific rat SP-D and inoculated the mice with P. aeruginosa. Contrary to predictions, bacterial counts in the lungs of SP-D(low)serpinB1(-/-) and SP-D(high) serpinB1(-/-) mice were 4 logs higher than wild-type and not different from serpinB1(-/-) mice. SP-D overexpression also failed to mitigate inflammation (TNF-α), lung injury (free protein, albumin), or excess neutrophil death (free myeloperoxidase, elastase). These pathological markers were higher for infected SP-D(high)serpinB1(-/-) mice than for serpinB1(-/-) mice, although the differences were not significant after controlling for multiple comparisons. The failure of transgenic SP-D to rescue antibacterial defense of serpinB1-deficient mice occurred despite 5-fold or 20-fold increased expression levels, largely normal structure, and dose-dependent bacteria-aggregating activity. SP-D of infected wild-type mice was intact in 43-kD monomers by reducing SDS-PAGE. By contrast, proteolytic fragments of 35, 17, and 8 kD were found in infected SP-D(low)serpinB1(-/-), SP-D(high) serpinB1(-/-) mice, and serpinB1(-/-) mice. Thus, although therapies to increase lung concentration of SP-D may have beneficial applications, the findings suggest that therapy with SP-D may not be beneficial for lung inflammation or infection if the underlying clinical condition includes excess proteolysis. PMID:23024061

  13. Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation

    PubMed Central

    Otterdal, Kari; Haukeland, John Willy; Yndestad, Arne; Dahl, Tuva B; Holm, Sverre; Segers, Filip M; Gladhaug, Ivar P; Konopski, Zbigniew; Damås, Jan Kristian; Halvorsen, Bente; Aukrust, Pål

    2015-01-01

    Objectives: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). Methods: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. Results: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. Conclusion: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression. PMID:26133108

  14. A comparison of kraft, PS, kraft-AQ and kraft-NaBH4 pulps of Brutia pine.

    PubMed

    Copur, Y; Tozluoglu, A

    2008-03-01

    The aim of this work was to study the effect of adding PS, AQ and NaBH(4) into kraft pulping with special attention given to NaBH(4). Kraft, kraft-AQ, PS, and kraft-NaBH(4) pulps were produced under the same cooking conditions and the pulps produced were compared in terms of pulp and paper properties. Kraft method was modified by adding 0.1% AQ, 4% PS and 2% and 4% NaBH(4) and the resultant pulps displayed an increase in pulp yield and reduction in both kappa number and screening rejects. On the other hand, there observed an increase in both pulp yield and kappa number when the kraft was modified to PS method. The benefits of NaBH(4) addition into kraft pulping was a significant reduction in kappa number and screening rejects and a significant increase in pulp yield. The most notable outcome of NaBH(4) was 66.6% increase in pulp brightness when 4% NaBH(4) was added into kraft pulping. Of unrefined pulps, unrefined kraft pulp displayed the highest strength of pulp, which is described as tear index at a constant tensile index. Of refined pulps, kraft-AQ showed the highest pulp strength when refined to 6000 and 12,000 revs in PFI mill. PMID:17531474

  15. Systemic alterations in the metabolome of diabetic NOD mice delineate increased oxidative stress accompanied by reduced inflammation and hypertriglyceremia.

    PubMed

    Fahrmann, Johannes; Grapov, Dmitry; Yang, Jun; Hammock, Bruce; Fiehn, Oliver; Bell, Graeme I; Hara, Manami

    2015-06-01

    Nonobese diabetic (NOD) mice are a commonly used model of type 1 diabetes (T1D). However, not all animals will develop overt diabetes despite undergoing similar autoimmune insult. In this study, a comprehensive metabolomic approach, consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS), ultra-high-performance liquid chromatography-accurate mass quadruple time-of-flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based methodologies, was used to capture metabolic alterations in the metabolome and lipidome of plasma from NOD mice progressing or not progressing to T1D. Using this multi-platform approach, we identified >1,000 circulating lipids and metabolites in male and female progressor and nonprogressor animals (n = 71). Statistical and multivariate analyses were used to identify age- and sex-independent metabolic markers, which best differentiated metabolic profiles of progressors and nonprogressors. Key T1D-associated perturbations were related with 1) increases in oxidation products glucono-δ-lactone and galactonic acid and reductions in cysteine, methionine and threonic acid, suggesting increased oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived eicosanoids, implying impaired states of systemic inflammation; 3) elevations in circulating triacylglyercides reflective of hypertriglyceridemia; and 4) reductions in major structural lipids, most notably lysophosphatidylcholines and phosphatidylcholines. Taken together, our results highlight the systemic perturbations that accompany a loss of glycemic control and development of overt T1D. PMID:25852003

  16. Systemic alterations in the metabolome of diabetic NOD mice delineate increased oxidative stress accompanied by reduced inflammation and hypertriglyceremia

    PubMed Central

    Fahrmann, Johannes; Grapov, Dmitry; Yang, Jun; Hammock, Bruce; Fiehn, Oliver; Bell, Graeme I.

    2015-01-01

    Nonobese diabetic (NOD) mice are a commonly used model of type 1 diabetes (T1D). However, not all animals will develop overt diabetes despite undergoing similar autoimmune insult. In this study, a comprehensive metabolomic approach, consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS), ultra-high-performance liquid chromatography-accurate mass quadruple time-of-flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based methodologies, was used to capture metabolic alterations in the metabolome and lipidome of plasma from NOD mice progressing or not progressing to T1D. Using this multi-platform approach, we identified >1,000 circulating lipids and metabolites in male and female progressor and nonprogressor animals (n = 71). Statistical and multivariate analyses were used to identify age- and sex-independent metabolic markers, which best differentiated metabolic profiles of progressors and nonprogressors. Key T1D-associated perturbations were related with 1) increases in oxidation products glucono-δ-lactone and galactonic acid and reductions in cysteine, methionine and threonic acid, suggesting increased oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived eicosanoids, implying impaired states of systemic inflammation; 3) elevations in circulating triacylglyercides reflective of hypertriglyceridemia; and 4) reductions in major structural lipids, most notably lysophosphatidylcholines and phosphatidylcholines. Taken together, our results highlight the systemic perturbations that accompany a loss of glycemic control and development of overt T1D. PMID:25852003

  17. Immunosuppression Decreases Inflammation and Increases AAV6-hSERCA2a-Mediated SERCA2a Expression

    PubMed Central

    Zhu, Xiaodong; McTiernan, Charles F.; Rajagopalan, Navin; Shah, Hemal; Fischer, David; Toyoda, Yoshiya; Letts, Dustin; Bortinger, Jonathan; Gibson, Gregory; Xiang, Wenyu; McCurry, Kenneth; Mathier, Michael; Glorioso, Joseph C.

    2012-01-01

    Abstract The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF). Increasing SERCA2a expression in HF models improves cardiac function. We used direct cardiac delivery of adeno-associated virus encoding human SERCA2a (AAV6-hSERCA2a) in HF and normal canine models to study safety, efficacy, and the effects of immunosuppression. Tachycardic-paced dogs received left ventricle (LV) wall injection of AAV6-hSERCA2a or solvent. Pacing continued postinjection for 2 or 6 weeks, until euthanasia. Tissue/serum samples were analyzed for hSERCA2a expression (Western blot) and immune responses (histology and AAV6-neutralizing antibodies). Nonpaced dogs received AAV6-hSERCA2a and were analyzed at 12 weeks; a parallel cohort received AAV-hSERCA2a and immunosuppression. AAV-mediated cardiac expression of hSERCA2a peaked at 2 weeks and then declined (to ∼50%; p<0.03, 6 vs. 2 weeks). LV end diastolic and end systolic diameters decreased in 6-week dogs treated with AAV6-hSERCA2a (p<0.05) whereas LV diameters increased in control dogs. Dogs receiving AAV6-hSERCA2a developed neutralizing antibodies (titer ≥1:120) and cardiac cellular infiltration. Immunosuppression dramatically reduced immune responses (reduced inflammation and neutralizing antibody titers <1:20), and maintained hSERCA2a expression. Thus cardiac injection of AAV6-hSERCA2a promotes local hSERCA2a expression and improves cardiac function. However, the hSERCA2a protein level is reduced by host immune responses. Immunosuppression alleviates immune responses and sustains transgene expression, and may be an important adjuvant for clinical gene therapy trials. PMID:22482463

  18. Inflammatory and immunological aspects of dental pulp repair

    PubMed Central

    Goldberg, Michel; Farges, Jean-Christophe; Lacerda-Pinheiro, Sally; Six, Ngampis; Jegat, Nadège; Decup, Frank; Septier, Dominique; Carrouel, Florence; Durand, Stéphanie; Chaussain-Miller, Catherine; DenBesten, Pamela; Veis, Arthur; Poliard, Anne

    2010-01-01

    The repair of dental pulp by direct capping with calcium hydroxide or by implantation of bioactive extracellular matrix (ECM) molecules implies a cascade of four steps: a moderate inflammation, the commitment of adult reserve stem cells, their proliferation and terminal differentiation. The link between the initial inflammation and cell commitment is not yet well established but appears as a potential key factor in the reparative process. Either the release of cytokines due to inflammatory events activates resident stem (progenitor) cells, or inflammatory cells or pulp fibroblasts undergo a phenotypic conversion into osteoblast/odontoblast-like progenitors implicated in reparative dentin formation. Activation of antigen-presenting dendritic cells by mild inflammatory processes may also promote osteoblast/odontoblast-like differentiation and expression of ECM molecules implicated in mineralization. Recognition of bacteria by specific odontoblast and fibroblast membrane receptors triggers an inflammatory and immune response within the pulp tissue that would also modulate the repair process. PMID:18602009

  19. Colonic inflammation and enhanced-beta-catenin signaling accompany an increase of the Lachnospiraceae/Streptococcaceae in the hind gut of high-fat diet-fed mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of an obesigenic / high-fat (HF) diet is associated with an increase of inflammation-related colon cancer risk and may alter the gut microbiota. To test the hypothesis that a HF feeding accelerates inflammatory processes and changes gut microbiome composition, C57BL/6 mice were fed a HF ...

  20. DENTAL PULP TISSUE ENGINEERING

    PubMed Central

    Demarco, FF; Conde, MCM; Cavalcanti, B; Casagrande, L; Sakai, V; Nör, JE

    2013-01-01

    Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research. PMID:21519641

  1. High Dose Lycopene Supplementation Increases Hepatic CYP2E1 Protein and Inflammation in Alcohol-Fed Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent in vitro evidence suggests that the antioxidant lycopene can prevent alcohol induced oxidative stress and inflammation. However, in vivo knowledge of possible interactions between escalating doses of lycopene and chronic alcohol ingestion are lacking. In the present study, we investigated p...

  2. Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells

    PubMed Central

    Fazio, Chiara; Piazzi, Giulia; Vitaglione, Paola; Fogliano, Vincenzo; Munarini, Alessandra; Prossomariti, Anna; Milazzo, Maddalena; D’Angelo, Leonarda; Napolitano, Manuela; Chieco, Pasquale; Belluzzi, Andrea; Bazzoli, Franco; Ricciardiello, Luigi

    2016-01-01

    Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA. PMID:26864323

  3. Increased Oxidative Stress and Inflammation Independent of Body Adiposity in Diabetic and Nondiabetic Controls in falciparum Malaria

    PubMed Central

    Acquah, Samuel; Boampong, Johnson Nyarko; Eghan Jnr, Benjamin Ackon

    2016-01-01

    Information on the extent to which oxidative stress and inflammation occur in the presence of falciparum malaria and type 2 diabetes mellitus in the same individual is limited. This study sought to investigate the extent of inflammation and oxidative stress in adult uncomplicated malaria by measuring fasting levels of lipid peroxides, C-reactive protein (CRP), and total antioxidant power (TAP) before and during falciparum malaria, in 100 respondents with type 2 diabetes and 100 age-matched controls in the Cape Coast metropolis of Ghana. Also, body adiposity index, body mass index, and waist-to-hip ratio were computed. Before and during falciparum malaria, diabetes patients exhibited higher (P < 0.05) levels of CRP and peroxides than controls but TAP and BAI were comparable (P > 0.05) between the two groups. Baseline CRP correlated positively (r = 0.341, P = 0.002) with peroxide only in the diabetic group. During malaria, TAP level in both study groups declined (P < 0.05) by 80% of their baseline levels. CRP correlated negatively (r = −0.352, P = 0.011) with TAP in the control but not the diabetic group. Uncomplicated falciparum malaria elevated inflammation and peroxidation but decreased antioxidant power independent of adiposity. This finding may have implication on cardiovascular health. PMID:27298824

  4. Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen

    PubMed Central

    Rosche, Kristin L.; Aljasham, Alanoud T.; Kipfer, James N.; Piatkowski, Bryan T.; Konjufca, Vjollca

    2015-01-01

    Infection of mice with Salmonella enterica serovar Typhimurium (Salmonella) causes systemic inflammatory disease and enlargement of the spleen (splenomegaly). Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71+Ter119+ reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs) and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP), marginal zone (MZ), and red pulp (RP) is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM), we show that Salmonella-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80+ macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220+, CD4+ and CD8+ lymphocytes, as well as MZ MOMA+ macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80+ macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80+ macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during Salmonella infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to Salmonella has implications for understanding Salmonella pathogenesis and for the design of more effective Salmonella-based vaccines. PMID:26068006

  5. Dental Pulp Testing: A Review

    PubMed Central

    Chen, Eugene; Abbott, Paul V.

    2009-01-01

    Dental pulp testing is a useful and essential diagnostic aid in endodontics. Pulp sensibility tests include thermal and electric tests, which extrapolate pulp health from sensory response. Whilst pulp sensibility tests are the most commonly used in clinical practice, they are not without limitations and shortcomings. Pulp vitality tests attempt to examine the presence of pulp blood flow, as this is viewed as a better measure of true health than sensibility. Laser Doppler flowmetry and pulse oximetry are examples of vitality tests. Whilst the prospect is promising, there are still many practical issues that need to be addressed before vitality tests can replace sensibility tests as the standard clinical pulp diagnostic test. With all pulp tests, the results need to be carefully interpreted and closely scrutinised as false results can lead to misdiagnosis which can then lead to incorrect, inappropriate, or unnecessary treatment. PMID:20339575

  6. Histological study of periradicular tissue responses to uninfected and infected devitalized pulps in dogs.

    PubMed

    Lin, Louis M; Di Fiore, Peter M; Lin, Jarshen; Rosenberg, Paul A

    2006-01-01

    Uninfected necrotic tissue, such as that which follows a myocardial or cerebral infarct, is capable of inducing an inflammatory reaction. Eventually, the infarct is organized by granulation tissue. Why then, does uninfected devitalized pulp tissue, such as in traumatized teeth, not cause periradicular inflammation and does not become organized by granulation tissue? Four beagle dogs were used in this experiment. A total of 48 teeth, which included 24 maxillary and 24 mandibular incisors, were aseptically devitalized, leaving residual pulp tissues in the root canals, and equally divided into two groups. Group A (24 uninfected): A sterile cotton pellet was placed deep into the canal orifice before the pulp chamber and access opening were closed with a layer of zinc-oxide eugenol cement followed by glass ionomer cement. Group B (24 infected): The teeth were left open to the oral cavity for 7 days and then closed with a cotton pellet and zinc-oxide eugenol and glass ionomer cement. The animals were sacrificed one year after the experiment and prepared for histological examination of periradicular tissue responses to uninfected and infected devitalized pulp tissues. The results indicate that uninfected devitalized pulp tissues did not continuously release inflammatory mediators and cause persistent periradicular inflammation over a period of one year. However, infected devitalized pulp tissues induced various degrees of periradicular inflammation. Only the apical few millimeters of uninfected devitalized pulp tissue in the root canals were organized by granulation tissue from vital periodontal ligament tissue. PMID:16410065

  7. Copper-zinc superoxide dismutase activity in dental pulp after dental preparation.

    PubMed

    Varvara, G; Pinchi, V; Caputi, S; D'Arcangelo, C; Scarano, A; Sinjari, B; Murmura, G

    2012-01-01

    The superoxide dismutases (SODs) are the major enzymatic defence mechanism against toxic reactive oxygen species generated during normal oxidative metabolism and during the respiratory burst associated with inflammation. To further clarify the potential role of copper-zinc (Cu/Zn)-SOD during inflammation of pulp tissue in humans, the aim was to determine whether significant changes in Cu/Zn-SOD activity occur in healthy dental pulp after dental preparation. The condition of the pulp was assessed using clinical and radiographic evaluation. Thirty systemically healthy patients were the source of the pulp tissue, which was collected by longitudinally grooving and splitting teeth that were matched between the control dental pulp and the prepared tooth (test) dental pulp. Cu/Zn-SOD activity was determined through spectrophotometric methods, with Mann-Whitney tests used to assess the significance of the differences between the groups. The Cu/Zn-SOD activity was 168.2+/-46.4 mU.mg−1 total protein (range: 96-212 mU.mg−1) in the control group, and 328.2+/-84.2 mU.mg−1 total protein (range: 280-420 mU.mg−1) in the test group. The difference between the groups was statistically significant, at P <0.001. These results demonstrate a potential role for Cu/Zn-SOD during dental pulp inflammation in humans after dental preparation. PMID:23241127

  8. Effect of immunologic reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis

    SciTech Connect

    Ramage, J.K.; Stanisz, A.; Scicchitano, R.; Hunt, R.H.; Perdue, M.H.

    1988-06-01

    In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens.

  9. Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation.

    PubMed

    Suzuki, K; Lovera, M; Schmachtenberg, O; Couve, E

    2015-10-01

    The dental pulp in human primary teeth is densely innervated by a plethora of nerve endings at the coronal pulp-dentin interface. This study analyzed how the physiological root resorption (PRR) process affects dental pulp innervation before exfoliation of primary teeth. Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and Büngner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages. PMID:26149320

  10. Manganese Peroxidase, Produced by Trametes versicolor during Pulp Bleaching, Demethylates and Delignifies Kraft Pulp

    PubMed Central

    Paice, M. G.; Reid, I. D.; Bourbonnais, R.; Archibald, F. S.; Jurasek, L.

    1993-01-01

    Previous work has shown that Trametes (Coriolus) versicolor bleaches kraft pulp brownstock with the concomitant release of methanol. In this work, the fungus is shown to produce both laccase and manganese peroxidase (MnP) but not lignin peroxidase during pulp bleaching. MnP production was enhanced by the presence of pulp and/or Mn(II) ions. The maximum level of secreted MnP was coincident with the maximum rate of fungal bleaching. Culture filtrates isolated from bleaching cultures produced Mn(II)- and hydrogen peroxide-dependent pulp demethylation and delignification. Laccase and MnP were separated by ion-exchange chromatography. Purified MnP alone produced most of the demethylation and delignification exhibited by the culture filtrates. On the basis of the methanol released and the total and phenolic methoxyl contents of the pulp, it appears that MnP shows a preference for the oxidation of phenolic lignin substructures. The extensive increase in brightness observed in the fungus-treated pulp was not found with MnP alone. Therefore, either the MnP effect must be optimized or other enzymes or compounds from the fungus are also required for brightening. Images PMID:16348850

  11. Human Pulp Response to Direct Pulp Capping and Miniature Pulpotomy with MTA after Application of Topical Dexamethasone: A Randomized Clinical Trial

    PubMed Central

    Mousavi, Seyed Amir; Ghoddusi, Jamileh; Mohtasham, Nooshin; Shahnaseri, Shirin; Paymanpour, Payam; Kinoshita, Jun-Ichiro

    2016-01-01

    Introduction: The aim of this randomized clinical trial was to compare the histologic pulp tissue response to one-step direct pulp capping (DPC) and miniature pulpotomy (MP) with mineral trioxide aggregate (MTA) after application of dexamethasone in healthy human premolars. Methods and Materials: Forty intact premolars from 10 orthodontic patients, were randomly chosen for DPC (n=20) or MP (n=20). In 10 teeth from each group, after exposure of the buccal pulp horn, topical dexamethasone was applied over the pulp. In all teeth the exposed/miniaturely resected pulp tissue was covered with MTA and cavities were restored with glass ionomer. Teeth vitality was evaluated during the next 7, 21, 42, and 60 days. Signs and/or symptoms of irreversible pulpitis or pulp necrosis were considered as failure. According to the orthodontic schedule, after 60 days the teeth were extracted and submitted for histological examination. The Kruskal-Wallis and Fisher’s exact tests were used for statistical analysis of the data (P=0.05). Results: Although dexamethasone specimens showed less inflammation, calcified bridge, pulpal blood vasculature, collagen fibers and granulation tissue formation were not significantly different between the groups (P>0.05). Conclusion: Topical dexamethasone did not hindered pulp healing but reduced the amount of underlying pulpal tissue inflammation after DPC and MP in healthy human premolars. PMID:27141213

  12. Increased inflammation and decreased insulin sensitivity indicate metabolic disturbances in zoo-managed compared to free-ranging black rhinoceros (Diceros bicornis).

    PubMed

    Schook, Mandi W; Wildt, David E; Raghanti, Mary Ann; Wolfe, Barbara A; Dennis, Patricia M

    2015-01-01

    Black rhinoceros (rhinos) living in zoos express a host of unusual disease syndromes that are associated with increased morbidity and mortality, including hemolytic anemia, rhabdomyolysis, hepatopathy and ulcerative skin disease, hypophosphatemia and iron overload. We hypothesized that iron overload is a consequence and indicator of disturbances related to inflammation and insulin/glucose metabolism. The objectives of this study were to: (1) generate the first baseline information on biomarkers of inflammation (tumor necrosis factor alpha [TNFα], serum amyloid A [SAA]), insulin sensitivity (insulin, glucose and proxy calculations of insulin sensitivity), phosphate and iron stores (ferritin) using banked serum from free-ranging black rhinos; and (2) then compare serum biomarkers between zoo-managed (n=86 individuals) and free-ranging (n=120) animals. Enzyme immunoassays were validated for serum and then biomarker levels analyzed using mixed models while controlling for sex, age and year of sample collection. Concentrations of TNFα, SAA, insulin and insulin-to glucose ratio were higher (P<0.05) in black rhinos managed in ex situ conditions compared to free-living counterparts. Findings indicate that the captive environment is contributing to increased inflammation and decreased insulin sensitivity in this endangered species. PMID:25980685

  13. Substance P expression in human tooth pulp in relation to caries and pain experience.

    PubMed

    Rodd, H D; Boissonade, F M

    2000-12-01

    The neuropeptide substance P (SP) is found within a subpopulation of nociceptive afferent nerve fibres and has been shown to be upregulated in a variety of sites following peripheral inflammation. The aim of this study was to investigate the expression of SP within human teeth, both in health and disease, and to seek a correlation between reported pain history and SP expression within pulpal nerves. Coronal pulps were removed from 62 permanent mandibular molars with a known pain history. Teeth were categorised as intact, moderately or grossly carious. Using indirect immunofluorescence, sections were double-labelled for the general neuronal marker protein gene product 9.5 (PGP 9.5) and for SP. Image analysis was then used to quantify the percentage area of PGP 9.5-labelled tissue which was also labelled for SP. Throughout the pulp, the expression of SP was found to be significantly increased with the progression of caries. Furthermore, SP expression was significantly greater in grossly carious painful specimens than in grossly carious asymptomatic specimens. These data would suggest that the expression of SP within pulpal nerves undergoes dynamic changes following caries, which may have an important clinical significance in terms of inflammation and pain experience. PMID:11153921

  14. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

    PubMed Central

    Schmitz, J.; Evers, N.; Awazawa, M.; Nicholls, H.T.; Brönneke, H.S.; Dietrich, A.; Mauer, J.; Blüher, M.; Brüning, J.C.

    2016-01-01

    Objective Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. Methods We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Results Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). Conclusions These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue

  15. Alkaline phosphatase activity in normal and inflamed dental pulps.

    PubMed

    Spoto, G; Fioroni, M; Rubini, C; Tripodi, D; Di Stilio, M; Piattelli, A

    2001-03-01

    Alkaline phosphatase (ALP) seems to be important in the formation of mineralized tissues. High levels of ALP have been demonstrated in dental pulp cells. In the present study ALP activity was analyzed in normal healthy human dental pulps, in reversible pulpitis, and in irreversible pulpitis. Enzymatic ALP control values for the normal healthy pulps were 110.96+/-20.93. In the reversible pulpitis specimens the ALP activity increased almost eight times to 853.6+/-148.27. In the irreversible pulpitis specimens the values decreased sharply to 137.15+/-21.28 and were roughly equivalent to those seen in normal healthy pulps. The differences between the groups (control vs. reversible pulpitis and reversible pulpitis vs. irreversible pulpitis) were statistically significant. These results could point to a role of ALP in the initial pulp response after injury. PMID:11487147

  16. Effect of low level laser therapy on dental pulp during orthodontic movement

    PubMed Central

    Domínguez, Ángela; Ballesteros, Rosa Emilia; Viáfara, Jairo Hernán; Tamayo, Oscar Mario

    2013-01-01

    AIM: To validate the protocol described here to be used in future clinical trials related to the effect of laser therapy on dental pulp. METHODS: Histologically treated samples from eight human healthy premolar teeth obtained from the middle root level were distributed in four groups: group 1 (G1) absolute control; group 2 (G2) only laser irradiation; group 3 (G3) exposed only to orthodontics; and group 4 (G4) treated with orthodontics and laser. Laser treatment was performed at 830 nm wavelength, 100 mW (energy 80 J/cm2, 2.2 J), for 22 s in the vestibular surface and 22 s in the palatal surface, 1 mm away from the dental root mucosa. Three staining methods were performed: hematoxylin-eosin (HE), Masson’s Trichrome method and Gomori’s method. RESULTS: The pulp histology parameters were evaluated and the results classified in to 3 parts: an inflammatory response, soft tissue response (dental pulp) and hard tissue response (dentin and predentin). There was no inflammation (chronic or acute) in any of the evaluated groups. The zones of pulp necrosis were found in one premolar of G3 and in one of G4; in groups G2 and G4 there was higher angiogenesis than in the other two groups. G4 group presented the highest level of vascularization. A reduced nerve density was observed in G3. A G2 specimen showed increased nerve density. A higher rate of calcification was observed in G1 compared to G2. Denticles, either real or false, were observed in G1, G2 and G3. Sclerosis of dentin and focal dentin loss was observed among all the groups. Secondary dentin was present in one sample in G1 and G2. A necrosis zone was found in one sample of G3 and G4. No differences between groups were observed in the odontoblast irregularity layer but the layer was wider in the group treated with laser only. A notable difference was detected in reduction of the cell-free layer between the groups G1 and G4. The findings in pulp tissue favor its adaptative response against dental movement induced

  17. The preservative polyquaternium-1 increases cytoxicity and NF-kappaB linked inflammation in human corneal epithelial cells

    PubMed Central

    Paimela, Tuomas; Ryhänen, Tuomas; Kauppinen, Anu; Marttila, Liisa; Salminen, Antero

    2012-01-01

    Purpose In numerous clinical and experimental studies, preservatives present in eye drops have had detrimental effects on ocular epithelial cells. The aim of this study was to compare the cytotoxic and inflammatory effects of the preservative polyquaternium-1 (PQ-1) containing Travatan (travoprost 0.004%) and Systane Ultra eye drops with benzalkonium chloride (BAK) alone or BAK-preserved Xalatan (0.005% latanoprost) eye drops in HCE-2 human corneal epithelial cell culture. Methods HCE-2 cells were exposed to the commercial eye drops Travatan, Systane Ultra, Xalatan, and the preservative BAK. Cell viability was determined using colorimetric MTT (3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by release of lactate dehydrogenase (LDH). Induction of apoptosis was measured with a using a colorimetric caspase-3 assay kit. DNA binding of the nuclear factor kappa B (NF-κB) transcription factor, and productions of the proinflammatory cytokines, interleukins IL-6 and IL-8, were determined using an enzyme-linked immunosorbent assay (ELISA) method. Results Cell viability, as measured by the MTT assay, declined by up to 50% after exposure to Travatan or Systane Ultra solutions which contain 0.001% PQ-1. BAK at 0.02% rather than at 0.001% concentration evoked total cell death signs on HCE-2 cells. In addition, cell membrane permeability, as measured by LDH release, was elevated by sixfold with Travatan and by a maximum threefold with Systane Ultra. Interestingly, Travatan and Systane Ultra activated NF-κB and elevated the secretion of inflammation markers IL-6 by 3 to eightfold and IL-8 by 1.5 to 3.5 fold, respectively, as analyzed with ELISA. Conclusions Eye drops containing PQ-1 evoke cytotoxicity and enhance the NF-κB driven inflammation reaction in cultured HCE-2 cells. Our results indicate that these harmful effects of ocular solutions preserved with PQ-1 should be further evaluated in vitro and in vivo. PMID:22605930

  18. Biobleaching of banana fibre pulp using Bacillus subtilis C O1 xylanase produced from wheat bran under solid-state cultivation.

    PubMed

    Manimaran, A; Vatsala, T M

    2007-11-01

    A cellulase-free xylanase produced by Bacillus subtilis C 01 from wheat bran under solid-state cultivation was tested for its efficacy in biobleaching of raw banana fibre and banana pulp obtained through a mechanical pulping process. Banana pulp samples treated with crude xylanase (450 nkat g(-1) pulp) resulted in a 19.6% increase in the brightness as compared to untreated pulp. The presence of chromophores, hydrophobic compounds and an increased reducing sugar (10.79 mg g(-1) pulp) quantity in the bleached solution after enzymatic treatment indicated the removal of materials that were absorbed at 237 nm from the banana pulp. PMID:17712584

  19. High-energy electron irradiation of annual plants (bagasse) for an efficient production of chemi-mechanical pulp fibers

    NASA Astrophysics Data System (ADS)

    Pathak, Shailesh; Ray, A. K.; Großmann, Harald; Kleinert, Rene

    2015-12-01

    The paper industry is one of the largest consumers of energy and energy consumption has been increased several times in last few decades. Bagasse chemical pulping has very low yield about 45-55% and also generates high pollution load in the effluent as compared to mechanical pulping, g. Thermo-mechanical pulp (TMP). On the other hand,-->e.g. thermo-mechanical pulp (TMP). On the other hand, the specific energy consumption is very high for TMP pulps. ETMP (Energy efficient Thermo-Mechanical Pulping) or ECTMP (Energy efficient Chemi-Thermo Mechanical Pulping) is an innovative idea for reducing the energy demand in TMP refining. In the present investigation, energy efficient mechanical pulping potential of bagasse was studied using TMP, CTMP and ECTMP pulping methodology with electron irradiation pretreatment. It is evident from the results that more than 50% energy saving potential of irradiation pre-treatment was achieved.

  20. The Epithelial Anion Transporter Pendrin Is Induced by Allergy and Rhinovirus Infection, Regulates Airway Surface Liquid, and Increases Airway Reactivity and Inflammation in an Asthma Model1

    PubMed Central

    Nakagami, Yasuhiro; Favoreto, Silvio; Zhen, Guohua; Park, Sung-Woo; Nguyenvu, Louis T.; Kuperman, Douglas A.; Dolganov, Gregory M.; Huang, Xiaozhu; Boushey, Homer A.; Avila, Pedro C.; Erle, David J.

    2008-01-01

    Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses and cause increases in airway epithelial cell mucus, electrolyte and water secretion into the airway surface liquid (ASL). Since ASL dehydration can cause airway inflammation and obstruction, ion transporters could play a role in pathogenesis of asthma exacerbations. We previously reported that expression of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13. Here we show that pendrin plays a role in allergic airway disease and in regulation of ASL thickness. Pendrin-deficient mice had less allergen-induced airway hyperreactivity and inflammation than control mice although other aspects of the Th2 response were preserved. In cultures of IL-13-stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness, suggesting that reductions in allergen-induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydration. To determine whether pendrin might also play a role in virus-induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally occurring common colds caused by rhinovirus and found a 4.9-fold-increase in mean expression during colds. Studies of cultured human bronchial epithelial cells indicated that this increase could be explained by the combined effects of rhinovirus and IFN-γ, a Th1 cytokine induced during virus infection. We conclude that pendrin regulates ASL thickness and may be an important contributor to asthma exacerbations induced by viral infections or allergens. PMID:18641360

  1. Ability of healthy and inflamed human dental pulp to reduce hydrogen peroxide.

    PubMed

    Esposito, Paola; Varvara, Giuseppe; Murmura, Giovanna; Terlizzi, Antonio; Caputi, Sergio

    2003-10-01

    This study examined the defensive ability of human dental pulp against H2O2 in healthy and reversible and irreversible pulpitis tissues through determination of catalase activity by spectrophotometric methods. Thirty-five systemically healthy patients were donors of the pulp tissue, and pulp conditions were assessed using clinical and X-ray evaluations. Catalase activity was 1.61 +/- 0.23 U mg(-1) protein in the healthy tissues, 2.99 +/- 0.45 U mg(-1) protein in the reversible pulpitis tissues, and 2.44 +/- 467 mU mg(-1) protein in the irreversible pulpitis tissues. All differences between the groups were statistically significant. These results point to a role for catalase during dental pulp inflammation in humans, and therefore demonstrate an inherent biological defense system against reactive oxidants in human dental pulp. PMID:12974692

  2. Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes.

    PubMed

    Ruiz-Ojeda, Francisco Javier; Gomez-Llorente, Carolina; Aguilera, Concepción María; Gil, Angel; Rupérez, Azahara Iris

    2016-01-01

    Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX) activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5) were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2) and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes. PMID:27023799

  3. Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes

    PubMed Central

    Ruiz-Ojeda, Francisco Javier; Gomez-Llorente, Carolina; Aguilera, Concepción María; Gil, Angel; Rupérez, Azahara Iris

    2016-01-01

    Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX) activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5) were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2) and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes. PMID:27023799

  4. Effects of Camphorquinone on Cytotoxicity, Cell Cycle Regulation and Prostaglandin E2 Production of Dental Pulp Cells: Role of ROS, ATM/Chk2, MEK/ERK and Hemeoxygenase-1

    PubMed Central

    Chang, Mei-Chi; Lin, Li-Deh; Wu, Min-Tsz; Chan, Chiu-Po; Chang, Hsiao-Hua; Lee, Ming-Shu; Sun, Tzu-Ying; Jeng, Po-Yuan; Yeung, Sin-Yuet; Lin, Hsueh-Jen; Jeng, Jiiang-Huei

    2015-01-01

    Camphorquinone (CQ) is a popularly-used photosensitizer in composite resin restoration. In this study, the effects of CQ on cytotoxicity and inflammation-related genes and proteins expression of pulp cells were investigated. The role of reactive oxygen species (ROS), ATM/Chk2/p53 and hemeoxygenase-1 (HO-1) and MEK/ERK signaling was also evaluated. We found that ROS and free radicals may play important role in CQ toxicity. CQ (1 and 2 mM) decreased the viability of pulp cells to about 70% and 50% of control, respectively. CQ also induced G2/M cell cycle arrest and apoptosis of pulp cells. The expression of type I collagen, cdc2, cyclin B, and cdc25C was inhibited, while p21, HO-1 and cyclooxygenase-2 (COX-2) were stimulated by CQ. CQ also activated ATM, Chk2, and p53 phosphorylation and GADD45α expression. Besides, exposure to CQ increased cellular ROS level and 8-isoprostane production. CQ also stimulated COX-2 expression and PGE2 production of pulp cells. The reduction of cell viability caused by CQ can be attenuated by N-acetyl-L-cysteine (NAC), catalase and superoxide dismutase (SOD), but can be promoted by Zinc protoporphyin (ZnPP). CQ stimulated ERK1/2 phosphorylation, and U0126 prevented the CQ-induced COX-2 expression and prostaglandin E2 (PGE2) production. These results indicate that CQ may cause cytotoxicity, cell cycle arrest, apoptosis, and PGE2 production of pulp cells. These events could be due to stimulation of ROS and 8-isoprostane production, ATM/Chk2/p53 signaling, HO-1, COX-2 and p21 expression, as well as the inhibition of cdc2, cdc25C and cyclin B1. These results are important for understanding the role of ROS in pathogenesis of pulp necrosis and pulpal inflammation after clinical composite resin filling. PMID:26658076

  5. Effects of Camphorquinone on Cytotoxicity, Cell Cycle Regulation and Prostaglandin E2 Production of Dental Pulp Cells: Role of ROS, ATM/Chk2, MEK/ERK and Hemeoxygenase-1.

    PubMed

    Chang, Mei-Chi; Lin, Li-Deh; Wu, Min-Tsz; Chan, Chiu-Po; Chang, Hsiao-Hua; Lee, Ming-Shu; Sun, Tzu-Ying; Jeng, Po-Yuan; Yeung, Sin-Yuet; Lin, Hsueh-Jen; Jeng, Jiiang-Huei

    2015-01-01

    Camphorquinone (CQ) is a popularly-used photosensitizer in composite resin restoration. In this study, the effects of CQ on cytotoxicity and inflammation-related genes and proteins expression of pulp cells were investigated. The role of reactive oxygen species (ROS), ATM/Chk2/p53 and hemeoxygenase-1 (HO-1) and MEK/ERK signaling was also evaluated. We found that ROS and free radicals may play important role in CQ toxicity. CQ (1 and 2 mM) decreased the viability of pulp cells to about 70% and 50% of control, respectively. CQ also induced G2/M cell cycle arrest and apoptosis of pulp cells. The expression of type I collagen, cdc2, cyclin B, and cdc25C was inhibited, while p21, HO-1 and cyclooxygenase-2 (COX-2) were stimulated by CQ. CQ also activated ATM, Chk2, and p53 phosphorylation and GADD45α expression. Besides, exposure to CQ increased cellular ROS level and 8-isoprostane production. CQ also stimulated COX-2 expression and PGE2 production of pulp cells. The reduction of cell viability caused by CQ can be attenuated by N-acetyl-L-cysteine (NAC), catalase and superoxide dismutase (SOD), but can be promoted by Zinc protoporphyin (ZnPP). CQ stimulated ERK1/2 phosphorylation, and U0126 prevented the CQ-induced COX-2 expression and prostaglandin E2 (PGE2) production. These results indicate that CQ may cause cytotoxicity, cell cycle arrest, apoptosis, and PGE2 production of pulp cells. These events could be due to stimulation of ROS and 8-isoprostane production, ATM/Chk2/p53 signaling, HO-1, COX-2 and p21 expression, as well as the inhibition of cdc2, cdc25C and cyclin B1. These results are important for understanding the role of ROS in pathogenesis of pulp necrosis and pulpal inflammation after clinical composite resin filling. PMID:26658076

  6. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability.

    PubMed

    Erbel, Christian; Dengler, Thomas J; Wangler, Susanne; Lasitschka, Felix; Bea, Florian; Wambsganss, Nadine; Hakimi, Maani; Böckler, Dittmar; Katus, Hugo A; Gleissner, Christian A

    2011-01-01

    A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has hardly been explored. Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess cellular source of IL-17A expression and lesion morphology. Carotid plaques from patients with ischemic symptoms were characterized by a highly activated inflammatory milieu including accumulation of T cells (p = 0.04) and expression of IL-6 and VCAM1 (p = 0.02, 0.01). Expression of IL-17A and its positive regulators IL-21 and IL-23 was present in atherosclerotic lesions, significantly upregulated in atheromas of symptomatic patients (p = 0.005, 0.004, 0.03), and expression of IL-17A and IL-21 showed a strong correlation (p = 0.002, r = 0.52). The cellular sources of lesional IL-17A expression are T cells, macrophages, B cells and plasma cells. Vulnerable/ruptured (complicated) plaques were significantly associated with IL-17A expression levels (p = 0.003). In addition, IL-17A showed a marked negative correlation with the potent anti-inflammatory/atheroprotective cytokine IL-10 (p = 0.0006, r = -0.46). Furthermore, treatment with a HMG-CoA reductase inhibitor or acetylsalicylic acid showed reduced levels of IL-21, IL-23 and VCAM1 (all p < 0.05), but did not influence IL-17A. The association of IL-17A with ischemic symptoms and vulnerable plaque characteristics suggests that the pro-inflammatory cytokine IL-17A may contribute to atherosclerosis und plaque instability. PMID:21116822

  7. Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.

    PubMed

    Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A; Janssen, Paulus M L; Martin, Paul T

    2015-10-01

    Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. PMID:26435413

  8. Long-Term Exposure to Concentrated Ambient PM2.5 Increases Mouse Blood Pressure through Abnormal Activation of the Sympathetic Nervous System: A Role for Hypothalamic Inflammation

    PubMed Central

    Xu, Xiaohua; Bai, Yuntao; Zhong, Jixin; Chen, Minjie; Liang, Yijia; Zhao, Jinzhuo; Liu, Dongyao; Morishita, Masako; Sun, Qinghua; Spino, Catherine; Brook, Robert D.; Harkema, Jack R.; Rajagopalan, Sanjay

    2013-01-01

    Background: Exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) increases blood pressure (BP) in humans and animal models. Abnormal activation of the sympathetic nervous system may have a role in the acute BP response to PM2.5 exposure. The mechanisms responsible for sympathetic nervous system activation and its role in chronic sustenance of hypertension in response to PM2.5 exposure are currently unknown. Objectives: We investigated whether central nervous system inflammation may be implicated in chronic PM2.5 exposure-induced increases in BP and sympathetic nervous system activation. Methods: C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAPs) for 6 months, and we analyzed BP using radioactive telemetric transmitters. We assessed sympathetic tone by measuring low-frequency BP variability (LF-BPV) and urinary norepinephrine excretion. We also tested the effects of acute pharmacologic inhibitors of the sympathetic nervous system and parasympathetic nervous system. Results: Long-term CAPs exposure significantly increased basal BP, paralleled by increases in LF-BPV and urinary norepinephrine excretion. The increased basal BP was attenuated by the centrally acting α2a agonist guanfacine, suggesting a role of increased sympathetic tone in CAPs exposure–induced hypertension. The increase in sympathetic tone was accompanied by an inflammatory response in the arcuate nucleus of the hypothalamus, evidenced by increased expression of pro-inflammatory genes and inhibitor kappaB kinase (IKK)/nuclear factor–kappaB (NF-κB) pathway activation. Conclusion: Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation. Citation: Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, Zhao J, Liu D, Morishita M, Sun Q, Spino C, Brook RD, Harkema JR, Rajagopalan S. 2014. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic

  9. A Novel Combinatorial Therapy With Pulp Stem Cells and Granulocyte Colony-Stimulating Factor for Total Pulp Regeneration

    PubMed Central

    Iohara, Koichiro; Murakami, Masashi; Takeuchi, Norio; Osako, Yohei; Ito, Masataka; Ishizaka, Ryo; Utunomiya, Shinji; Nakamura, Hiroshi; Matsushita, Kenji

    2013-01-01

    Treatment of deep caries with pulpitis is a major challenge in dentistry. Stem cell therapy represents a potential strategy to regenerate the dentin-pulp complex, enabling conservation and restoration of teeth. The objective of this study was to assess the efficacy and safety of pulp stem cell transplantation as a prelude for the impending clinical trials. Clinical-grade pulp stem cells were isolated and expanded according to good manufacturing practice conditions. The absence of contamination, abnormalities/aberrations in karyotype, and tumor formation after transplantation in an immunodeficient mouse ensured excellent quality control. After autologous transplantation of pulp stem cells with granulocyte-colony stimulating factor (G-CSF) in a dog pulpectomized tooth, regenerated pulp tissue including vasculature and innervation completely filled in the root canal, and regenerated dentin was formed in the coronal part and prevented microleakage up to day 180. Transplantation of pulp stem cells with G-CSF yielded a significantly larger amount of regenerated dentin-pulp complex compared with transplantation of G-CSF or stem cells alone. Also noteworthy was the reduction in the number of inflammatory cells and apoptotic cells and the significant increase in neurite outgrowth compared with results without G-CSF. The transplanted stem cells expressed angiogenic/neurotrophic factors. It is significant that G-CSF together with conditioned medium of pulp stem cells stimulated cell migration and neurite outgrowth, prevented cell death, and promoted immunosuppression in vitro. Furthermore, there was no evidence of toxicity or adverse events. In conclusion, the combinatorial trophic effects of pulp stem cells and G-CSF are of immediate utility for pulp/dentin regeneration, demonstrating the prerequisites of safety and efficacy critical for clinical applications. PMID:23761108

  10. The pulp capping procedure in primary teeth "revisited".

    PubMed

    Kopel, H M

    1997-01-01

    The purpose of this review is to "revisit" an earlier paper (1992) on the subject of direct pulp capping in primary teeth and bring some new considerations for the procedure by the use of dentin bonding adhesives. It has come to be recognized that the customary employment of calcium hydroxide for this therapy has some shortcomings that reduce the prognosis for a favorable outcome. For at least a decade, many investigations have found that postoperative sensitivity, thermal stimuli, pulp inflammation and pathosis can be attributed not to the composition of various dental materials and their insertion techniques, but to microleakage with subsequent bacterial invasion at the enamel/restoration and the dentin/pulp interfaces. It is imperative, as pointed out, that there be an impervious resinous bond between the dentin and the dentinopulpal complex which can be achieved by the use of dentinal adhesive agents to eliminate microleakage outward movement of pulpal fluids. Various steps in the bonding technique for the treatment of deep dentin caries and/or a pulp exposure has raised some concerns for their effect on the pulp. This review discusses these concerns, which can lead to the conclusion that the use of dentinal bonding adhesives is a safe and biologically feasible procedure, whether it be in permanent or primary teeth. PMID:9391709

  11. Carrageenan Inhibits Insulin Signaling through GRB10-mediated Decrease in Tyr(P)-IRS1 and through Inflammation-induced Increase in Ser(P)307-IRS1

    PubMed Central

    Bhattacharyya, Sumit; Feferman, Leo; Tobacman, Joanne K.

    2015-01-01

    Inflammation induced by exposure to the common food additive carrageenan leads to insulin resistance by increase in Ser(P)307-insulin receptor substrate 1 (IRS1) and subsequent decline in the insulin-stimulated increase in Ser(P)473-AKT. Inhibition of carrageenan-induced inflammation reversed the increase in Ser(P)307-IRS1 but did not completely reverse the carrageenan-induced decline in Ser(P)473-AKT. To identify the additional mechanism responsible for the decrease in Ser(P)473-AKT, studies were performed in human HepG2 cells and in C57BL/6J mice. Following carrageenan, expression of GRB10 (growth factor receptor-bound 10 protein), an adaptor protein that binds to the insulin receptor and inhibits insulin signaling, increased significantly. GRB10 silencing blocked the carrageenan-induced reduction of the insulin-stimulated increase in Tyr(P)-IRS1 and partially reversed the decline in Ser(P)473-AKT. The combination of GRB10 silencing with BCL10 silencing and the reactive oxygen species inhibitor Tempol completely reversed the decline in Ser(P)473-AKT. After carrageenan, GRB10 promoter activity was enhanced because of activation by GATA2. A direct correlation between Ser(P)473-AKT and Ser(P)401-GATA2 was evident, and inhibition of AKT phosphorylation by the PI3K inhibitor LY294002 blocked Ser401-GATA2 phosphorylation and the increase in GRB10 expression. Studies indicated that carrageenan inhibited insulin signaling by two mechanisms: through the inflammation-mediated increase in Ser(P)307-IRS1, a negative regulator of insulin signaling, and through a transcriptional mechanism leading to increase in GRB10 expression and GRB10-inhibition of Tyr(P)-IRS1, a positive regulator of insulin signaling. These mechanisms converge to inhibit the insulin-induced increase in Ser(P)473-AKT. They provide internal feedback, mediated by Ser(P)473-AKT, Ser(P)401-GATA2, and nuclear GATA2, which links the opposing effects of serine and tyrosine phosphorylations of IRS1 and can

  12. Increasing the Vegetable Intake Dose Is Associated with a Rise in Plasma Carotenoids without Modifying Oxidative Stress or Inflammation in Overweight or Obese Postmenopausal Women123

    PubMed Central

    Crane, Tracy E.; Kubota, Chieri; West, Julie L.; Kroggel, Mark A.; Wertheim, Betsy C.; Thomson, Cynthia A.

    2011-01-01

    The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women. PMID:21865569

  13. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b)...

  14. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b)...

  15. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b)...

  16. Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse

    PubMed Central

    Gao, Helen G. L.; Fisher, Paul W.; Lambi, Alex G.; Wade, Christine K.; Barr-Gillespie, Ann E.; Popoff, Steven N.; Barbe, Mary F.

    2013-01-01

    We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed. PMID:24015193

  17. Retroperitoneal inflammation

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001255.htm Retroperitoneal inflammation To use the sharing features on this page, please enable JavaScript. Retroperitoneal inflammation is swelling that occurs in the retroperitoneal space. ...

  18. Alkaline polyol pulping and enzymatic hydrolysis of hardwood: effect of pulping severity and pulp composition on cellulase activity and overall sugar yield.

    PubMed

    Hundt, Martin; Schnitzlein, Klaus; Schnitzlein, Michael G

    2013-05-01

    The saccharification of beech wood using alkaline polyol pulping (AlkaPolP) and enzymatic hydrolysis was investigated. It will be demonstrated that the AlkaPolP process yields high quality pulps which can easily be hydrolyzed by cellulases. In order to find optimum reaction conditions chips of Fagus sylvatica were pretreated by alkaline glycerol at temperatures between 190 and 230 °C for 15, 20, and 25 min. The impacts of temperature and time were expressed using a severity factor R0. The dependencies of the conversion during enzymatic hydrolysis on severity, pulp yield, delignification and pulp composition are shown. In further experiments it was investigated if the sugar yields can be increased by the application of ultrasound or surfactants before enzyme addition. Up to 95% of the initial cellulose in wood were converted into glucose using cellulases from Trichoderma reesei and β-glucosidase from Aspergillus niger. PMID:23570715

  19. Considerations for the direct pulp capping procedure in primary teeth: a review of the literature.

    PubMed

    Kopel, H M

    1992-01-01

    In reviewing the various studies concerning the direct pulp capping procedure in primary teeth, using rigid criteria for case selection and procedure appears to insure a significant amount of success. It is acknowledged that vital primary pulp tissue is capable of healing without resorting to complete pulpectomy, although statistically direct pulp capping has been found to be less successful in primary teeth than indirect pulp therapy or coronal amputation (pulpotomy). To achieve success for direct pulp capping in primary teeth, the considerations involve: selecting teeth with minimal or no clinical signs of pulpal inflammation; or pretreating the carious tooth with a sedative restoration before excavating the caries; disinfecting the cavity floor; enlarging the actual exposure, and flushing out dentinal debris with mild solutions; controlling bleeding by not allowing a clot to form; placing a hard-set, CaOH material over the exposure, followed by a fast-setting, zinc oxide-eugenol cement to achieve a hermetic seal; and lastly, placing a stainless steel crown to minimize microleakage and prevent a fractured or defective restoration. These procedural steps can hardly ensure complete success in direct pulp capping of a primary tooth; but, based on the many cited investigations in this review, a significant amount of success can be expected without resorting more frequently to invasive techniques. Surely the evidence presented leading to the feasibility of direct pulp capping in primary teeth merits further investigations, before dogmatically rejecting this procedure of pulp therapy. PMID:1583199

  20. One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients

    PubMed Central

    Ballesteros, Martha Nydia; Valenzuela, Fabrizio; Robles, Alma E.; Artalejo, Elizabeth; Aguilar, David; Andersen, Catherine J.; Valdez, Herlindo; Fernandez, Maria Luz

    2015-01-01

    There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35–65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation. PMID:25970149

  1. Increased microRNA-155 and decreased microRNA-146a may promote ocular inflammation and proliferation in Graves' ophthalmopathy.

    PubMed

    Li, Kaijun; Du, Yi; Jiang, Ben-Li; He, Jian-Feng

    2014-01-01

    Graves' ophthalmopathy is an inflammatory autoimmune disease of the orbit, characterized by inflammation and proliferation of the orbital tissue caused by CD4+T cells and orbital fibroblasts. Despite recent substantial findings regarding its cellular and molecular foundations, the pathogenesis of Graves' ophthalmopathy remains unclear. Accumulating data suggest that microRNAs play important roles in the pathophysiology of autoimmunity and proliferation. Specifically, microRNA-155 (miR-155) can promote autoimmune inflammation by enhancing inflammatory T cell development. In contrast to miR-155, microRNA-146a (miR-146a) can inhibit the immune response by suppressing T cell activation. Furthermore, miR-155 and miR-146a are involved in cell proliferation, differentiation, and many other life processes. Thus, miR-155 and miR-146a, with opposite impacts on inflammatory responses carried out by T lymphocytes, appear to have multiple targets in the pathogenesis of Graves' ophthalmopathy. Our previous work showed that the expression of miR-146a was significantly decreased in peripheral blood mononuclear cells from Graves' ophthalmopathy patients compared with normal subjects. Accordingly, we proposed that the expression of miR-155 increased and the expression of miR-146a decreased in the target cells (CD4+T cells and orbital fibroblasts), thus promoting ocular inflammation and proliferation in Graves' ophthalmopathy. The proposed hypothesis warrants further investigation of the function of the differentially expressed microRNAs, which may shed new light on the pathogenesis of Graves' ophthalmopathy and lead to new strategies for its management. PMID:24743332

  2. One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients.

    PubMed

    Ballesteros, Martha Nydia; Valenzuela, Fabrizio; Robles, Alma E; Artalejo, Elizabeth; Aguilar, David; Andersen, Catherine J; Valdez, Herlindo; Fernandez, Maria Luz

    2015-05-01

    There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35-65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation. PMID:25970149

  3. Characterisation of mechanical pulp fines from alkaline peroxide pulping of EFB

    NASA Astrophysics Data System (ADS)

    Kamaludin, Nurul Hasanah; Ghazali, Arniza; Daud, Wan Rosli Wan

    2012-09-01

    EFB (empty fruit bunch) was subjected to alkaline peroxide pulping for generation of fibrous mass as raw material for the making of pulp-based products. During refining, co-produced fines were collected by fractionation on square-mesh screens of 200-, 250-, 300- and 400- mesh sizes, placed at the refining discharge by order of increasing mesh. Each set of the produced paper was incorporated with 12% fines for microscopic analysis. It appears that sheared vessel elements and fibrils were predominant and they make up the mass rendering collapsibility of cell wall for good product formation. The study acknowledged the form of fines functioning as natural filler in pulp network and worthy of utilization for reduction of total suspended solid.

  4. Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause, an age-related loss of ovarian hormone production, promotes increased adiposity and associated metabolic pathologies. However, the diet-independent mechanism(s) by which loss of ovarian function promotes increased adipose tissue mass and insulin resistance remain unclear. We investigate...

  5. Agricultural fibres for pulp and paper manufacture in developed countries

    SciTech Connect

    Wong, A.

    1995-11-01

    Agricultural fibres are routinely used for the manufacture of paper products in developing countries. The agriculture (non-wood) pulp industry accounts more than 50% of the national pulp production in China and in India. In contrast, paper manufacturers of the developed countries have relied largely on wood pulp fibres since the 1950`s. During the past 3 decades, the global wood pulp production capacities has expanded substantially. There is a renewed interest to use agriculture-based fibres in place of wood, for the production of pulp and paper in developing countries. The alternative is driven, in part, by the growing shortage of commercial wood supply as caused by the over-cutting of the standing forest and the accelerated re-allocation of forest land for ecological and recreational uses. Although the shortage of wood supply can be alleviated partially by the adoption of higher-yield wood pulping technologies and by the increased use of waste paper. But ultimately, these remedial steps will be inadequate to meet the growing demand for paper products. There are several important factors which affect the use of agricultural fibres for pulp and paper manufacture in developed countries. For some on-purpose fibre crops, continued farm subsidy and repeal of certain sections of the Narcotics Act would be required. Agri-pulp production from agricultural cropping residues appears to be the most practical economic means to supplement the fibre needs of the paper industry. In the social context, agri-pulp implementation in North America would also provide lower taxes that would be accrued from the elimination of substantial annual subsidies to grain farmers from the government.

  6. Wnt5a Promotes Inflammatory Responses via Nuclear Factor κB (NF-κB) and Mitogen-activated Protein Kinase (MAPK) Pathways in Human Dental Pulp Cells*

    PubMed Central

    Zhao, Yuan; Wang, Chen-Lin; Li, Rui-Min; Hui, Tian-Qian; Su, Ying-Ying; Yuan, Quan; Zhou, Xue-Dong; Ye, Ling

    2014-01-01

    Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-α stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-α, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/chemokine production induced by TNF-α. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-α. However, no TNF-α and IL-1β was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-κB-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-α. PMID:24891513

  7. Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging, and lung metastases in patients with breast cancer.

    PubMed

    Morris, Patrick G; Zhou, Xi Kathy; Milne, Ginger L; Goldstein, Daniel; Hawks, Laura C; Dang, Chau T; Modi, Shanu; Fornier, Monica N; Hudis, Clifford A; Dannenberg, Andrew J

    2013-05-01

    Elevated levels of COX-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n = 200), lung metastases (n = 100), and metastases to other sites (n = 100). Patients completed a questionnaire, provided urine, and had measurements of height and weight. Urinary PGE-M was quantified by mass spectrometry. Ever smokers with lung metastasis who had not been exposed to nonsteroidal anti-inflammatory drugs (NSAIDs) had the highest PGE-M levels. PGE-M levels were increased in association with elevated body mass index (BMI; P < 0.001), aging (P < 0.001), pack-year smoking history (P = 0.02), lung metastases (P = 0.02), and recent cytotoxic chemotherapy (P = 0.03). Conversely, use of NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M levels (P < 0.001). On the basis of the current findings, PGE-M is likely to be a useful biomarker for the selection of high-risk subgroups to determine the use of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women. PMID:23531446

  8. Serum IL-12 Is Increased in Mexican Obese Subjects and Associated with Low-Grade Inflammation and Obesity-Related Parameters

    PubMed Central

    Suárez-Álvarez, K.; Solís-Lozano, L.; Leon-Cabrera, S.; González-Chávez, A.; Gómez-Hernández, G.; Quiñones-Álvarez, M. S.; Serralde-Zúñiga, A. E.; Hernández-Ruiz, J.; Ramírez-Velásquez, J.; Galindo-González, F. J.; Zavala-Castillo, J. C.; De León-Nava, M. A.; Robles-Díaz, G.; Escobedo, G.

    2013-01-01

    Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF-α), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF-α (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans. PMID:23533314

  9. In vivo selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion

    PubMed Central

    Deng, Huayun; Zhang, Jishen; Li, Shichang; Wei, Haifeng; Yang, Cheng; Xu, Leqin; Jin, Rongrong; Li, Zhenxi; Zhou, Wang; Ding, JianDong; Chu, Jianjun; Jia, Lianshun; Jia, Qi; Tan, Chengjun; Liu, Mingyao; Xiao, Jianru

    2015-01-01

    We developed a murine spine metastasis model by screening five metastatic non-small cell lung cancer cell lines (PC-9, A549, NCI-H1299, NCI-H460, H2030). A549 cells displayed the highest tendency towards spine metastases. After three rounds of selection in vivo, we isolated a clone named A549L6, which induced spine metastasis in 80% of injected mice. The parameters of the A549L6 cell spinal metastatic mouse models were consistent with clinical spine metastasis features. All the spinal metastatic mice developed symptoms of nerve compression after 40 days. A549L6 cells had increased migration, invasiveness and decreased adhesion compared to the original A549L0 cells. In contrast, there was no significant differences in cell proliferation, apoptosis and sensitivity to chemotherapeutic agents such as cisplatin. Comparative transcriptomic analysis and Real-time PCR analysis showed that expression of signaling molecules regulating several tumor properties including migration (MYL9), metastasis (CEACAM6, VEGFC, CX3CL1, CST1, CCL5, S100A9, IGF1, NOTCH3), adhesion (FN1, CEACAM1) and inflammation (TRAF2, NFκB2 and RelB) were altered in A549L6 cells. We suggest that migration, adhesion and inflammation related genes contribute to spine metastatic capacity. PMID:26090868

  10. Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice.

    PubMed

    Zeng, Huawei; Ishaq, Suzanne L; Zhao, Feng-Qi; Wright, André-Denis G

    2016-09-01

    Consumption of an obesigenic/high-fat diet (HFD) is associated with a high colon cancer risk and may alter the gut microbiota. To test the hypothesis that long-term high-fat (HF) feeding accelerates inflammatory process and changes gut microbiome composition, C57BL/6 mice were fed HFD (45% energy) or a low-fat (LF) diet (10% energy) for 36 weeks. At the end of the study, body weights in the HF group were 35% greater than those in the LF group. These changes were associated with dramatic increases in body fat composition, inflammatory cell infiltration, inducible nitric oxide synthase protein concentration and cell proliferation marker (Ki67) in ileum and colon. Similarly, β-catenin expression was increased in colon (but not ileum). Consistent with gut inflammation phenotype, we also found that plasma leptin, interleukin 6 and tumor necrosis factor α concentrations were also elevated in mice fed the HFD, indicative of chronic inflammation. Fecal DNA was extracted and the V1-V3 hypervariable region of the microbial 16S rRNA gene was amplified using primers suitable for 454 pyrosequencing. Compared to the LF group, the HF group had high proportions of bacteria from the family Lachnospiraceae/Streptococcaceae, which is known to be involved in the development of metabolic disorders, diabetes and colon cancer. Taken together, our data demonstrate, for the first time, that long-term HF consumption not only increases inflammatory status but also accompanies an increase of colonic β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of C57BL/6 mice. PMID:27362974

  11. Binding and desulfurization characteristics of pulp black liquor in biocoalbriquettes.

    PubMed

    Kim, Heejoon; Lu, Guoqing; Li, Tianji; Sadakata, Masayoshi

    2002-04-01

    To control pollutant emissions from coal combustion in some developing countries, biocoalbriquette, an artificially produced solid fuel, was developed. Both the breaking strength and production costs of the biocoalbriquette have become essentially the most important factors in popularizing it in these countries. To increase the breaking strength and decrease the production costs, it is proposed in this study to use pulp black liquor, a byproduct from the pulp production industry, as a binder. The influences of pulp black liquor on the briquetting and combustion characteristics were investigated. Furthermore, the desulfurization characteristics of pulp black liquor were also evaluated through combustion experiments. The study results show that the briquetting pressure has a limited effect on the breaking strength. An increase in the briquetting pressure yields greater breaking strength of up to the 50 MPa. Above 50 MPa, the breaking strength changes very little with the briquetting pressure. The use of pulp black liquor has had a greater effect on increasing the breaking strength than on changing the briquetting pressure and also on improving the combustion characteristics of the biocoalbriquette. On the other hand, pulp black liquor has some desulfurization capabilities. When used as a binder, it not only increases the breaking strength and decreases the necessary briquetting pressure, but it also improves some characteristics of the combustion and reduces the pollutants emission. PMID:11999073

  12. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    EPA Science Inventory

    Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

  13. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Chronic infection by Helicobacter pylori (H. pylori) is the most common cause of gastric cancer. H. pylori induced oxidative stress and zinc deficiency results in increased sensitivity to the stress. In Ecuador, the prevalence of gastric cancer and zinc deficiency is high. We hypothesize...

  14. Developmental Exposure of Mice to Dioxin Promotes Transgenerational Testicular Inflammation and an Increased Risk of Preterm Birth in Unexposed Mating Partners

    PubMed Central

    Yeoman, Kallie B.; Archibong, Anthony; Arosh, Joe A.; Osteen, Kevin G.

    2014-01-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Using a mouse model, we previously found that adult female mice exposed in utero to TCDD (F1 generation) as well as multiple subsequent generations (F2-F4) exhibited reduced fertility and an increased incidence of spontaneous preterm birth. Additional studies revealed that male F1 mice with a similar in utero/developmental TCDD exposure also exhibited diminished fertility and conferred an increased risk of preterm birth to their unexposed mating partners. Herein, we extend these previous observations, reporting that reduced fertility in male F1 mice is linked to testicular inflammation which coincides with apoptosis of developing spermatocytes, sub-fertility and an increased risk of preterm birth in their unexposed mating partners. Significantly, in the absence of additional toxicant exposure, testicular inflammation and reduced fertility persisted in F2 and F3 males and their control mating partners also frequently exhibited spontaneous preterm birth. Although a steady, global decline in male fertility has been noted over the last few decades, the reasons for these changes have not been firmly established. Likewise, the PTB rate in the U.S. and other countries has paralleled industrial development, suggesting a possible relationship between environmental toxicant exposure and adverse pregnancy outcomes. Most current clinical strategies to prevent preterm birth are focused solely on the mother and have yielded limited benefits. In contrast, our studies strongly suggest that the preconception testicular health of the father is a critical determinant of pregnancy outcomes in mice. Future clinical studies should examine the potential contribution of the male to gestation length in women and whether efforts to reduce the incidence of preterm birth should be initiated in both parents prior to pregnancy. PMID:25127480

  15. Increased Tenascin C And Toll-Like Receptor 4 Levels in Visceral Adipose Tissue as a Link between Inflammation and Extracellular Matrix Remodeling in Obesity

    PubMed Central

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J.; Salvador, Javier

    2012-01-01

    Context: Obesity is associated with an altered inflammatory and extracellular matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with proinflammatory effects. Objective: We aimed to explore the expression levels of TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. We also analyzed the effect of the stimulation with TNF-α and lipopolysaccharide (LPS) on both SVFC and adipocytes. Patients and Methods: Samples obtained from 75 subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and SVFC. In addition, Tnc expression was measured in two mice models of obesity. Results: We show, for the first time, that VAT expression levels of TNC are increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) as well as in obese patients with nonalcoholic steatohepatitis (P < 0.01). Furthermore, expression levels of Tnc in epididymal adipose tissue from two different mice models of obesity were significantly increased (P < 0.01). TNC and TLR4 were mainly expressed by SVFC, and its expression was significantly enhanced (P < 0.01) by TNF-α treatment. LPS treatment also increased mRNA levels of TNC. Moreover, the addition of exogenous TNC induced (P < 0.05) TLR4 and CCL2 mRNA expression in human adipocyte cultures. Conclusions: These findings indicate that TNC is involved in the etiopathology of obesity via visceral adipose tissue inflammation representing a link with ECM remodeling. PMID:22851489

  16. Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation

    PubMed Central

    Ngo, Ha Thi; Hetland, Ragna Bogen; Nygaard, Unni Cecilie; Steffensen, Inger-Lise

    2015-01-01

    We have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-ApcMin/+ X C57BL/6J-Lepob/+ mice. Obesity was induced by the obese (ob) mutation in the lep gene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by the multiple intestinal neoplasia (Min) mutation in the adenomatous polyposis coli (Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (in ApcMin/+ mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFα levels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice. PMID:26347815

  17. [Orbital inflammation].

    PubMed

    Mouriaux, F; Coffin-Pichonnet, S; Robert, P-Y; Abad, S; Martin-Silva, N

    2014-12-01

    Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy. PMID:25455557

  18. Diminished acute phase response and increased hepatic inflammation of aged rats in response to intraperitoneal injection of lipopolysaccharide.

    PubMed

    Gomez, Christian R; Acuña-Castillo, Claudio; Pérez, Claudio; Leiva-Salcedo, Elías; Riquelme, Denise M; Ordenes, Gamaliel; Oshima, Kiyoko; Aravena, Mauricio; Pérez, Viviana I; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2008-12-01

    Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult. PMID:19126842

  19. Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice.

    PubMed

    Mardare, Cornelia; Krüger, Karsten; Liebisch, Gerhard; Seimetz, Michael; Couturier, Aline; Ringseis, Robert; Wilhelm, Jochen; Weissmann, Norbert; Eder, Klaus; Mooren, Frank-Christoph

    2016-01-01

    The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST) or a high fat diet (HFD) and subjected to regular endurance training (ET) or resistance training (RT). After 10 weeks body weight, glucose tolerance, fatty acids (FAs), circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p < 0.05). An increase of plasma FA, ceramides, and inflammatory mediators in adipose tissue and serum was found (p < 0.05). Both endurance and resistance training decreased body weight (p < 0.05) and reduced serum ceramides (p < 0.005). While RT attenuated the increase of NLRP-3 (RT) expression in adipose tissue, ET was effective in reducing TNF-α and IL-18 expression. Furthermore, ET reduced levels of MIP-1γ, while RT decreased levels of IL-18, MIP-1γ, Timp-1, and CD40 in serum (p < 0.001), respectively. Although both exercise regimes improved glucose tolerance (p < 0.001), ET was more effective than RT. These results suggest that exercise improves HFD-induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines. PMID:26788518

  20. Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia.

    PubMed

    Choy, Fong Chan; Klarić, Thomas S; Leong, Wai Khay; Koblar, Simon A; Lewis, Martin D

    2016-08-01

    Stroke is the second leading cause of death and the most frequent cause of adult disability. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an activity-dependent transcription factor whose expression is induced in various brain insults, including cerebral ischaemia. Although previous studies have demonstrated that Npas4 plays a critical role in protecting neurons against neurodegenerative insults, the neuroprotective effect of Npas4 in response to ischaemic brain injury remains unknown. In this study, we used a loss-of-function approach to examine the neuroprotective potential of Npas4 in the context of ischaemic damage. Using oxygen and glucose deprivation, we demonstrated that the knockdown of Npas4 in mouse cortical neurons resulted in increased susceptibility to cell death. The protective effect of Npas4 was further investigated in vivo using a photochemically-induced stroke model in mice. We found a significantly larger lesion size and increased neurodegeneration in Npas4 knockout mice as compared to wild-type mice. Moreover, we also showed that ablation of Npas4 caused an increase in activated astrocytes and microglia, pro-inflammatory cytokines interleukin-6 and tumour necrosis factor alpha levels and a switch from apoptotic to necrotic cell death. Taken together, these data suggest that Npas4 plays a neuroprotective role in ischaemic stroke by limiting progressive neurodegeneration and neuroinflammation. PMID:26661154

  1. Effects of laccase-natural mediator systems on kenaf pulp.

    PubMed

    Andreu, Glòria; Vidal, Teresa

    2011-05-01

    This paper reports the first application of laccase-mediator systems (LMS) to kenaf pulp. Five natural phenolic compounds (acetosyringone, syringaldehyde, p-coumaric acid, vanillin and acetovanillone) were used as mediators in combination with laccase in an L stage in order to elucidate their effect on delignification. After LMS treatment, pulp samples were subjected to two alkaline treatments (an E or P stage). The results obtained were compared with those provided by the laccase-1-hydroxybenzotriazole (HBT) system. All natural mediators increased kappa number, decreased brightness and changed optical properties of the pulp after the L stage, suggesting that natural mediators tend to couple to fibers during a laccase-mediator treatment. The greatest delignification and bleaching effects after the P stage were obtained with syringaldehyde and acetosyringone, providing an effective means for delignifying kenaf, whereas those based on the other three could be used to functionalize kenaf with a view to obtaining pulp with novel properties. PMID:21444198

  2. Effects of increase in fish oil intake on intestinal eicosanoids and inflammation in a mouse model of colitis

    PubMed Central

    2013-01-01

    Background Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory diseases affecting about 1% of western populations. New eating behaviors might contribute to the global emergence of IBD. Although the immunoregulatory effects of omega-3 fatty acids have been well characterized in vitro, their role in IBD is controversial. Methods The aim of this study was to assess the impact of increased fish oil intake on colonic gene expression, eicosanoid metabolism and development of colitis in a mouse model of IBD. Rag-2 deficient mice were fed fish oil (FO) enriched in omega-3 fatty acids i.e. EPA and DHA or control diet for 4 weeks before colitis induction by adoptive transfer of naïve T cells and maintained in the same diet for 4 additional weeks. Onset of colitis was monitored by colonoscopy and further confirmed by immunological examinations. Whole genome expression profiling was made and eicosanoids were measured by HPLC-MS/MS in colonic samples. Results A significant reduction of colonic proinflammatory eicosanoids in FO fed mice compared to control was observed. However, neither alteration of colonic gene expression signature nor reduction in IBD scores was observed under FO diet. Conclusion Thus, increased intake of dietary FO did not prevent experimental colitis. PMID:23725086

  3. High-Fat Diet Reduces the Formation of Butyrate, but Increases Succinate, Inflammation, Liver Fat and Cholesterol in Rats, while Dietary Fibre Counteracts These Effects

    PubMed Central

    Jakobsdottir, Greta; Xu, Jie; Molin, Göran; Ahrné, Siv; Nyman, Margareta

    2013-01-01

    Introduction Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. Objective To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. Material and Methods Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. Results and Discussion Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet. PMID:24236183

  4. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b) Classification... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pulp tester. 872.1720 Section 872.1720 Food...

  5. Cyclic GMP phosphodiesterase activity role in normal and inflamed human dental pulp.

    PubMed

    Spoto, G; Ferrante, M; D'Intino, M; Rega, L; Dolci, M; Trentini, P; Ciavarelli, L

    2004-01-01

    Cyclic GMP phosphodiesterase (cGMP PDE) plays an important role in pulp tissues. High levels of cGMP PDE are found in dental pulp cells. In the present study cGMP PDE activity was analyzed in normal healthy human dental pulps, in reversible pulpitis and in irreversible pulpitis. Enzymatic cGMP PDE control values for normal healthy pulps were 4.74+/-0.32 nmol/mg of proteins. In reversible pulpitis the cGMP PDE activity increased almost 3 times. In irreversible pulpitis specimens the values increased 4.5 times compared with the normal healthy pulps activity. The differences between the groups (control vs. reversible pulpitis and vs. irreversible pulpitis) were statistically significant. These results point to a role of cGMP PDE in the initial pulp response after injury. PMID:16857102

  6. Cyclic Amp phosphodiesterase activity in normal and inflamed human dental pulp.

    PubMed

    Spoto, G; Menna, V; Serra, E; Santoleri, F; Perfetti, G; Ciavarelli, L; Trentini, P

    2004-01-01

    Cyclic AMP phosphodiesterase (cAMP PDE) seems to be important in pulp tissues. High levels of cAMP PDE have been demonstrated to be in dental pulp cells. In the present study cAMP PDE activity was analyzed in normal healthy human dental pulps, in reversible pulpitis and in irreversible pulpitis. Enzymatic cAMP PDE control values for normal healthy pulps were 12.14 +/- 3.74 nmols/mg of proteins. In reversible pulpitis the cAMP PDE activity increased almost 2.5 times. In irreversible pulpitis specimens the values increased 4.5 times compared with normal healthy pulps activity. The differences between the groups (control vs. reversible pulpitis and vs. irreversible pulpitis) were statistically significant. These results could point to a role of cAMP PDE in the initial pulp response after injury. PMID:16857100

  7. Avoiding total reduced sulfur (TRS) emissions from sodium sulfite pulping recovery processes

    SciTech Connect

    Norman, J.C.; Sell, N.J. ); Ciriacks, J.C. )

    1990-06-01

    This paper reports that one of the current trends in paper-making with cellulose pulping is the use of high-yield processes. With yields greater than 65%, these processes include mechanical pulps (groundwood and thermomechanical pulps or TMP), and semichemical types (chemi-TMP or CTMP). Groundwood and TMP make up about 10% of North American pulp production. Semichemical pulp makes up about 7% and is mostly used for corrugating medium. High-yield pulping for linerboard, particularly using the alkaline sulfite process, is also likely to be used in the future. High-yield pulping is based primarily on the sulfite process using mostly sodium-based chemicals. A disadvantage of this process is the unavailability of a recovery system for the inorganic pulping chemicals. Generally, mills have not accepted any particular recovery system for this process. For this and other reasons, sulfite processes constitute only 3-4% of the total North American pulp production. If high-yield processes continue to increase in popularity, a sodium sulfite chemical recovery system will be needed. A number of chemical recovery systems have been developed in the past 30 years for sodium-based sulfite pulping processes, with most of the mills successfully using this process located in Scandinavia.

  8. Innervation of human tooth pulp in relation to caries and dentition type.

    PubMed

    Rodd, H D; Boissonade, F M

    2001-01-01

    The neural status of carious teeth, particularly those associated with a painful pulpitis, is largely unknown. This study sought to determine differences in the innervation density of human primary and permanent teeth and whether caries or painful pulpitis was associated with anatomical changes in pulpal innervation. Coronal pulps were removed from 120 primary and permanent molars with a known pain history. Teeth were categorized as intact, moderately carious, or grossly carious. Using indirect immunofluorescence, we labeled sections for the general neuronal marker, protein gene product 9.5. Using image analysis, we found permanent teeth to be significantly more densely innervated than primary teeth. While there was no significant correlation with reported pain experience, neural density in both dentitions increased significantly with caries. Analysis of these data suggests that caries-induced changes in neural density may be functionally more important in the regulation of pulpal inflammation and healing than in the processing and perception of dental pain. PMID:11269734

  9. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation

    PubMed Central

    Forsyth, Christopher B.; Shaikh, Maliha; Cavanaugh, Kate; Tang, Yueming; Vitaterna, Martha Hotz; Song, Shiwen

    2013-01-01

    The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases – many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness) in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state. PMID:23825629

  10. Vaccenic acid suppresses intestinal inflammation by increasing anandamide and related N-acylethanolamines in the JCR:LA-cp rat.

    PubMed

    Jacome-Sosa, Miriam; Vacca, Claudia; Mangat, Rabban; Diane, Abdoulaye; Nelson, Randy C; Reaney, Martin J; Shen, Jianheng; Curtis, Jonathan M; Vine, Donna F; Field, Catherine J; Igarashi, Miki; Piomelli, Daniele; Banni, Sebastiano; Proctor, Spencer D

    2016-04-01

    Vaccenic acid (VA), the predominant ruminant-derivedtransfat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cprats were assigned to a control diet with or without VA (1% w/w),cis-9,trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2-AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P< 0.001), but did not change AA in tissue PLs. There was no additive effect of combining VA+CLA on 2-AG relative to VA alone (P> 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P< 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFα and interleukin 1β (P< 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine. PMID:26891736

  11. Modification of high-lignin kraft pulps with laccase. Part 2. Xylanase-enhanced strength benefits.

    PubMed

    Chandra, Richard P; Ragauskas, Arthur J

    2005-01-01

    The effects of xylanase pretreatment of high lignin content softwood (SW) kraft pulp on subsequent pulp treatment with laccase in combination with gallic acid were investigated. Although xylanase pretreatment was ineffective in enhancing the laccase-facilitated biografting of gallic acid to kraft fibers, it was beneficial for subsequent treatment with laccase exclusively. Treating pulp fibers with xylanase followed by laccase provided a collective 25% and 46% increase in dry and wet tensile strength properties, respectively. PMID:16080715

  12. Novel Neuroprotective Mechanisms of Memantine: Increase in Neurotrophic Factor Release from Astroglia and Anti-Inflammation by Preventing Microglial Over-Activation

    PubMed Central

    Wu, Hung-Ming; Tzeng, Nian-Sheng; Qian, Li; Wei, Sung-Jen; Hu, Xiaoming; Rawls, Scott M.; Flood, Patrick; Hong, Jau-Shyong; Lu, Ru-band

    2013-01-01

    Memantine provides clinically relevant efficacy in patients with Alzheimer's disease and Parkinson’s diseases. In addition to blockade of N-methyl-D-aspartate receptor on neurons, memantine has neurotrophic and neuroprotective effects in in vivo and in vitro studies, however, the mechanism underlying these effects remains unclear. To address this question, primary midbrain neuron-glia cultures and reconstituted cultures were used, and lipopolysaccharide (LPS), an endotoxin from bacteria, was used to produce inflammation-mediated dopaminegic neuronal death. Here, we show that memantine exerted both potent neurotrophic and neuroprotective effects on dopaminergic neurons in rat neuron-glia cultures. The neurotrophic effect of memantine was glia-dependent, since memantine failed to show any positive effect on dopaminergic neurons in neuron-enriched cultures. More specifically, it appears that astroglia, not microglia, are the source of the memantine-elicited neurotrophic effects through the increased production of GDNF. Mechanistic studies revealed that GDNF upregulaton was associated with histone hyperacetylation by inhibiting the cellular histone deacetylase activity. In addition, memantine also displays neuroprotective effects against LPS-induced dopaminergic neuronal damage through its inhibition of microglia over-activation revealed by both OX-42 immunostaining and by the reduction of pro-inflammatory factors production such as extracelluar superoxide anion, intracellular reactive oxygen species, nitric oxide, prostaglandin E2, and tumor necrosis factor-α. These results suggest that memantine therapy for neurodegenerative diseases acts in part through alternative novel mechanisms by reducing microglia-associated inflammation and stimulating the release of neurotrophic factors from astroglia. PMID:19536110

  13. Tissue Engineering Considerations in Dental Pulp Regeneration

    PubMed Central

    Nosrat, Ali; Kim, Jong Ryul; Verma, Prashant; S. Chand, Priya

    2014-01-01

    Regenerative endodontic procedure is introduced as a biologically based treatment for immature teeth with pulp necrosis. Successful clinical and radiographic outcomes following regenerative procedures have been reported in landmark case reports. Retrospective studies have shown that this conservative treatment allows for continued root development and increases success and survival rate of the treated teeth compared to other treatment options. Although the goal of treatment is regeneration of a functional pulp tissue, histological analyses show a different outcome. Developing predictable protocols would require the use of key elements for tissue engineering: stem cells, bioactive scaffolds, and growth factors. In this study we will review the evidence based steps and outcomes of regenerative endodontics. PMID:24396373

  14. Durability of pulp fiber-cement composites

    NASA Astrophysics Data System (ADS)

    Mohr, Benjamin J.

    Wood pulp fibers are a unique reinforcing material as they are non-hazardous, renewable, and readily available at relatively low cost compared to other commercially available fibers. Today, pulp fiber-cement composites can be found in products such as extruded non-pressure pipes and non-structural building materials, mainly thin-sheet products. Although natural fibers have been used historically to reinforce various building materials, little scientific effort has been devoted to the examination of natural fibers to reinforce engineering materials until recently. The need for this type of fundamental research has been emphasized by widespread awareness of moisture-related failures of some engineered materials; these failures have led to the filing of national- and state-level class action lawsuits against several manufacturers. Thus, if pulp fiber-cement composites are to be used for exterior structural applications, the effects of cyclical wet/dry (rain/heat) exposure on performance must be known. Pulp fiber-cement composites have been tested in flexure to examine the progression of strength and toughness degradation. Based on scanning electron microscopy (SEM), environmental scanning electron microscopy (ESEM), energy dispersive spectroscopy (EDS), a three-part model describing the mechanisms of progressive degradation has been proposed: (1) initial fiber-cement/fiber interlayer debonding, (2) reprecipitation of crystalline and amorphous ettringite within the void space at the former fiber-cement interface, and (3) fiber embrittlement due to reprecipitation of calcium hydroxide filling the spaces within the fiber cell wall structure. Finally, as a means to mitigate kraft pulp fiber-cement composite degradation, the effects of partial portland cement replacement with various supplementary cementitious materials (SCMs) has been investigated for their effect on mitigating kraft pulp fiber-cement composite mechanical property degradation (i.e., strength and toughness

  15. Canola straw chemimechanical pulping for pulp and paper production.

    PubMed

    Hosseinpour, Reza; Fatehi, Pedram; Latibari, Ahmad Jahan; Ni, Yonghao; Javad Sepiddehdam, S

    2010-06-01

    Non-wood is one of the most important raw materials for pulp and paper production in several countries due to its abundance and cost-effectiveness. However, the pulping and papermaking characteristics of canola straw have rarely been investigated. The objective of this work was to determine the potential application of canola straw in the chemimechanical pulping (CMP) process. At first, the chemical composition and characteristics of canola straw were assessed and compared with those of other non-woods. Then, the CMP pulping of canola straw was conducted using different dosages of sodium sulfite and sodium hydroxide. The results showed that, by applying a mild chemical pretreatment, i.e., 4-12% (wt.) NaOH and 8-12% (wt.) Na(2)SO(3), in the CMP pulping of canola straw, the pulp brightness reached almost 40%ISO, and the strength properties were comparable to those of bagasse CMP and of wheat straw CMP. The impact of post-refining on the properties of canola straw CMP was also discussed in this work. PMID:20144862

  16. Factors affecting the corrosivity of pulping liquors

    NASA Astrophysics Data System (ADS)

    Hazlewood, Patrick Evan

    Increased equipment failures and the resultant increase in unplanned downtime as the result of process optimization programs continue to plague pulp mills. The failures are a result of a lack of understanding of corrosion in the different pulping liquors, specifically the parameters responsible for its adjustment such as the role and identification of inorganic and organic species. The current work investigates the role of inorganic species, namely sodium hydroxide and sodium sulfide, on liquor corrosivity at a range of process conditions beyond those currently experienced in literature. The role of sulfur species, in the activation of corrosion and the ability of hydroxide to passivate carbon steel A516-Gr70, is evaluated with gravimetric and electrochemical methods. The impact of wood chip weathering on process corrosion was also evaluated. Results were used to identify black liquor components, depending on the wood species, which play a significant role in the activation and inhibition of corrosion for carbon steel A516-Gr70 process equipment. Further, the effect of black liquor oxidation on liquor corrosivity was evaluated. Corrosion and stress corrosion cracking performance of selected materials provided information on classes of materials that may be reliably used in aggressive pulping environments.

  17. Dual function of Ccr5 during Langat virus encephalitis - Reduction of neutrophil-mediated CNS inflammation and increase in T cell-mediated viral clearance

    PubMed Central

    Michlmayr, Daniela; Bardina, Susana V.; Rodriguez, Carlos A.; Pletnev, Alexander G.; Lim, Jean K.

    2016-01-01

    Tick-borne encephalitis virus (TBEV) is a vector-transmitted flavivirus that causes potentially fatal neurological infection. There are thousands of cases reported annually, and despite the availability of an effective vaccine, the incidence of TBEV is increasing worldwide. Importantly, up to thirty percent of affected individuals will develop long-term neurologic sequelae. We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus, Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis when compared to wild type (WT) controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of WT T cells, but not Ccr5-deficient T cells, was able to significantly improve survival outcome in LGTV-infected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr5−/− mice was documented at the late stage of infection. Antibody-mediated depletion of neutrophils in Ccr5−/− mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS when compared to isotype control-treated mice. Ccr5 is crucial in not only directing T cells towards the LGTV-infected brain, but also in suppressing neutrophil-mediated inflammation within the CNS. PMID:27183602

  18. Dual Function of Ccr5 during Langat Virus Encephalitis: Reduction in Neutrophil-Mediated Central Nervous System Inflammation and Increase in T Cell-Mediated Viral Clearance.

    PubMed

    Michlmayr, Daniela; Bardina, Susana V; Rodriguez, Carlos A; Pletnev, Alexander G; Lim, Jean K

    2016-06-01

    Tick-borne encephalitis virus (TBEV) is a vector-transmitted flavivirus that causes potentially fatal neurologic infection. There are thousands of cases reported annually, and despite the availability of an effective vaccine, the incidence of TBEV is increasing worldwide. Importantly, up to 30% of affected individuals develop long-term neurologic sequelae. We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis compared with wild-type controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of wild-type T cells, but not Ccr5-deficient T cells, significantly improved survival outcome in LGTV-infected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr5(-/-) mice was documented at the late stage of infection. Ab-mediated depletion of neutrophils in Ccr5(-/-) mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS compared with isotype control-treated mice. Ccr5 is crucial in directing T cells toward the LGTV-infected brain, as well as in suppressing neutrophil-mediated inflammation within the CNS. PMID:27183602

  19. Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes

    PubMed Central

    Heemskerk, Mattijs M.; Giera, Martin; el Bouazzaoui, Fatiha; Lips, Mirjam A.; Pijl, Hanno; Willems van Dijk, Ko; van Harmelen, Vanessa

    2015-01-01

    Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT. PMID:26378572

  20. Depth and activity of carious lesions as indicators for the regenerative potential of dental pulp after intervention.

    PubMed

    Bjørndal, Lars; Demant, Sune; Dabelsteen, Sally

    2014-04-01

    Studies on dental regeneration involving interventions for pulp therapy such as regeneration and revascularization procedures are promising for the injured tooth; however, a complete replication of the original pulp tissue does not seem to take place. In cases in which we wish to preserve or maintain parts of the pulp during treatment, it is apparent that the effectiveness of healing or biological regeneration is dependent on the degree of inflammation of the pulp tissue. Thus, the control or prevention of a pulp infection is still a major issue for the clinicians. Data indicate that the typical reason for performing endodontic treatment is deep caries. The biological concept of vital pulp therapy associated with deep caries takes the treatment and evaluation of the unexposed as well as the exposed pulp into account. Interestingly, the clinical diagnosis is typically the same. Deep caries with reversible pulpitis may receive differing treatments such as excavation procedures aiming to avoid pulp exposure or more pulp invasive treatments such as pulp capping or pulpotomy. This should not be the case. Consequently, huge treatment variation is noted among clinicians based on the same caries diagnosis. Which treatment should be selected? High-quality trials are needed, and it is important to obtain information on the actual lesion depth and an estimate of the lesion activity before treatment. These may be basic indicators for the regenerative potential of dental pulp. Recent clinical trials dealing with the treatment of deep caries lesion are discussed, including pulp invasive and noninvasive concepts, to attempt to solve the task of getting the best clinical outcome for adult patients. PMID:24698699

  1. Vital Pulp Therapy of a Mature Molar with Concurrent Hyperplastic Pulpitis, Internal Root Resorption and Periradicular Periodontitis: A Case Report.

    PubMed

    Asgary, Saeed; Kemal Çalışkan, Mehmet

    2015-01-01

    Vital pulp therapy (VPT) of permanent mature teeth is continuously ascertaining to be a more reliable endodontic treatment. The purpose of this case report was to describe successful VPT of a mature mandibular left first molar with concurrent hyperplastic pulpitis, internal root resorption and periradicular periodontitis in a 35-year-old male patient. After complete caries removal and access cavity preparation, the dental pulp was removed from the coronal third of the roots. To protect the remaining pulp, calcium-enriched mixture (CEM) cement was placed and adapted into the cavities; the tooth was then restored with amalgam. Six months after VPT, radiographic examination showed evidence of periradicular healing. Clinically, the tooth was functional without signs and symptoms of infection/inflammation. The successful outcome of this case suggests that diseased dental pulp (i.e. irreversible pulpitis) has the potential to heal after pulp protection with CEM biocement. PMID:26523145

  2. Vital Pulp Therapy of a Mature Molar with Concurrent Hyperplastic Pulpitis, Internal Root Resorption and Periradicular Periodontitis: A Case Report

    PubMed Central

    Asgary, Saeed; Kemal Çalışkan, Mehmet

    2015-01-01

    Vital pulp therapy (VPT) of permanent mature teeth is continuously ascertaining to be a more reliable endodontic treatment. The purpose of this case report was to describe successful VPT of a mature mandibular left first molar with concurrent hyperplastic pulpitis, internal root resorption and periradicular periodontitis in a 35-year-old male patient. After complete caries removal and access cavity preparation, the dental pulp was removed from the coronal third of the roots. To protect the remaining pulp, calcium-enriched mixture (CEM) cement was placed and adapted into the cavities; the tooth was then restored with amalgam. Six months after VPT, radiographic examination showed evidence of periradicular healing. Clinically, the tooth was functional without signs and symptoms of infection/inflammation. The successful outcome of this case suggests that diseased dental pulp (i.e. irreversible pulpitis) has the potential to heal after pulp protection with CEM biocement. PMID:26523145

  3. Recycling cellulase towards industrial application of enzyme treatment on hardwood kraft-based dissolving pulp.

    PubMed

    Wang, Qiang; Liu, Shanshan; Yang, Guihua; Chen, Jiachuan; Ji, Xingxiang; Ni, Yonghao

    2016-07-01

    Cost-effectiveness is vital for enzymatic treatment of dissolving pulp towards industrial application. The strategy of cellulase recycling with fresh cellulase addition was demonstrated in this work to activate the dissolving pulp, i.e. decreasing viscosity and increasing Fock reactivity. Results showed that 48.8-35.1% of cellulase activity can be recovered from the filtered liquor in five recycle rounds, which can be reused for enzymatic treatment of dissolving pulp. As a result, the recycling cellulase with addition fresh cellulase of 1mg/g led to the pulp of viscosity 470mL/g and Fock reactivity 80%, which is comparable with cellulase charge of 2mg/g. Other pulp properties such as alpha-cellulose, alkaline solubility and molecular weight distribution were also determined. Additionally, a zero-release of recycling cellulase treatment was proposed to integrate into the dissolving pulp production process. PMID:27099940

  4. Management of nonprocess elements in low-effluent bleached kraft pulp mills

    SciTech Connect

    Bryant, P.S.

    1995-12-31

    Increasing environmental regulation for the discharge of chlorinated organics in bleach plant effluents has required most manufacturers in the pulp and paper industry to reduce the charge of elemental chlorine in the bleaching of kraft pulp. The best long term solution for reducing effluent pollutants from bleached kraft pulp mills is to move towards low-effluent (closed-cycle) bleaching. Closure of operating bleach plants would dramatically reduce both the volume and the pollutant concentration of pulp mill effluents. However, closing the mill creates many operational problems including a concentration build-up of nonprocess elements (NPE`s) in process streams. NPE`s usually enter the pulp process as trace constituents of wood. Recent studies have lead to a fundamental understanding of how NPE`s partition between the solid cellulose phase and the liquid aqueous phase in pulp mill process streams. This knowledge will help in the design, operation and optimization of future low-effluent bleach plants.

  5. Histological evaluation of pulp tissue from second primary molars correlated with clinical and radiographic caries findings

    PubMed Central

    Gopinath, Vellore Kannan; Anwar, Khurshid

    2014-01-01

    Background: Managing dental caries in young children is demanding due to the elusions present on the right diagnostic criteria for treatment. The present study evaluated the histological status of pulp tissues extracted from primary second molar with caries involvement. Histological findings are correlated with clinical and radiographic assessment. Materials and Methods: Simple experimental study was conducted on upper or lower second primary molars with occlusal (22 teeth) or proximal (22 teeth) dental caries. Selected children were below 6 years of age. Percentage of caries involvement, residual dentin thickness (RDT), radiographic assessment of interradicular and periapical areas, clinical caries depth and signs and symptoms are the parameters considered for comparing with the histological findings. The specimens were grouped based on the nature of the inflammatory process as acute or chronic. The data were analyzed by Student t-test to compare histological types of inflammation with clinical parameters. P value < 0.05 was considered as significant. Results: Four cases revealed severe acute inflammation in coronal and relatively mild acute inflammation in radicular pulp. In the rest of the specimen coronal and radicular pulp had similar acute or chronic inflammatory changes. Histological evidence of pulpitis correlated with dental caries depth of ≥80%, RDT of ≤1 mm, radiographic rarefactions in the interradicular regions and symptoms of pain. Conclusion: Primary second molars with more than two-third caries involvement with symptoms of pain histologically showed inflammation of both coronal and radicular pulp tissues in all cases. PMID:24932190

  6. Genetic and pharmacological inactivation of the purinergic P2RX7 receptor dampens inflammation but increases tumor incidence in a mouse model of colitis-associated cancer.

    PubMed

    Hofman, Paul; Cherfils-Vicini, Julien; Bazin, Marie; Ilie, Marius; Juhel, Thierry; Hébuterne, Xavier; Gilson, Eric; Schmid-Alliana, Annie; Boyer, Olivier; Adriouch, Sahil; Vouret-Craviari, Valérie

    2015-03-01

    Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD). Binding of extracellular ATP to the purinergic receptor P2RX7 has emerged as a critical event in controlling intestinal inflammation, acting to limit elevation of proinflammatory mast cells and cytokines and promote survival of regulatory T cells (Treg) and enteric neurons. In this study, we investigated the effect of P2RX7 blockade in an established mouse model of CAC. Using genetic and pharmacologic tools, we found unexpectedly that while P2RX7 mediated inflammatory responses, it also acted at an early time to suppress CAC development. P2RX7 blockade enhanced proliferation of intestinal epithelial cells and protected them from apoptosis. The proliferative effects of P2RX7 blockade were associated with an increased production of TGFβ1 that was sufficient to stimulate the proliferation of intestinal epithelial cells. Finally, P2RX7 blockade also altered immune cell infiltration and promoted Treg accumulation within lesions of the digestive system. Taken together, our findings reveal an unexpected role for P2RX7 in preventing CAC, suggesting cautions in the use of P2RX7 inhibitors to treat IBD given the possibility of increasing risks CAC as a result. PMID:25564520

  7. Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice.

    PubMed

    Zhang, Jingjing; Cheng, Yanli; Gu, Junlian; Wang, Shudong; Zhou, Shanshan; Wang, Yuehui; Tan, Yi; Feng, Wenke; Fu, Yaowen; Mellen, Nicholas; Cheng, Rui; Ma, Jianxing; Zhang, Chi; Li, Zhanquan; Cai, Lu

    2016-04-01

    Fenofibrate (FF), as a peroxisome-proliferator-activated receptor α (PPARα) agonist, has been used clinically for decades to lower lipid levels. In the present study, we examined whether FF can be repurposed to prevent the pathogenesi of the heart in Type 1 diabetes and to describe the underlying mechanism of its action. Streptozotocin (STZ)-induced diabetic mice and their age-matched control mice were treated with vehicle or FF by gavage every other day for 3 or 6 months. FF prevented diabetes-induced cardiac dysfunction (e.g. decreased ejection fraction and hypertrophy), inflammation and remodelling. FF also increased cardiac expression of fibroblast growth factor 21 (FGF21) and sirtuin 1 (Sirt1) in non-diabetic and diabetic conditions. Deletion of FGF21 gene (FGF21-KO) worsened diabetes-induced pathogenic effects in the heart. FF treatment prevented heart deterioration in the wild-type diabetic mice, but could not do so in the FGF21-KO diabetic mice although the systemic lipid profile was lowered in both wild-type and FGF21-KO diabetic mice. Mechanistically, FF treatment prevented diabetes-impaired autophagy, reflected by increased microtubule-associated protein 1A/1B-light chain 3, in the wild-type diabetic mice but not in the FGF21-KO diabetic mice. Studies with H9C2 cells in vitro demonstrated that exposure to high glucose (HG) significantly increased inflammatory response, oxidative stress and pro-fibrotic response and also significantly inhibited autophagy. These effects of HG were prevented by FF treatment. Inhibition of either autophagy by 3-methyladenine (3MA) or Sirt1 by sirtinol (SI) abolished FF's prevention of HG-induced effects. These results suggested that FF could prevent Type 1 diabetes-induced pathological and functional abnormalities of the heart by increasing FGF21 that may up-regulate Sirt1-mediated autophagy. PMID:26795437

  8. Strength loss in kraft pulping

    NASA Astrophysics Data System (ADS)

    Iribarne, Jose

    Unbleached kraft pulps from two U.S. mills were 21% and 26% weaker than comparable laboratory pulps from the same chip sources, when assessed as the tear index at a tensile index of 70 kN.m/kg. The phenomena involved were clarified by characterizing the differences between the mill and laboratory pulps in terms of fundamental fiber properties. All of the strength loss could be explained by a reduction in intrinsic fiber strength of 9% to 11%, as estimated from wet zero-span tensile tests and fiber length distributions. Most of the effects of different fiber shape and length were isolated by PFI mill refining and decrilling, respectively. The higher fiber coarseness of mill pulps was a factor in their maximum density and bond strength, but changes in these variables were analogous to those of laboratory pups due to similar swelling. Specific bond strength, determined from a wet pressing experiment, was similar in mill and laboratory pulps. Neither carbohydrate composition nor crystalline structure, assessed through x-ray diffraction analysis, were significant factors in the observed fiber strength differences. The mill pulps were not more heterogeneous than the laboratory pulps, within the resolution of a fractionation experiment. The number of weak points in each pulp was assessed through analysis of the amount of fiber cutting during PFI mill refining and treatments with potassium superoxide or cellulase. The results suggested that the chemistry of kraft pulping preferentially weaken short, slender fibers, while mechanical stresses during the hot discharge of batch digesters mainly affect long, thick fibers. The greater number of weak points in the long-fiber fractions of mill pulps is probably associated with their lower wet zero-span tensile indices. Automated optical detection of major singularities with a prototype instrument suggested that only the weak points induced by mechanical stress could be detected by local variations in birefringence. In contrast

  9. Role of Oxidized Lipids and TRP Channels in Orofacial Pain and Inflammation.

    PubMed

    Hargreaves, K M; Ruparel, S

    2016-09-01

    Acute or chronic inflammation comprises a highly prevalent type of orofacial pain and is mediated by the generation of endogenous agonists that activate numerous receptors expressed on terminals of trigeminal (TG) nociceptive afferent neurons. One such studied receptor is transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a ligand-gated cation channel that is expressed on a major subclass of nociceptors and is found in many orofacial tissues, including dental pulp. Antagonists to TRPV1 reveal an important role for this channel in mediating hypersensitivity in preclinical models of inflammatory or neuropathic pain. Recent studies have demonstrated that endogenous TRPV1 agonists are generated by oxidation of omega-6 polyunsaturated fatty acids, including both linoleic acid and arachidonic acid. A major mechanism triggering the release of oxidative linoleic acid metabolites (OLAMs) and oxidative arachidonic acid metabolites (OAAMs) is the action of oxidative enzymes. Oxidative enzymes such as cytochrome P450 isozymes are rapidly upregulated in TG neurons after orofacial inflammation and increase the capacity of TG neurons to generate OLAMs. Cytochrome P450 isozymes are also increased in immune cells in irreversibly inflamed human dental pulp, and extracts of this tissue have significantly increased capacity to generate OLAMs. Together, these studies point to a novel pain mechanism involving the enzymatic generation of endogenous OLAM and OAAM agonists of TRPV1. This finding provides a rationale for an entirely new class of analgesics by inhibition of oxidative enzyme activity. PMID:27307050

  10. Inflammation increases pyruvate dehydrogenase kinase 4 (PDK4) expression via the Jun N-Terminal Kinase (JNK) pathway in C2C12 cells.

    PubMed

    Park, Hana; Jeoung, Nam Ho

    2016-01-22

    Chronic inflammation augments the deleterious effects of several diseases, particularly diabetes, cancer, and sepsis. It is also involved in the process of metabolic shift from glucose oxidation to lactate production. Although several studies suggest that the change in activity of the pyruvate dehydrogenase complex (PDC) is a major factor causing this metabolic change, the exact mechanism of the inflammatory state remains unclear. In this study, we investigated the effect of lipopolysaccharide (LPS) on the expression of pyruvate dehydrogenase kinase 4 (PDK4), which is strongly associated with inactivation of the PDC in C2C12 myoblasts. In C2C12 myoblasts, LPS exposure led to increased PDK4 mRNA and protein expression levels as well as lactate production in culture medium. However, the expression levels of other PDK isoenzymes (PDK1 - 3) remained unchanged. Additionally, we observed that LPS treatment induced phosphorylation of Jun N-Terminal Kinases (JNK). To confirm the role of JNK, we inhibited the JNK pathway and observed that PDK4 expression and lactate production were decreased, but p38 and ERK were not significantly changed. Taken together, our results suggest that LPS induces PDK4 expression and alters glucose metabolism via the JNK pathway. PMID:26740179

  11. TCF bleaching of soda-anthraquinone and diethanolamine pulp from oil palm empty fruit bunches.

    PubMed

    Jiménez, L; Serrano, L; Rodríguez, A; Ferrer, A

    2009-02-01

    The AOpAZRP bleaching sequence (A is an acid treatment, Op an oxygen and peroxide stage, Z an ozone stage, R a reductive treatment and P a peroxide stage) have been applied to oil palm empty fruit bunches (EFB) soda-anthraquinone and diethanolamine pulp. On similar Kappa numbers for the two types of pulp (14.2 and 17.3), paper from unbleached soda-anthraquinone pulp exhibited increased tensile index (25.8 Nm/g), stretch (2.35%), burst index (1.69 kN/g), tear index (0.50 mN m(2)/g) and brightness (60.6%) relative to paper for unbleached diethanolamine pulp; but the latter type of pulp exhibited higher viscosity (659 mL/g) than the former. Upon bleaching with the AOpAZRP sequence, diethanolamine pulp exhibited higher viscosity (783 mL/g), and the properties of the paper sheets were close to or even better to those from soda-anthraquinone pulp, namely: 22.2 vs 20.4 Nm/g tensile index, 1.30 vs 1.42 kN/g burst index, 0.71 vs 0.70 mN m(2)/g tear index and 71.3% vs 77.5% brightness. Therefore, the properties of paper from diethanolamine pulp evolved more favourably during bleaching than did those of paper from soda-anthraquinone pulp. PMID:18809321

  12. Roles of electricity: Pulp and papermaking

    SciTech Connect

    Burwell, C.C.; Mills, M.; McCarthy, D.

    1986-09-01

    The report begins with a brief description of the industry. The pulp and paper business, while seemingly homogeneous, is enormously variable in detail. In this brief analysis, the reader is provided with an overview of the subject - a view of the forest, so to speak, not of the trees - sufficient to grasp the forces causing change in the industry. It will be seen that these changes, in general, are dictating an increasing dependence on electricity. The focus of this analysis has been to shed light on the increasing role for electricity in the age-old process of papermaking.

  13. Dissolving pulp from jute stick.

    PubMed

    Matin, Mhafuza; Rahaman, M Mostafizur; Nayeem, Jannatun; Sarkar, Mamon; Jahan, M Sarwar

    2015-01-22

    Jute stick is woody portion of jute plant, which remain as leftover after extracting bast fibre. Presently, it is being used for fencing in the rural area. In this investigation, biorefinery concept was initiated in producing dissolving pulp from jute stick by pre-hydrolysis kraft process. At 170°C for 1h of pre-hydrolysis, 70% of hemicelluloses was dissolved with negligible loss of α-cellulose. At this condition, 75% of dissolved sugars in the pre-hydrolysis liquor were in the oligomeric form. The pre-hydrolysed jute stick was subsequently pulped by kraft process with the variation of active alkali. The pulp yield was 36.2% with kappa number 18.5 at the conditions of 16% active alkali for 2h of cooking at 170°C. Final pulp was produced with 92% α-cellulose and 89% brightness after D0EpD1EpD1 bleaching. The produced dissolving pulp can be used in rayon production. PMID:25439866

  14. Pulp tissue in sex determination: A fluorescent microscopic study

    PubMed Central

    Nayar, Amit; Singh, Harkanwal Preet; Leekha, Swati

    2014-01-01

    Aims: To determine and compare the reliability of pulp tissue in determination of sex and to analyze whether caries have any effect on fluorescent body test. Materials and Methods: This study was carried on 50 maxillary and mandibular teeth (25 male teeth and 25 female teeth), which were indicated for extraction. The teeth are categorized into 5 groups, 10 each (5 from males and 5 from females) on the basis of caries progression. The pulp cells are stained with quinacrine hydrochloride and observed with fluorescent microscope for fluorescent body. Gender is determined by identification of Y chromosome fluorescence in dental pulp. Results: Fluorescent bodies were found to be more in sound teeth in males as the caries increase the mean percentage of fluorescent bodies observed decreases in males. We also observed the fluorescent spots in females, and the value of the spot increases in female as the caries progresses, thereby giving false positive results in females. Conclusion: Sex determination by fluorescent staining of the Y chromosome is a reliable technique in teeth with healthy pulps or caries with enamel or up to half way of dentin. Teeth with caries involving pulp cannot be used for sex determination. PMID:25125912

  15. Stability and microstructure of freeze-dried guava pulp (Psidium guajava L.) with added sucrose and pectin.

    PubMed

    Conceição, Márcia Cavalcante; Fernandes, Tatiana Nunes; de Resende, Jaime Vilela

    2016-06-01

    Freeze-dried guava pulp powders, formulated with the addition of sucrose (0-20 g/100 g pulp) and pectin (0-1.0 g/100 g pulp), were obtained, and their stability was evaluated with respect to the water adsorption isotherms, thermal analysis and microstructure. The GAB (Guggenheim-Anderson-de Boer), Peleg and BET (Brunauer-Emmett-Teller) models were used to evaluate the water adsorption. The microstructure was examined using optical microscopy with polarized light and scanning electron microscopy (SEM). The GAB and BET parameters showed that the moisture content of the monolayer (Xm) increases with increasing pectin concentration in the adsorption isotherms. Optical microscopy micrographs showed that the pulp consisting of sucrose showed crystalline structures present in a higher amount and size, and this behavior is enhanced with increasing relative moisture. SEM showed that the increase in sucrose and pectin concentrations produced powders with lower porosity, providing greater stability to the product. The glass transition temperature increased slightly with increasing pectin concentration and decreased with increasing moisture content in the guava pulp powder. The kinetic curves, ratio of the increase of the water content against the storage time, of the guava pulp treated with 20 g sucrose per 100 g pulp and higher pectin concentration (0.5 or 1.0 g pectin per 100 g pulp) showed reduced adsorption and yielded freeze-dried pulps that were more stable. PMID:27478221

  16. CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model

    PubMed Central

    Wert, Katherine J.; Bassuk, Alexander G.; Wu, Wen-Hsuan; Gakhar, Lokesh; Coglan, Diana; Mahajan, MaryAnn; Wu, Shu; Yang, Jing; Lin, Chyuan-Sheng; Tsang, Stephen H.; Mahajan, Vinit B.

    2015-01-01

    A single amino acid mutation near the active site of the CAPN5 protease was linked to the inherited blinding disorder, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM #193235). In homology modeling with other calpains, this R243L CAPN5 mutation was situated in a mobile loop that gates substrate access to the calcium-regulated active site. In in vitro activity assays, the mutation increased calpain protease activity and made it far more active at low concentrations of calcium. To test whether the disease allele could yield an animal model of ADNIV, we created transgenic mice expressing human (h) CAPN5R243L only in the retina. The resulting hCAPN5R243L transgenic mice developed a phenotype consistent with human uveitis and ADNIV, at the clinical, histological and molecular levels. The fundus of hCAPN5R243L mice showed enhanced autofluorescence (AF) and pigment changes indicative of reactive retinal pigment epithelial cells and photoreceptor degeneration. Electroretinography showed mutant mouse eyes had a selective loss of the b-wave indicating an inner-retina signaling defect. Histological analysis of mutant mouse eyes showed protein extravasation from dilated vessels into the anterior chamber and vitreous, vitreous inflammation, vitreous and retinal fibrosis and retinal degeneration. Analysis of gene expression changes in the hCAPN5R243L mouse retina showed upregulation of several markers, including members of the Toll-like receptor pathway, chemokines and cytokines, indicative of both an innate and adaptive immune response. Since many forms of uveitis share phenotypic characteristics of ADNIV, this mouse offers a model with therapeutic testing utility for ADNIV and uveitis patients. PMID:25994508

  17. CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model.

    PubMed

    Wert, Katherine J; Bassuk, Alexander G; Wu, Wen-Hsuan; Gakhar, Lokesh; Coglan, Diana; Mahajan, MaryAnn; Wu, Shu; Yang, Jing; Lin, Chyuan-Sheng; Tsang, Stephen H; Mahajan, Vinit B

    2015-08-15

    A single amino acid mutation near the active site of the CAPN5 protease was linked to the inherited blinding disorder, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM #193235). In homology modeling with other calpains, this R243L CAPN5 mutation was situated in a mobile loop that gates substrate access to the calcium-regulated active site. In in vitro activity assays, the mutation increased calpain protease activity and made it far more active at low concentrations of calcium. To test whether the disease allele could yield an animal model of ADNIV, we created transgenic mice expressing human (h) CAPN5(R243L) only in the retina. The resulting hCAPN5(R243L) transgenic mice developed a phenotype consistent with human uveitis and ADNIV, at the clinical, histological and molecular levels. The fundus of hCAPN5(R243L) mice showed enhanced autofluorescence (AF) and pigment changes indicative of reactive retinal pigment epithelial cells and photoreceptor degeneration. Electroretinography showed mutant mouse eyes had a selective loss of the b-wave indicating an inner-retina signaling defect. Histological analysis of mutant mouse eyes showed protein extravasation from dilated vessels into the anterior chamber and vitreous, vitreous inflammation, vitreous and retinal fibrosis and retinal degeneration. Analysis of gene expression changes in the hCAPN5(R243L) mouse retina showed upregulation of several markers, including members of the Toll-like receptor pathway, chemokines and cytokines, indicative of both an innate and adaptive immune response. Since many forms of uveitis share phenotypic characteristics of ADNIV, this mouse offers a model with therapeutic testing utility for ADNIV and uveitis patients. PMID:25994508

  18. High-alkali low-temperature polysulfide pulping (HALT) of Scots pine.

    PubMed

    Paananen, Markus; Sixta, Herbert

    2015-10-01

    High-alkali low-temperature polysulfide pulping (HALT) was effectively utilised to prevent major polysaccharide losses while maintaining the delignification rate. A yield increase of 6.7 wt% on wood was observed for a HALT pulp compared to a conventionally produced kappa number 60 pulp with comparable viscosity. Approximately 70% of the yield increase was attributed to improved galactoglucomannan preservation and 30% to cellulose. A two-stage oxygen delignification sequence with inter-stage peroxymonosulphuric acid treatment was used to ensure delignification to a bleachable grade. In a comparison to conventional pulp, HALT pulp effectively maintained its yield advantage. Diafiltration trials indicate that purified black liquor can be directly recycled, as large lignin fractions and basically all dissolved polysaccharides were separated from the alkali-rich BL. PMID:26119050

  19. Ultrasonic Sensor to Characterize Wood Pulp During Refining

    SciTech Connect

    Greenwood, Margaret S.; Panetta, Paul D.; Bond, Leonard J.; McCaw, M. W.

    2006-12-22

    A novel sensor concept has been developed for measuring the consistency, the degree of refining, the water retention value (WRV), and the consistency of wood pulp during the refining process. The measurement time is less than 5 minutes and the sensor can operate in a slip-stream of the process line or as an at-line instrument. The consistency is obtained from a calibration, in which the attenuation of ultrasound through the pulp suspension is measured as a function of the solids weight percentage. The degree of refining and the WRV are determined from settling measurements. The settling of a pulp suspension (consistency less than 0.5 Wt%) is observed, after the mixer that keeps the pulp uniformly distributed is turned off. The attenuation of ultrasound as a function of time is recorded and these data show a peak, after a certain delay, defined as the “peak time.” The degree of refining increases with the peak time, as demonstrated by measuring pulp samples with different degrees of refining. The WRV can be determined using the relative peak time, defined as the ratio T2/T1, where T1 is an initial value of the peak time and T2 is the value after additional refining. This method offers an additional WRV test for the industry, because the freeness test is not specific for the WRV.

  20. Characterization of active paper packaging incorporated with ginger pulp oleoresin

    NASA Astrophysics Data System (ADS)

    Wiastuti, T.; Khasanah, L. U.; Atmaka Kawiji, W.; Manuhara, G. J.; Utami, R.

    2016-02-01

    Utilization of ginger pulp waste from herbal medicine and instant drinks industry in Indonesia currently used for fertilizer and fuel, whereas the ginger pulp still contains high oleoresin. Active paper packaging were developed incorporated with ginger pulp oleoresin (0%, 2%, 4%, and 6% w/w). Physical (thickness, tensile strength, and folding endurance, moisture content), sensory characteristics and antimicrobial activity of the active paper were evaluated. Selected active paper then were chemically characterized (functional groups). The additional of ginger pulp oleoresin levels are reduced tensile strength, folding endurance and sensory characteristic (color, texture and overall) and increased antimicrobial activity. Due to physical, sensory characteristic and antimicrobial activity, active paper with 2% ginger pulp oleoresin incorporation was selected. Characteristics of selected paper were 9.93% of water content; 0.81 mm of thickness; 0.54 N / mm of tensile strength; 0.30 of folding endurance; 8.43 mm inhibits the growth of Pseudomonas fluorescence and 27.86 mm inhibits the growth of Aspergillus niger (antimicrobial activity) and neutral preference response for sensory properties. For chemical characteristic, selected paper had OH functional group of ginger in 3422.83 cm-1 of wave number and indicated contain red ginger active compounds.

  1. C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.

    PubMed

    Lee, Y H; Kim, H S; Kim, J S; Yu, M K; Cho, S D; Jeon, J G; Yi, H K

    2016-04-01

    Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases. PMID:26661713

  2. Nestin expressions of exposed pulp after direct pulp capping by calcium hydroxide and platelet rich plasma

    PubMed Central

    Puspita, Sartika; Utoro, Totok; Haniastuti, Tetiana

    2016-01-01

    Objective: The aim of this study was to evaluate nestin expression of pulp tissue following direct pulp capping with platelet-rich plasma (PRP). Materials and Methods: The thirty sound teeth from Sprague-Dawley rats were used and divided into two groups: Groups 1, teeth were capped with calcium hydroxide/Ca(OH)2 (n = 15) and Group 2 with PRP (n = 15). After 1st, 7th, and 21st days, respectively, 5 teeth each group (American Dental Association 41) were processed for light microscopic examination. Expressions of nestin were assessed by immunohistochemical techniques. Results: Nestin expression of Ca(OH)2 on the distance place of exposure at 1st and 7th days were 80% and at 21st day were 60%. Nestin expression of PRP on the distance place at 1st day was 80%, 7th 100%, and 21st day was 80%. At day 21 observation, Kruskal–Wallis test shows nestin expression was increased significantly in PRP groups (P < 0.05), but it was not increase significantly compare with Ca(OH)2. Conclusion: PRP had ability as a direct pulp capping material to induce nestin expression. PMID:27403050

  3. Formation of carbonyl groups on cellulose during ozone treatment of pulp: consequences for pulp bleaching.

    PubMed

    Pouyet, Frédéric; Chirat, Christine; Potthast, Antje; Lachenal, Dominique

    2014-08-30

    The formation of carbonyl groups during the ozone treatment (Z) of eucalyptus (Eucalyptus grandis and Eucalyptus urophylla hybrid) kraft pulps and their behaviors during subsequent alkaline stages were investigated by the CCOA method with carbazole-9-carboxylic acid [2-(2-aminooxethoxy)-ethoxy] amide (CCOA) as the carbonyl-selective fluorescence label. Several pulp samples with or without lignin and hexenuronic acids (hexA) were used to elucidate the effects of these components when present in unbleached kraft pulp. Both hexA and lignin increased the formation of carbonyl groups on cellulose and hemicellulose during ozonation. It was concluded that radicals are likely formed when ozone reacts with either lignin or hexA. These carbonyl groups were involved in cellulose depolymerization during subsequent alkaline extraction stages with sodium hydroxide (E) and alkaline hydrogen peroxide (P, in ZEP or ZP). Their numbers decreased after E but increased during P when H2O2 was not stabilized enough. Several ways to minimize the occurrence of carbonyl group formation are suggested. PMID:24815405

  4. Exposure to O-16 particle irradiation causes age-like decrements in rats through increased oxidative stress, inflammation and loss of autophagy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposing young rats to particles of high energy and charge (HZE particles) enhances indices of oxidative stress and inflammation, disrupts the functioning of neuronal communication, and alters cognitive behaviors. Even though exposure to these highly charged particles occurs at low fluence rates, p...

  5. Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia

    PubMed Central

    Hwang, Y; Kim, J; Shin, J-Y; Kim, J-II; Seo, J-S; Webster, M J; Lee, D; Kim, S

    2013-01-01

    Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease. PMID:24169640

  6. Biological pretreatment for thermomechanical (TMP) and chemithermomechanical (CTMP) pulping processes

    SciTech Connect

    Myers, G.C.; Akhtar, M.; Lentz, M.

    1996-10-01

    Treatment of wood chips with lignin-degrading fungi prior to preparing a refiner mechanical pulp (RMP) has substantially reduced energy consumption and increased paper strength properties. This study reports on thermomechanical (TMP) and chemithermo-mechanical pulping (CTMP) of fungus treated wood chips. Loblolly pine chips were innoculated with Ceriporiopsis subvermispora, strain L14807 SS-3, and incubated two weeks in a chip silo. A pressurized 305 mm diameter disk refiner was used to prepare TMP and CTMP`s from fungal treated and non-treated wood chips. Two procedures were used to prepare the CTMP`s, injecting a sodium hydroxide and hydrogen peroxide solution into the pressurized refiner, and impregnating the wood chips with a sodium sulfite solution. Energy consumption during pulp preparation and handsheet strength and optical properties will be presented and discussed.

  7. Biocomposition and reaction of pulp tissues to restorative treatments.

    PubMed

    Cox, C F; Hafez, A A

    2001-01-01

    Dentistry has experienced exponential growth in the biologic and physiologic knowledge of enamel, dentin, and pulp tissues. In one decade, material development has exceeded clinical testing limits, allowing their arrival to the commercial market without proper validation. This article clarifies the enigma of acid etching; explaining and clarifying the diverse opinions and issues of material toxicity between in vitro and in vivo usage test perspectives. This article also demystifies the biology of pulp healing regarding calcium hydroxide and adhesive systems to promote dentin bridge formation. Lastly, this article provides biologically lucid pulp exposure treatment regimens with agents such as NaOCl, allowing clinicians to increase their long-term clinical success. PMID:11210698

  8. [Utilization of organic resources in paper pulp waste liquid].

    PubMed

    Lin, Qiaojia; Liu, Jinghong; Yang, Guidi; Huang, Biao

    2005-04-01

    In this paper, one hundred percent of condensed sulfate paper pulp waste liquid was used as the raw material of adhesive, and the activation of its lignin as well as the improving effects of phenol formaldehyde resin and polyfunctional aqueous polymer isocyanate (PAPI) were studied. The results showed that adding formaldehyde to the waste liquid could increase the reactivity of contained lignin, and adding 30% phenol formaldehyde resin or 20% PAPI could make the waste liquid in place of pure phenol formaldehyde resin for producing class I plywood. Furthermore, the cost could be reduced by 55.5% and 49.0%, respectively, in comparing with pure phenol formaldehyde resin. This approach fully used the organic resources in paper pulp waste liquid, reduced environment pollution at the same time, and had unexceptionable economic, social and ecological benefits. The feasibility of preparing adhesives from paper pulp waste liquid was also analyzed by infrared spectrum. PMID:16011170

  9. Electron treatment of wood pulp for the viscose process

    NASA Astrophysics Data System (ADS)

    Stepanik, T. M.; Ewing, D. E.; Whitehouse, R.

    2000-03-01

    Electron processing is currently being evaluated by several viscose producers for integration into their process. The viscose industry converts dissolving wood pulp into products such as staple fibre, filament, cord, film, packaging, and non-edible sausage casings. These materials are used in the clothing, drapery, hygiene, automobile, food, and packaging industries. Viscose producers are facing increasingly high production costs and stringent environmental regulations that have forced some plants to close. Electron treatment of wood pulp can significantly reduce the amounts of chemicals used for producing viscose and the production of hazardous pollutants. Acsion Industries has worked with companies worldwide to demonstrate the benefits of using electron treated pulp for producing viscose (rayon). This paper describes the viscose process, the benefits of using electron treatment in the viscose process, and Acsion's efforts in developing this technology.

  10. Current fungal biotechnologies: Guidelines useful for pulping and bleaching

    SciTech Connect

    Kirk, T.K.

    1996-10-01

    This symposium deals with the potential use of fungi in pulping wood and bleaching pulp. The fungi useful in this regard are higher basidiomycetes, which are nature`s major degraders of lignin. Their ligninolytic enzyme systems were discovered 14 years ago, and have been studied intensely since then. However, neither these enzymes nor the fungi themselves have been harnessed commercially in biotechnological processes-with the exception that some of the fungi are grown as food. Using the fungi in pulp manufacturing processes, therefore, must be approached without the benefit of direct guidelines, which increases the uncertainty and risk. It is instructive, therefore, to review current commercial fungal-based bio-technologies, components of which provide information useful to the development and evaluation of proposed processes. This paper will briefly review existing types of biotechnical processes that are based on filamentous fungi, and discuss how that information is being used to guide development of new processes for biopulping and biobleaching.