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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. The role of cytokines in pulp inflammation.

    PubMed

    Kokkas, A; Goulas, A; Stavrianos, C; Anogianakis, G

    2011-01-01

    Pulpitis is a typical inflammatory disease of dental pulp, characterized by the local accumulation of inflammatory mediators, including cytokines and chemokines. In addition to serving as intercellular messengers mediating the inflammatory response, cytokines and chemokines induce the expression and stimulate the activity of molecular and cellular agents which participate actively in destructive and reparative processes in the pulp. It is the balance between these processes which eventually determines the extent of pulp inflammation and the viability of the affected tooth. Over the last decade, a number of studies have attempted to correlate cytokine gene expression in the pulp with various stages of inflammation, with possible diagnostic applications in mind. A small survey of relevant information is presented in this paper.

  4. Epigenetic regulation in dental pulp inflammation

    PubMed Central

    Hui, T; Wang, C; Chen, D; Zheng, L; Huang, D; Ye, L

    2016-01-01

    Dental caries, trauma, and other possible factors could lead to injury of the dental pulp. Dental infection could result in immune and inflammatory responses mediated by molecular and cellular events and tissue breakdown. The inflammatory response of dental pulp could be regulated by genetic and epigenetic events. Epigenetic modifications play a fundamental role in gene expression. The epigenetic events might play critical roles in the inflammatory process of dental pulp injury. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Infections and other environmental factors have profound effects on epigenetic modifications and trigger diseases. Despite growing evidences of literatures addressing the role of epigenetics in the field of medicine and biology, very little is known about the epigenetic pathways involved in dental pulp inflammation. This review summarized the current knowledge about epigenetic mechanisms during dental pulp inflammation. Progress in studies of epigenetic alterations during inflammatory response would provide opportunities for the development of efficient medications of epigenetic therapy for pulpitis. PMID:26901577

  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.

  6. 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

  7. 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

  8. Stimulation of Dentin Regeneration by Using Acemannan in Teeth with Lipopolysaccharide-induced Pulp Inflammation.

    PubMed

    Songsiripradubboon, Siriporn; Kladkaew, Sarunya; Trairatvorakul, Chutima; Sangvanich, Polakit; Soontornvipart, Kumpanart; Banlunara, Wijit; Thunyakitpisal, Pasutha

    2017-07-01

    This study investigated the effects of acemannan, a polysaccharide from Aloe vera, on human deciduous pulp cells in vitro and the response after vital pulp therapy in dog deciduous teeth. Human primary dental pulpal cells were treated with acemannan in vitro and evaluated for proliferation, alkaline phosphatase activity, type I collagen, bone morphogenetic protein (BMP-2), BMP-4, vascular endothelial growth factor, and dentin sialoprotein expression and mineralization. Osteogenesis-related gene expression was analyzed by complementary DNA microarray. Pulpal inflammation was induced in dog teeth for 14 days. The inflamed pulp was removed, retaining the healthy pulp. The teeth were randomly divided into 3 treatment groups: acemannan, mineral trioxide aggregate, and formocresol. Sixty days later, the teeth were extracted and evaluated histopathologically. Acemannan significantly increased pulp cell proliferation, alkaline phosphatase, type I collagen, BMP-2, BMP-4, vascular endothelial growth factor, and dentin sialoprotein expression and mineralization approximately 1.4-, 1.6-, 1.6-, 5.5-, 2.6-, 3.8-, 1.8-, and 4.8-fold, respectively, compared with control. In vivo, partial pulpotomy treatment using acemannan generated outcomes similar to mineral trioxide aggregate treatment, resulting in mineralized bridge formation with normal pulp tissue without inflammation or pulp necrosis. In contrast, the formocresol group demonstrated pulp inflammation without mineralized bridge formation. Acemannan is biocompatible with the dental pulp. Furthermore, acemannan stimulated dentin regeneration in teeth with reversible pulpitis. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. Stress increases periodontal inflammation

    PubMed Central

    RIVERA, CÉSAR; MONSALVE, FRANCISCO; SUAZO, IVÁN; BECERRA, JAVIERA

    2012-01-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  10. Static Magnetic Field Attenuates Lipopolysaccharide-Induced Inflammation in Pulp Cells by Affecting Cell Membrane Stability

    PubMed Central

    Tsao, Jeng-Ting; Lee, Lin-Wen; Lin, Che-Tong

    2015-01-01

    One of the causes of dental pulpitis is lipopolysaccharide- (LPS-) induced inflammatory response. Following pulp tissue inflammation, odontoblasts, dental pulp cells (DPCs), and dental pulp stem cells (DPSCs) will activate and repair damaged tissue to maintain homeostasis. However, when LPS infection is too serious, dental repair is impossible and disease may progress to irreversible pulpitis. Therefore, the aim of this study was to examine whether static magnetic field (SMF) can attenuate inflammatory response of dental pulp cells challenged with LPS. In methodology, dental pulp cells were isolated from extracted teeth. The population of DPSCs in the cultured DPCs was identified by phenotypes and multilineage differentiation. The effects of 0.4 T SMF on DPCs were observed through MTT assay and fluorescent anisotropy assay. Our results showed that the SMF exposure had no effect on surface markers or multilineage differentiation capability. However, SMF exposure increases cell viability by 15%. In addition, SMF increased cell membrane rigidity which is directly related to higher fluorescent anisotropy. In the LPS-challenged condition, DPCs treated with SMF demonstrated a higher tolerance to LPS-induced inflammatory response when compared to untreated controls. According to these results, we suggest that 0.4 T SMF attenuates LPS-induced inflammatory response to DPCs by changing cell membrane stability. PMID:25884030

  11. EZH2, a potential regulator of dental pulp inflammation and regeneration.

    PubMed

    Hui, Tianqian; A, Peng; Zhao, Yuan; Wang, Chenglin; Gao, Bo; Zhang, Ping; Wang, Jun; Zhou, Xuedong; Ye, Ling

    2014-08-01

    Dental pulp has limited capability to regenerate, which happens in the early stage of pulpitis. An ambiguous relationship exists; inflammation may impair or support pulp regeneration. Epigenetics, which is involved in cell proliferation and inflammation, could regulate human dental pulp cell (HDPCs) regeneration. The aim of this study was to determine the role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2), in the inflammation, proliferation, and regeneration of dental pulp. We used trimethylated histone H3 lysine 27(H3K27me3) and its lysine demethylase 6B (KDM6B) to monitor functional effects of altered EZH2 levels. We detected epigenetic marks (EZH2, H3K27me3, and KDM6B) in pulp tissue by immunohistochemistry and immunofluorescence. EZH2 levels in HDPCs in inflammatory responses or differentiation were analyzed by quantitative polymerase chain reaction and Western blot. Quantitative polymerase chain reaction was used to assess the effects of EZH2 inhibition on interleukins in HDPCs upon tumor necrosis factor alpha stimulation. Cell proliferation was tested by cell counting kit-8, cell cycle, and apoptosis analysis. HDPC differentiation was investigated by quantitative polymerase chain reaction, alkaline phosphatase activity, and oil red O staining. EZH2 and H3K27me3 were decreased, whereas KDM6B was increased in infected pulp tissue and cells, which were similar to HDPC differentiation. EZH2 inhibition suppressed IL-1b, IL-6, and IL-8 messenger RNA (mRNA) in HDPCs upon inflammatory stimuli and impeded HDPC proliferation by decreasing cell number, arresting cell cycle, and increasing apoptosis. Suppressed EZH2 impaired adipogenesis, peroxisome proliferator-activated receptor r (PPAR-r), and CCAAT-enhancer binding protein a (CEBP/a) mRNA in adipogenic induction while enhancing alkaline phosphatase activity, Osx, and bone sialoprotein (BSP) mRNA in mineralization induction of HDPCs. EZH2 inhibited HDPC osteogenic differentiation while enhancing

  12. 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

  13. 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

  14. 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

  15. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    PubMed

    Matsuura, Shingo; Shimizu, Kohei; Shinoda, Masamichi; Ohara, Kinuyo; Ogiso, Bunnai; Honda, Kuniya; Katagiri, Ayano; Sessle, Barry J; Urata, Kentaro; Iwata, Koichi

    2013-01-01

    In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK) and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP) immunohistochemistry in the trigeminal ganglion (TG) were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG) and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA) or saline was applied into the upper first molar tooth pulp (M1) in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2) on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR) TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC) into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth-pulp pain

  16. Mechanisms Underlying Ectopic Persistent Tooth-Pulp Pain following Pulpal Inflammation

    PubMed Central

    Matsuura, Shingo; Shimizu, Kohei; Shinoda, Masamichi; Ohara, Kinuyo; Ogiso, Bunnai; Honda, Kuniya; Katagiri, Ayano; Sessle, Barry J.; Urata, Kentaro; Iwata, Koichi

    2013-01-01

    In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK) and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP) immunohistochemistry in the trigeminal ganglion (TG) were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG) and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund’s adjuvant (CFA) or saline was applied into the upper first molar tooth pulp (M1) in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2) on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR) TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC) into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth-pulp

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

    PubMed

    Ohara, Kinuyo; Shimizu, Kohei; Matsuura, Shingo; Ogiso, Bunnai; Omagari, Daisuke; Asano, Masatake; Tsuboi, Yoshiyuki; Shinoda, Masamichi; Iwata, Koichi

    2013-11-23

    The purpose of the present study is to evaluate the mechanisms underlying tongue-referred pain associated with tooth pulp inflammation. 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. 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. The present findings indicate that Hsp70 transported from the tooth pulp to TG neurons or expressed in TG neurons is released from

  18. Association of S100 calcium-binding protein A12, receptor for advanced glycation endproducts, and nuclear factor-κB expression with inflammation in pulp tissues from tooth caries.

    PubMed

    Khorasani, Mohammad M Y; Andam-Shahsavari, Pouria; Zainodini, Nahid; Khoramdelazad, Hossein; Nosratabadi, Reza

    2017-08-20

    S100 calcium-binding protein A1 (S100A12) is a pro-inflammatory molecule which is secreted during inflammation and induces chemotaxis and the production of pro-inflammatory cytokines via interaction with receptor for advanced glycation endproducts (RAGE) and subsequent, activation of nuclear factor-κB (NF-κB). The present study was designed to determine the expression levels of S100A12, RAGE, and NF-κB in the inflamed pulp of carried teeth. In the present study, mRNA from 50 inflamed pulp and 50 healthy pulp were used for expression studies using real-time polymerase chain reaction. The expression levels of S100A12, RAGE, and NF-κB were compared between inflamed and healthy tissues. The results revealed that the expression of S100A12, but not of RAGE or NF-κB, was significantly decreased in inflamed pulp when compared to healthy pulp. mRNA levels of RAGE were also increased in the inflamed pulp taken from men when compared with women. The results suggest that S100A12 does not participate in the induction of inflammation in dental pulp. However, RAGE can participate in the inflammation in the pulp of males. © 2017 John Wiley & Sons Australia, Ltd.

  19. Davallialactone reduces inflammation and repairs dentinogenesis on glucose oxidase-induced stress in dental pulp cells.

    PubMed

    Lee, Young-Hee; Kim, Go-Eun; Song, Yong-Beom; Paudel, Usha; Lee, Nan-Hee; Yun, Bong-Sik; Yu, Mi-Kyung; Yi, Ho-Keun

    2013-11-01

    The chronic nature of diabetes mellitus (DM) raises the risk of oral complication diseases. In general, DM causes oxidative stress to organs. This study aimed to evaluate the cellular change of dental pulp cells against glucose oxidative stress by glucose oxidase with a high glucose state. The purpose of this study was to test the antioxidant character of davallialactone and to reduce the pathogenesis of dental pulp cells against glucose oxidative stress. The glucose oxidase with a high glucose concentration was tested for hydroxy peroxide (H2O2) production, cellular toxicity, reactive oxygen species (ROS) formation, induction of inflammatory molecules and disturbance of dentin mineralization in human dental pulp cells. The anti-oxidant effect of Davallilactone was investigated to restore dental pulp cells' vitality and dentin mineralization via reduction of H2O2 production, cellular toxicity, ROS formation and inflammatory molecules. The treatment of glucose oxidase with a high glucose concentration increased H2O2 production, cellular toxicity, and inflammatory molecules and disturbed dentin mineralization by reducing pulp cell activity. However, davallialactone reduced H2O2 production, cellular toxicity, ROS formation, inflammatory molecules, and dentin mineralization disturbances even with a long-term glucose oxidative stress state. The results of this study imply that the development of oral complications is related to the irreversible damage of dental pulp cells by DM-induced oxidative stress. Davallialactone, a natural antioxidant, may be useful to treat complicated oral disease, representing an improvement for pulp vital therapy. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. Inflammation and Regeneration in the Dentin-pulp Complex: Net Gain or Net Loss?

    PubMed

    Cooper, Paul R; Chicca, Ilaria J; Holder, Michael J; Milward, Michael R

    2017-09-01

    using AMPs and histones, limiting the spread of the infection, data also indicate that NETs can exacerbate inflammation and their components are cytotoxic. This review considers the potential role of NETs within pulpal infections and how these structures may influence the pulp's vitality and regenerative responses. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. 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

    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. 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. PEG-PEI is a promising vector for gene therapy. miR-146a and bFGF play critical roles in inflammation response and tissue regeneration of DPCs.

  3. 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

  4. 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

  5. Overexpression of receptor for advanced glycation end products and high-mobility group box 1 in human dental pulp inflammation.

    PubMed

    Tancharoen, Salunya; Tengrungsun, Tassanee; Suddhasthira, Theeralaksna; Kikuchi, Kiyoshi; Vechvongvan, Nuttavun; Tokuda, Masayuki; 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.

  6. 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

  7. Use of ascorbic and citric acids to increase dialyzable iron from vinal (Prosopis ruscifolia) pulp.

    PubMed

    Bernardi, C; Freyre, M; Sambucetti, M E; Pirovani, M E

    2004-01-01

    Vinal (Prosopis ruscifolia) is an ecologically important wild leguminous tree that grows spontaneously in Argentine deforested lands, the fruit of which is consumed by humans and animals. Because considerable iron content with low to intermediate availability has been previously reported in vinal pulps, its enhancement would be of interest. Iron availability was determined as iron dialyzability using an in vitro technique. Response surface methodology was used to evaluate iron availability increase after adding ascorbic and/or citric acids to vinal pulp at different mM acid/mM Fe ratios. Those ratios ranged from 0.05:1 to 9.95:1 and from 0.5:1 to 99.5:1 for ascorbic acid/Fe (AA:Fe) and citric acid/Fe (CA:Fe), respectively. The obtained second- and first-order polynomial equations showed that AA:Fe and CA:Fe molar ratios linear terms had a significant effect on iron dialyzability increase (P < or = 0.05). It was possible to enhance iron availability to a maximum of 4.6 times. Additional confirmatory experiments were made adding the same organic acids to different vinal pulps and to a traditional cake prepared with vinal pulp called "patay." There were no significant differences (p > 0.05) between predicted values obtained by the model and experimental results.

  8. Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation.

    PubMed

    Igbe, Ighodaro; Ching, Fidelis P; Eromon, Aigbe

    2010-01-01

    The anti-inflammatory effect of the aqueous fruit pulp extract of Hunteria umbellata K. Schum (Apocynaceae) was evaluated using the carrageenan- and dextran-induced rat paw edema, xylene-induced ear edema and formalin-induced arthritis inflammation tests. Oral administration of the extract produced significant (p < 0.05) antiedematogenic effect with a dose of 500 mg/kg throughout the period of the experiment in the dextran induced paw edema and at the 3 h in the carrageenan model. The extract (250 and 500 mg/kg) exhibited a dose-related and significant (p < 0.01) inhibition of xylene induced ear edema and the effect was similar to that produced by dexamethasone (1 mg/kg). In the chronic inflammation (formalin induced arthritis) the extract did not show any significant anti-inflammatory activity. Oral acute toxicity assays did not show any mortality at 15 g/kg of the plant extract. The results indicate that the aqueous extract of H. umbellata possesses acute inflammatory activity which may be mediated by either inhibition or by blocking the release of prostaglandins and histamine, thus supporting the usage of the plant in traditional medicine treatment of inflammation.

  9. 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

  10. 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.

  11. [Non-contact measurement of the increase in pulp temperature during thermal debonding].

    PubMed

    Baumann, M; Ruppenthal, T

    1991-01-01

    Thermal debonding of ceramic brackets is now used for some time. In this context the possibility of a thermal damage of the pulp is one of the main questions. With the aid of a touchless infrared thermography device (SST/Theta 1,000; Heimann, FRG-Wiesbaden) the consequences of thermal debonding with the "Ceramic Debonding Unit" (Dentaurum, Pforzheim) have been studied. A use according to the manufacturer's device led to temperature changes up to 3 degrees C as maximum. Therefore our in vitro results indicate that the orderly use of the system is safe for the pulp. If the debonding fails, the temperature increase is much higher if the resistance wire is left in place. The influence of different composites is discussed.

  12. Alkaline peroxide treatment of ECF bleached softwood kraft pulps: part 2. effect of increased fiber charge on refining, wet-end application, and hornification

    Treesearch

    Zheng Dang; Thomas Elder; Jeffery S. Hsieh; Arthur J. Ragauskas

    2007-01-01

    The effect of increased fiber charge on refining, cationic starch adsorption, and hornification was examined. Two pulps were investigated: (1) a softwood (SW) kraft pulp (KP) which was bleached elementally chlorine-free (ECF) and sewed as control; and (2) a control pulp treated with alkaline peroxide, which had a higher fiber charge. It was shown that increased fiber...

  13. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    PubMed

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  14. Exacerbated and prolonged inflammation impairs wound healing and increases scarring.

    PubMed

    Qian, Li-Wu; Fourcaudot, Andrea B; Yamane, Kazuyoshi; You, Tao; Chan, Rodney K; Leung, Kai P

    2016-01-01

    Altered inflammation in the early stage has long been assumed to affect subsequent steps of the repair process that could influence proper wound healing and remodeling. However, the lack of explicit experimental data makes the connection between dysregulated wound inflammation and poor wound healing elusive. To bridge this gap, we used the established rabbit ear hypertrophic scar model for studying the causal effect of dysregulated inflammation. We induced an exacerbated and prolonged inflammatory state in these wounds with the combination of trauma-related stimulators of pathogen-associated molecular patterns from heat-killed Pseudomonas aeruginosa and damage-associated molecular patterns from a dermal homogenate. In stimulated wounds, a heightened and lengthened inflammation was observed based on quantitative measurements of IL-6 expression, tissue polymorphonuclear leukocytes infiltration, and tissue myeloperoxidase activity. Along with the high level of inflammation, wound healing parameters (epithelial gap and others) at postoperative day 7 and 16 were significantly altered in stimulated wounds compared to unstimulated controls. By postoperative day 35, scar elevation of stimulated wounds was higher than that of control wounds (scar elevation index: 1.90 vs. 1.39, p < 0.01). Moreover, treatment of these inflamed wounds with Indomethacin (at concentrations of 0.01, 0.1, and 0.4%) reduced scar elevation but with adverse effects of delayed wound closure and increased cartilage hypertrophy. In summary, successful establishment of this inflamed wound model provides a platform to understand these detrimental aspects of unchecked inflammation and to further test agents that can modulate local inflammation to improve wound outcomes. © 2016 by the Wound Healing Society.

  15. Peripheral inflammation increases the deleterious effect of CNS inflammation on the nigrostriatal dopaminergic system.

    PubMed

    Hernández-Romero, Ma Carmen; Delgado-Cortés, M José; Sarmiento, Manuel; de Pablos, Rocío M; Espinosa-Oliva, Ana María; Argüelles, Sandro; Bández, Manuel J; Villarán, Ruth F; Mauriño, Raquel; Santiago, Marti; Venero, José L; Herrera, Antonio J; Cano, Josefina; Machado, Alberto

    2012-06-01

    Evidence supports the role of inflammation in the development of neurodegenerative diseases. In this work, we are interested in inflammation as a risk factor by itself and not only as a factor contributing to neurodegeneration. We tested the influence of a mild to moderate peripheral inflammation (injection of carrageenan into the paws of rats) on the degeneration of dopaminergic neurons in an animal model based on the intranigral injection of lipopolysaccharide (LPS), a potent inflammatory agent. Overall, the treatment with carrageenan increased the effect of the intranigral injection of LPS on the loss of dopaminergic neurons in the SN along with all the other parameters studied, including: serum levels of the inflammatory markers TNF-α, IL-1β, IL-6 and C-reactive protein; activation of microglia, expression of proinflammatory cytokines, the adhesion molecule ICAM and the enzyme iNOS, loss of astrocytes and damage to the blood brain barrier (BBB). The possible implication of BBB rupture in the increased loss of dopaminergic neurons has been studied using another Parkinson's disease animal model based on the intraperitoneal injection of rotenone. In this experiment, loss of dopaminergic neurons was also strengthened by carrageenan, without affecting the BBB. In conclusion, our data show that a mild to moderate peripheral inflammation can exacerbate the degeneration of dopaminergic neurons caused by a harmful stimulus.

  16. 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.

  17. 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

  18. Increased prevalence of intestinal inflammation in patients with liver cirrhosis

    PubMed Central

    Saitoh, Osamu; Sugi, Kazunori; Kojima, Keishi; Matsumoto, Hisashi; Nakagawa, Ken; Kayazawa, Masanobu; Tanaka, Seigou; Teranishi, Tsutomu; Hirata, Ichiro; Katsu, Ken-ichi

    1999-01-01

    AIM: To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis. METHODS: In 42 cirrhotic patients and 20 control subjects, the following fecal proteins were measured by enzyme-linked immunosorbent assay: albumin (Alb), transferrin (Tf), and α1-antitrypsin (α1-AT) as a marker for intestinal protein loss, hemoglobin (Hb) for bleeding, PMN-elastase for intestinal inflammation, and secretory IgA for intestinal immunity. RESULTS: The fecal concentrations of Hb, Alb, Tf, α1-AT, an d PMN-elastase were increased in 13 (31%), 8 (19%), 10 (24%), 6 (14%), and 11 (26%) cases among 42 patients, respectively. Fecal concentration of secretory IgA was decreased in 7 (17%) of 42 patients. However, these fecal concentrations were not related to the severity or etiology of liver cirrhosis. The serum Alb level was significantly decreased in patients with intestinal protein loss compared to that in patients without intestinal protein loss. CONCLUSION: These findings suggest that: ① besides the well-known pathological conditions, such as bleeding and protein loss, intestinal inflammation and decreased intestinal immunity are found in cirrhotic patients; ② intestinal protein loss contributes to hypoalbuminemia in cirrhotic patients, and ③ intestinal inflammation should not be over looked in cirrhotic patients, since it may contribute to or cause intestinal protein loss and other various path ological conditions. PMID:11819475

  19. Increasing efficiency of enzymatic hemicellulose removal from bamboo for production of high-grade dissolving pulp.

    PubMed

    Zhao, Lingfeng; Yuan, Zhaoyang; Kapu, Nuwan Sella; Chang, Xue Feng; Beatson, Rodger; Trajano, Heather L; Martinez, D Mark

    2017-01-01

    To improve the efficiency of enzymatic hemicellulose removal from bamboo pre-hydrolysis kraft pulp, mechanical refining was conducted prior to enzyme treatment. Refining significantly improved the subsequent hemicellulose removal efficiency by xylanase treatment. Results showed that when PFI refining was followed by 3h xylanase treatment, the xylan content of the bamboo pre-hydrolysis kraft pulp (after first stage oxygen delignification) could be decreased to 2.72% (w/w). After bleaching of enzyme treated pulp, the alpha-cellulose content was 93.4% (w/w) while the xylan content was only 2.38%. The effect of refining on fibre properties was investigated in terms of freeness, water retention value, fibre length and fibrillation characteristics. The brightness, reactivity and viscosity were also determined to characterize the quality of final pulp. Results demonstrated the feasibility of combining refining and xylanase treatment to produce high quality bamboo dissolving pulp.

  20. 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

  1. 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.

  2. 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

  3. Formulation and sensory evaluation of Prosopis alba (Algarrobo) pulp cookies with increased iron and calcium dialyzabilities.

    PubMed

    Bernardi, C; Drago, S; Sabbag, N; Sanchez, H; Freyre, M

    2006-03-01

    Prosopis alba (algarrobo) is an important indigenous specie, which fruits are used as food and feed since ancient times. Cookies containing algarrobo pulp (AP) with increased iron and calcium availabilities were formulated and sensory evaluated. AP is preferred as food ingredient because of its high sugar content and pleasant flavour. Formulated cookies mean proximal composition was 8.9 g/100 g protein, 7.2 g/100 g dietary fiber, 25 g/100 g total sugar, and 18.5 g/100 g crude fat with iron and calcium contents 30 ppm and 340 ppm, respectively. Ascorbic (AA) and citric (CA) acids at different mM acid: mM Fe were added in order to increase mineral availabilities being evaluated by an in vitro method. Those ratios were 5:1 and 10:1 for AA:Fe whereas for CA:Fe were 50:1 and 100:1 and combinations of them. After chosen the best AA:Fe and CA:Fe ratios (5:1 and 50:1, respectively), sensory evaluation with trained sensory panel and a consumer acceptability test with one hundred and seventy untrained judges were carried out. Acceptability test showed that 77.65% of the people (< 25 years old 41.76%, 25-50 years old 20.00% and > 50 years old 15.89%) tasting final formulated cookies indicated that they "like very much" or "moderately like" and there were not consumers rejecting them.

  4. Seed dispersal by pulp consumers, not "legitimate" seed dispersers, increases Guettarda viburnoides population growth.

    PubMed

    Loayza, Andrea P; Knight, Tiffany

    2010-09-01

    We examined the effect of seed dispersal by Purplish Jays (Cyanocorax cyanomelas; pulp consumers) and the Chestnut-eared Araçari (Pteroglossus castanotis; "legitimate" seed dispersers) on population growth of the small tree Guettarda viburnoides (Rubiaceae) in northeastern Bolivian savannas. Because each bird species differs with respect to feeding and post-feeding behavior, we hypothesized that seed dispersal by each species will contribute differently to the rate of increase of G. viburnoides, but that seed dispersal by either species will increase population growth when compared to a scenario with no seed dispersal. To examine the effects of individual dispersers on the future population size of G. viburnoides, we projected population growth rate using demographic models for G. viburnoides that explicitly incorporate data on quantitative and qualitative aspects of seed dispersal by each frugivore species. Our model suggests that seed dispersal by C. cyanomelas leads to positive population growth of G. viburnoides, whereas seed dispersal by P. castanotis has a detrimental effect on the population growth of this species. To our knowledge, this is the first study to report negative effects of a "legitimate" seed disperser on the population dynamics of the plant it consumes. Our results stress the importance of incorporating frugivore effects into population projection matrices, to allow a comprehensive analysis of the effectiveness of different dispersers for plant population dynamics.

  5. Increased uptake by splenic red pulp macrophages contributes to rapid platelet turnover in WASP(-) mice.

    PubMed

    Prislovsky, Amanda; Strom, Ted S

    2013-09-01

    Thrombocytopenia caused by rapid platelet consumption contributes to the severe thrombocytopenia of Wiskott-Aldrich syndrome (WAS) and to the milder thrombocytopenia seen in murine WAS. We show that rapid clearance of ¹¹¹In-labeled murine WASP(-) platelets correlates with enhanced splenic uptake. Using platelets labeled with a pH-sensitive fluorescent marker (pHrodo), we quantify normal platelet uptake by red pulp macrophages (RPMs), and demonstrate its enhancement after in vivo opsonization of platelets. The spleens of WASP(-) mice contain an increased number of RPM, and rapid clearance of WASP(-) platelets in WASP(-) mice in turn generates an increased number of pHrodo(+) splenic RPMs. To separately assess the platelet intrinsic and recipient-dependent functions involved in the clearance and splenic phagocyte uptake of WASP(-) platelets, we performed "crossed" pHrodo(+) platelet injection studies (wild type [WT] to WASP(-), WASP(-) to WT). We show that an extrinsic effect of recipient WASP deficiency on the clearance of WASP(-) platelets correlates with increased platelet uptake by RPMs. An intrinsic effect of platelet WASP deficiency on platelet clearance does not, however, correlate with increased total uptake by WT or WASP(-) RPMs. In contrast to other published findings, we find no evidence of a baseline or antibody-induced increase in phosphatidyl serine exposure on WASP(-) platelets. Our findings suggest that an increased number of RPMs in WASP(-) mice contributes significantly to the increased platelet consumption rate in WASP(-) mice. This might explain the consistent efficacy of splenectomy in murine and clinical WAS. Published by Elsevier Inc.

  6. 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

  7. Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

    PubMed

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [(11)C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

  8. Biomechanical pulping with Phlebiopsis gigantea reduced energy consumption and increased paper strength : [summary

    Treesearch

    Chad J. Behrendt; Robert A. Blanchette; Masood. Akhtar; Scott. Enebak; Sara. Iverson; Diane. Williams

    2000-01-01

    Biomechanical pulping of whole logs pretreated with Phlebiopsis gigantea was investigated in several studies using loblolly and red pine. Results from these studies showed P. gigantea was able to colonize 90 to 100% of the freshly cut logs after 8 weeks, with little variation between replicate treatments. Up to a 59% decrease in resinous wood extractives was observed...

  9. 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.

  10. VEGFR-2 reduces while combined VEGFR-2 and -3 signaling increases inflammation in apical periodontitis

    PubMed Central

    Virtej, Anca; Papadakou, Panagiota; Sasaki, Hajime; Bletsa, Athanasia; Berggreen, Ellen

    2016-01-01

    Background In apical periodontitis, oral pathogens provoke an inflammatory response in the apical area that induces bone resorptive lesions. In inflammation, angio- and lymphangiogenesis take place. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key players in these processes and are expressed in immune cells and endothelial cells in the lesions. Objective We aimed at testing the role of VEGFR-2 and -3 in periapical lesion development and investigated their role in lymphangiogenesis in the draining lymph nodes. Design We induced lesions by pulp exposure in the lower first molars of C57BL/6 mice. The mice received IgG injections or blocking antibodies against VEGFR-2 (anti-R2), VEGFR-3 (anti-R3), or combined VEGFR-2 and -3, starting on day 0 until day 10 or 21 post-exposure. Results Lesions developed faster in the anti-R2 and anti-R3 group than in the control and anti-R2/R3 groups. In the anti-R2 group, a strong inflammatory response was found expressed as increased number of neutrophils and osteoclasts. A decreased level of pro-inflammatory cytokines was found in the anti-R2/R3 group. Lymphangiogenesis in the draining lymph nodes was inhibited after blocking of VEGFR-2 and/or -3, while the largest lymph node size was seen after anti-R2 treatment. Conclusions We demonstrate an anti-inflammatory effect of VEGFR-2 signaling in periapical lesions which seems to involve neutrophil regulation and is independent of angiogenesis. Combined signaling of VEGFR-2 and -3 has a pro-inflammatory effect. Lymph node lymphangiogenesis is promoted through activation of VEGFR-2 and/or VEGFR-3. PMID:27650043

  11. Diabetes increases pancreatitis induced systemic inflammation but has little effect on inflammation and cell death in the lung

    PubMed Central

    Zechner, Dietmar; Spitzner, Marie; Müller-Graff, Tassilo; Vollmar, Brigitte

    2014-01-01

    Acute pancreatitis (AP) can lead to a systemic inflammatory response that often results in acute lung injury and single or multiple organ failure. In a previous study we demonstrated that diabetes aggravates the local pathophysiological process during AP. In this study we explore, if diabetes also increases pancreatitis induced systemic inflammation and causes lung injury. Acute pancreatitis was induced in untreated and streptozotocin-treated diabetic mice by injection of cerulein. Systemic inflammation was studied by IL-6 ELISA in blood plasma and white blood cell count. Lung inflammation and lung injury were quantified by chloroacetate esterase staining, evaluation of the alveolar cellularity index and cleaved caspase-3 immunohistochemistry. In normoglycaemic mice AP increased the IL-6 concentration in plasma and caused lymphocytopenia. Diabetes significantly increased the IL-6 concentration in plasma and further reduced the number of lymphocytes during AP, whereas diabetes had little effect on these parameters in the absence of pancreatitis. However, diabetes only marginally increased lung inflammation and did not lead to cell death of the lung epithelium during AP. We conclude that diabetes increases parameters of systemic inflammation during AP, but that this increase is insufficient to cause lung injury. PMID:25401425

  12. Regenerative potential of dental pulp.

    PubMed

    Trope, Martin

    2008-07-01

    The regenerative potential of dental pulp, particularly in mature teeth, has been considered extremely limited. However, our improved understanding of pulpal inflammation and repair and improved dental materials and technologies make vital pulp therapy a viable alternative to root canal treatment. This article explores our knowledge in this regard and the future potential of saving or even regenerating the pulp as a routine dental procedure.

  13. Regenerative potential of dental pulp.

    PubMed

    Trope, Martin

    2008-01-01

    The regenerative potential of dental pulp, particularly in mature teeth, has been considered extremely limited. However, our improved understanding of pulpal inflammation and repair and improved dental materials and technologies make vital pulp therapy a viable alternative to root canal treatment. This article explores our knowledge in this regard and the future potential of saving or even regenerating the pulp as a routine dental procedure.

  14. Novel insights into the aetiology and pathophysiology of increased airway inflammation during COPD exacerbations.

    PubMed

    Tsoumakidou, Maria; Siafakas, Nikolaos M

    2006-05-22

    Airway inflammation increases during acute exacerbations of COPD. Extrinsic factors, such as airway infections, increased air pollution, and intrinsic factors, such as increased oxidative stress and altered immunity may contribute to this increase. The evidence for this and the potential mechanisms by which various aetiological agents increase inflammation during COPD exacerbations is reviewed. The pathophysiologic consequences of increased airway inflammation during COPD exacerbations are also discussed. This review aims to establish a cause and effect relationship between etiological factors of increased airway inflammation and COPD exacerbations based on recently published data. Although it can be speculated that reducing inflammation may prevent and/or treat COPD exacerbations, the existing anti-inflammatory treatments are modestly effective.

  15. Active Nanomaterials to Meet the Challenge of Dental Pulp Regeneration

    PubMed Central

    Keller, Laetitia; Offner, Damien; Schwinté, Pascale; Morand, David; Wagner, Quentin; Gros, Catherine; Bornert, Fabien; Bahi, Sophie; Musset, Anne-Marie; Benkirane-Jessel, Nadia; Fioretti, Florence

    2015-01-01

    The vitality of the pulp is fundamental to the functional life of the tooth. For this aim, active and living biomaterials are required to avoid the current drastic treatment, which is the removal of all the cellular and molecular content regardless of its regenerative potential. The regeneration of the pulp tissue is the dream of many generations of dental surgeons and will revolutionize clinical practices. Recently, the potential of the regenerative medicine field suggests that it would be possible to achieve such complex regeneration. Indeed, three crucial steps are needed: the control of infection and inflammation and the regeneration of lost pulp tissues. For regenerative medicine, in particular for dental pulp regeneration, the use of nano-structured biomaterials becomes decisive. Nano-designed materials allow the concentration of many different functions in a small volume, the increase in the quality of targeting, as well as the control of cost and delivery of active molecules. Nanomaterials based on extracellular mimetic nanostructure and functionalized with multi-active therapeutics appear essential to reverse infection and inflammation and concomitantly to orchestrate pulp cell colonization and differentiation. This novel generation of nanomaterials seems very promising to meet the challenge of the complex dental pulp regeneration. PMID:28793649

  16. Focal adhesion kinase maintains, but not increases the adhesion of dental pulp cells.

    PubMed

    Qian, Yuyan; Shao, Meiying; Zou, Wenlin; Wang, Linyan; Cheng, Ran; Hu, Tao

    2017-04-01

    Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.

  17. TNF-alpha stimulation increases dental pulp stem cell migration in vitro through integrin alpha-6 subunit upregulation.

    PubMed

    Shi, Lei; Fu, Shanqi; Fahim, Sidra; Pan, Shuang; Lina, He; Mu, Xiaodan; Niu, Yumei

    2017-03-01

    The dissemination of stem cells into tissues requiring inflammatory and reparative response is fundamentally dependent upon their chemotactic migration. Expression of TNF-α is up regulated in inflamed pulps. Dental pulp cells are also known to express integrin α6 subunit. Expression of integrin subunit α6 has been linked to the acquisition of migratory potential in a wide variety of cell types in both pathological and physiological capacities. Therefore, in this study we examined the effects of a pleiotropic cytokine TNF-α on the migration of hDPSCs and investigated its relationship with expression of integrin α6 in hDPSCs during chemotactic migration. hDPSC cultures were established. Protein expression profile of α6 integrin subunit was determined. Effect of exogenous TNF-α (50ng/mL) on hDPSCs' migration potential was evaluated by transwell inserts and in vitro scratch assay. Upregulation/downregulation of TNF-α mediated migration was assayed in presence/absence of integrin α6 respectively. To suppress integrin α6 expression, cells were transfected with integrin α6 siRNA and then cell migration and cytoskeletal changes were evaluated. Our results showed significant increase of hDPSCs' migration after stimulation with TNF-α. By knockdown of integrin α6, which is upregulated by TNF-α, we observed a decrease in the TNF-α directed chemotaxis of hDPSCs. In this study, we show that activation of integrin α6 brought about by TNF-α led to an increase in migratory activity in DPSCs in vitro thus describing a novel association between a cytokine TNF-α and α6 chain of an adhesion receptor integrin in regulating migration of hDPSCs. Copyright © 2016. Published by Elsevier Ltd.

  18. IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse

    PubMed Central

    2012-01-01

    Background IL-6 is a pleiotropic cytokine that modulates inflammatory responses and plays critical roles in muscle maintenance and remodeling. In the mouse model (mdx) of Duchenne Muscular Dystrophy, IL-6 and muscle inflammation are elevated, which is believed to contribute to the chronic inflammation and failure of muscle regeneration in DMD. The purpose of the current study was to examine the effect of blocking IL-6 signaling on the muscle phenotype including muscle weakness and pathology in the mdx mouse. Methods A monoclonal antibody against the IL-6 receptor (IL-6r mAb) that blocks local and systemic IL-6 signaling was administered to mdx and BL-10 mice for 5 weeks and muscle function, histology, and inflammation were examined. Results IL-6r mAb treatment increased mdx muscle inflammation including total inflammation score and ICAM-1 positive lumens in muscles. There was no significant improvement in muscle strength nor muscle pathology due to IL-6r mAb treatment in mdx mice. Conclusions These results showed that instead of reducing inflammation, IL-6 signaling blockade for 5 weeks caused an increase in muscle inflammation, with no significant change in indices related to muscle regeneration and muscle function. The results suggest a potential anti-inflammatory instead of the original hypothesized pro-inflammatory role of IL-6 signaling in the mdx mice. PMID:22716658

  19. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation[S

    PubMed Central

    Bot, Martine; de Jager, Saskia C. A.; MacAleese, Luke; Lagraauw, H. Maxime; van Berkel, Theo J. C.; Quax, Paul H. A.; Kuiper, Johan; Heeren, Ron M. A.; Biessen, Erik A. L.; Bot, Ilze

    2013-01-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. PMID:23396975

  20. NF-kB Induction in Airway Epithelium Increases Lung Inflammation in Allergen Challenged Mice

    PubMed Central

    Sheller, James R.; Polosukhin, Vasiliy V.; Mitchell, Daphne; Cheng, D-S.; Peebles, R. Stokes; Blackwell, Timothy S.

    2012-01-01

    NF-kB is a critical transcription factor for the production of many inflammatory cytokines. It is activated in the airway epithelium of human asthmatics and in mice after allergic stimulation. To examine the role of NF-kB activation in allergic inflammation we generated transgenic mouse lines that allowed for the inducible stimulation of NF-kB in airway epithelial cells. After allergic sensitization with ovalbumin and alum, mice were challenged daily with ovalbumin aerosols and NF-kB was activated in airway epithelium by administration of doxycycline. Enhancement of airway epithelial NF-kB expression alone did not lead to increased airway responsiveness to methacholine. However induction of epithelial NF-kB during allergic inflammation caused airway hyperresponsiveness, increased airway neutrophilic and lymphocytic inflammation and goblet cell hyperplasia. Accompanying the exaggerated inflammation was an increase in the cytokines, G-CSF, IL-15, and KC. Interestingly, the counter regulatory interleukin, IL-10, was suppressed by NF-kB activation. The epithelial NF-kB dependent modulation of these cytokines provides a plausible explanation for the increased inflammation seen with overexpression of NF-kB. Modulation of airway epithelial NF-kB activation enhances the airway hyperresponsiveness and mucus secretion found in the mouse lung during allergic inflammation. NF-kB represents a potential target for pharmacologic intervention in human asthma. PMID:19995280

  1. Replacing cereals with dehydrated citrus pulp in a soybean oil supplemented diet increases vaccenic and rumenic acids in ewe milk.

    PubMed

    Santos-Silva, José; Dentinho, Maria T; Francisco, Alexandra; Portugal, Ana P; Belo, Ana T; Martins, António P L; Alves, Susana P; Bessa, Rui J B

    2016-02-01

    This study evaluates the effect of the replacement of cereals by dried citrus pulp (DCP) in diets supplemented with 5% of soybean oil, on ewe milk yield and composition, including milk fatty acid (FA). Four Serra da Estrela multiparous ewes in the second month of lactation were used in a double 2×2 Latin square design. Ewes were individually penned and milked twice a day with an 8-h interval. Each experimental period included 14 d of diet adaptation followed by 5d of measurements and sampling. The 2 diets included on dry matter basis 450 g/kg of corn silage and 550 g/kg of either a soybean oil-supplemented concentrate meal containing barley and maize (cereal) or dried citrus pulp (DCP; citrus). Feed was offered ad libitum, considering 10% of orts, and intake was measured daily. Milk yield was higher and dry matter intake tended to be higher with the citrus diet. Milk composition and technological properties for cheese production were not affected by treatments, except for lactose, which was lower with the citrus diet. Replacement of cereals by DCP resulted in a 3-percentage-point decrease of both 18:0 and cis-9-18:1 that were mostly compensated by the 4.19- and 1.68-percentage-point increases of trans-11-18:1 and cis-9,trans-11-18:2, respectively. The intake of C18 FA tended to increase with the citrus diet compared with the cereal diet, but the apparent transfer of 18:2n-6 and of 18:3n-3 did not differ between diets. The milk output of C18 FA increased with the citrus compared with the cereal diet, mostly due to the increase of trans-11-18:1 and cis-9,trans-11-18:2 because the daily milk output of 18:0, trans-10-18:1, cis-9-18:1, 18:2n-6 and 18:3n-3 did not differ between diets. Replacing cereals with DCP in an oil-supplemented diet resulted in a selective increase of trans-11-18:1 and cis-9,trans-11-18:2 in milk, with no major effect on other biohydrogenation intermediates.

  2. Hydrogen sulphide increases hepatic differentiation of human tooth pulp stem cells compared with human bone marrow stem cells.

    PubMed

    Okada, M; Ishkitiev, N; Yaegaki, K; Imai, T; Tanaka, T; Fukuda, M; Ono, S; Haapasalo, M

    2014-12-01

    To determine the differences in stem cell properties, in hepatic differentiation and in the effects of hydrogen sulphide (H2 S) on hepatic differentiation between human bone marrow stem cells (hBMC) and stem cells from human exfoliated primary tooth pulp (SHED). CD117(+) cells were magnetically separated and subjected to hepatic differentiation. CD117(+) cell lineages were characterized for transcription factors indicative of stem cells by qRT-PCR. For the last 9 days of the differentiation, the test cells were exposed to 0.1 ng mL(-1) H2 S. Immunocytochemistry and flow cytometry of albumin, alpha-fetoprotein and carbamoyl phosphate synthetase were carried out after differentiation. Urea concentration and glycogen synthesis were also determined. Genes expressed in SHED were also expressed in BMC. No difference in expression level of hepatic markers was shown by immunofluorescence. SHED showed more positive cells than hBMC (P < 0.01). H2 S increased the number of positive cells in both cultures (P < 0.01). Urea concentration and glycogen synthesis increased significantly after H2 S exposure (P < 0.001 and P < 0.05, respectively). Real-time PCR data were analysed by RT(2) profiler RT-PCR Array Data Analysis version 3.5 (Qiagen), and ELISA data were analysed by Bonferroni's multiple comparison using Windows spss version 16 (SPSS Inc, Chicago, IL, USA). Bonferroni's multiple comparison test was also carried out after angle transformation for the percentage data of flow cytometer using Windows spss(®) version 16 (SPSS Inc). Statistical significance was accepted at P < 0.05. Stem cells from human exfoliated primary tooth pulp and BMC have similar properties. The level of hepatic differentiation in SHED compared with BMC was the same or higher. H2 S increased the level of hepatic differentiation. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  3. Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain.

    PubMed

    Goeden, Nick; Velasquez, Juan; Arnold, Kathryn A; Chan, Yen; Lund, Brett T; Anderson, George M; Bonnin, Alexandre

    2016-06-01

    Maternal inflammation during pregnancy affects placental function and is associated with increased risk of neurodevelopmental disorders in the offspring. The molecular mechanisms linking placental dysfunction to abnormal fetal neurodevelopment remain unclear. During typical development, serotonin (5-HT) synthesized in the placenta from maternal l-tryptophan (TRP) reaches the fetal brain. There, 5-HT modulates critical neurodevelopmental processes. We investigated the effects of maternal inflammation triggered in midpregnancy in mice by the immunostimulant polyriboinosinic-polyribocytidylic acid [poly(I:C)] on TRP metabolism in the placenta and its impact on fetal neurodevelopment. We show that a moderate maternal immune challenge upregulates placental TRP conversion rapidly to 5-HT through successively transient increases in substrate availability and TRP hydroxylase (TPH) enzymatic activity, leading to accumulation of exogenous 5-HT and blunting of endogenous 5-HT axonal outgrowth specifically within the fetal forebrain. The pharmacological inhibition of TPH activity blocked these effects. These results establish altered placental TRP conversion to 5-HT as a new mechanism by which maternal inflammation disrupts 5-HT-dependent neurogenic processes during fetal neurodevelopment. The mechanisms linking maternal inflammation during pregnancy with increased risk of neurodevelopmental disorders in the offspring are poorly understood. In this study, we show that maternal inflammation in midpregnancy results in an upregulation of tryptophan conversion to serotonin (5-HT) within the placenta. Remarkably, this leads to exposure of the fetal forebrain to increased concentrations of this biogenic amine and to specific alterations of crucially important 5-HT-dependent neurogenic processes. More specifically, we found altered serotonergic axon growth resulting from increased 5-HT in the fetal forebrain. The data provide a new understanding of placental function playing a key

  4. Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain

    PubMed Central

    Goeden, Nick; Velasquez, Juan; Arnold, Kathryn A.; Chan, Yen; Lund, Brett T.; Anderson, George M.

    2016-01-01

    Maternal inflammation during pregnancy affects placental function and is associated with increased risk of neurodevelopmental disorders in the offspring. The molecular mechanisms linking placental dysfunction to abnormal fetal neurodevelopment remain unclear. During typical development, serotonin (5-HT) synthesized in the placenta from maternal l-tryptophan (TRP) reaches the fetal brain. There, 5-HT modulates critical neurodevelopmental processes. We investigated the effects of maternal inflammation triggered in midpregnancy in mice by the immunostimulant polyriboinosinic-polyribocytidylic acid [poly(I:C)] on TRP metabolism in the placenta and its impact on fetal neurodevelopment. We show that a moderate maternal immune challenge upregulates placental TRP conversion rapidly to 5-HT through successively transient increases in substrate availability and TRP hydroxylase (TPH) enzymatic activity, leading to accumulation of exogenous 5-HT and blunting of endogenous 5-HT axonal outgrowth specifically within the fetal forebrain. The pharmacological inhibition of TPH activity blocked these effects. These results establish altered placental TRP conversion to 5-HT as a new mechanism by which maternal inflammation disrupts 5-HT-dependent neurogenic processes during fetal neurodevelopment. SIGNIFICANCE STATEMENT The mechanisms linking maternal inflammation during pregnancy with increased risk of neurodevelopmental disorders in the offspring are poorly understood. In this study, we show that maternal inflammation in midpregnancy results in an upregulation of tryptophan conversion to serotonin (5-HT) within the placenta. Remarkably, this leads to exposure of the fetal forebrain to increased concentrations of this biogenic amine and to specific alterations of crucially important 5-HT-dependent neurogenic processes. More specifically, we found altered serotonergic axon growth resulting from increased 5-HT in the fetal forebrain. The data provide a new understanding of placental

  5. 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

  6. 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.

  7. 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

  8. Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups.

    PubMed

    Vázquez-Medina, José Pablo; Crocker, Daniel E; Forman, Henry Jay; Ortiz, Rudy M

    2010-07-15

    Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

  9. Increased proliferation and adhesion properties of human dental pulp stem cells in PLGA scaffolds via simulated microgravity.

    PubMed

    He, L; Pan, S; Li, Y; Zhang, L; Zhang, W; Yi, H; Song, C; Niu, Y

    2016-02-01

    To explore the possibility of utilizing a rotary cell culture system (RCCS) to model simulated microgravity and investigate its effects on the proliferation, adhesion, migration and cytoskeletal organization of human dental pulp stem cells (hDPSCs) on poly (lactic-co-glycolic acid) (PLGA) scaffolds. Isolated and identified hDPSCs grown on PLGA scaffolds were exposed to simulated microgravity (SMG) or normal gravity (NG) conditions for 3 days. MTT cell proliferation assays, BrdU incorporation assays, flow cytometry analysis and Western blotting were undertaken to identify the proliferation ability of hDPSCs under SMG conditions. Additionally, immunofluorescence detection, SEM observations and cell migration and adhesion assays were performed to compare adhesion, migration and cytoskeletal changes in hDPCSs subjected to SMG conditions. To further investigate the mechanisms, human pathway-focused matrix and adhesion PCR array analyses were performed. The Student's t-test was used for statistical analyses. SMG promoted proliferation and adhesion, decreased migration and reorganized the cytoskeletal organization of hDPSCs compared with the NG group. PCR array analyses revealed that following SMG treatment, ITGA6 (integrin alpha-6), ITGAV (integrin alpha-V), ITGB1 (integrin beta-1), LAMB1 (laminin beta-1) and TNC (tenascin-C) were significantly upregulated (P < 0.05). SMG may regulate the behaviour of hDPSCs grown in PLGA scaffolds in an integrin-mediated manner, which may contribute to tooth tissue engineering by increasing their expandability and scaffold adhesion. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  10. Significant increases in pulping efficiency in C4H-F5H-transformed poplars: improved chemical savings and reduced environmental toxins.

    PubMed

    Huntley, Shannon K; Ellis, Dave; Gilbert, Margarita; Chapple, Clint; Mansfield, Shawn D

    2003-10-08

    The gene encoding ferulate 5-hydroxylase (F5H) was overexpressed in poplar (Populus tremula x Populus alba) using the cinnamate-4-hydroxylase (C4H) promoter to drive expression specifically in cells involved in the lignin biosynthetic pathway and was shown to significantly alter the mole percentage of syringyl subunits in the lignin, as determined by thioacidolysis. Analysis of poplar transformed with a C4H-F5H construct demonstrated significant increases in chemical (kraft) pulping efficiency from greenhouse-grown trees. Compared to wild-type wood, decreases of 23 kappa units and increases of >20 ISO brightness units were observed in trees exhibiting high syringyl monomer concentrations. These changes were associated with no significant modification in total lignin content and no observed phenotypic differences. C4H-F5H-transformed trees could increase pulp throughputs at mills by >60% while concurrently decreasing chemicals employed during processing (chemical pulping and bleaching) and, consequently, the amount of deleterious byproducts released into the environment.

  11. Alveolar macrophage depletion increases the severity of acute inflammation following nonlethal unilateral lung contusion in mice.

    PubMed

    Machado-Aranda, David; V Suresh, Madathilparambil; Yu, Bi; Dolgachev, Vladislov; Hemmila, Mark R; Raghavendran, Krishnan

    2014-04-01

    Lung contusion (LC) is a common injury resulting from blunt thoracic trauma. LC is an important risk factor for the development acute lung injury, adult respiratory distress syndrome, and ventilator-associated pneumonia, all of which increase mortality from trauma. LC produces a nonspecific immune cellular response. Neutrophil recruitment is known to increase the severity of inflammation during LC. However, the exact role of macrophages in modulating the response to LC has not been well described. We used a cortical contusion impactor to induce unilateral LC in mice. Thoracic micro computed tomographic scans of these animals were obtained to document radiologic changes over time following LC. To understand the role of macrophages during LC, liposomal clodronate was used to deplete macrophage levels before traumatic insult. Acute inflammatory attributes after LC were assessed, by measuring pressure-volume mechanics; quantifying bronchial alveolar lavage levels of leukocytes, albumin, and cytokines; and finally examining lung specimen histopathology at 5, 24, 48, and 72 hours after injury. After LC, alveolar macrophage numbers were significantly reduced and exhibited slowed recovery. Simultaneously, there was a significant increase in bronchial alveolar lavage neutrophil counts. The loss of macrophages could be attributed to both cellular apoptosis and necrosis. Pretreatment with clodronate increased the severity of lung inflammation as measured by worsened pulmonary compliance, increased lung permeability, amplification of neutrophil recruitment, and increases in early proinflammatory cytokine levels. The presence of regulatory alveolar macrophages plays an important role in the pathogenesis of acute inflammation following LC.

  12. Alveolar macrophage depletion increases the severity of acute inflammation following nonlethal unilateral lung contusion in mice

    PubMed Central

    Machado-Aranda, David; Suresh, Madathilparambil V.; Yu, Bi; Dolgachev, Vladislov; Hemmila, Mark R.; Raghavendran, Krishnan

    2015-01-01

    BACKGROUND Lung contusion (LC) is a common injury resulting from blunt thoracic trauma. LC is an important risk factor for the development acute lung injury, adult respiratory distress syndrome, and ventilator-associated pneumonia, all of which increase mortality from trauma. LC produces a nonspecific immune cellular response. Neutrophil recruitment is known to increase the severity of inflammation during LC. However, the exact role of macrophages in modulating the response to LC has not been well described. METHODS We used a cortical contusion impactor to induce unilateral LC in mice. Thoracic micro computed tomographic scans of these animals were obtained to document radiologic changes over time following LC. To understand the role of macrophages during LC, liposomal clodronate was used to deplete macrophage levels before traumatic insult. Acute inflammatory attributes after LC were assessed, by measuring pressure-volume mechanics; quantifying bronchial alveolar lavage levels of leukocytes, albumin, and cytokines; and finally examining lung specimen histopathology at 5, 24, 48, and 72 hours after injury. RESULTS After LC, alveolar macrophage numbers were significantly reduced and exhibited slowed recovery. Simultaneously, there was a significant increase in bronchial alveolar lavage neutrophil counts. The loss of macrophages could be attributed to both cellular apoptosis and necrosis. Pretreatment with clodronate increased the severity of lung inflammation as measured by worsened pulmonary compliance, increased lung permeability, amplification of neutrophil recruitment, and increases in early proinflammatory cytokine levels. CONCLUSION The presence of regulatory alveolar macrophages plays an important role in the pathogenesis of acute inflammation following LC. PMID:24662861

  13. 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.

  14. [Multiple pulp stones: report of a case and literature review].

    PubMed

    Feng, Xiao-jie; Luo, Xin; Li, Ren; Dong, Wei; Qi, Meng-chun

    2015-08-01

    Pulp stones were denaturation of pulp tissue, which were usually found in the pulp chamber. Generally, they were associated with caries and pulposis, and the occurrence of pulp stone increased with age. Pulp stones were frequently found by radiographic examination, and appeared as radiopaque lesions which were round or ovoid in shape. We reported an unusual case of multiple pulp stones with normal clinical crowns in a young female patient and analyzed the possible etiology.

  15. Increased daily movement associates with reduced mortality among COPD patients having systemic inflammation.

    PubMed

    Loprinzi, P D; Walker, J F

    2016-03-01

    Emerging research demonstrates an interrelationship between systemic inflammation, physical activity and premature all-cause mortality among chronic obstructive pulmonary disease (COPD) patients. Less common in this literature is the use of objective measures of physical activity and representative samples of COPD patients. To examine the association between objectively measured physical activity and all-cause mortality among a national sample of COPD patients, with stratification by inflammatory status. Data from the 2003 to 2006 NHANES were employed, with follow-up through 2011. Physical activity was objectively measured via accelerometry; COPD was assessed via physician-diagnosis; and inflammation was assessed via C-reactive protein (CRP) levels from a blood sample. Analysis included 385 adults (20+ years) with COPD. The median follow-up period was 78 months (IQR = 64-90), with 82 COPD patients dying during this period. After adjustment, physical activity was not associated with all-cause mortality among the entire sample (HR = 0.80; 95% CI: 0.61-1.05) or those with no systemic inflammation (HR = 0.89; 95% CI: 0.63-1.24). However, for every 60 min increase in physical activity per day, COPD patients with elevated CRP had a 31% reduced risk of all-cause mortality (HR = 0.69; 95% CI: 0.51-0.93). Physical activity may help to promote survival among COPD patients, particularly those with elevated inflammation. © 2016 John Wiley & Sons Ltd.

  16. Increase of oxidation and inflammation in nervous and immune systems with aging and anxiety.

    PubMed

    Vida, Carmen; González, Eva M; De la Fuente, Mónica

    2014-01-01

    According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the agerelated impairment of organism functions, including those of the nervous and immune systems, as well as of the neuroimmune communication, which explains the altered homeostasis and the resulting increase of morbidity and mortality. Overproduction of oxidant compounds can induce an inflammatory response, since oxidants are inflammation effectors. Thus, oxidation and inflammation are interlinked processes and have many feedback loops. However, the nature of their potential interactions, mainly in the brain and immune cells, and their key involvement in aging remain unclear. Moreover, in the context of the neuroimmune communication, it has been described that an oxidative-inflammatory situation occurs in subjects with anxiety, and this situation contributes to an immunosenescence, alteration of survival responses and shorter life span. As an example of this, a model of premature aging in mice, in which animals show a poor response to stress and high levels of anxiety, an oxidative stress in their immune cells and tissues, as well as a premature immunosenescence and a shorter life expectancy, will be commented in the present review. This model supports the hypothesis that anxiety can be a situation of chronic oxidative stress and inflammation, especially in brain and immune cells, and this accelerates the rate of aging.

  17. 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.

  18. Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance

    PubMed Central

    Cavalli, Giulio; Justice, Jamie N.; Boyle, Kristen E.; D’Alessandro, Angelo; Eisenmesser, Elan Z.; Herrera, Jonathan J.; Hansen, Kirk C.; Nemkov, Travis; Stienstra, Rinke; Garlanda, Cecilia; Mantovani, Alberto; Seals, Douglas R.; Dagna, Lorenzo; Joosten, Leo A. B.; Ballak, Dov B.; Dinarello, Charles A.

    2017-01-01

    IL-1 family member interleukin 37 (IL-37) has broad antiinflammatory properties and functions as a natural suppressor of innate inflammation. In this study, we demonstrate that treatment with recombinant human IL-37 reverses the decrease in exercise performance observed during systemic inflammation. This effect was associated with a decrease in the levels of plasma and muscle cytokines, comparable in extent to that obtained upon IL-1 receptor blockade. Exogenous administration of IL-37 to healthy mice, not subjected to an inflammatory challenge, also improved exercise performance by 82% compared with vehicle-treated mice (P = 0.01). Treatment with eight daily doses of IL-37 resulted in a further 326% increase in endurance running time compared with the performance level of mice receiving vehicle (P = 0.001). These properties required the engagement of the IL-1 decoy receptor 8 (IL-1R8) and the activation of AMP-activated protein kinase (AMPK), because both inhibition of AMPK and IL-1R8 deficiency abrogated the positive effects of IL-37 on exercise performance. Mechanistically, treatment with IL-37 induced marked metabolic changes with higher levels of muscle AMPK, greater rates of oxygen consumption, and increased oxidative phosphorylation. Metabolomic analyses of plasma and muscles of mice treated with IL-37 revealed an increase in AMP/ATP ratio, reduced levels of proinflammatory mediator succinate and oxidative stress-related metabolites, as well as changes in amino acid and purine metabolism. These effects of IL-37 to limit the metabolic costs of chronic inflammation and to foster exercise tolerance provide a rationale for therapeutic use of IL-37 in the treatment of inflammation-mediated fatigue. PMID:28193888

  19. Angiogenic signaling triggered by cariogenic bacteria in pulp cells.

    PubMed

    Soden, R I; Botero, T M; Hanks, C T; Nör, J E

    2009-09-01

    The inflammation observed in the dental pulp of teeth with deep caries lesions is characterized by a significant increase in blood vessel density. It is known that lipoteichoic acid (LTA) from Gram-positive cariogenic bacteria induces expression of vascular endothelial growth factor (VEGF) in dental pulp cells. The hypothesis underlying this study was that LTA induces VEGF expression in dental pulp cells through TLR2 and PI3k/Akt signaling. Odontoblast-like cells (MDPC-23) and undifferentiated pulp cells (OD-21) were exposed to LTA from Streptococcus sanguis, and the role of TLR2, PI3K/Akt, and IKK signaling in LTA-induced VEGF expression was evaluated. These studies demonstrated that TLR2 signaling through the PI3K-Akt pathway is necessary for LTA-induced VEGF expression in pulp cells. In contrast, inhibition of IKK signaling did not prevent VEGF up-regulation in response to LTA. Understanding signaling pathways triggered by cariogenic bacteria may reveal novel therapeutic targets for the clinical management of pulpitis.

  20. Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation[S

    PubMed Central

    Barden, Anne; Mas, Emilie; Croft, Kevin D.; Phillips, Michael; Mori, Trevor A.

    2014-01-01

    Resolution of inflammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.4g/day) for 7 days with random assignment to take aspirin (300 mg/day) or placebo from day 5 to day 7. Blood was collected at baseline (day 0), day 5, and day 7. Plasma 18R/S-HEPE, E-series resolvins, 17R/S-HDHA, D-series resolvins, 14R/S-HDHA, and MaR-1 were measured by LC/MS/MS. At baseline concentrations of E- and D- series resolvins and the upstream precursors 18R/S-HEPE, 17R/S-HDHA ranged from 0.1nM to 0.2nM. 14R/S-HDHA was 3-fold higher than the other SPMs at baseline but MaR-1 was below the limit of detection. Supplementation with n-3 fatty acids significantly increased RvE1, 18R/S-HEPE, 17R/S-HDHA, and 14R/S-HDHA but not other SPMs. The addition of aspirin after 5 days of n-3 fatty acids did not affect concentrations of any SPM. N-3 fatty acid supplementation for 5 days results in concentrations of SPMs that are biologically active in healthy humans. Aspirin administered after n-3 fatty acids did not offer any additional benefit in elevating the levels of SPMs. PMID:25187667

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    PubMed

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

    2016-01-13

    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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Mineral trioxide aggregate and portland cement for direct pulp capping in dog: a histopathological evaluation.

    PubMed

    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.

  8. Role of human pulp fibroblasts in angiogenesis.

    PubMed

    Tran-Hung, L; Mathieu, S; About, I

    2006-09-01

    After pulp amputation, complete pulp healing requires not only reparative dentin production but also fibroblast proliferation, nerve fiber growth, and neoangiogenesis. This study was designed to investigate the role of pulp fibroblasts in angiogenesis. Human pulp fibroblasts from third molars co-cultured with human umbilical vein endothelial cells induced the organization of endothelial cells and the formation of tubular structures corresponding to capillaries in vivo. The direct contact between both cells was not necessary to induce angiogenesis, and the observed effect was due to soluble factors. This was confirmed with neutralizing antibodies against FGF-2 and VEGF, which decreased the angiogenic effects of these soluble factors. Immunohistochemistry showed that both FGF-2 and VEGF were expressed in human dental pulp fibroblasts, and this expression increased after injury. These results suggest that the pulp fibroblasts secrete angiogenic factors, which are necessary for complete pulp healing, particularly at the pulp injury site.

  9. Inflammation and increased IDO in hippocampus contribute to depression-like behavior induced by estrogen deficiency.

    PubMed

    Xu, Yongjun; Sheng, Hui; Tang, Zhiping; Lu, Jianqiang; Ni, Xin

    2015-07-15

    Estrogen deficiency is involved in the development of depression. However, the mechanism underlying estrogen modulates depression-like behavior remains largely unknown. Inflammation and indoleamine-2,3-dioxygenase (IDO) have been shown to play pivotal roles in various depression models. The objective of the present study was to investigate whether estrogen deficiency-induced depression-like behavior is associated with inflammation and IDO activation in brain. The results showed that ovariectomy resulted in depression-like behavior in female rats and caused a decrease in 5-HT content and an increase in levels of IDO, IFN-γ, IL-6, toll like receptor (TLR)-4 and phosphorylated NF-κB (p65 subunit) in hippocampus but not in prefrontal cortex (PFC). 17β-Estradiol (E2) treatment ameliorated depression-like behavior and restored above neurochemical alternations in hippocampus in ovariectomized rats. Partial correlation analysis showed that the levels of phosphorylated p65, IFN-γ and IL-6 in hippocampus correlated to serum E2 level. Our study suggests that estrogen inhibits inflammation and activates of IDO and maintains 5-HT level in hippocampus, thereby ameliorating depression-like behavior.

  10. Increased vascular inflammation in early menopausal women is associated with hot flush severity.

    PubMed

    Bechlioulis, Aris; Naka, Katerina K; Kalantaridou, Sophia N; Kaponis, Apostolos; Papanikolaou, Odysseas; Vezyraki, Patra; Kolettis, Theofilos M; Vlahos, Antonis P; Gartzonika, Konstantina; Mavridis, Anestis; Michalis, Lampros K

    2012-05-01

    Menopause has been related to an increased atherosclerotic risk. Presence and severity of hot flushes in menopausal women have been associated with impaired endothelial function and advanced subclinical atherosclerosis. The objective of the study was to evaluate the effect of menopausal transition on vascular inflammation indices and investigate the association of hot flush severity with these indices in early menopausal women. This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women (controls). Serum high-sensitivity C-reactive protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured. P-selectin and sCD40L were increased in early menopausal compared with control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C-reactive protein levels did not differ (P = 0.4) between the groups. Hot flush severity was the most important independent predictor of P-selectin levels (P = 0.011) in early menopausal women. Women with moderate/severe/very severe hot flushes had increased P-selectin compared with women with no/mild hot flushes or controls (P < 0.05 for both). The sCD40L levels were also higher in menopausal women with moderate/severe/very severe hot flushes compared with controls (P = 0.03) but did not differ significantly compared with women with no/mild hot flushes (P = 0.2). Increased indices of vascular inflammation in early menopausal compared with age-matched premenopausal women may indicate a higher atherosclerotic risk. Increased severity of hot flushes was associated with adverse changes in vascular inflammation, further supporting the emerging role of hot flushes in cardiovascular prognosis in these women.

  11. Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model.

    PubMed

    Yoshiyama, Yasumasa; Kojima, Ayako; Itoh, Kimiko; Uchiyama, Tomoyuki; Arai, Kimihito

    2012-01-01

    Anticholinergics, and drugs with anticholinergic properties, are widely and frequently prescribed, especially to the elderly. It is well known that these drugs decrease cognitive function and increase the risk of dementia. Although the mechanism of anticholinergic drug-induced cognitive impairment has been assumed to be functionally reduced acetylcholine (ACh) neurotransmission, some data have indicated that anticholinergics might enhance the pathology of Alzheimer's disease. In this study, we investigated the pathological effects of anticholinergics on neurodegeneration. We chronically administered two anticholinergics, trihexyphenidyl (TP) and propiverine (PP) (the latter with less central anticholinergic action), to neurodegenerative tauopathy model mice 2 to 10 months old. Furthermore, because the ACh nervous system regulates both central and peripheral inflammation, we administered TP or PP to PS19 mice in which we had artificially induced inflammation by lipopolysaccharide injection. Tau pathology, synaptic loss, and neurodegeneration in the hippocampal region, as well as tau insolubility and phosphorylation, were markedly increased in TP-treated mice and mildly increased in PP-treated mice. Furthermore, immunohistochemical analysis revealed microglial proliferation and activation. Moreover, anticholinergics increased interleukin-1β expression in both the spleen and brain of the tauopathy model mice intraperitoneally injected with lipopolysaccharide to induce systemic inflammation. Interestingly, these alterations were more strongly observed in TP-treated mice than in PP-treated mice, consistent with the level of central anticholinergic action. Anticholinergic drugs not only impair cognitive function by decreased ACh neurotransmission, but also accelerate neurodegeneration by suppressing an ACh-dependent anti-inflammatory system. Anticholinergics should be less readily prescribed to reduce the risk of dementia.

  12. Inflammatory response of human dental pulp to at-home and in-office tooth bleaching

    PubMed Central

    Vaz, Maysa Magalhães; Lopes, Lawrence Gonzaga; Cardoso, Paula Carvalho; de Souza, João Batista; Batista, Aline Carvalho; Costa, Nádia Lago; Torres, Érica Miranda; Estrela, Carlos

    2016-01-01

    ABSTRACT Tooth bleaching is a technique of choice to obtain a harmonious smile, but bleaching agents may damage the dental pulp. Objective: This study evaluated the inflammatory responses of human dental pulp after the use of two bleaching techniques. Material and Methods: Pulp samples were collected from human third molars extracted for orthodontic reasons and divided into three groups: control - no tooth bleaching (CG) (n=7); at-home bleaching with 15% carbamide peroxide (AH) (n = 10), and in-office bleaching with 38% hydrogen peroxide (IO) (n=12). Pulps were removed and stained with hematoxylin-eosin for microscopic analysis of inflammation intensity, collagen degradation, and pulp tissue organization. Immunohistochemistry was used to detect mast cells (tryptase+), blood vessels (CD31+), and macrophages (CD68+). Chi-square, Kruskal-Wallis, and Mann Whitney tests were used for statistical analysis. The level of significance was set at p<.05. Results: The inflammation intensity and the number of macrophages were significantly greater in IO than in AH and CG (p<0.05). The results of CD31+ (blood vessels per mm2) were similar in CG (61.39±20.03), AH (52.29±27.62), and IO (57.43±8.69) groups (p>0.05). No mast cells were found in the pulp samples analyzed. Conclusion: In-office bleaching with 38% hydrogen peroxide resulted in more intense inflammation, higher macrophages migration, and greater pulp damage then at-home bleaching with 15% carbamide peroxide, however, these bleaching techniques did not induce migration of mast cells and increased the number of blood vessels. PMID:27812622

  13. Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice.

    PubMed

    Ohlsson, Claes; Hammarstedt, Ann; Vandenput, Liesbeth; Saarinen, Niina; Ryberg, Henrik; Windahl, Sara H; Farman, Helen H; Jansson, John-Olov; Movérare-Skrtic, Sofia; Smith, Ulf; Zhang, Fu-Ping; Poutanen, Matti; Hedjazifar, Shahram; Sjögren, Klara

    2017-10-01

    Females are, in general, more insulin sensitive than males. To investigate whether this is a direct effect of sex-steroids (SS) in white adipose tissue (WAT), we developed a male mouse model overexpressing the aromatase enzyme, converting testosterone (T) to estradiol (E2), specifically in WAT (Ap2-arom mice). Adipose tissue E2 levels were increased while circulating SS levels were unaffected in male Ap2-arom mice. Importantly, male Ap2-arom mice were more insulin sensitive compared with WT mice and exhibited increased serum adiponectin levels and upregulated expression of Glut4 and Irs1 in WAT. The expression of markers of macrophages and immune cell infiltration was markedly decreased in WAT of male Ap2-arom mice. The adipogenesis was enhanced in male Ap2-arom mice, supported by elevated Pparg expression in WAT and enhanced differentiation of preadipocyte into mature adipocytes. In summary, increased adipose tissue aromatase activity reduces adipose tissue inflammation and improves insulin sensitivity in male mice. We propose that estrogen increases insulin sensitivity via a local effect in WAT on adiponectin expression, adipose tissue inflammation, and adipogenesis. Copyright © 2017 the American Physiological Society.

  14. 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

  15. Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation

    PubMed Central

    Parrott, J M; Redus, L; Santana-Coelho, D; Morales, J; Gao, X; O'Connor, J C

    2016-01-01

    The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression. Here we utilized two novel transgenic mouse strains to directly test the hypothesis that neurotoxic kynurenine metabolism causes depressive-like behavior following peripheral immune activation. Wild-type (WT) or kynurenine 3-monooxygenase (KMO)-deficient (KMO−/−) mice were administered either lipopolysaccharide (LPS, 0.5 mg kg−1) or saline intraperitoneally. Depressive-like behavior was measured across multiple domains 24 h after immune challenge. LPS precipitated a robust depressive-like phenotype, but KMO−/− mice were specifically protected from LPS-induced immobility in the tail suspension test (TST) and reduced spontaneous alternations in the Y-maze. Direct administration of 3-hydroxykynurenine, the metabolic product of KMO, caused a dose-dependent increase in depressive-like behaviors. Mice with targeted deletion of 3-hydroxyanthranilic acid dioxygenase (HAAO), the enzyme that generates quinolinic acid, were similarly challenged with LPS. Similar to KMO−/− mice, LPS failed to increase immobility during the TST. Whereas kynurenine metabolism was generally increased in behaviorally salient brain regions, a distinct shift toward KMO-dependent kynurenine metabolism occurred in the dorsal hippocampus in response to LPS. Together, these results demonstrate that KMO is a pivotal mediator of hippocampal-dependent depressive-like behaviors induced by

  16. Critically ill patients with acute cholecystitis are at increased risk for extensive gallbladder inflammation.

    PubMed

    Papadakis, Marios; Ambe, Peter C; Zirngibl, Hubert

    2015-01-01

    Acute cholecystitis is a common diagnosis and surgery is the standard of care for young and fit patients. However, due to high risk of postoperative morbidity and mortality, surgical management of critically ill patients remains a controversy. It is not clear, whether the increased risk of perioperative complications associated with the management of critically ill patients with acute cholecystitis is secondary to reduced physiologic reserve per se or to the severity of gallbladder inflammation. A retrospective analysis of prospectively collected data of patients undergoing laparoscopic cholecystectomy for acute cholecystitis in a university hospital over a three-year-period was performed. The ASA scores at the time of presentation were used to categorize patients into two groups. The study group consisted of critically ill patients with ASA 3 and 4, while the control group was made up of fit patients with ASA 1 and 2. Both groups were compared with regard to perioperative data, postoperative outcome and extent of gallbladder inflammation on histopathology. Two hundred and seventeen cases of acute cholecystitis with complete charts were available for analysis. The study group included 67 critically ill patients with ASA 3 and 4, while the control group included 150 fit patients with ASA 1 and 2. Both groups were comparable with regard to perioperative data. Histopathology confirmed severe cholecystitis in a significant number of cases in the study group compared to the control group (37 % vs. 18 %, p = 0.03). Significantly higher rates of morbidity and mortality were recorded in the study group (p < 0.05). Equally, significantly more patients from the study group were managed in the ICU (40 % vs. 8 %, p = 0.001). Critically ill patients presenting with acute cholecystitis are at increased risk for extensive gallbladder inflammation. The increased risk of morbidity and mortality seen in such patients might partly be secondary to severe acute

  17. Response of inflamed pulps of rat molars after capping with pulp-capping material containing fluocinolone acetonide.

    PubMed

    Louwakul, Phumisak; Lertchirakarn, Veera

    2015-04-01

    Capping inflamed dental pulp tissue is currently a controversial issue. To reduce pulp inflammation and stimulate pulp healing, a pulp-capping material containing fluocinolone acetonide (PCFA) has been developed. This study was aimed to evaluate the inflammatory response and hard tissue formation of inflamed dental pulps of rat maxillary molars after capping with Dycal, mineral trioxide aggregate (MTA), or PCFA. Sixty maxillary rat molars were exposed to the oral environment for 48 hours. The exposed pulps were randomly divided into 6 groups (n = 10) according to pulp-capping materials (Dycal, MTA, or PCFA) and time (8 or 30 days). The cavities were capped and sealed with Fuji II LC. The animals were sacrificed after 8 and 30 days. Histologic specimens were prepared and evaluated for inflammatory response and hard tissue formation. Eight days after pulp capping, all experimental groups showed disruption of the odontoblast layer in areas corresponding to the pulpal exposure. Acute inflammation was found in 80%, 60%, and 40% of samples in the Dycal, MTA, and PCFA groups, respectively. PCFA significantly decreased the pulp inflammation compared with Dycal. After 30 days, slight to moderate inflammation was found in all experimental groups. Hard tissue formation was found in 78%, 63%, and 100% of samples in the Dycal, MTA, and PCFA groups, respectively. No significant difference was found among the experimental groups. Pulp capping with PCFA reduced the inflammation and stimulated hard tissue formation in the exposed pulps of rat molars. It may be used as a pulp-capping agent in inflamed pulps. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  18. Hypertension, inflammation and T lymphocytes are increased in a rat model of HELLP syndrome

    PubMed Central

    Wallace, Kedra; Morris, Rachael; Kyle, Patrick B.; Cornelius, Denise; Darby, Marie; Scott, Jeremy; Moseley, Janae; Chatman, Krystal; LaMarca, Babbette

    2014-01-01

    Objective An animal model of hemolysis, elevated liver enzymes, low platelet count (HELLP) was used to determine if T lymphocytes accompany hypertension and increased inflammatory cytokines. Methods sFlt-1 (4.7 μg/kg/day) and sEndoglin (7 μg/kg/day) were infused into normal pregnant rats (HELLP rats) for 8 days. Results HELLP was associated with increased mean arterial pressure (p = 0.0001), hemolysis (p = 0.044), elevated liver enzymes (p = 0.027), and reduced platelets (p = 0.035). HELLP rats had increased plasma levels of TNFα (p = 0.039), IL-6 (p = 0.038) and IL-17 (p = 0.04). CD4+ and CD8+ T lymphocytes were increased. Conclusion These data support the hypothesis that T cells are associated with hypertension and inflammation. PMID:24380504

  19. Novel bleaching of thermomechanical pulp for improved paper properties

    Treesearch

    Marguerite S. Sykes; John H. Klungness; Freya. Tan

    2002-01-01

    Production of mechanical pulp is expected to increase significantly to meet the growing global demand for paper. Mechanical pulping uses wood resources more efficiently with less negative impact on the environment than does chemical pulping. However, several problems related to mechanical pulping need to be resolved: high energy consumption, low paper strength...

  20. SOME ASPECTS OF THE CHEMISTRY OF POLYSULFIDE PULPING,

    DTIC Science & Technology

    Kraft pulping with the addition of polysulfide, i.e. polysulfide pulping, is one of the few methods available which can be used to increase the yield...and change the properties of kraft pulp. The chemistry of aqueous polysulfide solutions and the concurrent reactions occurring in polysulfide pulping

  1. Endodontic-orthodontic relationships: expression of no synthase in human dental pulp during orthodontic tooth movement.

    PubMed

    D ' Attilio, M; De Angelis, F; Vadini, M; Rodolfino, D; Trubiani, O; Di Nardo Di Maio, F; D' Arcangelo, C

    2012-01-01

    Inflamed human pulp tissue presents an increase in the level of nitric oxide synthase (NOS). The aim of this study is to verify the presence of NOS in human pulp of teeth that are subject to orthodontic force. 20 healthy subjects, wearers of fixed braces on the upper arch, were selected. An open coil-spring in NiTi was applied on the upper premolar test tooth (TT); the controlateral control tooth (CCT) was subjected to orthodontic treatment but not to the further force of the open coil-spring; the antagonist control tooth (ACT) did not undergo any orthodontic treatment. Pulps were taken from test, contralateral control and antagonist control teeth immediately after the extractions which were done at 15 and 30 days from the start of application of the orthodontic force. The pulp tissue was analyzed through immunohistochemical and molecular biology examinations. The results showed tooth pulps subject to orthodontic treatment were very inflamed in the first 15 days with high levels of iNOS and low levels of eNOS; after 30 days a decrease of the inflammation and an increase of the pulp vascularization were observed together with a reduction of iNOS and an increase of eNOS respectively.

  2. BIIL 284 reduces neutrophils numbers but increases P. aeruginosa bacteraemia and inflammation in mouse lungs

    PubMed Central

    Döring, Gerd; Bragonzi, Alessandra; Paroni, Moira; Aktürk, Firdevs-Fatma; Cigana, Cristina; Schmidt, Annika; Gilpin, Deirdre; Heyder, Susanne; Born, Torsten; Smaczny, Christina; Kohlhäufl, Martin; Wagner, Thomas O. F.; Loebinger, Michael R.; Bilton, Diana; Tunney, Michael M.; Elborn, J. Stuart; Pier, Gerald B.; Konstan, Michael W.; Ulrich, Martina

    2014-01-01

    Background A clinical study to investigate the leukotriene B4 (LTB4)-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients. Methods P. aeruginosa DNA in the blood of CF patients during and after acute pulmonary exacerbations and in stable patients with non-CF bronchiectasis (NCFB) and healthy individuals was assessed by PCR. The effect of BIIL 284 treatment was tested in an agar beads murine model of Pseudomonas aeruginosa lung infection. Bacterial count and inflammation were evaluated in lung and other organs. Result Most CF patients (98%) and all patients with NCFB and healthy individuals had negative P. aeruginosa DNA in their blood. Similarly, the P. aeruginosa-infected mice showed bacterial counts in the lung but not blood or spleen. BIIL 284 treatment decreased pulmonary neutrophils and increased P. aeruginosa numbers in mouse lungs leading to significantly higher bacteremia rates and lung inflammation compared to placebo treated animals. Conclusions Decreased airway neutrophils induced lung proliferation and severe bacteraemia in a murine model of P. aeruginosa lung infection. These data suggest that caution should be taken when administering anti-inflammatory compounds to patients with bacterial infections. PMID:24183915

  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. Increase in Levels of BDNF is Associated with Inflammation and Oxidative Stress during Cardiopulmonary Bypass

    PubMed Central

    Amoureux, Sébastien; Sicard, Pierre; Korandji, Claudia; Borey, Angélique; Benkhadra, Salima; Sequeira-Le Grand, Anabelle; Vergely, Catherine; Girard, Claude; Rochette, Luc

    2008-01-01

    Cardiopulmonary Bypass (CPB) is thought to generate reactive oxygen species associated with a systemic inflammation and neurotrophins seem to be involved in cardiovascular inflammatory reactions. The aim of this study was to determine the impact of CPB on plasma neurotrophins levels and to appreciate the links existing between inflammation, oxidative stress and neurotrophins. Blood samples were taken from 27 patients undergoing cardiac surgery: before CPB, during ischemia and at reperfusion under CPB. Oxidative stress was evaluated using an Electron Spin Resonance technique by superoxide detection, and antioxidant defences by measurement of Endogenous Peroxidase Activity (EPA). The evolution of two neurotrophins: Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) was assessed with an ELISA method. An inflammatory index was determined by a multiplex flow cytometry method. The inflammatory index showed that MCP-1, P-selectin, t-PA and interleukins 6, 8 and 10 levels increased during CPB (p<0.05). Superoxide production and EPA were higher during ischemia and reperfusion than before CPB (p<0.05). BDNF plasma levels were higher at reperfusion (p<0.05). NGF levels did not change. Our study shows an increase of BDNF levels, associated with an inflammatory phenomenon and a redox modification, in the plasma of patients undergoing cardiac surgery under CPB. The role played by this neurotrophin in this complex situation still needs to be elucidated, in particular its cellular origin. It is also necessary to understand whether BDNF has a beneficial or deleterious effect during CPB. PMID:23675091

  5. BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.

    PubMed

    Döring, Gerd; Bragonzi, Alessandra; Paroni, Moira; Aktürk, Firdevs-Fatma; Cigana, Cristina; Schmidt, Annika; Gilpin, Deirdre; Heyder, Susanne; Born, Torsten; Smaczny, Christina; Kohlhäufl, Martin; Wagner, Thomas O F; Loebinger, Michael R; Bilton, Diana; Tunney, Michael M; Elborn, J Stuart; Pier, Gerald B; Konstan, Michael W; Ulrich, Martina

    2014-03-01

    A clinical study to investigate the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients. P. aeruginosa DNA in the blood of CF patients during and after acute pulmonary exacerbations and in stable patients with non-CF bronchiectasis (NCFB) and healthy individuals was assessed by PCR. The effect of BIIL 284 treatment was tested in an agar bead murine model of P. aeruginosa lung infection. Bacterial count and inflammation were evaluated in lung and other organs. Most CF patients (98%) and all patients with NCFB and healthy individuals had negative P. aeruginosa DNA in their blood. Similarly, the P. aeruginosa-infected mice showed bacterial counts in the lung but not in the blood or spleen. BIIL 284 treatment decreased pulmonary neutrophils and increased P. aeruginosa numbers in mouse lungs leading to significantly higher bacteremia rates and lung inflammation compared to placebo treated animals. Decreased airway neutrophils induced lung proliferation and severe bacteremia in a murine model of P. aeruginosa lung infection. These data suggest that caution should be taken when administering anti-inflammatory compounds to patients with bacterial infections. © 2013.

  6. The caspase inhibitor zVAD increases lung inflammation in pneumovirus infection in mice.

    PubMed

    van den Berg, Elske; Bal, Suzanne M; Kuipers, Maria T; Matute-Bello, Gustavo; Lutter, René; Bos, Albert P; van Woensel, Job B M; Bem, Reinout A

    2015-03-01

    Severe respiratory syncytial virus (RSV) disease is a frequent cause of acute respiratory distress syndrome (ARDS) in young children, and is associated with marked lung epithelial injury and neutrophilic inflammation. Experimental studies on ARDS have shown that inhibition of apoptosis in the lungs reduces lung epithelial injury. However, the blockade of apoptosis in the lungs may also have deleterious effects by hampering viral clearance, and importantly, by enhancing or prolonging local proinflammatory responses. The aim of this study was to determine the effect of the broad caspase inhibitor Z-VAD(OMe)-FMK (zVAD) on inflammation and lung injury in a mouse pneumovirus model for severe RSV disease. Eight- to 11-week-old female C57BL/6OlaHsd mice were inoculated with the rodent-specific pneumovirus pneumonia virus of mice (PVM) strain J3666 and received multiple injections of zVAD or vehicle (control) during the course of disease, after which they were studied for markers of apoptosis, inflammation, and lung injury on day 7 after infection. PVM-infected mice that received zVAD had a strong increase in neutrophil numbers in the lungs, which was associated with decreased neutrophil apoptosis. Furthermore, zVAD treatment led to higher concentrations of several proinflammatory cytokines in the lungs and more weight loss in PVM-infected mice. In contrast, zVAD did not reduce apoptosis of lung epithelial cells and did not affect the degree of lung injury, permeability, and viral titers in PVM disease. We conclude that zVAD has an adverse effect in severe pneumovirus disease in mice by enhancing the lung proinflammatory response. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. The caspase inhibitor zVAD increases lung inflammation in pneumovirus infection in mice

    PubMed Central

    van den Berg, Elske; Bal, Suzanne M; Kuipers, Maria T; Matute-Bello, Gustavo; Lutter, René; Bos, Albert P; van Woensel, Job B M; Bem, Reinout A

    2015-01-01

    Severe respiratory syncytial virus (RSV) disease is a frequent cause of acute respiratory distress syndrome (ARDS) in young children, and is associated with marked lung epithelial injury and neutrophilic inflammation. Experimental studies on ARDS have shown that inhibition of apoptosis in the lungs reduces lung epithelial injury. However, the blockade of apoptosis in the lungs may also have deleterious effects by hampering viral clearance, and importantly, by enhancing or prolonging local proinflammatory responses. The aim of this study was to determine the effect of the broad caspase inhibitor Z-VAD(OMe)-FMK (zVAD) on inflammation and lung injury in a mouse pneumovirus model for severe RSV disease. Eight- to 11-week-old female C57BL/6OlaHsd mice were inoculated with the rodent-specific pneumovirus pneumonia virus of mice (PVM) strain J3666 and received multiple injections of zVAD or vehicle (control) during the course of disease, after which they were studied for markers of apoptosis, inflammation, and lung injury on day 7 after infection. PVM-infected mice that received zVAD had a strong increase in neutrophil numbers in the lungs, which was associated with decreased neutrophil apoptosis. Furthermore, zVAD treatment led to higher concentrations of several proinflammatory cytokines in the lungs and more weight loss in PVM-infected mice. In contrast, zVAD did not reduce apoptosis of lung epithelial cells and did not affect the degree of lung injury, permeability, and viral titers in PVM disease. We conclude that zVAD has an adverse effect in severe pneumovirus disease in mice by enhancing the lung proinflammatory response. PMID:25780096

  8. Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease▿

    PubMed Central

    Dhiman, Monisha; Estrada-Franco, Jose Guillermo; Pando, Jasmine M.; Ramirez-Aguilar, Francisco J.; Spratt, Heidi; Vazquez-Corzo, Sara; Perez-Molina, Gladys; Gallegos-Sandoval, Rosa; Moreno, Roberto; Garg, Nisha Jain

    2009-01-01

    In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O2− source) and nitrate/nitrite contents (denotes iNOS activation and NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological NO and O2− concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies

  9. High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation.

    PubMed

    Jansen, Felix; Yang, Xiaoyan; Franklin, Bernardo S; Hoelscher, Marion; Schmitz, Theresa; Bedorf, Jörg; Nickenig, Georg; Werner, Nikos

    2013-04-01

    Diabetes is a major risk factor for cardiovascular diseases. Circulating endothelial microparticles (EMP) are increased in diabetic patients, but their potential contribution in atherogenesis is unclear. We sought to determine the role of EMP derived under high glucose conditions in the development of atherosclerosis. EMP were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMP were defined as 'injured' EMP (iEMP) and their effects were compared with EMP generated from 'healthy' untreated HCAEC. iEMP injection significantly impaired endothelial function in ApoE(-/-) mice compared with EMP and vehicle treatment. Immunofluorescent experiments showed increased macrophage infiltration and adhesion protein expression in atherosclerotic lesions of iEMP-treated ApoE(-/-) mice compared with controls. To further investigate the underlying mechanism of iEMP-induced vascular inflammation, additional in vitro experiments were performed. iEMP, but not EMP, induced activation of HCAEC in a time- and dose-dependent manner and increased monocyte adhesion. Further experiments demonstrated that iEMP induced activation of HCAEC by phosphorylation of p38 into its biologically active form phospho-p38. Inhibition of p38 activation abrogated iEMP-dependent induction of adhesion proteins and monocyte adhesion on HCAEC. Moreover, we could demonstrate that iEMP show increased NADPH oxidase activity and contain significantly higher level of reactive oxygen species (ROS) than EMP. iEMP triggered ROS production in HCAEC and thereby activate p38 in an ROS-dependent manner. High glucose condition increases NADPH oxidase activity in endothelial microparticles that amplify endothelial inflammation and impair endothelial function by promoting activation of the endothelium. These findings provide new insights into the pathogenesis of diabetes-associated atherosclerosis.

  10. Niacin Increases Adiponectin and Decreases Adipose Tissue Inflammation in High Fat Diet-Fed Mice

    PubMed Central

    Wanders, Desiree; Graff, Emily C.; White, B. Douglas; Judd, Robert L.

    2013-01-01

    Aims To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Materials and Methods Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2−/− (niacin receptor−/−) mice. Results Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2−/− mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARγ C/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1β in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Conclusions Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner. PMID:23967184

  11. High proportions of Staphylococcus epidermidis in dental caries harbor multiple classes of antibiotics resistance, significantly increase inflammatory interleukins in dental pulps.

    PubMed

    Devang Divakar, Darshan; Muzaheed; Aldeyab, Sultan Salem; Alfawaz, Sara A; AlKheraif, Abdulaziz Abdullah; Ahmed Khan, Aftab

    2017-08-01

    Staphylococcus epidermidis is one of most prevalent in dental caries or dental pulp which has the capability of horizontal genetic transfer between different bacterial species in the oropharynx, suggesting that it may evolve with the dissemination of resistant determinants, This study was performed to molecularly characterize and differentiate S. epidermidis isolated from dental caries and healthy individual. Also, two important cytokines in inflammation were assayed caused due to S. epidermidis of health and dental caries sources. Dental caries strains were more resistant with high MIC 50 and MIC 90 value. These isolates also showed the presence of mecA gene and another virulence gene i. e sea and seb comparatively more than healthy individual isolates. SCCmec types, III and IV was more prevalent in dental caries isolates where an as healthy individual was more non-typable. Additionally, the quantity of IL-1β and IL-8 caused due to dental caries isolates was seen more which indicate dental caries isolates are able to induce. This study showed that S. epidermidis a normal flora of oropharyngeal are more diverse to those strains which cause dental caries. S. epidermidis owns a prodigious genetic plasticity that permits to obtain, lose or regulate genetic elements that provide compensations to improve its colonization in the host. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8)

    PubMed Central

    Gutiérrez-Fernández, Ana; Inada, Masaki; Balbín, Milagros; Fueyo, Antonio; Pitiot, Ana S.; Astudillo, Aurora; Hirose, Kenji; Hirata, Michiko; Shapiro, Steven D.; Noël, Agnès; Werb, Zena; Krane, Stephen M.; López-Otín, Carlos; Puente, Xose S.

    2008-01-01

    Matrix metalloproteinases (MMPs) have been implicated in numerous tissue-remodeling processes. The finding that mice deficient in collagenase-2 (MMP-8) are more susceptible to develop skin cancer, prompted us to investigate the role of this protease in cutaneous wound healing. We have observed a significant delay in wound closure in MMP8−/− mice and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points. These changes were accompanied by alterations in the TGF-β1 signaling pathway and by an apoptosis defect in MMP8−/− mice. The delay in wound healing observed in MMP8−/− mice was rescued by bone marrow transplantation from wild-type mice. Analysis of other MMPs showed that MMP8−/− mice had a significant increase in the expression of MMP-9, suggesting that both proteases might act coordinately in this process. This possibility was further supported by the novel finding that MMP-8 and MMP-9 form specific complexes in vivo. Taken together, these data indicate that MMP-8 participates in wound repair by contributing to the resolution of inflammation and open the possibility to develop new strategies for treating wound healing defects. PMID:17392479

  13. Rac-null leukocytes are associated with increased inflammation-mediated alveolar bone loss.

    PubMed

    Sima, Corneliu; Gastfreund, Shoshi; Sun, Chunxiang; Glogauer, Michael

    2014-02-01

    Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.

  14. Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation.

    PubMed

    Sehra, Sarita; Krishnamurthy, Purna; Koh, Byunghee; Zhou, Hong-Ming; Seymour, Lee; Akhtar, Nahid; Travers, Jeffrey B; Turner, Matthew J; Kaplan, Mark H

    2016-11-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T-cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function. Our results demonstrate that over 90% of the Stat6VT transgenic mice carrying the Ft alleles (Stat6VTxFt(-/-) ) develop severe atopic dermatitis lesions by 3-5 months of age, compared with only 40% of Stat6VT mice that develop disease by 6-7 months of age. Further, histopathological analysis of skin tissues from Stat6VTxFt(-/-) mice revealed extensive thickening of the dermis with increased inflammatory infiltrates as compared with Stat6VT mice. Our study suggests that skin barrier defects and altered Th2 responses independently cooperate in the pathogenesis of allergic skin inflammation, similar to effects observed in patients with AD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 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

  16. Eosinophilic airway inflammation is increased in children with asthma and food allergies.

    PubMed

    Kulkarni, Neeta; Ragazzo, Vincenzo; Costella, Silvia; Piacentini, Giorgio; Boner, Attilio; O'Callaghan, Christopher; Fiocchi, Alessandro; Kantar, Ahmad

    2012-02-01

    Asthma is associated with food allergies in a significant number of children, with evidence linking allergies to asthma severity and morbidity. In this study, we tested our hypothesis that the eosinophilic lower airway inflammation is higher in asthmatic children with food allergies. The aims of the study were to compare the eosinophilic inflammatory markers in asthmatic children with and without food allergies. Children with asthma, with (n = 22) and (n = 53) without food allergies were included. All subjects were classified according to the GINA guidelines (2009) and had received at least 3 months of anti-inflammatory therapy prior to testing. Fractional exhaled nitric oxide and sputum differential counts were performed using standard techniques.   Children with asthma and food allergies had significantly higher fractional exhaled nitric oxide median (range) [(22.4 (6.1-86.9) vs. 10.3 (2.7-38.7) (p = 0.01)] and sputum eosinophil percentage [15.5 (5.0-53.0) vs. 2.0 (0-20) (p < 0.001)] compared with asthmatic children without allergies. These results suggest that the children with asthma and food allergies have increased eosinophilic inflammation of the airways. © 2011 John Wiley & Sons A/S.

  17. Tendon overload results in alterations in cell shape and increased markers of inflammation and matrix degradation.

    PubMed

    Thorpe, C T; Chaudhry, S; Lei, I I; Varone, A; Riley, G P; Birch, H L; Clegg, P D; Screen, H R C

    2015-08-01

    Tendon injury is thought to involve both damage accumulation within the matrix and an accompanying cell response. While several studies have characterized cell and matrix response in chronically injured tendons, few have assessed the initial response of tendon to overload-induced damage. In this study, we assessed cell response to cyclic loading. Fascicle bundles from the equine superficial digital flexor tendon were exposed to cyclic loading in vitro, designed to mimic a bout of high-intensity exercise. Changes in cell morphology and protein-level alterations in markers of matrix inflammation and degradation were investigated. Loading resulted in matrix damage, which was accompanied by cells becoming rounder. The inflammatory markers cyclooxygenase-2 and interleukin-6 were increased in loaded samples, as were matrix metalloproteinase-13 and the collagen degradation marker C1,2C. These results indicate upregulation of inflammatory and degradative pathways in response to overload-induced in vitro, which may be initiated by alterations in cell strain environment because of localized matrix damage. This provides important information regarding the initiation of tendinopathy, suggesting that inflammation may play an important role in the initial cell response to tendon damage. Full understanding of the early tenocyte response to matrix damage is critical in order to develop effective treatments for tendinopathy. © 2014 The Authors. Scandinavian Journal of Medicine & Science in Sports published by John Wiley & Sons Ltd.

  18. Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation.

    PubMed

    Gibson, Peter G; Henry, Richard L; Shah, Smita; Powell, Heather; Wang, He

    2003-09-01

    The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11; P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms. Copyright 2003 Wiley-Liss, Inc.

  19. Increased Risk of Nasopharyngeal Carcinoma with Increasing Levels of Diet-Associated Inflammation in an Italian Case-Control Study.

    PubMed

    Shivappa, Nitin; Hébert, James R; Zucchetto, Antonella; Montella, Maurizio; Libra, Massimo; Garavello, Werner; Rossi, Marta; La Vecchia, Carlo; Serraino, Diego

    2016-10-01

    Components of diet can modulate inflammation and therefore may have an important role in the development of nasopharyngeal carcinoma (NPC). Little is known about the inflammatory potential of diet in relation to nasopharyngeal carcinogenesis. Data from an Italian multicenter case-control study conducted between 1992 and 2008 and including 198 cases with incident, histologically confirmed NPC, and 594 controls hospitalized for acute nonneoplastic diseases were used to estimate the relation between a dietary inflammatory index (DII) and the risk of NPC. The DII was computed based on the intake of selected dietary factors assessed by a validated 78-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) adjusted for study center, place of living, sex, age, year of interview, education, tobacco smoking, alcohol drinking, and energy intake using the residual method. Subjects with higher DII scores had an increased risk of NPC, with each DII point increasing risk by nearly 20% [OR: 1.19; 95% confidence interval (CI): 1.05-1.36]. Compared to subjects in the lowest DII tertile, those in the highest tertile had >60% higher risk of NPC (OR: 1.64; 95% CI: 1.06-2.55; Ptrend = 0.04). These results indicate that inflammatory potential of diet plays a role in NPC.

  20. Citrus pulp for cattle.

    PubMed

    Arthington, John D; Kunkle, William E; Martin, Amy M

    2002-07-01

    Citrus pulp is classified as an energy concentrate by-product feed. Citrus by-products fed to beef cattle include citrus molasses, citrus meal, wet citrus pulp, dried citrus pulp, and pelleted citrus pulp; however, in current production systems, pulp (wet, dry, and pelleted) is the only by-product commonly used. Citrus pulp production in the United States is limited to specific subtropical regions, of which south central Florida remains the largest with additional production in California and Texas.

  1. 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.

  2. Characteristics of dental pulp in human upper first premolar teeth based on immunohistochemical and morphometric examinations.

    PubMed

    Tomaszewska, Joanna Maria; Miskowiak, Bogdan; Matthews-Brzozowska, Teresa; Wierzbicki, Piotr

    2013-01-01

    Teeth extracted for orthodontic reasons are commonly considered as healthy. Therefore, it is possible to examine structure of the dental pulp can be fully recognized and how it is affected by malocclusion. The aim of the study was to evaluate by immunohistochemistry (IHC) and morphometry dental pulp in human upper first premolar teeth extracted for orthodontic reasons. The material comprised 36 teeth of 20 patients in the age range 16-26 years. By the use of IHC markers the presence of immunocompetent cells (CD20, CD45RO, and CD68), blood vessels (CD31) and nerves (PGP9.5) were examined in the pulp. Inflammatory infiltrates and tissue atrophy were observed in 24 and 10 teeth, respectively. Strong positive correlation between the width of the odontoblastic layer, the number of rows of odontoblast nuclei and the increase of MVA (microvessel area) in the pulp of atrophic teeth was found. The cellular infiltrations found in H&E-stained sections were identified by IHC as memory T cells (CD45RO+) and B lymphocytes (CD20+) with macrophages (CD68+) present at the periphery. The CD20 antigen was intensively expressed in 13 teeth, CD45RO in 33 teeth, and CD68 in 20 teeth. Thus, despite the lack of any clinical signs of pulp disease many teeth extracted for orthodontic reasons show focal pulp inflammation and atrophy which probably results from the malocclusion stress accompanying teeth crowding.

  3. Neuropeptide Y Y1 receptor in human dental pulp cells of noncarious and carious teeth.

    PubMed

    El Karim, I A; Lamey, P-J; Linden, G J; Lundy, F T

    2008-10-01

    To determine the distribution of the NPY Y1 receptor in carious and noncarious human dental pulp tissue using immunohistochemistry. A subsidiary aim was to confirm the presence of the NPY Y1 protein product in membrane fractions of dental pulp tissue from carious and noncarious teeth using western blotting. Twenty two dental pulp samples were collected from carious and noncarious extracted teeth. Ten samples were processed for immunohistochemistry using a specific antibody to the NPY Y1 receptor. Twelve samples were used to obtain membrane extracts which were electrophoresed, blotted onto nitrocellulose and probed with NPY Y1 receptor antibody. Kruskal-Wallis one-way analysis of variance was employed to test for overall statistical differences between NPY Y1 levels in noncarious, moderately carious and grossly carious teeth. Neuropeptide Y Y1 receptor immunoreactivity was detected on the walls of blood vessels in pulp tissue from noncarious teeth. In carious teeth NPY Y1 immunoreactivity was observed on nerve fibres, blood vessels and inflammatory cells. Western blotting indicated the presence and confirmed the variability of NPY Y1 receptor protein expression in solubilised membrane preparations of human dental pulp tissue from carious and noncarious teeth. Neuropeptide Y Y1 is expressed in human dental pulp tissue with evidence of increased expression in carious compared with noncarious teeth, suggesting a role for NPY Y1 in modulation of caries induced pulpal inflammation.

  4. Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

    PubMed Central

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

  5. Increased Blood Clotting, Microvascular Density, and Inflammation in Eotaxin-Secreting Tumors Implanted into Mice

    PubMed Central

    Samoszuk, Michael; Deng, Tom; Hamamura, Mark J.; Su, Min-Ying; Asbrock, Nicholas; Nalcioglu, Orhan

    2004-01-01

    An important theme that is emerging in cancer research is the interaction between tumor cells and the host stroma. Because many types of human cancer are infiltrated by eosinophils that are believed to mediate an anti-tumor cytotoxic effect, we developed and studied a transfected B16 murine melanoma cell line that secretes high levels (510 pg/ml/100,000 cells/day) of eotaxin, a chemokine that recruits and activates primarily eosinophils. Here we report that there was increased inflammation (eosinophils, mast cells, mononuclear cells), blood clotting, and microvascular density within the tumors produced by subcutaneous implants of eotaxin-secreting tumor cells in 10 C57BL/6 compared to tumors produced by wild-type tumor cells. The extensive blood clotting in the eotaxin-transfected tumors was associated with significantly decreased blood flow to the tumors as measured by magnetic resonance imaging [(mean maximum signal enhancement of eotaxin-secreting tumors, 147 ± 57 (n = 7) compared to 202 ± 36 signal enhancement units (n = 8) for the wild-type melanoma cells; P = 0.04 by two-tailed, unpaired t-test]. Surprisingly, there was no significant difference between the growth rates or mean masses of the eotaxin-secreting tumors (750 ± 280 mg, n = 10) and the wild-type tumors (780 ± 290, n = 10) after 20 days of growth in vivo, despite the significantly slower growth rate in vitro of the eotaxin-secreting tumor cells. We conclude that eotaxin and the resultant tumor-infiltrating inflammatory cells are not likely to mediate a significant anti-tumor effect in vivo. Instead, elevated eotaxin is associated with increased inflammation, microvascular density, and blood clotting. Thus, eotaxin and eosinophils may play a more complex role in modulating the growth of tumors than the simple, anti-tumor cytotoxic effect that has been previously proposed. PMID:15277219

  6. Acemannan, an extracted product from Aloe vera, stimulates dental pulp cell proliferation, differentiation, mineralization, and dentin formation.

    PubMed

    Jittapiromsak, Nawaporn; Sahawat, Dusida; Banlunara, Wijit; Sangvanich, Polkit; Thunyakitpisal, Pasutha

    2010-06-01

    This study investigated the effect of acemannan (Aloe vera gel polysaccharide) on dentin formation. Primary human dental pulp cells were treated with acemannan. New DNA synthesis, bone morphogenetic protein-2, alkaline phosphatase activity, dentin sialoprotein expression, and mineralization were determined by [(3)H]-thymidine incorporation, enzyme-linked immunosorbent assay, biochemical assay, western blotting, and Alizarin Red staining, respectively. Then the upper first molars of 24 male Sprague Dawley rats were intentionally exposed and capped with either acemannan or calcium hydroxide. At day 28, the teeth were histopathologically examined and evaluated for the degree of inflammation, dentin bridge formation, and pulp tissue organization. The results revealed that acemannan significantly increased pulp cell proliferation, bone morphogenetic protein-2, alkaline phosphatase activity, dentin sialoprotein expression, and mineralization, compared with the untreated group. The acemannan-treated group also exhibited a complete homogeneous calcified dentin bridge and good pulp tissue organization, whereas neither was detected in the calcium hydroxide-treated and sham groups. In the acemannan-treated group, either mild or no inflammation was found, whereas the other groups had various degrees of inflammation. The data suggest that acemannan promotes dentin formation by stimulating primary human dental pulp cell proliferation, differentiation, extracellular matrix formation, and mineralization. Acemannan also has pulpal biocompatibility and promotes soft tissue organization.

  7. 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 Central

    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; Germain, Stéphane

    2016-01-01

    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. Significance The results from the present study show that fibroblast growth factor-2 (FGF-2) priming is more

  8. Aldosterone Increases Early Atherosclerosis and Promotes Plaque Inflammation Through a Placental Growth Factor‐Dependent Mechanism

    PubMed Central

    McGraw, Adam P.; Bagley, Jessamyn; Chen, Wei‐Sheng; Galayda, Carol; Nickerson, Heather; Armani, Andrea; Caprio, Massimiliano; Carmeliet, Peter; Jaffe, Iris Z.

    2013-01-01

    Background Aldosterone levels correlate with the incidence of myocardial infarction and mortality in cardiovascular patients. Aldosterone promotes atherosclerosis in animal models, but the mechanisms are poorly understood. Methods and Results Aldosterone was infused to achieve pathologically relevant levels that did not increase blood pressure in the atherosclerosis‐prone apolipoprotein E–knockout mouse (ApoE−/−). Aldosterone increased atherosclerosis in the aortic root 1.8±0.1‐fold after 4 weeks and in the aortic arch 3.7±0.2‐fold after 8 weeks, without significantly affecting plaque size in the abdominal aorta or traditional cardiac risk factors. Aldosterone treatment increased lipid content of plaques (2.1±0.2‐fold) and inflammatory cell content (2.2±0.3‐fold), induced early T‐cell (2.9±0.3‐fold) and monocyte (2.3±0.3‐fold) infiltration into atherosclerosis‐prone vascular regions, and enhanced systemic inflammation with increased spleen weight (1.52±0.06‐fold) and the circulating cytokine RANTES (regulated and normal T cell secreted; 1.6±0.1‐fold). To explore the mechanism, 7 genes were examined for aldosterone regulation in the ApoE−/− aorta. Further studies focused on the proinflammatory placental growth factor (PlGF), which was released from aldosterone‐treated ApoE−/− vessels. Activation of the mineralocorticoid receptor by aldosterone in human coronary artery smooth muscle cells (SMCs) caused the release of factors that promote monocyte chemotaxis, which was inhibited by blocking monocyte PlGF receptors. Furthermore, PlGF‐deficient ApoE−/− mice were resistant to early aldosterone‐induced increases in plaque burden and inflammation. Conclusions Aldosterone increases early atherosclerosis in regions of turbulent blood flow and promotes an inflammatory plaque phenotype that is associated with rupture in humans. The mechanism may involve SMC release of soluble factors that recruit activated leukocytes to the

  9. [Vital pulp therapy of damaged dental pulp].

    PubMed

    Xuedong, Zhou; Dingming, Huang; Jianguo, Liu; Zhengwei, Huang; Xin, Wei; Deqin, Yang; Jin, Zhao; Liming, Chen; Lin, Zhu; Yanhong, Li; Jiyao, Li

    2017-08-01

    The development of an expert consensus on vital pulp therapy can provide practical guidance for the improvement of pulp damage care in China. Dental pulp disease is a major type of illness that adversely affects human oral health. Pulp capping and pulpotomy are currently the main methods for vital pulp therapy. Along with the development of minimal invasion cosmetic dentistry, using different treatment technologies and materials reasonably, preserving healthy tooth tissue, and extending tooth save time have become urgent problems that call for immediate solution in dental clinics. This paper summarizes the experiences and knowledge of endodontic experts. We develop a clinical path of vital pulp therapy for clinical work by utilizing the nature, approach, and degree of pulp damage as references, defense and self-repairing ability of pulp as guidance, and modern technologies of diagnosis and treatment as means.

  10. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    PubMed Central

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  11. HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation.

    PubMed

    Hove-Skovsgaard, Malene; Gaardbo, Julie Christine; Kolte, Lilian; Winding, Kamilla; Seljeflot, Ingebjørg; Svardal, Asbjørn; Berge, Rolf Kristian; Gerstoft, Jan; Ullum, Henrik; Trøseid, Marius; Nielsen, Susanne Dam

    2017-03-29

    Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-)). Groups were matched on age and sex. High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS. The percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 μM (0.63-0.72) compared to HIV + T2D- (0.60 μM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 μM (0.51-63) p = 0.008), and HIV-T2D- (0.55 μM (0.52-0.58) p < 0.001). No differences in TMAO between groups were found. However, a positive correlation between ADMA and TMAO was found in the total population (rs = 0.32, p = 0.001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001). Elevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.

  12. Side-stream smoking reduces intestinal inflammation and increases expression of tight junction proteins

    PubMed Central

    Wang, Hui; Zhao, Jun-Xing; Hu, Nan; Ren, Jun; Du, Min; Zhu, Mei-Jun

    2012-01-01

    AIM: To investigate the effect of side-stream smoking on gut microflora composition, intestinal inflammation and expression of tight junction proteins. METHODS: C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks. Cecal contents were collected for microbial composition analysis. Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins. RESULTS: Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria, Clostridium but decreased Fermicutes (Lactoccoci and Ruminococcus), Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice. Meanwhile, side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα, accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6. The contents of tight junction proteins, claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking. In addition, side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling, while inhibiting AMP-activated protein kinase in the large intestine. CONCLUSION: Side-stream smoking altered gut microflora composition and reduced the inflammatory response, which was associated with increased expression of tight junction proteins. PMID:22611310

  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. Fixed prosthodontics: avoiding pulp death.

    PubMed

    1995-11-01

    Fixed prostheses & crowns have become a major part of dental services due to aging population & increase in retention of natural teeth. In some practices, alarming numbers of endodontic procedures are necessary because of pulp damage after prosthesis cementation. Third party payment companies show many teeth receiving crowns require endodontic therapy within 5 years. Following report describes: (1) 14 potential causes of endodontic need related to fixed prosthodontics; & (2) state-of-art concepts to prevent pulp damage.

  15. [Evaluation of the long-term curative effect of pulp mummification].

    PubMed

    Wang, Z; Wang, J

    1995-07-01

    Fifty--three teeth with pulpitis treated by pulp mummification and followed--up for fifteen years were examined. Of them, excellent result was achieved in 11 teeth (20.75%), good in 8 teeth (15.10%) and failure in 34 teeth (64.15%). Radiologically, 8 good cases were characterized by badly delineated periodontal ligament, increased periodontal ligament space in width, indistinct lamina dura and/or local increase in the density of bone; 34 failure cases were characterized by the radiolucent area or small lesion around apex with clear radiopaque line on the circumference of the area or local increase in the density of bone. These radiographs showed that chronic inflammations existed in periapex. Although further investigations are needed to identify the reasons leading to chronic inflammations, the results should be considered seriously when pulp mummification is upon selection.

  16. Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis.

    PubMed

    Yokoi, Hideki; Kasahara, Masato; Mori, Kiyoshi; Ogawa, Yoshihisa; Kuwabara, Takashige; Imamaki, Hirotaka; Kawanishi, Tomoko; Koga, Kenichi; Ishii, Akira; Kato, Yukiko; Mori, Keita P; Toda, Naohiro; Ohno, Shoko; Muramatsu, Hisako; Muramatsu, Takashi; Sugawara, Akira; Mukoyama, Masashi; Nakao, Kazuwa

    2012-01-01

    Long-term peritoneal dialysis induces peritoneal fibrosis with submesothelial fibrotic tissue. Although angiogenesis and inflammatory mediators are involved in peritoneal fibrosis, precise molecular mechanisms are undefined. To study this, we used microarray analysis and compared gene expression profiles of the peritoneum in control and chlorhexidine gluconate (CG)-induced peritoneal fibrosis mice. One of the 43 highly upregulated genes was pleiotrophin, a midkine family member, the expression of which was also upregulated by the solution used to treat mice by peritoneal dialysis. This growth factor was found in fibroblasts and mesothelial cells within the underlying submesothelial compact zones of mice, and in human peritoneal biopsy samples and peritoneal dialysate effluent. Recombinant pleiotrophin stimulated mitogenesis and migration of mouse mesothelial cells in culture. We found that in wild-type mice, CG treatment increased peritoneal permeability (measured by equilibration), increased mRNA expression of TGF-β1, connective tissue growth factor and fibronectin, TNF-α and IL-1β expression, and resulted in infiltration of CD3-positive T cells, and caused a high number of Ki-67-positive proliferating cells. All of these parameters were decreased in peritoneal tissues of CG-treated pleiotrophin-knockout mice. Thus, an upregulation of pleiotrophin appears to play a role in fibrosis and inflammation during peritoneal injury.

  17. 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.

  18. RAF1 is increased in labouring myometrium and modulates inflammation-induced pro-labour mediators.

    PubMed

    Lappas, Martha

    2016-04-01

    Inflammation plays a central role in the terminal process of human labour and delivery, including myometrial contractions. RAF1 proto-oncogene serine/threonine-protein kinase (RAF1) can activate ERK (official gene symbol MAPK1) and/or nuclear factor-kappa B (NF-κB) to regulate genes involved in inflammation. There are, however, no studies on the role of RAF1 in the processes of human labour and delivery. Thus, the aims of this study were to determine the effect of i) human labour and pro-inflammatory cytokines interleukin 1 beta (IL1B) and tumour necrosis factor (TNF) alpha on RAF1 protein expression in myometrium and ii) siRNA knockdown of RAF1 on pro-inflammatory and pro-labour mediators in human myometrial primary cells. Term labour was associated with an increase in RAF1 protein expression. Furthermore, RAF1 protein expression was increased in myometrial cells treated with IL1B and TNF, two likely factors contributing to preterm birth. Knockdown of RAF1 by siRNA in primary myometrial cells significantly decreased IL1B- and TNF-induced IL1A, IL1B, IL6, (C-X-C motif) ligand 8 (CXCL8)and chemokine (C-C motif) ligand 2 (CCL2) mRNA abundance and IL6, IL8 and CCL2; prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels and prostaglandin PGF2 α release; and NF-κB activation. Furthermore, RAF1 knockdown was associated with decreased activation of ERK in the presence of IL1B but not TNF. Concordantly, the ERK inhibitor U0126 significantly decreased IL1B-induced IL6, CXCL8, CCL2 and PTGS2 mRNA abundance; IL6, CXCL8, CCL2 and PGF2 α release; and NF-κB activation. In conclusion, IL1B induces the expression and secretion of pro-labour mediators through the RAF1-MAPK1-NF-κB signalling pathway. TNF, on the other hand, regulates pro-labour mediators through the RAF1-NF-κB signalling pathway via an MAPK1-independent mechanism. © 2016 Society for Reproduction and Fertility.

  19. The effect of unilateral sympathectomy and cavity preparation on peptidergic nerves and immune cells in rat dental pulp.

    PubMed

    Haug, S R; Berggreen, E; Heyeraas, K J

    2001-05-01

    Recent evidence suggests interactions between primary afferent nociceptors and postganglionic sympathetic efferents in the pathogenesis of inflammation. The effect of unilateral removal of the superior cervical ganglion on the innervation pattern of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY), as well as the occurrence of immune cells in the injured and uninjured rat molar pulp, was investigated. Light microscopic immunocytochemistry demonstrated that the molar pulps contralateral to the sympathectomy contained a NPY-IR nerve fiber network more dense and heavily stained than unoperated control rats. The NPY-IR fibers showed, however, no sprouting after deep cavity preparation. There was no compensatory increase in CGRP- and SP-IR nerve fibers in the dental pulp after unilateral sympathectomy, although a significant increase in cells IR to CGRP and SP was found in the ipsilateral trigeminal ganglion. Unilateral sympathectomy induced a significant increase in immune cell density both in the inflamed and in the uninflamed dental pulp bilaterally. Our results demonstrate, for the first time, a trophic effect of the sympathetic nerves on immune cells in the dental pulp, indicating that an imbalance of sympathetic nerves may induce inflammation and pain in teeth.

  20. 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.

  1. Central autonomic network mediates cardiovascular responses to acute inflammation: Relevance to increased cardiovascular risk in depression?

    PubMed Central

    Harrison, Neil A.; Cooper, Ella; Voon, Valerie; Miles, Ken; Critchley, Hugo D.

    2013-01-01

    Inflammation is a risk factor for both depression and cardiovascular disease. Depressed mood is also a cardiovascular risk factor. To date, research into mechanisms through which inflammation impacts cardiovascular health rarely takes into account central effects on autonomic cardiovascular control, instead emphasizing direct effects of peripheral inflammatory responses on endothelial reactivity and myocardial function. However, brain responses to inflammation engage neural systems for motivational and homeostatic control and are expressed through depressed mood state and changes in autonomic cardiovascular regulation. Here we combined an inflammatory challenge, known to evoke an acute reduction in mood, with neuroimaging to identify the functional brain substrates underlying potentially detrimental changes in autonomic cardiovascular control. We first demonstrated that alterations in the balance of low to high frequency (LF/HF) changes in heart rate variability (a measure of baroreflex sensitivity) could account for some of the inflammation-evoked changes in diastolic blood pressure, indicating a central (rather than solely local endothelial) origin. Accompanying alterations in regional brain metabolism (measured using 18FDG-PET) were analysed to localise central mechanisms of inflammation-induced changes in cardiovascular state: three discrete regions previously implicated in stressor-evoked blood pressure reactivity, the dorsal anterior and posterior cingulate and pons, strongly mediated the relationship between inflammation and blood pressure. Moreover, activity changes within each region predicted the inflammation-induced shift in LF/HF balance. These data are consistent with a centrally-driven component originating within brain areas supporting stressor evoked blood pressure reactivity. Together our findings highlight mechanisms binding psychological and physiological well-being and their perturbation by peripheral inflammation. PMID:23416033

  2. Postoperative inflammation in the abdominal cavity increases adhesion formation in a laparoscopic mouse model.

    PubMed

    Corona, Roberta; Verguts, Jasper; Schonman, Ron; Binda, Maria Mercedes; Mailova, Karina; Koninckx, Philippe Robert

    2011-03-15

    To investigate acute inflammation in the peritoneal cavity in adhesion formation. Prospective randomized, controlled trial. University laboratory research center. 9- to 10-week-old BALB/c female mice. In a laparoscopic mouse model, acute inflammation in the peritoneal cavity evaluated in CO(2) pneumoperitoneum enhanced adhesions, by CO(2) pneumoperitoneum plus manipulation, and in the latter group plus dexamethasone. Qualitative and quantitative adhesion scores and an acute inflammation score (neoangiogenesis, diapedesis, and leukocyte accumulation). Adhesions at the lesion site were enhanced by the CO(2) pneumoperitoneum, further enhanced by manipulation, and decreased by the administration of dexamethasone. The acute inflammation scores (total, neoangiogenesis, diapedesis, and leukocyte accumulation) strongly correlated with the total adhesion score. Inflammation scores were similar at both the surgical lesion and the parietal peritoneum. Acute inflammation of the entire peritoneum cavity is an important mechanism involved in adhesion formation and enhances adhesion formation at the lesion site. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

    DOE PAGES

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

    2016-08-01

    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

  4. Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas

    PubMed Central

    Azuma, Sakiko; Yokoyama, Yukihiro; Yamamoto, Akiko; Kyokane, Kazuhiro; Niida, Shumpei; Ishiguro, Hiroshi; Ko, Minoru S. H.

    2013-01-01

    We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas. PMID:23599043

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

    SciTech Connect

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

    2016-08-01

    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 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.

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

    SciTech Connect

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

    2016-08-01

    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 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.

  7. 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.

  8. 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

  9. Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury

    PubMed Central

    Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

    2017-01-01

    Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates. PMID:27422938

  10. Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury.

    PubMed

    Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

    2017-01-01

    Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation

  11. 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

  12. Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

    PubMed Central

    Bruno, Andreina; Alessi, Marinella; Soresi, Simona; Bonanno, Anna; Riccobono, Loredana; Montalbano, Angela Marina; Albano, Giusy Daniela; Gjomarkaj, Mark; Profita, Mirella

    2011-01-01

    Background Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils. Methods We measured the levels of leptin, tumor necrosis factor alpha (TNF-α) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry. Results In plasma of COPD patients, leptin was inversely correlated with TNF-α and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-α. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-α were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers. Conclusion Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation. PMID:22096369

  13. Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers.

    PubMed

    Bruno, Andreina; Alessi, Marinella; Soresi, Simona; Bonanno, Anna; Riccobono, Loredana; Montalbano, Angela Marina; Albano, Giusy Daniela; Gjomarkaj, Mark; Profita, Mirella

    2011-01-01

    Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils. We measured the levels of leptin, tumor necrosis factor alpha (TNF-α) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry. In plasma of COPD patients, leptin was inversely correlated with TNF-α and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-α. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-α were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers. Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation.

  14. Increased prokineticin 2 expression in gut inflammation: role in visceral pain and intestinal ion transport.

    PubMed

    Watson, Robert P; Lilley, Elliot; Panesar, Moh; Bhalay, Gurdip; Langridge, Steven; Tian, Shin-Shay; McClenaghan, Conor; Ropenga, Anna; Zeng, Fanning; Nash, Mark S

    2012-01-01

    Prokineticin 2 (PROK2) is an inflammatory cytokine-like molecule expressed predominantly by macrophages and neutrophils infiltrating sites of tissue damage. Given the established role of prokineticin signaling on gastrointestinal function, we have explored Prok2 gene expression in inflammatory conditions of the gastrointestinal tract and assessed the possible consequences on gut physiology. Prokineticin expression was examined in normal and colitic tissues using qPCR and immunohistochemistry. Functional responses to PROK2 were studied using calcium imaging and a novel antagonist, Compound 3, used to determine the role of PROK2 and prokineticin receptors in inflammatory visceral pain and ion transport. Prok2 gene expression was up-regulated in biopsy samples from ulcerative colitis patients, and similar elevations were observed in rodent models of inflammatory colitis. Prokineticin receptor 1 (PKR1) was localized to the enteric neurons and extrinsic sensory neurons, whereas Pkr2 expression was restricted to sensory ganglia. In rats, PROK2-increased intracellular calcium levels in cultured enteric and dorsal root ganglia neurons, which was blocked by Compound 3. Moreover, PROK2 acting at prokineticin receptors stimulated intrinsic neuronally mediated ion transport in rat ileal mucosa. In vivo, Compound 3 reversed intracolonic mustard oil-induced referred allodynia and TNBS-induced visceral hypersensitivity, but not non-inflammatory, stress-induced visceral pain. Elevated Prok2 levels, as a consequence of gastrointestinal tract inflammation, induce visceral pain via prokineticin receptors. This observation, together with the finding that PROK2 can modulate intestinal ion transport, raises the possibility that inhibitors of PROK2 signaling may have clinical utility in gastrointestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease. © 2011 Blackwell Publishing Ltd.

  15. Increased ischaemia-modified albumin is associated with inflammation in acute rheumatic fever.

    PubMed

    Karataş, Zehra; Baysal, Tamer; Şap, Fatih; Alp, Hayrullah; Mehmetoğlu, Idris

    2014-06-01

    Ischaemia-modified albumin, a novel biochemical marker for tissue ischaemia, was found to be associated with oxidative stress. The purpose of this study was to assess the role of ischaemia-modified albumin in the diagnosis of acute rheumatic fever and also to evaluate the ischaemia-modified albumin levels in children with heart valve disease. The study groups, aged 5-18 years, consisted of 128 individuals - 40 with acute rheumatic fever, 35 with congenital heart valve disease, 33 with chronic rheumatic heart disease, and 20 healthy control subjects. The ischaemia-modified albumin, erythrocyte sedimentation rate, and C-reactive protein levels of the acute rheumatic fever group were significantly higher than those in the chronic rheumatic heart disease, congenital heart valve disease, and control groups, separately (p < 0.001). The ischaemia-modified albumin levels in both carditis and isolated arthritis subgroups of children with acute rheumatic fever were significantly higher than in the control group (p < 0.001, p < 0.01, respectively). However, there was no statistically significant difference between the chorea subgroup and control subjects. In addition, significant correlations were observed between ischaemia-modified albumin and acute phase reactants of patients with acute rheumatic fever (p < 0.001 for both erythrocyte sedimentation rate and C-reactive protein). The ischaemia-modified albumin levels of chronic rheumatic heart disease, congenital heart valve disease, and control subjects were similar. The increased level of ischaemia-modified albumin in children with acute rheumatic fever seems to be associated with inflammation. However, further studies are needed to provide stronger evidence.

  16. Increased acylated plasma ghrelin, but improved lipid profiles 24-h after consumption of carob pulp preparation rich in dietary fibre and polyphenols.

    PubMed

    Gruendel, Sindy; Garcia, Ada L; Otto, Baerbel; Wagner, Karen; Bidlingmaier, Martin; Burget, Lukas; Weickert, Martin O; Dongowski, Gerhard; Speth, Maria; Katz, Norbert; Koebnick, Corinna

    2007-12-01

    We have recently shown that a polyphenol-rich insoluble dietary fibre preparation from carob pulp (Ceratonia siliqua L; carob fibre) decreased postprandial acylated ghrelin, TAG and NEFA during an acute liquid meal challenge test. However, delayed effects of carob fibre consumption are unknown. Therefore, a randomized controlled crossover study in nineteen healthy volunteers consuming foods with or without 50 g carob fibre was conducted. On the subsequent day (day 2), glucose, TAG, total and acylated ghrelin as well as insulin, NEFA and leptin were assessed at baseline and at timed intervals for 300 min after ingestion of standardized bread. Consumption of carob fibre-enriched foods did not affect fasting concentrations of glucose, TAG, total ghrelin, NEFA, insulin and leptin. Fasting acylated ghrelin was increased on the day subsequent to carob fibre consumption compared with control (P = 0.046). After consumption of the standard bread on day 2, glucose response (P = 0.029) was increased, and TAG (P = 0.033) and NEFA (P < 0.001) responses were decreased compared with control. Postprandial responses of total and acylated ghrelin, insulin and leptin on day 2 were unaffected by carob fibre consumption the previous day. In conclusion, an increase in total and acylated plasma ghrelin accompanied by enhanced lipid metabolism after carob fibre consumption suggests higher lipid utilization and suppressed lipolysis on the day subsequent to carob fibre consumption. However, elevated glucose levels after carob fibre consumption need to be addressed in future studies.

  17. Dental Pulp Defence and Repair Mechanisms in Dental Caries.

    PubMed

    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.

  18. 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

  19. Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD

    PubMed Central

    Komatsu, Kensei; Lee, Ji-Yun; Miyata, Masanori; Hyang Lim, Jae; Jono, Hirofumi; Koga, Tomoaki; Xu, Haidong; Yan, Chen; Kai, Hirofumi; Li, Jian-Dong

    2013-01-01

    The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression. PMID:23575688

  20. Increased postnatal inflammation in mechanically ventilated preterm infants born to mothers with early-onset preeclampsia.

    PubMed

    Turunen, Riikka; Andersson, Sture; Laivuori, Hannele; Kajantie, Eero; Siitonen, Sanna; Repo, Heikki; Nupponen, Irmeli

    2011-01-01

    Preeclampsia and preterm labor often underlie preterm birth, and are associated with maternal inflammation. In preterm infants, respiratory distress syndrome (RDS) and mechanical ventilation are associated with systemic inflammation. We aimed to study whether early-onset preeclampsia or preterm labor modulate the systemic inflammation affecting preterm infants with RDS. We recruited mechanically ventilated infants with gestational ages <32 weeks; 11 infants were born after early-onset preeclampsia and 25 after preterm labor. Blood was drawn during postnatal days 1-7, and the mean values of days 1-2, 3-4 and 5-6 were used. Phagocyte CD11b expression was analyzed with flow cytometry, and plasma C-reactive protein (CRP) concentrations with immunoturbidimetry. As compared with infants born after preterm labor, infants born after early-onset preeclampsia had higher CD11b expression on days 1-6 on both neutrophils and monocytes. In addition, infants born after early-onset preeclampsia had higher CRP concentrations on days 2-6 (all p < 0.05). As compared with infants born after preterm labor to mothers without preeclampsia, infants born after early-onset preeclampsia presented with a stronger postnatal systemic inflammatory reaction. Antenatal exposure to preeclampsia may induce fetal leukocyte priming and regulation of inflammation, and thereby modify postnatal inflammatory reactions and morbidity. Copyright © 2011 S. Karger AG, Basel.

  1. Diabetes induces metabolic alterations in dental pulp.

    PubMed

    Leite, Mariana Ferreira; Ganzerla, Emily; Marques, Márcia Martins; Nicolau, José

    2008-10-01

    Diabetes can interfere in tissue nutrition and can impair dental pulp metabolism. This disease causes oxidative stress in cells and tissues. However, little is known about the antioxidant system in the dental pulp of diabetics. Thus, it would be of importance to study this system in this tissue in order to verify possible alterations indicative of oxidative stress. The aim of this study was to evaluate some parameters of antioxidant system of the dental pulp of healthy (n = 8) and diabetic rats (n = 8). Diabetes was induced by streptozotocin in rats. Six weeks after diabetes induction, a pool of the dental pulp of the 4 incisors of each rat (healthy and diabetic) was used for the determination of total protein and sialic acid concentrations and catalase and peroxidase activities. Data were compared by a Student t test (p pulps from both groups presented similar total protein concentrations and peroxidase activity. Dental pulps of diabetic rats exhibited significantly lower free, conjugated, and total sialic acid concentrations than those of control tissues. Catalase activity in diabetic dental pulps was significantly enhanced in comparison with that of control pulps. The result of the present study is indicative of oxidative stress in the dental pulp caused by diabetes. The increase of catalase activity and the reduction of sialic acid could be resultant of reactive oxygen species production.

  2. 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.

  3. 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

  4. Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of Duchenne muscular dystrophy.

    PubMed

    Gordon, Bradley S; Delgado Díaz, Diana C; Kostek, Matthew C

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a lethal genetic disease with no cure. Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identify an active dose of resveratrol in mdx mice and examine if this dose decreased inflammation and increased utrophin expression. 5-week old mdx mice were given 0, 10, 100, or 500 mg/kg of resveratrol everyday for 10 days. Sirt1 was measured by qRT-PCR and used to determine the most active dose. Muscle inflammation was measured by H&E staining, CD45 and F4/80 immunohistochemistry. IL-6, TNFα, PGC-1α, and utrophin gene expression were measured by qRT-PCR. Utrophin, Sirt1, and PGC-1α protein were quantified by western blot. The 100 mg/kg dose of resveratrol, the most active dose, increased Sirt1 mRNA 60 ± 10% (p < 0.01), reduced immune cell infiltration 21 ± 6% (H&E) and 42 ± 8% (CD45 immunohistochemistry (p < 0.05)), reduced macrophage infiltration 48 ± 10% (F4/80 immunohistochemistry (p < 0.05)), and increased IL-6, PGC-1α, and utrophin mRNA 247 ± 77%, 27 ± 17%, and 43 ± 23% respectively (p ≤ 0.05). Utrophin, Sirt1, and PGC-1α protein expression did not change. Resveratrol may be a therapy for DMD by reducing inflammation. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  5. 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)

  6. 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)

  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. Copyright © 2015 the American Physiological Society.

  8. Sugarcane bagasse pulps: biobleaching with commercial cartazyme HS and with Bacillus pumilus xylanase.

    PubMed

    Moriya, Regina Y; Gonçalves, Adilson R; Duarte, Marta C T

    2005-01-01

    Organosolv (ethanol/water and acetosolv) pulps were treated with Bacillus pumilus xylanase for 4, 8, and 12 h and compared with commercial Cartazyme HS xylanase-treated pulps. Treatment of ethanol/water pulps with B. pumilus xylanase increased viscosity by 40% in 8 h of treatment compared with pulps treated without enzyme. However, acetosolv pulps treated with B. pumilus xylanase lost viscosity. Ethanol/water pulps treated with Cartazyme had a viscosity of 18.5 cP in 4 h of treatment. In the acetosolv pulps treated with commercial enzyme, the loss of viscosity was 20% compared with pulps treated without enzyme. Ethanol/water pulps treated with B. pumilus and Cartazyme had similar effects: a 44% reduction in kappa number for pulps treated with enzyme followed by alkaline extraction compared with pulps treated with alkaline extraction. In acetosolv pulps treated with B. pumilus, the kappa number was from 12 to 18, compared with pulps treated without enzyme, which had a 40% reduction in 4 and 12 h and a 60% reduction in 8 h. Cartazyme-treated acetosolv pulps had a kappa number of 14 in 4 and 8 h of treatment. For 12 h of treatment, the kappa number was 8. Fourier transform infrared spectra of the pulps showed that enzyme-treated pulps had changes in the 1000 cm-1 absorption owing to a C-O bond present in esters. Using principal component analysis, it is possible to differentiate the unbleached pulps and enzyme-treated pulps.

  9. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation

    PubMed Central

    2013-01-01

    Background The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that microaspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. To test this, we sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (nine never-smokers, 14 former-smokers, and six current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes, and neutrophils. Results BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotypeSCT. Smoking had no effect on pneumotype allocation, α, or β diversity. PneumotypeSCT was associated with higher BAL lymphocyte-count (P= 0.007), BAL neutrophil-count (P= 0.034), and eNO (P= 0.022). Conclusion A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation. PMID:24450871

  10. Serum Markers of Endothelial Dysfunction and Inflammation Increase in Hypertension with Prediabetes Mellitus.

    PubMed

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-06-01

    The aim of this study was to examine endothelial dysfunction and inflammation in hypertension and prediabetes by studying adhesion molecules and inflammatory factors. This study included 133 outpatients. Participants were categorized into three groups based on the presence or absence of hypertension and prediabetes: control subjects without prediabetes and hypertension (N group, n = 39); patients with hypertension only (H group, n = 34); and patients with hypertension and prediabetes (HD group, n = 60). Hypertension was diagnosed according to JNC7 criteria. Prediabetes was defined according to 2010 American Diabetes Association criteria. Plasma was isolated from overnight fasting blood samples for enzyme-linked immunosorbent assay (ELISA) analysis of concentrations of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), P-selectin, and interleukin-6 (IL-6) as indicators of endothelial function and inflammation. We found that the H and HD groups showed significantly higher levels of all four biomarkers compared with the N group (all p < 0.01). The HD group also showed significantly higher levels of ICAM-1 (p = 0.042) and TNF-α (p < 0.01) compared with the H group; no significant differences in P-selectin (p = 0.59) and IL-6 (p = 0.70) levels were observed among these groups. Prediabetes and hypertension induce endothelial dysfunction and inflammation by elevating levels of soluble adhesion molecules and inflammatory cytokines. The comorbidity of these diseases may exacerbate inflammation and endothelial dysfunction by enhancing the expression of ICAM-1 and TNF-α.

  11. Research in bagasse pulp bleaching

    SciTech Connect

    Fernandez, N.; Naranjo, M.E.; Alvarez, J.; Sardinas, O.; Serrantes, M.

    1982-01-01

    Bleaching of soda and sulfate bagasse pulps by CED, CEH, CEHD, and O/alkali CED sequences gave products with Elrepho brightness 85-90, Post color no. 1.3-2.5, viscosity 20-28 cP, tear factor 60-78, and breaking length 3710-4590 m. Bleaching bagasse pulp with Na/sub 2/S/sub 2/O/sub 4/-NaClO increased its brightness increasing temperature, pH, and NaOCl consumption. Brightening of mechanical bagasse pulp with H/sub 2/O/sub 2/, Na/sub 2/S/sub 2/O/sub 4/, and NaClO reduced the consumption of peroxide, Na/sub 2/S/sub 2/O/sub 4/, and NaOCl by 0.5-0.8, 0.5-1.5, and 10-12%, respectively.

  12. Biological bleaching of chemical pulps.

    PubMed

    Bajpai, Pratima

    2004-01-01

    Use of biotechnology in pulp bleaching has attracted considerable attention and achieved interesting results in recent years. Enzymes of the hemicellulolytic type, particularly xylan-attacking enzymes, xylanases are now used commercially in the mills for pulp treatment and subsequent incorporation into bleach sequences. The aims of the enzymatic treatment depend on the actual mill conditions and may be related to environmental demands, reduction of chemical costs or maintenance or even improvement of product quality. The use of oxidative enzymes from white-rot fungi, that can directly attack lignin, is a second-generation approach, which could produce larger chemical savings than xylanase but has not yet been developed to the full scale. It is being studied in several laboratories in Canada, Japan, the U.S.A. and Europe. Certain white-rot fungi can delignify kraft pulps increasing their brightness and their responsiveness to brightening with chemicals. The fungal treatments are too slow but the enzyme manganese peroxidase and laccase can also delignify pulps and enzymatic processes are likely to be easier to optimize and apply than the fungal treatments. Development work on laccase and manganese peroxidase continues. This article presents an overview of developments in the application of hemicellulase enzymes, lignin-oxidizing enzymes and white-rot fungi in bleaching of chemical pulps. The basic enzymology involved and the present knowledge of the mechanisms of the action of enzymes as well as the practical results and advantages obtained on the laboratory and industrial scale are discussed.

  13. 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

  14. Vital pulp therapy-current progress of dental pulp regeneration and revascularization.

    PubMed

    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.

  15. 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

  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. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  17. Carob pulp preparation rich in insoluble dietary fibre and polyphenols increases plasma glucose and serum insulin responses in combination with a glucose load in humans.

    PubMed

    Gruendel, Sindy; Otto, Baerbel; Garcia, Ada L; Wagner, Karen; Mueller, Corinna; Weickert, Martin O; Heldwein, Walter; Koebnick, Corinna

    2007-07-01

    Dietary fibre consumption is associated with improved glucose homeostasis. In contrast, dietary polyphenols have been suggested to exert both beneficial and detrimental effects on glucose and insulin metabolism. Recently, we reported that a polyphenol-rich insoluble dietary fibre preparation from carob pulp (carob fibre) resulted in lower postprandial acylated ghrelin levels after a liquid meal challenge test compared with a control meal without supplementation. The effects may, however, differ when a different food matrix is used. Thus, we investigated the effects of carob fibre on glucose, insulin and ghrelin responses in healthy humans in combination with a glucose load. In a randomized single-blind cross-over study involving twenty healthy subjects (aged 22-62 years), plasma glucose, total and acylated ghrelin, and serum insulin were repeatedly assessed before and after the ingestion of 200 ml water with 50 g glucose and 0, 5, 10 or 20 g carob fibre over a period of 180 min. The intake of 5 and 10 g carob fibre increased the plasma glucose by 47 % and 64 % (P < 0.001), and serum insulin by 19.9 and 24.8 % (P < 0.001), compared with the control. Plasma acylated ghrelin concentrations did not change significantly after the consumption of carob-enriched glucose solution. Total ghrelin decreased only after 10 g carob fibre (P < 0.001) compared with control. In conclusion, we showed that polyphenol-rich carob fibre, administered within a water-glucose solution, increases postprandial glucose and insulin responses, suggesting a deterioration in glycaemic control.

  18. Purmorphamine increased adhesion, proliferation and expression of osteoblast phenotype markers of human dental pulp stem cells cultured on beta-tricalcium phosphate.

    PubMed

    Rezia Rad, Maryam; Khojaste, Moein; Hasan Shahriari, Mehrnoosh; Asgary, Saeed; Khojasteh, Arash

    2016-08-01

    Growth factors play a significant role in cell proliferation and differentiation during different stages of the bone repair. However, several limitations have been brought researchers attention to an osteoinductive small molecule including Purmorphamine. In this study, we aimed to evaluate the effect of Purmorphamine on adhesion, proliferation and differentiation of human dental pulp stem cells (hDPSCs) seaded on beta-tricalcium phosphate (β-TCP) granules. hDPSCs were established from extracted wisdom teeth of healthy volenteers. Cells at passage 3 were seeded on β-TCP in the presence or absence of Purmorphamine. Cell adhesion and proliferation were assessed using scanning electeron microscopy (SEM) and DNA counting assay, respectively, after 1, 3 and 5days. Then, hDPSCs seeded on β-TCP were subjected to osteogenic medium with or without Purmorphamine. After 7 and 14days osteogenic diffrentiation capability of hDPSCs were determined using real-time RT-PCR and alkaline phosphatase (ALP) activity assay. The significant increase in amount of DNA was observed at day 3 and 5 in the presence of Purmorphamine. SEM imaging also was confirmed the DNA counting assay; in all given time points, hDPSC attachment and growth was significantly higher in the presence of Purmorphamine. ALP activity was increased by Purmorphamine at both 7 and 14days of induction. Purmorphamine showed to effect on osteopontin expression at earlier stage of osteogenic differentiation, whereas for osteocalcin expression, this effect was more evident at later stage of differentiation. Purmorphamine had a promotive effect on adhesion, proliferation and osteogenic differentiation of hDPSCs cultured on β-TCP. The outcome of the current study would help in development of in vitro culture conditions for better osteogenic differentiation of hDPSCs prior to transplantation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

    PubMed

    Zhang, S; Chiang, C Y; Xie, Y F; Park, S J; Lu, Y; Hu, J W; Dostrovsky, J O; Sessle, B J

    2006-10-27

    We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.

  20. Pulp tissue reactions to a dentin bonding agent as a direct capping agent.

    PubMed

    Sübay, Rüstem Kemal; Demirci, Mustafa

    2005-03-01

    The aim of this study was to investigate the response of human pulp tissue to a dentin bonding agent, Scotchbond Multi-Purpose Plus (SMPP), in exposed class V cavities. Sixteen human premolar teeth were mechanically exposed. Ten pulps were capped with SMPP and six teeth were capped with Dycal. The cavities were filled with a composite. After 40 days, the teeth were extracted and processed for histologic evaluation. Of the 10 teeth capped with SMPP, eight showed moderate chronic inflammation, one was severely inflamed, and one pulp had no to slight inflammation. None of the teeth capped with SMPP showed dentin bridge formation. Of the six teeth capped with Dycal, three exhibited incomplete dentin bridges associated with no to slight inflammation, and three showed no to slight inflammation, without formation of dentin bridges. Direct capping with Dycal with subsequent sealing with SMPP may show favorable results in pulp tissue. SMPP may cause inflammatory changes when applied directly to exposed pulp tissue.

  1. Deficiency in macrophage-stimulating protein results in spontaneous intestinal inflammation and increased susceptibility toward epithelial damage in zebrafish.

    PubMed

    Witte, Merlijn; Huitema, Leonie F A; Nieuwenhuis, Edward E S; Brugman, Sylvia

    2014-12-01

    Several genome-wide association studies have identified the genes encoding for macrophage-stimulating protein (MSP) and its receptor RON (Recepteur d'Origine Nantais) as possible susceptibility factors in inflammatory bowel disease. While it has been shown that the MSP-RON signaling pathway is involved in tissue injury responses, current mouse models for MSP and RON deficiency have not clearly demonstrated a role of MSP-RON signaling in the context of intestinal inflammation. In this study, we report that the recently identified zebrafish Msp mutant (msp(t34230)) develops spontaneous intestinal inflammation over time. From 14 to 28 weeks postfertilization Msp-deficient zebrafish show intestinal eosinophilia, increased intestinal expression of inflammatory marker mmp9, and activation of intestinal goblet cells. Moreover, these Msp mutant zebrafish are more susceptible toward ethanol-induced epithelial damage, which resulted in increased infiltration and proliferation of immune cells within the lamina propria and prolonged intestinal proinflammatory cytokine responses in some mutant fish. In light of the recent development of many tools to visualize, monitor, and genetically modify zebrafish, these Msp-deficient zebrafish will enable in-depth in vivo analysis of epithelial and macrophage-specific MSP-RON signaling in the context of intestinal inflammation.

  2. 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.

  3. Imbalance in systemic inflammation and immune response following transarterial chemoembolization potentially increases metastatic risk in huge hepatocellular carcinoma.

    PubMed

    Xue, Tong-Chun; Jia, Qing-An; Ge, Ning-Ling; Chen, Yi; Zhang, Bo-Heng; Ye, Sheng-Long

    2015-11-01

    Inflammation plays a critical role in tumor metastasis. However, few inflammation-related biomarkers are currently available to predict the risk of metastasis for advanced hepatocellular carcinoma (HCC). Using huge tumors (diameter >10 cm) as a model, we evaluated the potential risk of pre- and post-treatment inflammatory responses in the development of metastasis of HCC patients undergoing transarterial chemoembolization (TACE). A logistic regression model was used to analyze the risk factors. One hundred and sixty-five patients with huge HCC were enrolled in the study. Metastases were identified in 25.5% (42/165) patients by imaging evaluation post-TACE. Neutrophils increased, whereas lymphocytes decreased significantly post-TACE. Univariate analysis showed that high post-treatment neutrophil-to-lymphocyte ratio (NLR; p = 0.003), low post-treatment lymphocyte count (p = 0.047), and high baseline NLR (p = 0.100) were potential risk factors for metastasis. Further, multivariate analysis showed that high post-treatment NLR, but not pre-treatment NLR, was an independent risk factor for metastasis; this was confirmed by receiver operating characteristic curve analysis. Post-treatment NLR, however, had no correlation to tumor response and overall survival of patients. In conclusion, post-treatment NLR but not pre-treatment NLR independently increases the risk of metastasis in huge HCC. Our findings suggest the potential contribution of treatment-related inflammation to metastasis in advanced HCC.

  4. Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan.

    PubMed

    Ganz, Tomas; Gabayan, Victoria; Liao, Hsiang-I; Liu, Lide; Oren, Ami; Graf, Thomas; Cole, Alexander M

    2003-03-15

    More than 70 years ago, Alexander Fleming discovered lysozyme and proposed that nonpathogenic bacteria fail to cause disease because they are very susceptible to destruction by lysozyme, an enzyme that is one of the principal proteins of phagocytes. Although much has been learned about the effects of lysozyme in vitro, its biological role in vivo has not been determined. We examined transgenic mice deficient in lysozyme M after challenge by the normally nonpathogenic and highly lysozyme-sensitive bacterium Micrococcus luteus. Despite partial compensation by newly expressed lysozyme P in macrophages, lysozyme M-deficient mice developed much more severe lesions than wild-type mice. The tissue injury was due to the failure of lysozyme M-deficient mice to inactivate peptidoglycan, resulting in an intense and prolonged inflammatory response. Our data indicate that tissue injury is normally limited by prompt degradation of bacterial macromolecules that trigger innate immunity and inflammation.

  5. Unilateral hindpaw inflammation produces a bilateral increase in NADPH-diaphorase histochemical staining in the rat lumbar spinal cord.

    PubMed

    Solodkin, A; Traub, R J; Gebhart, G F

    1992-12-01

    Tissue injury results in several changes in spinal cord neurons that contribute to hyperalgesia arising from the injured tissue. In models of unilateral hindpaw inflammation, changes in the neurochemistry and electrophysiology of dorsal horn neurons ipsilateral, and to a much lesser extent contralateral, to the inflamed paw have been reported. For example, the excitability of dorsal horn neurons increases, receptive field size increases, and the content of various proteins and neuropeptides in the dorsal horn (e.g. FOS, dynorphin, enkephalin) are affected following peripheral inflammatory insult. These changes are typically interpreted on the basis of their relevance to nociception.

  6. A comparative histological analysis of human pulp following direct pulp capping with Propolis, mineral trioxide aggregate and Dycal.

    PubMed

    Parolia, A; Kundabala, M; Rao, N N; Acharya, S R; Agrawal, P; Mohan, M; Thomas, M

    2010-03-01

    Permanent teeth pulp exposures have traditionally been treated with calcium hydroxide pulp capping. The aim of this study was to investigate the response of human pulp tissue which were mechanically exposed to a new material, Propolis and compare it with two existing and commonly used pulp capping agents (mineral trioxide aggregate and Dycal). Thirty-six intact human premolars were mechanically exposed. Teeth were divided into six groups of 6 teeth each and were capped with Propolis, mineral trioxide aggregate and Dycal. Final restoration was done with posterior composite resin using light cured glass ionomer cement as a liner. The teeth were then extracted on the 15th or the 45th day and processed for histological evaluation. Differences in inflammatory response and dentine bridge formation of the exposed pulp to the three different materials were statistically calculated using chi-square test and were found to be non-significant. There was more pulp inflammation in teeth treated with Dycal than with Propolis and MTA on the 15th as well as on the 45th day. Propolis and MTA showed bridge formation in more teeth, and the bridges were in closer proximity to pulp capping material than teeth treated with Dycal on the 45th day. The response of pulps to Propolis as a pulp capping agent was comparable to MTA and Dycal.

  7. Superimposed Gastric Aspiration Increases the Severity of Inflammation and Permeability Injury in a Rat Model of Lung Contusion

    PubMed Central

    Raghavendran, Krishnan; Davidson, Bruce A.; Huebschmann, John C.; Helinski, Jadwiga D.; Hutson, Alan D.; Dayton, Merrily T.; Notter, Robert H.; Knight, Paul R.

    2009-01-01

    Introduction Lung contusion (LC) from blunt thoracic trauma is a clinically-prevalent condition that can progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Patients with LC are at risk for gastric aspiration at the time of trauma, but the combined insults have not been well-studied in animal models. This study tests the hypothesis that concurrent gastric aspiration (combined acid and small gastric particles, CASP) at the time of trauma significantly increases permeability injury and inflammation compared with LC alone, and also modifies the inflammatory response to include distinct features compared with the aspiration component of injury. Materials and Methods Four groups of adult male Long-Evans rats were studied (LC, CASP, LC + CASP, uninjured controls). LC was induced in anesthetized rats at a fixed impact energy of 2.0J, and CASP (1.2mL/kg body weight, 40mg particles/mL, pH = 1.25) was instilled through an endotracheal tube. Lung injury and inflammation were assessed by arterial blood gases and levels of albumin, cells, and cytokines/chemokines in bronchoalveolar lavage (BAL) at 5 and 24hours. Results Rats with LC + CASP had lower mean PaO2/FiO2 ratios compared with LC alone at 24hours, and higher BAL albumin concentrations compared with either LC or CASP alone. Rats with LC + CASP versus LC had more severe inflammation based on higher levels of PMN in BAL at 5hours, increased whole lung myeloperoxidase (MPO) activity at 5 and 24hours, and increased levels of inflammatory mediators in BAL (TNFα, IL-1β, and MCP-1 at 5 and 24hours; IL-10, MIP-2, and CINC-1 at 5hours). Rats with LC + CASP also had distinct aspects of inflammation compared with CASP alone, i.e., significantly higher levels of IL-10 (5 and 24hours), IL-1β (24hours), CINC-1 (24hours), and MCP-1 (24hours), and significantly lower levels of MPO (5hours), MIP-2 (5hours), and CINC-1 (5hours). Conclusions Concurrent gastric aspiration can exacerbate permeability lung

  8. Superimposed gastric aspiration increases the severity of inflammation and permeability injury in a rat model of lung contusion.

    PubMed

    Raghavendran, Krishnan; Davidson, Bruce A; Huebschmann, John C; Helinski, Jadwiga D; Hutson, Alan D; Dayton, Merril T; Notter, Robert H; Knight, Paul R

    2009-08-01

    Lung contusion (LC) from blunt thoracic trauma is a clinically-prevalent condition that can progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Patients with LC are at risk for gastric aspiration at the time of trauma, but the combined insults have not been well-studied in animal models. This study tests the hypothesis that concurrent gastric aspiration (combined acid and small gastric particles, CASP) at the time of trauma significantly increases permeability injury and inflammation compared with LC alone, and also modifies the inflammatory response to include distinct features compared with the aspiration component of injury. Four groups of adult male Long-Evans rats were studied (LC, CASP, LC+CASP, uninjured controls). LC was induced in anesthetized rats at a fixed impact energy of 2.0 J, and CASP (1.2 mL/kg body weight, 40 mg particles/mL, pH=1.25) was instilled through an endotracheal tube. Lung injury and inflammation were assessed by arterial blood gases and levels of albumin, cells, and cytokines/chemokines in bronchoalveolar lavage (BAL) at 5 and 24 h. Rats with LC+CASP had lower mean PaO(2)/FiO(2) ratios compared with LC alone at 24 h, and higher BAL albumin concentrations compared with either LC or CASP alone. Rats with LC+CASP versus LC had more severe inflammation based on higher levels of PMN in BAL at 5 h, increased whole lung myeloperoxidase (MPO) activity at 5 and 24 h, and increased levels of inflammatory mediators in BAL (TNFalpha, IL-1beta, and MCP-1 at 5 and 24 h; IL-10, MIP-2, and CINC-1 at 5 h). Rats with LC+CASP also had distinct aspects of inflammation compared with CASP alone, i.e., significantly higher levels of IL-10 (5 and 24 h), IL-1beta (24 h), CINC-1 (24 h), and MCP-1 (24 h), and significantly lower levels of MPO (5 h), MIP-2 (5 h), and CINC-1 (5 h). Concurrent gastric aspiration can exacerbate permeability lung injury and inflammation associated with LC, and also generates a modified inflammatory

  9. Timp3 loss accelerates tumour invasion and increases prostate inflammation in a mouse model of prostate cancer.

    PubMed

    Adissu, Hibret A; McKerlie, Colin; Di Grappa, Marco; Waterhouse, Paul; Xu, Qiang; Fang, Hui; Khokha, Rama; Wood, Geoffrey A

    2015-12-01

    Altered expression and activity of proteases is implicated in inflammation and cancer progression. An important negative regulator of protease activity is TIMP3 (tissue inhibitor of metalloproteinase 3). TIMP3 expression is lacking in many cancers including advanced prostate cancer, and this may facilitate invasion and metastasis by allowing unrestrained protease activity. To investigate the role of TIMP3 in prostate cancer progression, we crossed TIMP3-deficient mice (Timp3(-/-)) to mice with prostate-specific deletion of the tumor suppressor Pten (Pten(-/-)), a well-established mouse model of prostate cancer. Tumor growth and progression were compared between Pten(-/-), Timp3(-/-) and control (Pten(-/-), Timp3(+/+)) mice at 16 weeks of age by histopathology and markers of proliferation, vascularity, and tumor invasion. Metalloproteinase activity within the tumors was assessed by gelatin zymography. Inflammatory infiltrates were assessed by immunohistochemistry for macrophages and lymphocytes whereas expression of cytokines and other inflammatory mediators was assessed by quantitative real time PCR and multiplex ELISA. Increased tumor growth, proliferation index, increased microvascular density, and invasion was observed in Pten(-/-), Timp3(-/-) prostate tumors compared to Pten(-/-), Timp3(+/+) tumors. Tumor cell invasion in Pten(-/-), Timp3(-/-) mice was associated with increased expression of matrix metalloprotease (MMP)-9 and activation of MMP-2. There was markedly increased inflammatory cell infiltration into the TIMP3-deficient prostate tumors along with increased expression of monocyte chemoattractant protein-1, cyclooxygenase-2, TNF-α, and interleukin-1β; all of which are implicated in inflammation and cancer. This study provides important insights into the role of altered protease activity in promoting prostate cancer invasion and implicates prostate inflammation as an important promoting factor in prostate cancer progression. © 2015 Wiley Periodicals

  10. Tumor necrosis factor alpha-induced inflammation is increased but apoptosis is inhibited by common food additive carrageenan.

    PubMed

    Bhattacharyya, Sumit; Dudeja, Pradeep K; Tobacman, Joanne K

    2010-12-10

    Tumor necrosis factor (TNF)-α, a homotrimeric, pleiotropic cytokine, is secreted in response to inflammatory stimuli in diseases such as rheumatoid arthritis and inflammatory bowel disease. TNF-α mediates both apoptosis and inflammation, stimulating an inflammatory cascade through the non-canonical pathway of NF-κB activation, leading to increased nuclear RelB and p52. In contrast, the common food additive carrageenan (CGN) stimulates inflammation through both the canonical and non-canonical pathways of NF-κB activation and utilizes the adaptor molecule BCL10 (B-cell leukemia/lymphoma 10). In a series of experiments, colonic epithelial cells and mouse embryonic fibroblasts were treated with TNF-α and carrageenan in order to simulate the possible effects of exposure to dietary CGN in the setting of a TNF-α-mediated inflammatory disease process. A marked increase in secretion of IL-8 occurred, attributable to synergistic effects on phosphorylated NF-κB-inducing kinase (NIK) in the non-canonical pathway. TNF-α induced the ubiquitination of TRAF2 (TNF receptor-associated factor 2), which interacts with NIK, and CGN induced phosphorylation of BCL10, leading to increased NIK phosphorylation. These results suggest that TNF-α and CGN in combination act to increase NIK phosphorylation, thereby increasing activation of the non-canonical pathway of NF-κB activation. In contrast, the apoptotic effects of TNF-α, including activation of caspase-8 and PARP-1 (poly(ADP-ribose) polymerase 1) fragmentation, were markedly reduced in the presence of CGN, and CGN caused reduced expression of Fas. These findings demonstrate that exposure to CGN drives TNF-α-stimulated cells toward inflammation rather than toward apoptotic cell death and suggest that CGN exposure may compromise the effectiveness of anti-TNF-α therapy.

  11. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    PubMed

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  12. 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

  13. Neuropeptide K-like immunoreactivity in human dental pulp.

    PubMed

    Casasco, A; Calligaro, A; Springall, D R; Casasco, M; Poggi, P; Valentino, K L; Polak, J M

    1990-01-01

    Nerve fibres displaying such immunoreactivity were revealed by indirect immunofluorescence. Neuropeptide K-like immunoreactive fibres, entering the pulp within large nerve trunks, were distributed around blood vessels as well as in the stroma. Some immunoreactive fibres were also observed in the para-odontoblastic region. In view of the biological activity of neuropeptide K, it is tentatively proposed that it may act in the dental pulp as a regulatory peptide involved in neurogenic inflammation, blood flow regulation and sensory transmission.

  14. Pulp stones: a review.

    PubMed

    Goga, R; Chandler, N P; Oginni, A O

    2008-06-01

    Pulp stones are a frequent finding on bitewing and periapical radiographs but receive relatively little attention in textbooks. A review of the literature was therefore performed, initially using the PubMed database and beginning the search with 'pulp calcifications' and 'pulp stones'. Each term provided more than 400 references, many of which related to pulp calcification in general rather than pulp stones, and focussed largely on the problems these changes presented to clinicians. A manual search using references from this source was carried out. Contemporary textbooks in endodontology were also consulted, and an historic perspective gained from a number of older books and references. The factors involved in the development of the pulp stones are largely unknown. Further research may determine the reasons for their formation, but with current endodontic instruments and techniques this is unlikely to alter their relevance to clinicians.

  15. Increased Endothelial Inflammation, sTie-2 and Arginase Activity in Umbilical Cords Obtained from Gestational Diabetic Mothers

    PubMed Central

    Giri, Hemant; Chandel, Shivam; Dwarakanath, Linga S.; Sreekumar, Sooriyakala; Dixit, Madhulika

    2013-01-01

    Objective The aim of this study was to determine subclinical inflammation in umbilical vein derived endothelial cells (HUVECs) obtained from Asian Indian subjects with gestational diabetes (GDM) and to determine levels of angiogenic factors and arginase activity in their cord blood. Methods This case-control study included 38 control and 30 GDM subjects. Subjects were confirmed as GDM based on 75g oral glucose tolerance test (OGTT) conducted in the second trimester of pregnancy. Angiogenic markers and arginase activity were measured in cord blood by ELISA and colorimetric methods respectively. Endothelial inflammation was assessed through adhesion of PKH26-labelled leukocytes onto HUVEC monolayer obtained from the study groups. Gene and surface expression of adhesion molecules were confirmed via reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry respectively. Results The study revealed increased adhesion of leukocytes to HUVECs isolated from GDM subjects compared to controls. HUVECs of babies born to GDM mothers had increased surface and mRNA expression of E-selectin. sTie2 levels were significantly higher in the cord blood for GDM subjects (3869 ± 370 ng/L) compared to controls (3045 ± 296 ng/L). Furthermore, arginase activity was higher in cord blood of GDM mothers as opposed to the control group (7.75 ± 2.4 µmoles of urea/ml/hour vs 2.88 ±0.49 µmoles of urea/ml/hour; p-value= 0.019). Spearman’s correlation analysis revealed positive correlation of cord blood arginase activity with glucose intolerance (ρ=0.596, p=0.004) and post load glucose values (ρ=0.472, p=0.031) of mothers observed during the second trimester of pregnancy. Conclusions HUVECs derived from Asian Indian GDM mothers, exhibit signs of sub-clinical endothelial inflammation along with increased levels of sTie2 and arginase activity in their cord blood serum. PMID:24376824

  16. Harnessing the natural regenerative potential of the dental pulp.

    PubMed

    Smith, Anthony J; Smith, James G; Shelton, Richard M; Cooper, Paul R

    2012-07-01

    Biological solutions for the repair and regeneration of the dental tissues offer significant potential for improved clinical treatment outcomes. Translation of dental tissue-engineering approaches to the clinic will make considerable contributions to these outcomes in the future, but exploiting the natural regenerative potential of dentin-pulp to enhance wound-healing responses offers solutions for maintaining pulp vitality now. Strategies to harness the natural regenerative potential of the pulp must be based on a sound biological understanding of the cellular and molecular events taking place, and require careful consideration of the interplay of infection, inflammation, and regeneration. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Pulp biology: progress during the past 25 years.

    PubMed

    Trowbridge, Henry O

    2003-04-01

    During the past 25 years there has been a rapid expansion in our knowledge of the dentine and pulp complex. This paper provides representative examples of important advances that researchers have made in this field. Topics to be considered include: differentiation of odontoblasts, dentine matrix proteins, extent of odontoblast processes, pulpal stem cells, apoptosis, interstitial fluid pressure in normal and inflamed pulps, class II antigen-presenting cells of the pulp, cytokines, antibodies, pulpal calcifications, tertiary dentine and pulpal inflammation associated with bacterial contamination of exposed dentine beneath restorations.

  18. Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss.

    PubMed

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Fernández-Real, José Manuel; Salvador, Javier; Frühbeck, Gema

    2011-01-01

    Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity

  19. Increased Levels of Calprotectin in Obesity Are Related to Macrophage Content: Impact on Inflammation and Effect of Weight Loss

    PubMed Central

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Fernández-Real, José Manuel; Salvador, Javier; Frühbeck, Gema

    2011-01-01

    Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage–related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity

  20. Basic effects of pulp refining on fiber properties--a review.

    PubMed

    Gharehkhani, Samira; Sadeghinezhad, Emad; Kazi, Salim Newaz; Yarmand, Hooman; Badarudin, Ahmad; Safaei, Mohammad Reza; Zubir, Mohd Nashrul Mohd

    2015-01-22

    The requirement for high quality pulps which are widely used in paper industries has increased the demand for pulp refining (beating) process. Pulp refining is a promising approach to improve the pulp quality by changing the fiber characteristics. The diversity of research on the effect of refining on fiber properties which is due to the different pulp sources, pulp consistency and refining equipment has interested us to provide a review on the studies over the last decade. In this article, the influence of pulp refining on structural properties i.e., fibrillations, fine formation, fiber length, fiber curl, crystallinity and distribution of surface chemical compositions is reviewed. The effect of pulp refining on electrokinetic properties of fiber e.g., surface and total charges of pulps is discussed. In addition, an overview of different refining theories, refiners as well as some tests for assessing the pulp refining is presented.

  1. Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice[S

    PubMed Central

    Shen, Wan; Chuang, Chia-Chi; Martinez, Kristina; Reid, Tanya; Brown, J. Mark; Xi, Lin; Hixson, Lindsay; Hopkins, Robin; Starnes, Joseph; McIntosh, Michael

    2013-01-01

    The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA. PMID:23401602

  2. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-09-23

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  3. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    PubMed Central

    Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  4. Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity.

    PubMed

    Chiricozzi, Andrea; Raimondo, Annunziata; Lembo, Serena; Fausti, Francesca; Dini, Valentina; Costanzo, Antonio; Monfrecola, Giuseppe; Balato, Nicola; Ayala, Fabio; Romanelli, Marco; Balato, Anna

    2016-12-01

    Psoriasis is a chronic skin disorder associated with several comorbid conditions. In psoriasis pathogenesis, the role of some cytokines, including TNF-α and IL-17, has been elucidated. Beside their pro-inflammatory activity, they may also affect glucose and lipid metabolism, possibly promoting insulin resistance and obesity. On the other hand, adipose tissue, secreting adipokines such as chemerin, visfatin, leptin, and adiponectin, not only regulates glucose and lipid metabolism, and endothelial cell function regulation, but it may contribute to inflammation. Areas covered: This review provides an updated 'state-of-the-art' about the reciprocal contribution of a small subset of conventional cytokines and adipokines involved in chronic inflammatory pathways, upregulated in both psoriasis and increased adiposity. A systematic search was conducted using the PubMed Medline database for primary articles. Expert commentary: Because psoriasis is associated with increased adiposity, it would be important to define the contribution of chronic skin inflammation to the onset of obesity and vice versa. Clarifying the pathogenic mechanism underlying this association, a therapeutic strategy having favorable effects on both psoriasis and increased adiposity could be identified.

  5. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE. PMID:27651919

  6. Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localised plaque inflammation.

    PubMed

    Skeoch, S; Cristinacce, P L Hubbard; Williams, H; Pemberton, P; Xu, D; Sun, J; James, J; Yuan, C; Hatsukami, T; Hockings, P D; Alexander, M Y; Waterton, J C; Bruce, I N

    2017-04-11

    In rheumatoid arthritis (RA), chronic inflammation is thought to drive increased cardiovascular risk through accelerated atherosclerosis. It may also lead to a more high-risk plaque phenotype. We sought to investigate carotid plaque phenotype in RA patients using Dynamic Contrast-Enhanced MRI (DCE-MRI) and Fludeoxyglucose Positron Emission Tomography(FDG-PET). In this pilot study, RA patients and age/sex-matched controls were evaluated for cardiovascular risk factors and carotid plaque on ultrasound. Subjects with plaque >2 mm thick underwent DCE-MRI, and a subgroup of patients had FDG-PET. Comparison of MRI findings between groups and correlation between clinical, serological markers and imaging findings was undertaken. 130 patients and 62 controls were recruited. Plaque was more prevalent in the RA group (53.1% vs 37.0%, p = 0.038) and was independently associated with IL6 levels (HR[95%CI]: 2.03 [1.26, 3.26] per quartile). DCE-MRI data were available in 15 patients and 5 controls. Higher prevalence of plaque calcification was noted in RA, despite similar plaque size (73.3% vs 20%, p = 0.04). FDG-PET detected plaque inflammation in 12/13 patients scanned and degree of inflammation correlated with hs-CRP (r = 0.58, p = 0.04). This study confirms increased prevalence of atherosclerosis in RA and provides data to support the hypothesis that patients have a high-risk plaque phenotype.

  7. Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

    PubMed

    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.

  8. Interleukin-15 (IL-15) Strongly Correlates with Increasing HIV-1 Viremia and Markers of Inflammation

    PubMed Central

    Swaminathan, Sanjay; Qiu, Ju; Rupert, Adam W.; Hu, Zonghui; Higgins, Jeanette; Dewar, Robin L.; Stevens, Randy; Rehm, Catherine A.; Metcalf, Julia A.; Sherman, Brad T.; Baseler, Michael W.; Lane, H. Clifford; Imamichi, Tomozumi

    2016-01-01

    Objective IL-15 has been postulated to play an important role in HIV-1 infection, yet there are conflicting reports regarding its expression levels in these patients. We sought to measure the level of IL-15 in a large, well characterised cohort of HIV-1 infected patients and correlate this with well known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14. Design and Methods IL-15 levels were measured in 501 people (460 patients with HIV-1 infection and 41 uninfected controls). The HIV-1 infected patients were divided into 4 groups based on viral load: <50 copies/ml, 51–10,000 copies/ml, 10,001–100,000 copies/ml and >100,000 copies/ml. The Mann Whitney test (non-parametric) was used to identify significant relationships between different patient groups. Results IL-15 levels were significantly higher in patients with viral loads >100,000 copies/ml (3.02 ± 1.53 pg/ml) compared to both uninfected controls (1.69 ± 0.37 pg/ml, p<0.001) or patients with a viral load <50 copies/ml (1.59 ± 0.40 pg/ml (p<0.001). There was a significant correlation between HIV-1 viremia and IL-15 levels (Spearman r = 0.54, p<0.001) and between CD4+ T cell counts and IL-15 levels (Spearman r = -0.56, p<0.001). Conclusions IL-15 levels are significantly elevated in HIV-1 infected patients with viral loads >100,000 copies/ml compared to uninfected controls, with a significant direct correlation noted between IL-15 and HIV-1 viremia and an inverse correlation between IL-15 levels and CD4+ T cell counts. These data support a potential role for IL-15 in the pathogenesis of HIV-associated immune activation. PMID:27880829

  9. Matrix Metalloproteinase-3 Accelerates Wound Healing following Dental Pulp Injury

    PubMed Central

    Zheng, Li; Amano, Kazuharu; Iohara, Koichiro; Ito, Masataka; Imabayashi, Kiyomi; Into, Takeshi; Matsushita, Kenji; Nakamura, Hiroshi; Nakashima, Misako

    2009-01-01

    Matrix metalloproteinases (MMPs) are implicated in a wide range of physiological and pathological processes, including morphogenesis, wound healing, angiogenesis, inflammation, and cancer. Angiogenesis is essential for reparative dentin formation during pulp wound healing. The mechanism of angiogenesis, however, still remains unclear. We hypothesized that certain MMPs expressed during pulp wound healing may support recovery processes. To address this issue, a rat pulp injury model was established to investigate expression of MMPs during wound healing. Real-time RT-PCR analysis showed that expression MMP-3 and MMP-9 (albeit lower extent) was up-regulated at 24 and 12 hours after pulp injury, respectively, whereas expression of MMP-2 and MMP-14 was not changed. MMP-3 mRNA and protein were localized in endothelial cells and/or endothelial progenitor cells in injured pulp in vivo. In addition, MMP-3 enhanced proliferation, migration, and survival of human umbilical vein endothelial cells in vitro. Furthermore, the topical application of MMP-3 protein on the rat-injured pulp tissue in vivo induced angiogenesis and reparative dentin formation at significantly higher levels compared with controls at 24 and 72 hours after treatment, respectively. Inhibition of endogenous MMP-3 by N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid resulted in untoward wound healing. These results provide suggestive evidence that MMP-3 released from endothelial cells and/or endothelial progenitor cells in injured pulp plays critical roles in angiogenesis and pulp wound healing. PMID:19834065

  10. Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial.

    PubMed

    Nair, P N R; Duncan, H F; Pitt Ford, T R; Luder, H U

    2008-02-01

    To investigate the pulpal response to direct pulp capping in healthy human teeth with mineral trioxide aggregate (MTA) as against calcium hydroxide cement (Dycal) as control. Twenty healthy human third molars had iatrogenic pulpotomy and direct pulp capping with MTA. Another 13 teeth were capped with Dycal as controls. The teeth were restored, with IRM, clinically reviewed and extracted after a number of pre-determined intervals (1 week, 1 month and 3 months). The specimens were fixed, decalcified, subdivided axially into two halves in the oro-buccal (lingual-buccal) plane, embedded in plastic, serial sectioned and evaluated qualitatively and quantitatively by correlative light and transmission electron microscopy with appropriate statistical evaluation of the quantitative data. Iatrogenic pulpal wounds treated with MTA were mostly free from inflammation after 1 week and became covered with a compact, hard tissue barrier of steadily increasing length and thickness within 3 months following capping. Control teeth treated with Dycal revealed distinctly less consistent formation of a hard tissue barrier that had numerous tunnel defects. The presence of pulpal inflammation up to the longest observation period (3 months) after capping, was a common feature in Dycal specimens. The MTA was clinically easier to use as a direct pulp-capping agent and resulted in less pulpal inflammation and more predictable hard tissue barrier formation than Dycal. Therefore, MTA or equivalent products should be the material of choice for direct pulp capping procedures instead of hard setting calcium hydroxide cements.

  11. 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

  12. Acute Joint Pathology and Synovial Inflammation is Associated with Increased Intra-Articular Fracture Severity in the Mouse Knee

    PubMed Central

    Lewis, John S.; Hembree, W. Chad; Furman, Bridgette D.; Tippets, Lauren; Cattel, Dennis; Huebner, Janet L.; Little, Dianne; DeFrate, Louis E.; Kraus, Virginia B.; Guilak, Farshid; Olson, Steven A.

    2012-01-01

    OBJECTIVE Post-traumatic arthritis is a frequent cause of disability and occurs most commonly and predictably after articular fracture. The objective of this investigation was to examine the effect of fracture severity on acute joint pathology in a novel murine model of intra-articular fracture. DESIGN Low and high energy articular fractures (n=25 per group) of the tibial plateau were created in adult male C57BL/6 mice. The acute effect of articular fracture severity on synovial inflammation, bone morphology, liberated fracture area, cartilage pathology, chondrocyte viability, and systemic cytokines and biomarkers levels was assessed at 0, 1, 3, 5, and 7 days post-fracture. RESULTS Increasing intra-articular fracture severity was associated with greater acute pathology in the synovium and bone compared to control limbs, including increased global synovitis and reduced periarticular bone density and thickness. Applied fracture energy was significantly correlated with degree of liberated cortical bone surface area, indicating greater comminution. Serum concentrations of hyaluronic acid (HA) were significantly increased one day post-fracture. While articular fracture significantly reduced chondrocyte viability, there was no relationship between fracture severity and chondrocyte viability, cartilage degeneration, or systemic levels of cytokines and biomarkers. CONCLUSIONS This study demonstrates that articular fracture is associated with a loss of chondrocyte viability and increased levels of systemic biomarkers, and that increased intra-articular fracture severity is associated with increased acute joint pathology in a variety of joint tissues, including synovial inflammation, cortical comminution, and bone morphology. Further characterization of the early events following articular fracture could aid in the treatment of post-traumatic arthritis. PMID:21619936

  13. Endothelial inflammation induced by excess glucose is associated with cytosolic glucose-6-phosphate but not increased mitochondrial respiration

    PubMed Central

    Sweet, Ian R; Gilbert, Merle; Maloney, Ezekiel; Hockenbery, David M.; Schwartz, Michael W.; Kim, Francis

    2009-01-01

    Aims/hypothesis Exposure of endothelial cells to high glucose levels suppresses responses to insulin, including induction of endothelial nitric oxide synthetase activity, through pro-inflammatory signaling via the IKKβ-NF-κB pathway. In the current study, we aimed to identify metabolic responses to glucose excess that mediate endothelial cell inflammation and insulin resistance. Since endothelial cells decrease their rate of oxygen consumption (OCR) in response to glucose, we hypothesized that increased mitochondrial function would not mediate these cell’s response to excess substrate. Methods The effects of glycolytic and mitochondrial fuels on metabolic intermediates and end products of glycolytic and oxidative metabolism, including glucose-6 phosphate (G6P), lactate, CO2, NAD(P)H, and OCR, were measured in cultured human microvascular endothelial cells and correlated with IKKβ activation. Results In response to increases in glucose concentration from low to physiological levels (0 to 5 mM), production of G6P, lactate, NAD(P)H and CO2 each increased as expected, while OCR was sharply reduced. IKKβ activation was detected at glucose concentrations above 5 mM, which was associated with parallel increases of G6P levels, whereas downstream metabolic pathways were insensitive to excess substrate. Conclusions/interpretation Activation of IKKβ by excess glucose correlates with increased levels of the glycolytic intermediate G6P, but not with lactate generation or OCR, which are inhibited well below saturation levels at physiologic glucose concentrations. These findings suggest that oxidative stress due to increased mitochondrial respiration is unlikely to mediate endothelial inflammation induced by excess glucose and suggests instead the involvement of G6P accumulation in the adverse effects of hyperglycemia on endothelial cells. PMID:19219423

  14. Thoracic aorta calcification but not inflammation is associated with increased cardiovascular disease risk: results of the CAMONA study.

    PubMed

    Blomberg, Björn A; de Jong, Pim A; Thomassen, Anders; Lam, Marnix G E; Vach, Werner; Olsen, Michael H; Mali, Willem P T M; Narula, Jagat; Alavi, Abass; Høilund-Carlsen, Poul F

    2017-02-01

    Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease (CVD). In this study we investigated the relationship between CVD risk and arterial inflammation ((18)F-FDG PET/CT imaging), vascular calcification metabolism (Na(18)F PET/CT imaging), and vascular calcium burden (CT imaging) of the thoracic aorta in a population at low CVD risk. Study participants underwent blood pressure measurements, blood analyses, and (18)F-FDG and Na(18)F PET/CT imaging. In addition, the 10-year risk for development of CVD, based on the Framingham risk score (FRS), was estimated. CVD risk was compared across quartiles of thoracic aorta (18)F-FDG uptake, Na(18)F uptake, and calcium burden on CT. A total of 139 subjects (52 % men, mean age 49 years, age range 21 - 75 years, median FRS 6 %) were evaluated. CVD risk was, on average, 3.7 times higher among subjects with thoracic aorta Na(18)F uptake in the highest quartile compared with those in the lowest quartile of the distribution (15.5 % vs. 4.2 %; P < 0.001). CVD risk was on average, 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution (18.0 % vs. 4.9 %; P < 0.001). CVD risk was similar in subjects in all quartiles of thoracic aorta (18)F-FDG uptake. Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta, but not with arterial inflammation.

  15. CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model.

    PubMed

    Sun, Xuan; Glynn, Danielle J; Hodson, Leigh J; Huo, Cecilia; Britt, Kara; Thompson, Erik W; Woolford, Lucy; Evdokiou, Andreas; Pollard, Jeffrey W; Robertson, Sarah A; Ingman, Wendy V

    2017-01-11

    Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter. Estrous cycles were tracked in adult transgenic and non-transgenic FVB mice, and mammary glands collected at the four different stages of the cycle. Dissected mammary glands were assessed for cyclical morphological changes, proliferation and apoptosis of epithelium, macrophage abundance and collagen deposition, and mRNA encoding matrix remodelling enzymes. Another cohort of control and transgenic mice received carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and tumour development was monitored weekly. CCL2 protein was also quantified in paired samples of human breast tissue with high and low mammographic density. Overexpression of CCL2 in the mammary epithelium resulted in an increased number of macrophages, increased density of stroma and collagen and elevated mRNA encoding matrix remodelling enzymes lysyl oxidase (LOX) and tissue inhibitor of matrix metalloproteinases (TIMP)3 compared to non-transgenic controls. Transgenic mice also exhibited increased susceptibility to development of DMBA-induced mammary tumours. In a paired sample cohort of human breast tissue, abundance of epithelial-cell-associated CCL2 was higher in breast tissue of high mammographic density compared to tissue of low mammographic density. Constitutive expression of CCL2 by the mouse mammary epithelium induces a state of low level chronic inflammation that increases stromal density and elevates cancer risk. We propose that CCL2-driven inflammation contributes to the increased risk of breast cancer observed in women

  16. Paper Pulp Panoply.

    ERIC Educational Resources Information Center

    Marque, Margo E.

    1999-01-01

    Explains that creating paper-pulp bowls is designed to acquaint students with the beginning vocabulary and finger dexterity needed to sculpt clay. Describes the process of making paper-pulp bowls and identifies important vocabulary words. Provides directions for making paper bowl forms and lists the materials. (CMK)

  17. Paper Pulp Panoply.

    ERIC Educational Resources Information Center

    Marque, Margo E.

    1999-01-01

    Explains that creating paper-pulp bowls is designed to acquaint students with the beginning vocabulary and finger dexterity needed to sculpt clay. Describes the process of making paper-pulp bowls and identifies important vocabulary words. Provides directions for making paper bowl forms and lists the materials. (CMK)

  18. 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

  19. Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury.

    PubMed

    Maldonado-Bouchard, Sioui; Peters, Kelsey; Woller, Sarah A; Madahian, Behrouz; Faghihi, Usef; Patel, Shivani; Bake, Shameena; Hook, Michelle A

    2016-01-01

    Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of (1) depression, (2) depression and anxiety, or (3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI.

  20. Increased Interleukin-32 Levels in Obesity Promote Adipose Tissue Inflammation and Extracellular Matrix Remodeling: Effect of Weight Loss.

    PubMed

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Valentí, Víctor; Moncada, Rafael; Landecho, Manuel F; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

    2016-12-01

    Interleukin (IL)-32 is a recently described cytokine involved in the regulation of inflammation. We aimed to explore whether IL-32 could function as an inflammatory and angiogenic factor in human obesity and obesity-associated type 2 diabetes. Samples obtained from 90 subjects were used in the study. Obese patients exhibited higher expression levels of IL-32 in visceral adipose tissue (AT) as well as in subcutaneous AT and peripheral blood mononuclear cells. IL32 was mainly expressed by stromovascular fraction cells, and its expression was significantly enhanced by inflammatory stimuli and hypoxia, whereas no changes were found after the incubation with anti-inflammatory cytokines. The addition of exogenous IL-32 induced the expression of inflammation and extracellular matrix-related genes in human adipocyte cultures, and IL32-silenced adipocytes showed a downregulation of inflammatory genes. Furthermore, adipocyte-conditioned media obtained from obese patients increased IL32 gene expression in human monocyte cultures, whereas the adipocyte-conditioned media from lean volunteers had no effect on IL32 mRNA levels. These findings provide evidence, for the first time, about the inflammatory and remodeling properties of IL-32 in AT, implicating this cytokine in obesity-associated comorbidities. © 2016 by the American Diabetes Association.

  1. INFLAMMATION IS INCREASED WITH ANXIETY- AND DEPRESSION-LIKE SIGNS IN A RAT MODEL OF SPINAL CORD INJURY

    PubMed Central

    Maldonado-Bouchard, Sioui; Peters, Kelsey; Woller, Sarah A.; Madahian, Behrouz; Faghihi, Usef; Patel, Shivani; Bake, Shameena; Hook, Michelle A

    2015-01-01

    Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of 1) depression, 2) depression and anxiety, or 3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI. PMID:26296565

  2. TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2.

    PubMed

    Rodrigues-Díez, Raquel; Rayego-Mateos, Sandra; Orejudo, Macarena; Aroeira, Luiz Stark; Selgas, Rafael; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2015-01-01

    The CCN family member 2 (CCN2, also known as connective tissue growth factor) may behave as a risk biomarker and a potential therapeutic target for renal disease. CCN2 participates in the regulation of inflammation and fibrosis. TGF-β is considered the main fibrogenic cytokine; however, in some pathological settings TGF-β also has anti-inflammatory properties. CCN2 has been proposed as a downstream profibrotic mediator of TGF-β, but data on TGF-β role in CCN2 actions are scarce. Our aim was to evaluate the effect of TGF-β blockade in CCN2-mediated experimental renal damage. Systemic administration of the C-terminal module of CCN2 to mice caused sustained renal inflammation. In these mice, TGF-β blockade, using an anti-TGF-β neutralizing antibody, significantly increased renal expression of the NGAL (a kidney injury biomarker), kidney infiltration by monocytes/macrophages, and upregulation of MCP-1 expression. The anti-inflammatory effect of TGF-β seems to be mediated by a dysregulation of the systemic Treg immune response, shown by decreased levels of circulating CD4(+)/Foxp3(+)Treg cells. Our experimental data support the idea that TGF-β exerts anti-inflammatory actions in the kidney and suggest that it is not an optimal therapeutic target.

  3. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

    PubMed

    Jaeggi, Tanja; Kortman, Guus A M; Moretti, Diego; Chassard, Christophe; Holding, Penny; Dostal, Alexandra; Boekhorst, Jos; Timmerman, Harro M; Swinkels, Dorine W; Tjalsma, Harold; Njenga, Jane; Mwangi, Alice; Kvalsvig, Jane; Lacroix, Christophe; Zimmermann, Michael B

    2015-05-01

    In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and

  4. Strength Training Decreases Inflammation and Increases Cognition and Physical Fitness in Older Women with Cognitive Impairment.

    PubMed

    Chupel, Matheus U; Direito, Fábio; Furtado, Guilherme E; Minuzzi, Luciéle G; Pedrosa, Filipa M; Colado, Juan C; Ferreira, José P; Filaire, Edith; Teixeira, Ana M

    2017-01-01

    Introduction: Cognitive impairment that affects older adults is commonly associated with an inflammatory imbalance, resulting in decreased physical fitness. Exercise has been pointed to mitigate immunosenescence and cognitive impairment associated with aging, while increase in physical fitness. However, few studies explored the relationship between changes in cytokine concentration and improvement on cognition due to elastic band strength training. The aim of this study was to investigate the effects of strength training on pro-and anti-inflammatory cytokines, hematological markers and physical fitness of older women with cognitive impairment. Methods: Thirty-three women (82.7 ± 5.7 years old) participated in the study and were divided in two groups: strength exercise training group (ST; n = 16) and Control Group (CG; n = 17) and were evaluated before and after 28 weeks of the exercise program. The CG did not undergo any type of exercise programs. Data for IL-10, TNF-α, IFN-γ, C-Reactive Protein (CRP), white blood counts (WBC), red blood counts (RBC), Mini Mental State Examination (MMSE) and physical fitness tests were analyzed in both moments. Results: IL-10 increased in the ST group without changes in CG. TNF-α and CRP increased in the control group while no changes were observed for IFN-γ in both groups. Strength training decreased leukocyte and lymphocyte counts and increase hemoglobin, mean cell volume and mean cell hemoglobin concentration. The MMSE score increased in strength training group but remained unchanged in the control group. A correlation between the variation of granulocyte counts and the MMSE scores was also observed within the total sample. An improvement in physical fitness was observed with strength training. Conclusion: Resistance exercise promoted better anti-inflammatory balance and physical performance simultaneously with an increase in cognitive profile in older women with cognitive impairment.

  5. Strength Training Decreases Inflammation and Increases Cognition and Physical Fitness in Older Women with Cognitive Impairment

    PubMed Central

    Chupel, Matheus U.; Direito, Fábio; Furtado, Guilherme E.; Minuzzi, Luciéle G.; Pedrosa, Filipa M.; Colado, Juan C.; Ferreira, José P.; Filaire, Edith; Teixeira, Ana M.

    2017-01-01

    Introduction: Cognitive impairment that affects older adults is commonly associated with an inflammatory imbalance, resulting in decreased physical fitness. Exercise has been pointed to mitigate immunosenescence and cognitive impairment associated with aging, while increase in physical fitness. However, few studies explored the relationship between changes in cytokine concentration and improvement on cognition due to elastic band strength training. The aim of this study was to investigate the effects of strength training on pro-and anti-inflammatory cytokines, hematological markers and physical fitness of older women with cognitive impairment. Methods: Thirty-three women (82.7 ± 5.7 years old) participated in the study and were divided in two groups: strength exercise training group (ST; n = 16) and Control Group (CG; n = 17) and were evaluated before and after 28 weeks of the exercise program. The CG did not undergo any type of exercise programs. Data for IL-10, TNF-α, IFN-γ, C-Reactive Protein (CRP), white blood counts (WBC), red blood counts (RBC), Mini Mental State Examination (MMSE) and physical fitness tests were analyzed in both moments. Results: IL-10 increased in the ST group without changes in CG. TNF-α and CRP increased in the control group while no changes were observed for IFN-γ in both groups. Strength training decreased leukocyte and lymphocyte counts and increase hemoglobin, mean cell volume and mean cell hemoglobin concentration. The MMSE score increased in strength training group but remained unchanged in the control group. A correlation between the variation of granulocyte counts and the MMSE scores was also observed within the total sample. An improvement in physical fitness was observed with strength training. Conclusion: Resistance exercise promoted better anti-inflammatory balance and physical performance simultaneously with an increase in cognitive profile in older women with cognitive impairment. PMID:28659812

  6. Pulpal vascular changes in inflammation.

    PubMed

    Takahashi, K

    1992-01-01

    Changes in pulpal vessels in experimentally induced acute and chronic pulpitis in dog tooth were investigated using corrosive resin casts and scanning electron microscopic examination. Following a cavity preparation without water spray, increased permeability of blood vessels occurred in the primary stage of acute pulpitis. This was evidenced by the extravasation of resin from the vessel. This phenomenon was found initially in the venular network as well as in the capillary network located under the dentin. The morphological change was minimal in the vascular network underneath the cavity. This is in contrast to an expanded and tortuous vascular network representing an ulceration which was found around an abscess in chronic pulpitis. Furthermore, formation of vascular loops and AVAlc close to the inflamed region may represent a protective change in the pulp against inflammation.

  7. 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

  8. Dental Pulp Reaction to Exposure at Different Time Intervals in Open Apex Canine Teeth of Cats

    PubMed Central

    Moradi, Saeed; Bidar, Maryam; Zarrabi, Mohammad Hasan; Talati, Ali

    2009-01-01

    INTRODUCTION: Open-apex teeth with irreversible pulpitis require complex and difficult treatment. Providing the right environment for apexogenesis and pulp protection is vital for their long term prognosis. The young pulp of open apex tooth, however, is better equipped against irritation and assault. The aim of this study was to evaluate pulp inflammation in open apex canine teeth of cats. MATERIALS AND METHODS: In this in vivo study, twelve cats with open apex canines were used. Pulps were iatrogenically exposed and the animals were sacrificed at one, seven, thirty and ninety days after pulp exposure. Samples were prepared for histological evaluations. RESULTS: During the first and seventh day, changes were limited to acute inflammation in the coronal pulp. During the first month pulp changes in 45.5% of samples were similar to the seventh day. In the other samples necrosis and abscess spread to the end of the root, and internal resorption and periapical abscess were observed. In 45.5% of samples in the apical region vital tissue was barely observed (during 90 days); in 54.5% of samples however, complete pulp necrosis, internal resorption and a large periapical lesion was observed. CONCLUSION: In one and seven-day periods pulp tissue was vital, however, in the thirty and ninety-day periods, minority of the pulp samples were vital. PMID:23940485

  9. Labor and inflammation increase the expression of oxytocin receptor in human amnion.

    PubMed

    Terzidou, Vasso; Blanks, Andrew M; Kim, Sung Hye; Thornton, Steven; Bennett, Phillip R

    2011-03-01

    The oxytocin/oxytocin receptor (OXT/OXTR) system plays an important role in the regulation of parturition. The amnion is a major source of prostaglandins and inflammatory cytokine synthesis, which increase both before and during labor. Amnion is a noncontractile tissue; therefore, the role played by OXT/OXTR in this tissue will be fundamentally different from the role played in myometrial contractions. In the present study, we demonstrate increased OXTR mRNA and protein concentrations in human amnion epithelial cells associated with the onset of labor. We show that incubation of primary human amnion epithelial cells with IL1B results in a rapid, transient up-regulation of OXTR mRNA expression, which peaks in prelabor samples after 6 h. Incubation of prelabor amnion epithelial cells with OXT results in a marked increase of prostaglandin E(2) synthesis, and we demonstrate that OXT activates the extracellular signal-regulated protein kinase signal transduction pathway to stimulate up-regulation of cyclo-oxygenase 2 in human amnion epithelial cells. The increased ability of human amnion to produce prostaglandins in response to OXT treatment suggests a complementary role for the OXT/OXTR system in the activation of human amnion and the onset of labor.

  10. 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

  11. xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation

    PubMed Central

    Zhang, Chi; Nambi, Subhalaxmi; Wang, Wenfei; Zhang, Mingxia; Wu, Junying; Deng, Guofang; Deng, Qunyi; Liu, Haiying; Zhou, Boping; Jin, Qi; Feng, Carl G; Sassetti, Christopher M; Wang, Fudi; Chen, Xinchun

    2016-01-01

    The physiological functions of macrophage, which plays a central role in the pathogenesis of tuberculosis, depend on its redox state. System xc-, a cystine-glutamate transporter, which consists of xCT and CD98, influences many ROS-dependent pathways by regulating the production of the antioxidant glutathione. xCT's ability to alter this critical host redox balance by increasing the glutathione synthesis aspect of phagocyte physiology suggested that it might influence tuberculosis pathogenesis. In this study, we found that the xCT expression was increased in peripheral blood monocyte of active tuberculosis. xCT expression in macrophage was induced by Mycobacterium tuberculosis (Mtb) through TLR2/Akt- and p38-dependent signaling pathway. Importantly, xCT deficiency conferred protection against tuberculosis, as xCT knock out mice displayed increased Mtb load and reduced pulmonary pathology in lung compared to wild type mice. xCT disruption enhanced the mycobateriacidal activity of macrophage through increasing the mycothiol oxidation. Importantly, chemical inhibition of xCT with sulfasalazine, a specific xCT inhibitor that is already approved by the FDA for treatment of inflammatory bowel disease, produces similar protective effects in vivo and in vitro, indicating xCT might be a novel and useful target for host-directed TB treatment strategy. PMID:27129162

  12. Labor and Inflammation Increase the Expression of Oxytocin Receptor in Human Amnion1

    PubMed Central

    Terzidou, Vasso; Blanks, Andrew M.; Kim, Sung Hye; Thornton, Steven; Bennett, Phillip R.

    2010-01-01

    The oxytocin/oxytocin receptor (OXT/OXTR) system plays an important role in the regulation of parturition. The amnion is a major source of prostaglandins and inflammatory cytokine synthesis, which increase both before and during labor. Amnion is a noncontractile tissue; therefore, the role played by OXT/OXTR in this tissue will be fundamentally different from the role played in myometrial contractions. In the present study, we demonstrate increased OXTR mRNA and protein concentrations in human amnion epithelial cells associated with the onset of labor. We show that incubation of primary human amnion epithelial cells with IL1B results in a rapid, transient up-regulation of OXTR mRNA expression, which peaks in prelabor samples after 6 h. Incubation of prelabor amnion epithelial cells with OXT results in a marked increase of prostaglandin E2 synthesis, and we demonstrate that OXT activates the extracellular signal-regulated protein kinase signal transduction pathway to stimulate up-regulation of cyclo-oxygenase 2 in human amnion epithelial cells. The increased ability of human amnion to produce prostaglandins in response to OXT treatment suggests a complementary role for the OXT/OXTR system in the activation of human amnion and the onset of labor. PMID:20926803

  13. Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly.

    PubMed

    Holecki, Michał; Chudek, Jerzy; Owczarek, Aleksander; Olszanecka-Glinianowicz, Magdalena; Bożentowicz-Wikarek, Maria; Duława, Jan; Mossakowska, Małgorzata; Zdrojewski, Tomasz; Skalska, Anna; Więcek, Andrzej

    2015-06-01

    Fibroblast growth factor 23 (FGF23) is a hormone involved in calcium-phosphate homoeostasis. The data of recently published studies suggest that FGF-23 may also play a role in some metabolic processes beyond mineral metabolism, such as insulin resistance or energy homoeostasis. The aim of the study was to attempt the relationships between plasma cFGF-23 (C-terminal) and iFGF-23 (intact) concentrations and the occurrence of obesity, insulin resistance and inflammation in elderly population. The analysis included 3115 elderly subjects (1485 women). During three visits, a questionnaire survey, comprehensive geriatric assessment and anthropometric measurements were performed as well as blood and urine samples were collected by trained nurses. Serum phosphorus, calcium, intact parathormone (iPTH), 25(OH)D3 , iFGF-23 and cFGF-23, insulin, glucose, albumin (also in urine), creatinine, hs-CRP, interleukin-6 and NT-proBNP concentrations were assessed. HOMA-IR was calculated according to the standard formula. Both forms of FGF23, iPTH and 25-OH-D3 levels were not related to the occurrence of obesity and insulin resistance. Increase in phosphorus, iPTH and NT-proBNP concentrations is associated with rise in plasma iFGF23 and cFGF23 levels. Additionally, increase in hs-CRP explained the elevated plasma iFGF23 levels. In multiple regression models, circulating iFGF23 and cFGF23 level's variability in elderly population were explained by changes in serum phosphorus, iPTH, eGFR, hs-CRP and NT-proBNP levels but not by BMI and HOMA-IR values. In conclusion, our study shows that increased levels of both circulating Fibroblast growth factor 23 forms in elderly subjects are associated with inflammation but not obesity or insulin resistance per se. © 2015 John Wiley & Sons Ltd.

  14. Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat.

    PubMed

    Zhang, X-L; Albers, K M; Gold, M S

    2015-01-22

    The goals of the present study were to determine (1) the properties of the nicotinic acetylcholine receptor (nAChR) currents in rat cutaneous dorsal root ganglion (DRG) neurons; (2) the impact of nAChR activation on the excitability of cutaneous DRG neurons; and (3) the impact of inflammation on the density and distribution of nAChR currents among cutaneous DRG neurons. Whole-cell patch-clamp techniques were used to study retrogradely labeled DRG neurons from naïve and complete Freund's adjuvant inflamed rats. Nicotine-evoked currents were detectable in ∼70% of the cutaneous DRG neurons, where only one of two current types, fast or slow currents based on rates of activation and inactivation, was present in each neuron. The biophysical and pharmacological properties of the fast current were consistent with nAChRs containing an α7 subunit while those of the slow current were consistent with nAChRs containing α3/β4 subunits. The majority of small diameter neurons with fast current were IB4- while the majority of small diameter neurons with slow current were IB4+. Preincubation with nicotine (1 μM) produced a transient (1 min) depolarization and increase in the excitability of neurons with fast current and a decrease in the amplitude of capsaicin-evoked current in neurons with slow current. Inflammation increased the current density of both slow and fast currents in small diameter neurons and increased the percentage of neurons with the fast current. With the relatively selective distribution of nAChR currents in putative nociceptive cutaneous DRG neurons, our results suggest that the role of these receptors in inflammatory hyperalgesia is likely to be complex and dependent on the concentration and timing of acetylcholine release in the periphery.

  15. Prenatal acetaminophen induces liver toxicity in dams, reduces fetal liver stem cells, and increases airway inflammation in adult offspring.

    PubMed

    Karimi, Khalil; Keßler, Timo; Thiele, Kristin; Ramisch, Katherina; Erhardt, Annette; Huebener, Peter; Barikbin, Roja; Arck, Petra; Tiegs, Gisa

    2015-05-01

    During pregnancy, acetaminophen is one of the very few medications recommended by physicians to treat fever or pain. Recent insights from epidemiological studies suggest an association between prenatal acetaminophen medication and an increased risk for development of asthma in children later in life. The underlying pathogenesis of such association is still unknown. We aimed to develop a mouse model to provide insights into the effect of prenatal acetaminophen on maternal, fetal and adult offspring's health. The toxic effect of acetaminophen was studied in mice on 1) maternal liver; mirrored by biomarkers of liver injury, centrilobular necrosis, and infiltration of granulocytes; 2) fetal liver; reflected by the frequency of hematopoietic stem cells, and 3) postnatal health; evaluated by the severity of allergic airway inflammation among offspring. We observed an increased susceptibility towards acetaminophen-induced liver damage in pregnant mice compared to virgins. Moreover, hematopoietic stem cell frequency in fetal liver declined in response to acetaminophen. Furthermore, a greater severity of airway inflammation was observed in offspring of dams upon prenatal acetaminophen treatment, identified lung infiltration by leukocytes and eosinophil infiltration into the airways. Our newly developed mouse model on prenatal use of acetaminophen reflects findings from epidemiological studies in humans. The availability of this model will allow improvement in our understanding of how acetaminophen-related hepatotoxicity is operational in pregnant individuals and how an increased risk for allergic diseases in response to prenatal acetaminophen is mediated. Such insights, once available, may change the recommendations for prenatal acetaminophen use. Copyright © 2014 European Association for the Study of the Liver. All rights reserved.

  16. Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat

    PubMed Central

    Zhang, Xiulin; Albers, Kathryn M.; Gold, Michael S.

    2014-01-01

    The goals of the present study were to determine 1) the properties of the nicotinic acetylcholine receptor (nAChR) currents in rat cutaneous DRG neurons; 2) the impact of nAChR activation on the excitability of cutaneous DRG neurons; and 3) the impact of inflammation on the density and distribution of nAChR currents among cutaneous DRG neurons. Whole cell patch clamp techniques were used to study retrogradely labeled DRG neurons from naïve and complete Freund's adjuvant inflamed rats. Nicotine-evoked currents were detectable in ~70% of the cutaneous DRG neurons, where only one of two current types, fast or slow currents based on rates of activation and inactivation, was present in each neuron. The biophysical and pharmacological properties of the fast current were consistent with nAChRs containing an α7 subunit while those of the slow current were consistent with nAChRs containing α3/β4 subunits. The majority of small diameter neurons with fast current were IB4- while the majority of small diameter neurons with slow current were IB4+. Preincubation with nicotine (1 μM) produced a transient (1 min) depolarization and increase in the excitability of neurons with fast current and a decrease in the amplitude of capsaicin-evoked current in neurons with slow current. Inflammation increased the current density of both slow and fast currents in small diameter neurons and increased the percentage of neurons with the fast current. With the relatively selective distribution of nAChR currents in putative nociceptive cutaneous DRG neurons, our results suggest that the role of these receptors in inflammatory hyperalgesia is likely to be complex and dependent on the concentration and timing of acetylcholine release in the periphery. PMID:25453771

  17. 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

  18. 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.

  19. 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.

  20. HEME OXYGENASE 2 DEFICIENCY INCREASES BRAIN SWELLING AND INFLAMMATION AFTER INTRACEREBRAL HEMORRHAGE

    PubMed Central

    WANG, J.; DORÉ, S.

    2015-01-01

    Intracerebral hemorrhage (ICH) remains a major medical problem and currently has no effective treatment. Hemorrhaged blood is highly toxic to the brain, and catabolism of the pro-oxidant heme, mainly released from hemoglobin, is critical for the resolution of hematoma after ICH. The degradation of the pro-oxidant heme is controlled by heme oxygenase (HO). We have previously reported a neuroprotective role for HO2 in early brain injury after ICH; however, in vivo data that specifically address the role of HO2 in brain edema and neuroinflammation after ICH are absent. Here, we tested the hypothesis that HO2 deletion would exacerbate ICH-induced brain edema, neuroinflammation, and oxidative damage. We subjected wild-type (WT) and HO2 knockout (−/−) mice to the collagenase-induced ICH model. Interestingly, HO2−/− mice had enhanced brain swelling and neuronal death, although HO2 deletion did not increase collagenase-induced bleeding; the exacerbation of brain injury in HO2−/− mice was also associated with increases in neutrophil infiltration, microglial/macrophage and astrocyte activation, DNA damage, peroxynitrite production, and cytochrome c immunoreactivity. In addition, we found that hemispheric enlargement was more sensitive than brain water content in the detection of subtle changes in brain edema formation in this model. Combined, these novel findings extend our previous observations and demonstrate that HO2 deficiency increases brain swelling, neuroinflammation, and oxidative damage. The results provide additional evidence that HO2 plays a critical protective role against ICH-induced early brain injury. PMID:18674596

  1. Lactulose mediates suppression of dextran sodium sulfate-induced colon inflammation by increasing hydrogen production.

    PubMed

    Chen, Xiao; Zhai, Xiao; Shi, Jiazi; Liu, Wen Wu; Tao, Hengyi; Sun, Xuejun; Kang, Zhimin

    2013-06-01

    Molecular hydrogen (H2) is a potent antioxidant and able to protect organs from oxidative stress injuries. Orally administered lactulose, a potent H2 inducer, is digested by colon microflora and significantly increases H2 production, indicating its potential anti-inflammatory action. To evaluate the anti-inflammatory effects of lactulose on dextran sodium sulfate (DSS)-induced colitis in mice. Mice were randomly assigned into seven groups, receiving regular distilled water, H2-rich saline (peritoneal injection), DSS, oral lactulose (0.1, 0.15, 0.2 ml/10 g, respectively), and lactulose (0.2 ml/10 g) + oral antibiotics. The mouse model of human ulcerative colitis was established by supplying mice with water containing DSS. The H2 breath test was used to determine the exhaled H2 concentration. Body weight, colitis score, colon length, pathological features and tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), maleic dialdehyde (MDA) and marrow peroxidase (MPO) levels in colon lesions were evaluated. After 7 days, DSS-induced loss of body weight, increase of colitis score, shortening of colon length, pathological changes and elevated levels of TNF-α, IL-1β, MDA, and MPO in colon lesions, were significantly suppressed by oral lactulose administration and intraperitoneally injected H2-rich saline. Ingestion of antibiotics significantly compromised the anti-inflammatory effects of lactulose. The H2 breath test showed that lactulose administration significantly induced hydrogen production and that antibiotics administration could inhibit H2 production. Lactulose can prevent the development of DSS-induced colitis and alleviate oxidative stress in the colon, as measured by MDA and MPO, probably by increasing endogenous H2 production.

  2. Apolipoprotein CIII Overexpression-Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death

    PubMed Central

    Paiva, Adriene A.; Raposo, Helena F.; Wanschel, Amarylis C. B. A.; Nardelli, Tarlliza R.

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα (8-fold) and IL-6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase-3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low-fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet-induced NAFLD. PMID:28163820

  3. Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.

    PubMed

    Yang, Tao-Hsiang; Yuan, Tzu-Hsuen; Hwang, Yaw-Huei; Lian, Ie-Bin; Meng, Menghsiao; Su, Che-Chun

    2016-11-01

    Heavy metal pollution in farm soils is a problem in some parts of Taiwan. Copper can be a factor associated with increased disease activities of rheumatoid arthritis (RA). Thus, the aim of this study was to investigate whether copper pollution in farm soils is associated with worsened RA. Clinical parameters from 122 RA patients were collected from a medical center in central Taiwan. Levels of heavy metals in the blood were measured using inductively coupled plasma mass spectrometry. Levels of copper in farm soils were retrieved from a national survey. These data were analyzed to find the factors related to RA disease activities. RA patients living where farm soils contained high levels of copper had increased white blood cell counts, erythrocyte sedimentation rate, and disease activity score 28, compared with patients living where copper levels were low. Among the nine types of heavy metal measured in the study, blood levels of copper and nickel correlated with erythrocyte sedimentation rate. Our cross-sectional data suggest a correlation between RA disease activity and the level of copper at township farm soils samples. Further longitudinal studies using more rigorous methodologies are warranted to examine whether this correlation is causal. Copyright © 2015. Published by Elsevier B.V.

  4. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

    PubMed

    Bot, Martine; de Jager, Saskia C A; MacAleese, Luke; Lagraauw, H Maxime; van Berkel, Theo J C; Quax, Paul H A; Kuiper, Johan; Heeren, Ron M A; Biessen, Erik A L; Bot, Ilze

    2013-05-01

    Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

  5. Changes in pulp web properties by addition of natural filler

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

    Development of the desired pulp-based products eco-properties are governed by factors like choice and suitability of raw material, the design and operation of pulping process and choice of additives. Fines recovered during refining discharge of an alkaline peroxide pulping system were collected based on their retention on varying mesh-sizes screens. Analysis shows that 12% of the 400-mesh fines added to the web enhances paper tensile strength by 100%. This defines the usefulness of fibrillar particles whose cell wall collapsibility increases the web density by increasing bonding ability and thus, strength of pulp-based products such as paper. The study acknowledges fines functioning as natural filler in pulp network and collection of fines from the refining discharge was found to reduce 70% turbidity and this improvement will help reduce the costs pertinent to generation of whitewater from the pulping system.

  6. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    PubMed

    Wu, Qun; Jiang, Di; Minor, Maisha; Chu, Hong Wei

    2014-01-01

    The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  7. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome.

    PubMed

    Camilleri, Michael; Lasch, Karen; Zhou, Wen

    2012-10-01

    Irritable bowel syndrome (IBS) is one of the most common gastrointestinal ailments among those seeking health care for gastrointestinal disorders. Despite its prevalence, IBS pathophysiology is still not completely understood. Continued elucidation of IBS etiological mechanisms will lead to a greater appreciation of possible therapeutic targets. In the past decade, there has been increasing focus on the possible connection between increased intestinal mucosal permeability, inflammation, and visceral hypersensitivity. Increased permeability in subsets of IBS patients has been observed and the possible mechanisms underlying this defect are just beginning to be understood. The objectives of this review are to summarize the role of the healthy intestinal epithelium as a barrier between the lumen and the rest of the body with a focus on tight junctions; to examine the lines of evidence that suggest that different triggers lead to increased intestinal mucosal permeability and disruption of tight junctions in IBS patients; and to explore how this increased permeability may elicit immune responses that affect afferent nerves, resulting in the pain associated with IBS.

  8. Estimates of sensitivity and specificity of electric pulp testing depend on pulp disease spectrum: a modelling study.

    PubMed

    Mejàre, I A; Bergenholtz, G; Petersson, K; Tranæus, S

    2015-01-01

    To demonstrate how the spectrum of diseased pulps may influence sensitivity and specificity in diagnostic studies on pulp status. An original sample from a previous study consisting of 59 teeth scheduled for root canal treatment was used where the relationship between the response to electric pulp testing and the visual status of the pulp was evaluated. To alter the spectrum of diseased pulps, a hypothetical sample of asymptomatic teeth with deep caries lesions was added to the original sample. Sensitivity and specificity were then compared for the two samples. In the original sample of 59 teeth, sensitivity was 72% and specificity 90%. When the spectrum of diseased pulps was altered, sensitivity decreased to 67% and specificity increased to 97%. The change in disease spectrum also decreased the prevalence of necrotic pulps. The spectrum of diseased pulps included in a diagnostic study on the accuracy of electric pulp testing, and indirectly also disease prevalence (here pulp necrosis), influences estimates of sensitivity and specificity. This implies that estimates of diagnostic accuracy from one study with a particular tooth population spectrum may not apply to another tooth population with a different disease spectrum. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  9. Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation.

    PubMed

    Kim, Jihyun; Lee, Da Young; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

    2017-01-01

    Recent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC. A total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP <0.06 mg/L, no NAFLD and hs-CRP ≥0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and NAFLD and hs-CRP ≥0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly measured by multi-detector computed tomography at four-year intervals and CAC development during those intervals was monitored in subjects with baseline CACS = 0. Over four years, 148 subjects (9.4%) developed CAC. The proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01), and it was also higher in subjects with hs-CRP ≥0.06 mg/L compared with those with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of subjects who developed CAC was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP ≥0.06 mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order (13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for CAC development was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/L (1.67, 95% CI 1.01-2.77), though it was attenuated after adjustment for body mass index. The concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC development over four years.

  10. OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

    PubMed Central

    Many, Gina M.; Yokosaki, Yasuyuki; Uaesoontrachoon, Kitipong; Nghiem, Peter P.; Bello, Luca; Dadgar, Sherry; Yin, Ying; Damsker, Jesse M.; Cohen, Heather B.; Kornegay, Joe N.; Bamman, Marcas M.; Mosser, David M.; Nagaraju, Kanneboyina

    2016-01-01

    New Findings What is the central question of this study? What is the functional relevance of OPN isoform expression in muscle pathology? What is the main finding and its importance? The full‐length human OPN‐a isoform is the most pro‐inflammatory isoform in the muscle microenvironment, acting on macrophages and myoblasts in an RGD‐integrin‐dependent manner. OPN‐a upregulates expression of tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Blocking TLR4 signalling inhibits the pro‐inflammatory effects of OPN‐a, suggesting that a potential mechanism of OPN action is by promoting TNC–TLR4 signalling. Although osteopontin (OPN) is an important mediator of muscle remodelling in health and disease, functional differences in human spliced OPN variants in the muscle microenvironment have not been characterized. We thus sought to define the pro‐inflammatory activities of human OPN isoforms (OPN‐a, OPN‐b and OPN‐c) on cells present in regenerating muscle. OPN transcripts were quantified in normal and dystrophic human and dog muscle. Human macrophages and myoblasts were stimulated with recombinant human OPN protein isoforms, and cytokine mRNA and protein induction was assayed. OPN isoforms were greatly increased in dystrophic human (OPN‐a > OPN‐b > OPN‐c) and dog muscle (OPN‐a = OPN‐c). In healthy human muscle, mechanical loading also upregulated OPN‐a expression (eightfold; P < 0.01), but did not significantly upregulate OPN‐c expression (twofold; P > 0.05). In vitro, OPN‐a displayed the most pronounced pro‐inflammatory activity among isoforms, acting on both macrophages and myoblasts. In vitro and in vivo data revealed that OPN‐a upregulated tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Inhibition of TLR4 signalling attenuated OPN‐mediated macrophage cytokine production. In summary, OPN‐a is the most abundant and functionally active human spliced isoform in the skeletal muscle

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

    PubMed Central

    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

  12. Glycohaemoglobin as a determinant of increased fibrinogen concentrations and low-grade inflammation in apparently healthy nondiabetic individuals.

    PubMed

    Rogowski, Ori; Shapira, Itzhak; Peretz, Hava; Berliner, Shlomo

    2008-02-01

    To determine the potential role of glycohaemoglobin as a possible determinant of increased fibrinogen concentrations and low-grade inflammation in a group of apparently healthy, nondiabetic individuals not expressing clinically overt atherothrombosis. We performed a cross-sectional analysis of the concentrations of glycohaemoglobin alongside the concentrations of quantitative fibrinogen and high-sensitivity C-reactive protein (hs-CRP). In all, 1511 males and 757 apparently healthy females, without diabetes mellitus or clinically evident atherothrombotic disease, were enrolled in the study during their routine annual health check-up. Glycohaemoglobin entered the linear regression models as a significant determinant of quantitative fibrinogen in both genders and of hs-CRP in men. We found this to be true even following the inclusion of multiple variables known to influence the intensity of low-grade inflammation, such as age, gender, waist circumference, body mass index, blood pressure, medications, hormone therapy, glucose levels (normal or impaired fasting glucose), smoking habits, family history of coronary artery disease, lipid profile as well as alcohol consumption and sports intensity. We found glycohaemoglobin to be a significant determinant of fibrinogen concentrations in apparently healthy nondiabetic individuals not yet presenting with evident atherothrombosis. This observation supports the idea that glycohaemoglobin might have an effect on fibrinogen concentrations in both genders and on hs-CRP in men. Moreover, our results suggest that glycohaemoglobin should be perceived as a continuous variable without a 'normal' cut-off point, as it may exhibit a detrimental role even when present in relatively low levels.

  13. Is pulp regeneration necessary for root maturation?

    PubMed

    Nosrat, Ali; Li, Kevin L; Vir, Kunwar; Hicks, M Lamar; Fouad, Ashraf F

    2013-10-01

    True regeneration of the dental pulp-dentin complex in immature teeth with necrotic pulps has not been shown histologically. It is not known to what extent this true tissue regeneration is necessary to achieve clinically acceptable outcomes. This case report describes the treatment of a patient with an immature maxillary right central incisor with a history of impact trauma and enamel-dentin crown fracture. A diagnosis of pulp necrosis with acute apical abscess was established. A regenerative endodontic protocol that used a paste containing Augmentin for 5 weeks as an intracanal medicament was used. Follow-ups at 9, 12, 17, and 31 months revealed complete osseous healing of the periapical lesion and formation of the root apex, but without increase in root length. Clinically, the tooth was functional, asymptomatic, and nonresponsive to pulp vitality tests. The crown discolored over time. On reentering the root canal, no tissues were observed under magnification inside the root canal space. The root canal treatment was completed with mineral trioxide aggregate obturation. Augmentin might be an acceptable choice for root canal disinfection in regenerative endodontic procedures. The protocol for regenerative endodontic treatment is not predictable for pulp-dentin regeneration. Formation of the root apex is possible without pulp regeneration. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. Bleaching kraft pulps with white-rot fungi

    SciTech Connect

    Reid, I.D.; Paice, M.G.; Bourbonnais, R.

    1996-10-01

    Certain white-rot fungi, notably Trametes versicolor, Phanerochaete sordida, and isolate IZU-154 can lower the residual lignin content and increase the brightness of kraft pulps without damaging the pulps` strength or yield. This biological delignification effect can be used in Elemental Chlorine Free and Totally Chlorine Free bleaching sequences. Physical contact between the fungal hyphae and the pulp fibers is not required, but the presence of the living fungus is necessary for continued delignification. In many but not a systems, delignification is correlated with manganese peroxidase activity. Experiments with pulps containing {sup 14}C-labelled lignin indicate that the residual lignin is solubilized, but not extensively mineralized, by T. versicolor. The solubilized lignin has the same molecular size as the residual lignin originally present in the pulp. Demethylation of the phenolic rings in the pulp is an early effect of incubation with the fungus.

  16. TMJ inflammation increases Fos expression in the nucleus raphe magnus induced by subsequent formalin injection of the masseter or hindpaw of rats.

    PubMed

    Oh, Sang-Hoon; Imbe, Hiroki; Iwai-Liao, Yasutomo

    2006-08-01

    The study was designed to examine the effect of persistent temporomandibular joint (TMJ) inflammation on neuronal activation in the descending pain modulatory system in response to noxious stimulus. Formalin was injected into the left masseter muscle or hindpaw of rats 10 days after injection of the left TMJ with saline or complete Freund's adjuvant (CFA). The results showed that 10-day persistent TMJ inflammation (induced by CFA) alone did not induce a significant increase in Fos-like immunoreactive (Fos-LI) neurons in the rostral ventromedial medulla (RVM) or locus coeruleus (LC), but that formalin injection of the masseter muscle or hindpaw induced a significant increase in Fos-LI neurons in the RVM and LC of rats with and without TMJ inflammation (P < 0.05). However, persistent TMJ inflammation significantly increased Fos-LI neurons in the nucleus raphe magnus (NRM) induced by subsequent formalin injection of the masseter muscle and hindpaw (70.2% increase and 53.8% increase, respectively, over the control TMJ-saline-injected rats; P < 0.05). The results suggest that persistent TMJ inflammation increases neuronal activity, in particularly in the NRM, by the plastic change of the descending pain modulatory system after ipsilateral application of a noxious stimulus to either orofacial area or a spatially remote body area.

  17. Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype.

    PubMed

    Xia, Haifa; Chen, Lin; Liu, Hong; Sun, Zhipeng; Yang, Wen; Yang, Yiyi; Cui, Shunan; Li, Shengnan; Wang, Yaxin; Song, Limin; Abdelgawad, Amro Fayez; Shang, You; Yao, Shanglong

    2017-12-01

    Recently, a serial of studies have demonstrated that lipid mediators derived from Omega-3 fatty acid docosahexaenoic acid have pro-resolving or anti-inflammatory effects in many inflammatory diseases. Here, we sought to evaluate whether Protectin DX (PDX, an isomer of Protecin D1), a newly identified lipid mediator, could protect mice against sepsis and explore the underling mechanism. Animal model of sepsis was established by cecum ligation and puncture (CLP). We found that PDX increased overall survival rate within eight days and attenuated multiple organ injury in septic mice. In addition, PDX reduced pro-inflammatory cytokines and bacterial load 24 h after CLP. Moreover, PDX promoted phagocytosis of peritoneal macrophages and increased the percentage of M2 macrophages in peritoneum of septic mice. In vitro, M2 macrophage markers (Arg1 and Ym1) and its transcriptional regulator (peroxisome proliferator-activated receptor-γ, PPAR-γ) were upregulated in Raw264.7 macrophages challenged with PDX. GW9662 (a PPAR-γ inhibitor) and PPAR-γ siRNA abrogated the induction of Arg1 and Ym1 by PDX in Raw264.7 cells. Taken together, our results suggest that PDX is able to promote M2 polarization, enhance phagocytosis activity of macrophage and accelerate resolution of inflammation, finally leading to increased survival rate of septic mice.

  18. Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis.

    PubMed

    Monick, Martha M; Cameron, Kelli; Staber, Janice; Powers, Linda S; Yarovinsky, Timur O; Koland, John G; Hunninghake, Gary W

    2005-01-21

    Respiratory syncytial virus (RSV) preferentially infects lung epithelial cells. Infection by RSV leads to an extended inflammatory response, characterized by the release of interleukin-8 (IL-8). Activation of ERK MAP kinase is required for both RSV-induced inflammation and the extended survival of infected cells. In this study, we analyzed the role of the epidermal growth factor receptor (EGFR) in RSV activation of ERK. We demonstrate for the first time that RSV activates EGFR in lung epithelial cells. Activation of EGFR results in increased ERK activity, contributing to both the inflammatory response (IL-8 release) and prolonging the survival of RSV-infected cells. Inhibition of EGFR with siRNA decreased both ERK activation and IL-8 production after RSV. In analyzing the effect of EGFR activation on survival of RSV-infected cells, we found that EGFR activation by RSV resulted in ERK-dependent alterations in the balance of pro- versus anti-apoptotic Bcl2 proteins. RSV altered the balance between pro- and anti-apoptotic Bcl2 proteins (increased BclxL and decreased BimEL) increasing the relative amount of pro-survival proteins. This occurred in an EGFR-dependent manner. This study supports an important role for EGFR activity in the lifespan and inflammatory potential of RSV-infected epithelial cells.

  19. Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson's disease patients.

    PubMed

    Zoladz, J A; Majerczak, J; Zeligowska, E; Mencel, J; Jaskolski, A; Jaskolska, A; Marusiak, J

    2014-06-01

    It has been demonstrated that physical training increases serum brain-derived neurotrophic factor (BDNF) in healthy people. The aim of this study was to establish the effect of physical training on the basal serum level of the BDNF in the Parkinson's disease patients (PD patients) in relation to their health status. Twelve PD patients (mean ± S.E.M: age 70 ± 3 years; body mass 70 ± 2 kg; height 163 ± 3 cm) performed a moderate-intensity interval training (three 1-hour training sessions weekly), lasting 8 weeks. Basal serum BDNF in the PD patients before training amounted to 10,977 ± 756 pg x mL(-1) and after 8 weeks of training it has increased to 14,206 ± 1256 pg x mL(-1) (i.e. by 34%, P=0.03). This was accompanied by an attenuation of total Unified Parkinson's Disease Rating Scale (UPDRS) (P=0.01). The training resulted also in a decrease of basal serum soluble vascular cell adhesion molecule 1 (sVCAM-1) (P=0.001) and serum tumor necrosis factor-α (TNF-α) (P=0.03) levels. We have concluded that the improvement of health status of the Parkinson's disease patients after training could be related to the increase of serum BDNF level caused by the attenuated inflammation in those patients.

  20. 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

  1. A comparison of human dental pulp response to calcium hydroxide and Biodentine as direct pulp-capping agents.

    PubMed

    Jalan, Anushka Lalit; Warhadpande, Manjusha M; Dakshindas, Darshan M

    2017-01-01

    Direct pulp capping involves the placement of a biocompatible agent on pulp tissue that has been inadvertently exposed from traumatic injury or by iatrogenic means. To compare the human pulp response to calcium hydroxide and Biodentine as direct pulp-capping agents. Pulp exposures were performed on the pulpal floor of forty human permanent premolars. The exposure sites were dressed with either Dycal or Biodentine as pulp-capping materials. After 45 days, teeth were extracted and processed for histological examination. The histological data were subjected to Wilcoxon rank-sum test. The dentinal bridges in teeth that were capped with Biodentine were significantly thicker (P < 0.0001) and more continuous (P = 0.0001) with less pulpal inflammation (P = 0.0044) in comparison to Dycal. Based on the result of this study, Biodentine can be suggested as the material of choice for direct pulp capping procedure instead of Dycal. However, further long-term follow-up in vivo human studies using Biodentine on cariously exposed pulpal teeth are warranted to derive a definite conclusion.

  2. A comparison of human dental pulp response to calcium hydroxide and Biodentine as direct pulp-capping agents

    PubMed Central

    Jalan, Anushka Lalit; Warhadpande, Manjusha M.; Dakshindas, Darshan M.

    2017-01-01

    Context: Direct pulp capping involves the placement of a biocompatible agent on pulp tissue that has been inadvertently exposed from traumatic injury or by iatrogenic means. Aim: To compare the human pulp response to calcium hydroxide and Biodentine as direct pulp-capping agents. Materials and Methods: Pulp exposures were performed on the pulpal floor of forty human permanent premolars. The exposure sites were dressed with either Dycal or Biodentine as pulp-capping materials. After 45 days, teeth were extracted and processed for histological examination. Statistical Analysis: The histological data were subjected to Wilcoxon rank-sum test. Results: The dentinal bridges in teeth that were capped with Biodentine were significantly thicker (P < 0.0001) and more continuous (P = 0.0001) with less pulpal inflammation (P = 0.0044) in comparison to Dycal. Conclusion: Based on the result of this study, Biodentine can be suggested as the material of choice for direct pulp capping procedure instead of Dycal. However, further long-term follow-up in vivo human studies using Biodentine on cariously exposed pulpal teeth are warranted to derive a definite conclusion. PMID:28855762

  3. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Increased Surfactant Protein D Fails to Improve Bacterial Clearance and Inflammation in serpinB1−/− Mice

    PubMed Central

    Stolley, J. Michael; Gong, Dapeng; Farley, Kalamo; Zhao, Picheng; Cooley, Jessica; Crouch, Erika C.; Benarafa, Charaf

    2012-01-01

    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-DlowserpinB1−/− and SP-Dhigh 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-DhighserpinB1−/− 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-DlowserpinB1−/−, SP-Dhigh 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

  6. Inflammation neither increases hepatic hepcidin nor affects intestinal (59)Fe-absorption in two murine models of bowel inflammation, hemizygous TNF(ΔARE/+) and homozygous IL-10(-/-) mice.

    PubMed

    Buffler, M; Becker, C; Windisch, W; Schümann, K

    2015-10-01

    Hepcidin-synthesis was reported to be stimulated by inflammation. In contrast, hepcidin synthesis was inhibited by TNFα and serum hepcidin was low. To elucidate these contradictions, we compare data on hepcidin expression, on iron absorption and homoeostasis and markers of inflammation between two murine models of intestinal inflammation and corresponding wild-types as determined by standard methods. In TNF(ΔARE/+) and IL-10(-/-)-mice hepatic hepcidin expression and protein content was significantly lower than in corresponding wild-types. However, (59)Fe whole-body retention showed no difference between knock-outs and corresponding wild-types 7d after gavage, in neither strain. Compared to wild-types, body weight, hepatic non-haem iron content, hemoglobin and hematocrit were significantly decreased in TNF(ΔARE/+) mice, while erythropoiesis increased. These differences were not seen in IL-10(-/-) mice. Duodenal IL-6 and TNFα content increased significantly in TNF(ΔARE/+) mice, while ferritin-H decreased along with hepatic hepcidin expression, ferritin L, and non-haem iron. In IL-10(-/-) mice, these changes were less marked or missing for non-haem iron. Duodenal ferritin-L and ferroportin increased significantly, while HFE decreased. Our results corroborate the conflicting combination of low hepcidin with inflammation and without increased intestinal iron absorption. Speculating on underlying mechanism, decreased hepcidin may result from stimulated erythropoiesis. Unaltered intestinal iron-absorption may compromise between the stimulation by increased erythropoiesis and inhibition by local and systemic inflammation. The findings suggest intense interaction between counterproductive mechanisms and ask for further research.

  7. 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

  8. Anthraquinone-A review of the rise and fall of a pulping catalyst

    Treesearch

    Peter W. Hart; Alan W. Rudie

    2014-01-01

    The application of anthraquinone (AQ) as a pulping catalyst has been well documented in scientific studies and mill applications. AQ is known to increase the rate of delignification, enabling a reduction in pulping time, temperature, or chemical charge and an increase in pulp yield. This review does not focus extensively on specific details of AQ use but rather on...

  9. Anthraquinone-A Review of the Rise and Fall of a Pulping Catalyst

    Treesearch

    Peter W. Hart; Alan W. Rudie

    2014-01-01

    The application of anthraquinone (AQ) as a pulping catalyst has been well documented in scientific studies and mill applications. AQ is known to increase the rate of delignification, enabling a reduction in pulping time, temperature, or chemical charge and an increase in pulp yield. Specific details of AQ use are not extensively reviewed in this work. The review...

  10. 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.

  11. Investigation of dental pulp stem cells isolated from discarded human teeth extracted due to aggressive periodontitis.

    PubMed

    Sun, Hai-Hua; Chen, Bo; Zhu, Qing-Lin; Kong, Hui; Li, Qi-Hong; Gao, Li-Na; Xiao, Min; Chen, Fa-Ming; Yu, Qing

    2014-11-01

    Recently, human dental pulp stem cells (DPSCs) isolated from inflamed dental pulp tissue have been demonstrated to retain some of their pluripotency and regenerative potential. However, the effects of periodontal inflammation due to periodontitis and its progression on the properties of DPSCs within periodontally compromised teeth remain unknown. In this study, DPSCs were isolated from discarded human teeth that were extracted due to aggressive periodontitis (AgP) and divided into three experimental groups (Groups A, B and C) based on the degree of inflammation-induced bone resorption approaching the apex of the tooth root before tooth extraction. DPSCs derived from impacted or non-functional third molars of matched patients were used as a control. Mesenchymal stem cell (MSC)-like characteristics, including colony-forming ability, proliferation, cell cycle, cell surface antigens, multi-lineage differentiation capability and in vivo tissue regeneration potential, were all evaluated in a patient-matched comparison. It was found that STRO-1- and CD146-positive DPSCs can be isolated from human teeth, even in very severe cases of AgP. Periodontal inflammation and its progression had an obvious impact on the characteristics of DPSCs isolated from periodontally affected teeth. Although all the isolated DPSCs in Groups A, B and C showed decreased colony-forming ability and proliferation rate (P < 0.05), the decreases were not consistent with the degree of periodontitis. Furthermore, the cells did not necessarily show significantly diminished in vitro multi-differentiation potential. Only DPSCs from Group A and the Control group formed dentin-like matrix in vivo when cell-seeded biomaterials were transplanted directly into an ectopic transplantation model. However, when cell-seeded scaffolds were placed in the root fragments of human teeth, all the cells formed significant dentin- and pulp-like tissues. The ability of DPSCs to generate dental tissues decreased when the

  12. Colonic insult impairs lymph flow, increases cellular content of the lymph, alters local lymphatic micro-environment and leads to sustained inflammation in the rat ileum

    PubMed Central

    Cromer, Walter; Wang, Wei; Zawieja, Scott D.; von der Weid, Pierre-Yves; Newell Rogers, M. Karen; Zawieja, David C.

    2015-01-01

    Background Lymphatic dysfunction has been linked to inflammation since the 1930’s. Lymphatic function in the gut and mesentery is grossly underexplored in models of IBD despite the use of lymphatic occlusion in early models of IBD. Activation of the innate and adaptive immune system is a hallmark of TNBS-induced inflammation and is linked to disruption of the intrinsic lymph pump. Recent identification of crosstalk between lymphatic vessel resident immune cells and regulation of lymphatic vessel contractility underscore the importance of the timing of lymphatic dysfunction during tissue inflammation in response to TNBS. Methods To evaluate lymphatic function in TNBS induced inflammation, lymph was collected and flow measured from mesenteric lymphatics. Cellularity and cytokine profile of the lymph was also measured. Histopathology was performed to determine severity of injury and immunofluorescent staining of the mesentery was done to evaluate changes in the population of immune cells that reside near and on gastro-intestinal collecting lymphatics. Results Lymph transport fell 24hrs after TNBS administration and began recovering at 72hrs. Significant reduction of lymph flow preceded significant increase in histopathological score and occurred simultaneously with increased MPO activity. These changes were preceded by increased MHCII+ cells surrounding mesenteric lymphatics leading to an altered lymphatic environment that would favor dysfunction. Conclusions Alterations in environmental factors that effect lymphatic function occur before the development of gross GI inflammation. Reduced lymphatic function in TNBS-mediated inflammation is likely an early factor in the development of injury and that recovery of function is associated with resolution of inflammation. PMID:25939039

  13. Functional Properties of Tooth Pulp Neurons Responding to Thermal Stimulation

    PubMed Central

    Ahn, D.K.; Doutova, E.A.; McNaughton, K.; Light, A.R.; Närhi, M.; Maixner, W.

    2012-01-01

    The response properties of tooth pulp neurons that respond to noxious thermal stimulation of the dental pulp have been not well-studied. The present study was designed to characterize the response properties of tooth pulp neurons to noxious thermal stimulation of the dental pulp. Experiments were conducted on 25 male ferrets, and heat stimulation was applied by a computer-controlled thermode. Only 15% of tooth pulp neurons (n = 39) responded to noxious thermal stimulation of the teeth. Tooth pulp neurons were found in both the superficial and deep nuclear regions of the subnucleus caudalis (Vc) and in the interface between the nucleus caudalis and interpolaris (Vc/Vi). Thirty-seven neurons had cutaneous receptive fields and were classified as either NS (16) or WDR (21) neurons. Repeated heat stimulation of the dental pulp sensitized and increased the number of electrically evoked potentials of tooth pulp neurons. These results provide evidence that both the Vc and Vc/Vi regions contain neurons that respond to noxious thermal stimulation of the dental pulp, and that these cells may contribute to the sensitization process associated with symptomatic pulpitis. PMID:22257665

  14. Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation

    PubMed Central

    Terrill, Jessica R.; Grounds, Miranda D; Arthur, Peter G.

    2016-01-01

    Background: The mdx mouse model for the fatal muscle wasting disease Duchenne Muscular Dystrophy (DMD) shows a very mild pathology once growth has ceased, with low levels of myofibre necrosis in adults. However, from about 3 weeks of post-natal age, muscles of juvenile mdx mice undergo an acute bout of severe necrosis and inflammation: this subsequently decreases and stabilises to lower adult levels by about 6 weeks of age. Prior to the onset of this severe dystropathology, we have shown that mdx mice are deficient in the amino acid taurine (potentially due to weaning), and we propose that this exacerbates myofibre necrosis and inflammation in juvenile mdx mice. Objectives: The purpose of this study was to increase taurine availability to pre-weaned juvenile mdx mice (from 14 days of age), to evaluate the impact on levels of myofibre necrosis and inflammation (at 22 days) during the acute period of severe dystropathology. Results: Untreated 22 day old mdx muscle was not deficient in taurine, with similar levels to normal C57 control muscle. However taurine treatment, which increased the taurine content of young dystrophic muscle (by 40%), greatly reduced myofibre necrosis (by 75%) and prevented significant increases in 3 markers of inflammation. Conclusion: Taurine was very effective at preventing the acute phase of muscle damage that normally results in myofibre necrosis and inflammation in juvenile mdx mice, supporting continued research into the use of taurine as a therapeutic intervention for protecting growing muscles of young DMD boys PMID:27679740

  15. Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis

    PubMed Central

    Hua, Susan; Dias, Thilani H.; Pepperall, Debbie-Gai; Yang, Yuan

    2017-01-01

    This study evaluates the prophylactic effect of the peripherally-selective mu-opioid receptor agonist, loperamide, administered topically in a liposomal gel formulation on pain, inflammation, and disease progression in the adjuvant-induced model of experimental rheumatoid arthritis in female Lewis rats. In a randomized, blinded and controlled animal trial, AIA rats were divided into six groups consisting of eleven rats per group based on the following treatments: loperamide liposomal gel, free loperamide gel, empty liposomal gel, diclofenac gel (Voltaren®), no treatment, and naive control. Topical formulations were applied daily for a maximum of 17 days—starting from day 0 at the same time as immunization. The time course of the effect of the treatments on antinocieption and inflammation was assessed using a paw pressure analgesiometer and plethysmometer, respectively. Arthritis progression was scored daily using an established scoring protocol. At the end of the study, hind paws were processed for histological analysis. Administration of loperamide liposomal gel daily across the duration of the study produced significant peripheral antinociception as expected; however, increased the severity of inflammation and accelerated arthritis progression. This was indicated by an increase in paw volume, behavioral and observational scoring, and histological analysis compared to the control groups. In particular, histology results showed an increase in pannus formation and synovial inflammation, as well as an upregulation of markers of inflammation and angiogenesis. These findings may have implications for the use of loperamide and other opioids in arthritis and potentially other chronic inflammatory diseases. PMID:28824428

  16. Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components

    PubMed Central

    Brown, D; Stone, V; Findlay, P; MacNee, W; Donaldson, K

    2000-01-01

    OBJECTIVES—Particulate air pollution has been shown to cause adverse health effects, and the ultrafine particle component has been implicated. The aim of the present study was to investigate whether an ultrafine particle exerted its effects through transition metals or other soluble factors released from the surface of the particles.
METHODS—Both in vitro and in vivo models were used to test the imflammogenicity of carbon black (CB) and ultrafine carbon black (UfCB) and the role of transition metals was investigated by treating the particles with desferrioxamine mesylate (desferal), a transition metal chelator. Rats were instilled with particles and the cell population assessed by bronchoalveolar lavage (BAL). Calcium homeostasis in macrophages was assessed with a fluorimetric technique.
RESULTS—UfCB was inflammogenic compared with CB when instilled into Wistar rat lungs, an effect which could not be ameliorated by desferal treatment of the particles. Particle leachates produced no significant inflammation in vivo. In vitro experiments showed that the cytosolic calcium ion concentration in Mono Mac 6 cells was increased significantly after UfCB treatment and treatment of particles with desferal did not alter these effects. Particle leachates had no effect on cytosolic calcium ion concentration. Iron was not detected in leachates of the particles with the desferal assay, however, ng/mg of particles were detectable in citrate leachates with inductively coupled plasma-mass spectrometry (ICP-MS).
CONCLUSIONS—The increased inflammogenicity of UfCB compared with CB cannot be explained by soluble transition metals released from or by accumulation of iron at the particle surface. Differences may be accounted for by increased surface area or particle number.


Keywords: ultrafine; calcium; transition metals PMID:10984341

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

    PubMed

    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

    2015-07-02

    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). 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. (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. 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.

  18. Cytokine-induced prostaglandin E2 production and cyclooxygenase-2 expression in dental pulp cells: downstream calcium signalling via activation of prostaglandin EP receptor.

    PubMed

    Chang, M-C; Chen, Y-J; Tai, T-F; Tai, M-R; Li, M-Y; Tsai, Y-L; Lan, W-H; Wang, Y-L; Jeng, J-H

    2006-10-01

    To determine whether (i) proinflammatory cytokines stimulate prostaglandin E(2) (PGE(2)) production and cyclooxygenase (COX) gene expression in dental pulp cells, and (ii) pulp cells that express different prostaglandin E(2) receptor (EP) isoforms and their activation by PGE(2) leads to downstream Ca(2+) signalling. Cultured human dental pulp cells were exposed to interleukin (IL)-1beta and tumour necrotic factor-alpha (TNF-alpha). The expression of COX-1 and COX-2 was measured with reverse transcriptase-polymerase chain reaction (RT-PCR). The production of PGE(2) was measured using an enzyme-linked immunosorbent assay. Expression of prostaglandin EP receptor isoforms was studied by RT-PCR, whereas fura-2 fluorescence was used to measure calcium mobilization. The Kruskal-Wallis test and Wilcoxon sum rank test with Bonferroni correction were used for statistical analysis. Interleukin-1beta and TNF-alpha stimulate PGE(2) production of human dental pulp cells (P < 0.05). IL-1beta stimulated the COX-2 but not COX-1 mRNA expression. Pulp cells express mainly EP2, EP3 and EP1 receptors as analysed by RT-PCR. PGE(2) (0.25-2 micromol L(-1)) stimulated the Ca(2+) mobilization as indicated by increase in fura-2 fluorescence. Interleukin-1beta and TNF-alpha may stimulate PGE(2) production in dental pulp cells. Activation of prostaglandin EP receptors in dental pulp cells by PGE(2) may induce Ca(2+) signalling to regulate cellular biological activity during inflammation.

  19. Inflammation-induced shift in spinal GABAA signaling is associated with a tyrosine kinase-dependent increase in GABAA current density in nociceptive afferents

    PubMed Central

    Zhu, Yi; Dua, Shiv

    2012-01-01

    To account for benzodiazepine-induced spinal analgesia observed in association with an inflammation-induced shift in the influence of the GABAA receptor antagonist gabazine on nociceptive threshold, the present study was designed to determine whether persistent inflammation is associated with the upregulation of high-affinity GABAA receptors in primary afferents. The cell bodies of afferents innervating the glabrous skin of the rat hind paw were retrogradely labeled, acutely dissociated, and studied before and after the induction of persistent inflammation. A time-dependent increase in GABAA current density was observed that was more than twofold by 72 h after the initiation of inflammation. This increase in current density included both high- and low-affinity currents and was restricted to neurons in which GABA increased intracellular Ca2+. No increases in GABAA receptor subunit mRNA or protein were detected in whole ganglia. In contrast, the increased current density was completely reversed by 20-min preincubation with the tyrosine kinase inhibitor genistein and partially reversed with the Src kinase inhibitor PP2. Genistein reversal was partially blocked by the dynamin inhibitor peptide P4. Changes in nociceptive threshold following spinal administration of genistein and muscimol to inflamed rats indicated that the pronociceptive actions of muscimol observed in the presence of inflammation were reversed by genistein. These results suggest that persistent changes in relative levels of tyrosine kinase activity following inflammation provide not only a sensitive way to dynamically regulate spinal nociceptive signaling but a viable target for the development of novel therapeutic interventions for the treatment of inflammatory pain. PMID:22914654

  20. Biogas generation apple pulp.

    PubMed

    Llaneza Coalla, H; Blanco Fernández, J M; Morís Morán, M A; López Bobo, M R

    2009-09-01

    In view of the pressing problem that appears in our region (Asturias, north of Spain) with the residues from the cider production, it was decided to test this kind of material as a co-substrate joint with slaughterhouse waste in a laboratory unit. The anaerobic digestion of apple pulp was investigated for biogas production. This paper presents the results where apple pulp was co-digested with slaughterhouse waste (pig intestine and bovine stomach content) in a biogas laboratory unit (10 l CSTR reactor). The production of biogas has reached very satisfactory values during the whole test (0.8m(3)kg(-1)OTS), verifying that the process is kept in stable conditions of pH (near 8.0), and the volatile fatty acids was always underneath 3000 mg/l, when the pulp amount was lower than 100g in mesophilic conditions. The fat concentration into the digester remained always below the value that causes inhibition of the methanogenic bacteria, 500 mg/l. Finally, methane concentration (77-80%) and H(2)S concentration (400 ppm) in the biogas, they were similar to those obtained when the test was run out in the absence of apple pulp. The process efficiency with respect to COD removal was high, near 80% of the total COD. Finally, inhibitory effects of methanogenic bacteria were observed when pulp concentration was around 10% in the input material.

  1. Influence of kraft pulping on carboxylate content of softwood kraft pulps

    Treesearch

    Zheng Dang; Thomas Elder; Arthur J. Ragauskas

    2006-01-01

    This study characterizes changes in fiber charge, which is the carboxylate content of fibers, for two sets of kraft pulps: (1) conventional laboratory cooked loblolly pine kraft pulps and (2) conventional pulping (CK) versus low solids pulping (LS) pulps. Laboratory kraft pulping of loblolly pine was carried out to study the influence of pulping conditions, including...

  2. 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

  3. Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality

    PubMed Central

    Iskander, Kendra N.; Vaickus, Max; Duffy, Elizabeth R.

    2016-01-01

    Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP) negatively influences outcomes. Following CLP mice were randomized to receive the antibiotic imipenem-cilastatin (25mg/kg) in dextrose 5% in Lactated Ringer’s solution every 12 hours for either three or five days. Serial monitoring over 28 days included body weight, temperature, pulse oximetry, and facial vein sampling for hematological analysis and glucose. A separate group of mice were euthanized on post-CLP day 5 to measure cytokines and peritoneal bacterial counts. The first study examined no antimicrobial therapy and demonstrated that antibiotics significantly improved survival compared to fluids only (p = 0.004). We next tested imipenem-cilastatin therapy for 3 days versus 5 days. Body weight, temperature, glucose, and pulse oximetry measurements remained generally consistent between both groups as did the hematological profile. Pro-inflammatory plasma cytokines were comparable between both groups for IL-6, IL-1β, MIP-2 and anti-inflammatory cytokines IL-10, and TNF SRI. At 5 days post-CLP, i.e. 2 days after the termination of antibiotics in the 3 day group, there were no differences in the number of peritoneal bacteria. Importantly, shortening the course of antibiotics by 40% (from 5 days to 3 days) did not decrease survival. Our results indicate that reducing the duration of broad-spectrum antibiotics in murine sepsis did not increase inflammation or mortality. PMID:27669150

  4. Increased Recruitment but Impaired Function of Leukocytes during Inflammation in Mouse Models of Type 1 and Type 2 Diabetes

    PubMed Central

    Pettersson, Ulrika Sofia; Christoffersson, Gustaf; Massena, Sara; Ahl, David; Jansson, Leif; Henriksnäs, Johanna; Phillipson, Mia

    2011-01-01

    Background Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation. Methodology/Principal Findings Diabetes was induced in C57Bl/6 mice by intravenous alloxan (causing severe hyperglycemia), or by high fat diet (moderate hyperglycemia). Leukocyte recruitment was studied in anaesthetized mice using intravital microscopy of exposed cremaster muscles, where numbers of rolling, adherent and emigrated leukocytes were quantified before and during exposure to the inflammatory chemokine MIP-2 (0.5 nM). During basal conditions, prior to addition of chemokine, the adherent and emigrated leukocytes were increased in both alloxan- (62±18% and 85±21%, respectively) and high fat diet-induced (77±25% and 86±17%, respectively) diabetes compared to control mice. MIP-2 induced leukocyte emigration in all groups, albeit significantly more cells emigrated in alloxan-treated mice (15.3±1.0) compared to control (8.0±1.1) mice. Bacterial clearance was followed for 10 days after subcutaneous injection of bioluminescent S. aureus using non-invasive IVIS imaging, and the inflammatory response was assessed by Myeloperoxidase-ELISA and confocal imaging. The phagocytic ability of leukocytes was assessed using LPS-coated fluorescent beads and flow cytometry. Despite efficient leukocyte recruitment, alloxan-treated mice demonstrated an impaired ability to clear bacterial infection, which we found correlated to a 50% decreased phagocytic ability of leukocytes in diabetic mice. Conclusions/Significance These results indicate that reduced ability to clear bacterial infections observed during experimentally induced diabetes is not due to reduced leukocyte recruitment since sustained hyperglycemia results in increased levels of adherent and emigrated leukocytes in mouse models of type 1 and type 2 diabetes. Instead

  5. CD44 Deficiency Is Associated with Increased Bacterial Clearance but Enhanced Lung Inflammation During Gram-Negative Pneumonia

    PubMed Central

    van der Windt, Gerritje J.W.; Florquin, Sandrine; de Vos, Alex F.; van't Veer, Cornelis; Queiroz, Karla C.S.; Liang, Jiurong; Jiang, Dianhua; Noble, Paul W.; van der Poll, Tom

    2010-01-01

    Klebsiella pneumoniae is a frequently isolated causative pathogen in respiratory tract infections. CD44 is a transmembrane adhesion molecule that has been implicated in several immunological processes. To determine the role of CD44 during Klebsiella pneumonia, we intranasally infected wild-type and CD44 knockout (KO) mice with 102 to 104 colony-forming units of K. pneumoniae or administered Klebsiella lipopolysaccharide. During lethal infection, CD44 deficiency was associated with reduced bacterial growth and dissemination accompanied by enhanced pulmonary inflammation. After infection with lower Klebsiella doses, CD44 KO mice but not wild-type mice demonstrated mortality. After infection with even lower bacterial doses, which were cleared by most mice of both strains, CD44 KO mice displayed enhanced lung inflammation 4 and 10 days postinfection, indicating that CD44 is important for the resolution of pulmonary inflammation after nonlethal pneumonia. In accordance, CD44 KO mice showed a diminished resolution of lung inflammation 4 days after intrapulmonary delivery of lipopolysaccharide. CD44 deficiency was associated with the accumulation of hyaluronan together with reduced gene expression levels of the negative regulators of Toll-like receptor signaling, interleukin-1R-associated kinase M, A20, and suppressor of cytokine signaling 3. In conclusion, the absence of CD44 affects various components and phases of the host response during Klebsiella pneumonia, reducing bacterial outgrowth and dissemination and enhancing pulmonary pathology during lethal infection, and diminishing the resolution of lung inflammation during sublethal infection. PMID:20864681

  6. CD44 deficiency is associated with increased bacterial clearance but enhanced lung inflammation during Gram-negative pneumonia.

    PubMed

    van der Windt, Gerritje J W; Florquin, Sandrine; de Vos, Alex F; van't Veer, Cornelis; Queiroz, Karla C S; Liang, Jiurong; Jiang, Dianhua; Noble, Paul W; van der Poll, Tom

    2010-11-01

    Klebsiella pneumoniae is a frequently isolated causative pathogen in respiratory tract infections. CD44 is a transmembrane adhesion molecule that has been implicated in several immunological processes. To determine the role of CD44 during Klebsiella pneumonia, we intranasally infected wild-type and CD44 knockout (KO) mice with 10(2) to 10(4) colony-forming units of K. pneumoniae or administered Klebsiella lipopolysaccharide. During lethal infection, CD44 deficiency was associated with reduced bacterial growth and dissemination accompanied by enhanced pulmonary inflammation. After infection with lower Klebsiella doses, CD44 KO mice but not wild-type mice demonstrated mortality. After infection with even lower bacterial doses, which were cleared by most mice of both strains, CD44 KO mice displayed enhanced lung inflammation 4 and 10 days postinfection, indicating that CD44 is important for the resolution of pulmonary inflammation after nonlethal pneumonia. In accordance, CD44 KO mice showed a diminished resolution of lung inflammation 4 days after intrapulmonary delivery of lipopolysaccharide. CD44 deficiency was associated with the accumulation of hyaluronan together with reduced gene expression levels of the negative regulators of Toll-like receptor signaling, interleukin-1R-associated kinase M, A20, and suppressor of cytokine signaling 3. In conclusion, the absence of CD44 affects various components and phases of the host response during Klebsiella pneumonia, reducing bacterial outgrowth and dissemination and enhancing pulmonary pathology during lethal infection, and diminishing the resolution of lung inflammation during sublethal infection.

  7. Increased severity of inflammation correlates with elevated expression of TRPV1 nerve fibers and nerve growth factor on interstitial cystitis/bladder pain syndrome.

    PubMed

    Liu, Bo-long; Yang, Fei; Zhan, Hai-lun; Feng, Zhi-ying; Zhang, Zhi-gang; Li, Wen-biao; Zhou, Xiang-fu

    2014-01-01

    Although evidence supports a role for inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We determined whether inflammation causes an elevated expression of nerve growth factor (NGF) and transient receptor potential vanilloid receptor subtype 1 (TRPV1) and correlated them with the symptoms. Bladder biopsies were obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin staining, immunostaining and Western blotting were performed to detect inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve fiber density was quantified and correlated with PUF scores. Increased severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p = 0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r = 0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were significantly increased in IC/BPS (p = 0.0193) and had a positive relationship with inflammation severity (r = 0.6138, p < 0.0001). Our study revealed increased severity of inflammation correlated with a higher expression of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with clinical symptoms. 2014 S. Karger AG, Basel.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  9. 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

  10. 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

    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.

  11. Pilot study of correlation of pulp stones with cardiovascular disease.

    PubMed

    Edds, A C; Walden, J E; Scheetz, J P; Goldsmith, L J; Drisko, C L; Eleazer, P D

    2005-07-01

    We propose that calcification of dental pulp may have a similar pathogenesis as calcified atheromas and could lead to use of routine dental radiographs as a rapid screening method for early identification of potential cardiovascular disease (CVD). Fifty-five dental patients ages 20 to 55 were chosen because pulp stones in pulpally noninflamed teeth were not expected in this age group. They completed a questionnaire regarding their CVD status and that of their parents and siblings. Entry criteria included at least one asymptomatic, minimally restored, noncarious molar and no history of gout, renal disease, or renal lithiasis. Patients' periapical radiographs of record were viewed to determine the presence of pulp stones. There was a significant relationship between pre-existing CVD and pulp stones (odds ratio of 4.4 with a 95% confidence interval of 1.1, 18.7), but no relationship was found for family history of CVD and pulp stones (odds ratio of 1.7 with a 95% confidence interval of 0.5, 5.5). Seventy-four percent (14/19) of patients with reported CVD had detectable pulp stones while only 39% (14/36) of patients without a history of CVD had pulp stones. This pilot study demonstrates that patients with CVD have an increased incidence of pulp stones in teeth with noninflamed pulps compared to patients with no history of CVD. No relationship was found between presence of pulp stones and family history of CVD. The findings suggest that dental radiographic determination of the presence or absence of pulp stones may have possibilities for use in CVD screening.

  12. 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. © International & American Associations for Dental Research 2015.

  13. Pulp bleeding color is an indicator of clinical and histohematologic status of primary teeth.

    PubMed

    Aaminabadi, Naser Asl; Parto, Marziyeh; Emamverdizadeh, Parya; Jamali, Zahra; Shirazi, Sajjad

    2017-06-01

    This study was carried out to investigate whether the changes in hematologic characteristic and color of pulpal bleeding is associated with clinical and histologic status of the pulp in primary teeth. A total of 211 primary molars in 103 patients, 3-6 years old, were treated. One hundred eight teeth had pulpectomy, 57 teeth had pulpotomy after pulp exposure during caries excavation, and 46 teeth had pulpotomy after accidental pulp exposure in sound dentin. After pulpal exposure, pulpal blood was collected in capillary tubes for blood color and hematologic assessment. Coronal and radicular pulp tissues were amputated for histologic assessment. Blood color was significantly darker in pulpectomy cases and samples with severe inflammation. The differences were clinically perceptible by the human eye. A significant negative correlation was detected between white blood cell (WBC) count and blood color. The counts of neutrophils and lymphocytes were significantly different between treatment groups. In addition, WBC, eosinophil, monocyte, neutrophil, and basophils counts were significantly different between degrees of inflammation in coronal pulp. Moreover, severe inflammation was higher in pulpectomy group versus pulpotomy groups. Pulp tissue calcification was also significantly higher in the pulpectomy cases. Considering the significant difference in pulpal blood color between the pulpectomy and pulpotomy cases, and between the different levels of pulpal inflammation; blood color can be a valid clinical diagnostic criterion of pulpal status and can be used for the selection of appropriate pulp treatment strategy. This study shows that pulp bleeding color can be used for selection of an appropriate pulp treatment method in primary teeth.

  14. Indirect pulp capping versus pulpotomy for treating deep carious lesions approaching the pulp in primary teeth: a systematic review.

    PubMed

    Smaïl-Faugeron, V; Porot, A; Muller-Bolla, M; Courson, F

    2016-06-01

    To assess dental practice regarding the use of indirect pulp capping or pulpotomy in children with deep carious lesions approaching the pulp in primary teeth and to compare the efficacy of the two pulp treatments. Systematic review. We searched the Cochrane Library, PubMed via MEDLINE, and EMBASE as well as the reference lists of included reports and ClinicalTrials.gov (for ongoing trials). Eligible studies were surveys of dental practice sent to dentists regarding the use of indirect pulp capping and pulpotomy in children with deep carious lesions approaching the pulp in primary teeth and any type of clinical study. Two review authors independently extracted data and assessed risk of bias in duplicate. Of the 481 potentially eligible articles, 11 were included in the review: 8 described surveys of dental practice, 1 a non-randomised study, and 2 ongoing randomised trials. The surveys of dental practice showed an overall increase in the teaching and practice of indirect pulp capping in primary teeth. The non- randomised study found a statistically significant difference in favour of indirect pulp capping for clinical and radiological success at 3 years but with high overall risk of bias. Despite the success rate of indirect pulp capping for treating deep carious lesions approaching the pulp in primary teeth, practitioners still hesitate to practice this technique because of lack of evidence and studies on this topic. Thus, for strong evidence, investigators are encouraged to conduct randomised trials comparing the efficacy of indirect pulp capping and pulpotomy for treating deep carious lesions approaching the pulp in primary teeth.

  15. 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

  16. Contribution of endoplasmic reticulum Ca2+ regulatory mechanisms to the inflammation-induced increase in the evoked Ca2+ transient in rat cutaneous dorsal root ganglion neurons

    PubMed Central

    Scheff, Nicole N.; Lu, Shao-Gang; Gold, Michael S.

    2013-01-01

    Persistent inflammation results in an increase in the magnitude and duration of high K+-evoked Ca2+ transients in putative nociceptive cutaneous dorsal root ganglion (DRG) neurons. The purpose of the present study was to determine whether recruitment of Ca2+-induced Ca2+ release (CICR) contributes to these inflammation-induced changes. Acutely dissociated, retrogradely labeled cutaneous DRG neurons from naïve and complete Freund’s adjuvant inflamed adult male Sprague Dawley rats were studied with ratiometric microfluorimetry. Ryanodine only attenuated the duration but not magnitude of the high K+-evoked Ca2+ transient in neurons from inflamed rats. However, there was no significant impact of inflammation on the potency or efficacy of ryanodine-induced block of the caffeine-evoked Ca2+ transient, or the impact of sarco-endoplasmic reticulum ATPase (SERCA) inhibition on the high K+-evoked Ca2+ transient. Furthermore, while there was no change in the magnitude, an inflammation-induced increase in the duration of the caffeine-evoked Ca2+ transient was only observed with a prolonged caffeine application. In contrast to the high K+-evoked Ca2+ transient, there was no evidence of direct mitrochondrial involvement or that of the Ca2+ extrusion mechanism, the Na+/Ca2+ exchanger, on the caffeine-evoked Ca2+ transient, and block of SERCA only increased the duration of this transient. These results indicate the presence of Ca2+ regulatory domains in cutaneous nociceptive DRG neurons within which cytosolic Ca2+ increased via influx and release are highly segregated. Furthermore, our results suggest that changes in neither CICR machinery nor the coupling between Ca2+ influx and CICR are primarily responsible for the inflammation-induced changes in the evoked Ca2+ transient. PMID:23642703

  17. Macrophage Deletion of SOCS1 Increases Sensitivity to LPS and Palmitic Acid and Results in Systemic Inflammation and Hepatic Insulin Resistance

    PubMed Central

    Graham, Kate L.; Galic, Sandra; Honeyman, Jane E.; Fynch, Stacey L.; Hewitt, Kimberly A.; Kay, Thomas W.

    2011-01-01

    OBJECTIVE Macrophage secretion of proinflammatory cytokines contributes to the pathogenesis of obesity-related insulin resistance. An important regulator of inflammation is the suppressor of cytokine signaling-1 (SOCS1), which inhibits the JAK-STAT and toll-like receptor-4 (TLR4) pathways. Despite the reported role of SOCS1 in inhibiting insulin signaling, it is surprising that a SOCS1 polymorphism that increases SOCS1 promoter activity is associated with enhanced insulin sensitivity despite obesity. In the current study, we investigated the physiological role of myeloid and lymphoid cell SOCS1 in regulating inflammation and insulin sensitivity. RESEARCH DESIGN AND METHODS We used mice generated by crossing SOCS1 floxed mice with mice expressing Cre recombinase under the control of the LysM-Cre promoter (SOCS1 LysM-Cre). These mice have deletion of SOCS1 in macrophages and lymphocytes. We assessed macrophage inflammation using flow cytometry and serum cytokine levels using Bioplex assays. We then measured insulin sensitivity using glucose tolerance tests and the euglycemic-hyperinsulinemic clamp. Using bone marrow–derived macrophages, we tested the effects of SOCS1 deletion in regulating responses to the TLR4 ligands: lipopolysaccharide (LPS) and palmitic acid. RESULTS SOCS1 LysM-Cre mice had increased macrophage expression of CD11c, enhanced sensitivity to LPS, and palmitic acid and increased serum concentrations of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein. Increased inflammation was associated with impaired glucose tolerance and hyperinsulinemia as a result of reduced hepatic but not skeletal muscle insulin sensitivity. CONCLUSIONS The expression of SOCS1 in hematopoietic cells protects mice against systemic inflammation and hepatic insulin resistance potentially by inhibiting LPS and palmitate-induced TLR4 signaling in macrophages. PMID:21646388

  18. Biomechanical pulping of kenaf

    Treesearch

    Aziz Ahmed; Masood Akhtar; Gary C. Myers; Gary M. Scott

    1999-01-01

    The objective of this study was to investigate the effect of fungal pretreatment of whole kenaf prior to refining on refiner electrical energy consumption, paper strength, and optical properties. We also explored the suitability of whole kenaf biomechanical pulp for making newsprint in terms of ISO brightness and strength properties. Kenaf was sterilized by autoclaving...

  19. Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis.

    PubMed

    Babbar, Naveen; Casero, Robert A

    2006-12-01

    Inflammation has been implicated in the development of many human epithelial cancers, including those of the stomach, lung, colon, and prostate. Tumor necrosis factor-alpha (TNF-alpha) is a potent pleiotropic, proinflammatory cytokine produced by many cells in response to injury and inflammation. Here, we show that TNF-alpha exposure results in increased production of reactive oxygen species (ROS), with a concomitant increase in the production of 8-oxo-deoxyguanosine, a marker for oxidative DNA damage, in human lung bronchial epithelial cells. The source of the ROS in TNF-alpha-treated cells was determined by both pharmacologic and small interfering RNA (siRNA) strategies to be spermine oxidase (SMO/PAOh1). SMO/PAOh1 oxidizes spermine into spermidine, 3-aminopropanal, and H(2)O(2). Inhibition of TNF-alpha-induced SMO/PAOh1 activity with MDL 72,527 or with a targeted siRNA prevented ROS production and oxidative DNA damage. Further, similar induction in SMO/PAOh1 is observed with treatment of another inflammatory cytokine, interleukin-6. The data are consistent with a model that directly links inflammation and DNA damage through the production of H(2)O(2) by SMO/PAOh1. Further, these results suggest a common mechanism by which inflammation from multiple sources can lead to the mutagenic changes necessary for the development and progression of epithelial cancers.

  20. 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.

  1. The influence of pulping and washing conditions on the properties of Eucalyptus grandis unbleached kraft pulps treated with chelants.

    PubMed

    Area, M C; Carvalho, M G V S; Ferreira, P J; Felissia, F E; Barboza, O M; Bengoechea, D I

    2010-03-01

    The influence of different addition points of a chelating agent and a counter-ion exchange on the properties of Eucalyptus grandis unbleached kraft pulps is studied. Seven pulps were considered: two laboratory kraft pulps with or without the inclusion of the chelant DTPMPA (diethylene triamine penta (methylene phosphonic acid)), a mill kraft pulp and four mill pulps after Ca(+2) or Na(+) counter-ion exchange followed, or not, by washing with DTPMPA addition. The laboratory pulps required lower beating energy than the industrial pulps for achieving 30 degrees SR, and the corresponding handsheets also showed better strength and optical properties, as well as a more homogeneous and smooth surface. The counter-ion exchange decreases the mechanical resistances and increases brightness. However, the effects of Ca(+2) are deeper than those of Na(+). DTPMPA added to pulping causes a decrease in calcium content whereas as a washing additive does not have a relevant impact on the mechanical and optical properties. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  2. 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

  3. Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation.

    PubMed

    Aich, Jyotirmoi; Mabalirajan, Ulaganathan; Ahmad, Tanveer; Agrawal, Anurag; Ghosh, Balaram

    2012-06-06

    Inositol polyphosphate phosphatases regulate the magnitude of phosphoinositide-3 kinase signalling output. Although inositol polyphosphate-4-phosphatase is known to regulate phosphoinositide-3 kinase signalling, little is known regarding its role in asthma pathogenesis. Here we show that modulation of inositol polyphosphate-4-phosphatase alters the severity of asthma. Allergic airway inflammation in mice led to calpain-mediated degradation of inositol polyphosphate-4-phosphatase. In allergic airway inflammation models, preventing inositol polyphosphate-4-phosphatase degradation by inhibiting calpain activity, or overexpression of inositol polyphosphate-4-phosphatase in mouse lungs, led to attenuation of the asthma phenotype. Conversely, knockdown of inositol polyphosphate-4-phosphatase severely aggravated the allergic airway inflammation and the asthma phenotype. Interestingly, inositol polyphosphate-4-phosphatase knockdown in lungs of naive mice led to spontaneous airway hyper-responsiveness, suggesting that inositol polyphosphate-4-phosphatase could be vital in maintaining the lung homeostasis. We suggest that inositol polyphosphate-4-phosphatase has an important role in modulating inflammatory response in asthma, and thus, uncover a new understanding of the complex interplay between inositol signalling and asthma, which could provide alternative strategies in asthma management.

  4. FGF23 and inflammation

    PubMed Central

    Sharaf El Din, Usama A A; Salem, Mona M; Abdulazim, Dina O

    2017-01-01

    Systemic inflammation is a recognized feature in chronic kidney disease (CKD). The role of systemic inflammation in the pathogenesis of vascular calcification was recently settled. FGF23 was recently accused as a direct stimulus of systemic inflammation. This finding explains the strong association of FGF23 to vascular calcification and increased mortality among CKD. PMID:28101453

  5. Ischemia-modified albumin (IMA) is increased in patients with chronic hepatitis C infection and related to markers of oxidative stress and inflammation.

    PubMed

    Zuwała-Jagiełło, Jolanta; Warwas, Maria; Pazgan-Simon, Monika

    2012-01-01

    Inflammation and oxidative stress have been reported in patients with chronic hepatitis C (CHC) infection, but their influence on ischemia-modified albumin (IMA) levels and diabetes prevalence remains unknown. Sixty-three CHC patients, 28 with diabetes, and 40 healthy controls were enrolled in the study. Circulating levels of oxidative stress markers [Nε-(carboxymethyl)lysine- advanced glycation end products (CML-AGEs) and advanced oxidation protein products-(AOPPs)], pro-inflammatory cytokines (interleukin-6, and tumor necrosis factor α), and high-sensitivity C-reactive protein (hsCRP) were assessed. Compared with the controls, the CHC patients with diabetes showed a significant increase in plasma concentrations of IMA, AOPPs, interleukin-6 and hsCRP (P < 0.05). The values of IMA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were found between hsCRP and presence of diabetes, IMA (both P < 0.01) and AOPP levels (P < 0.05). CML-AGEs did not show any significant correlation with IMA, markers of inflammation and presence of diabetes. In conclusion, we have documented significant elevation in plasma levels of IMA and AOPPs in CHC patients. In addition, circulating IMA was associated with inflammation markers and diabetes prevalence. This observation suggests a relationship between IMA and inflammation in CHC patients with diabetes, which may represent one of the mechanisms involved in the accelerated atherosclerosis in this population.

  6. 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

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

    PubMed

    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

    2016-02-11

    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.

  8. Anthocyanin-rich açai (Euterpe oleracea Mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells.

    PubMed

    Poulose, Shibu M; Fisher, Derek R; Larson, Jessica; Bielinski, Donna F; Rimando, Agnes M; Carey, Amanda N; Schauss, Alexander G; Shukitt-Hale, Barbara

    2012-02-01

    Age-related diseases of the brain compromise memory, learning, and movement and are directly linked with increases in oxidative stress and inflammation. Previous research has shown that supplementation with berries can modulate signaling in primary hippocampal neurons or BV-2 mouse microglial cells. Because of their high polyphenolic content, fruit pulp fractions of açai ( Euterpe oleracea Mart.) were explored for their protective effect on BV-2 mouse microglial cells. Freeze-dried açai pulp was fractionated using solvents with different polarities and analyzed using HPLC for major anthocyanins and other phenolics. Fractions extracted using methanol (MEOH) and ethanol (ETOH) were particularly rich in anthocyanins such as cyanidin, delphinidin, malvidin, pelargonidin, and peonidin, whereas the fraction extracted using acetone (ACE) was rich in other phenolics such as catechin, ferulic acid, quercetin, resveratrol, and synergic and vanillic acids. Studies were conducted to investigate the mitigating effects of açai pulp extracts on lipopolysaccharide (LPS, 100 ng/mL) induced oxidative stress and inflammation; treatment of BV-2 cells with acai fractions resulted in significant (p < 0.05) decreases in nitrite production, accompanied by a reduction in inducible nitric oxide synthase (iNOS) expression. The inhibition pattern was emulated with the ferulic acid content among the fractions. The protection of microglial cells by açai pulp extracts, particularly that of MEOH, ETOH, and ACE fractions, was also accompanied by a significant concentration-dependent reduction in cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (p38-MAPK), tumor necrosis factor-α (TNFα), and nuclear factor κB (NF-κB). The current study offers valuable insights into the protective effects of açai pulp fractions on brain cells, which could have implications for improved cognitive and motor functions.

  9. Relationship between lignin structure and delignification degree in Pinus pinaster kraft pulps.

    PubMed

    Baptista, C; Robert, D; Duarte, A P

    2008-05-01

    This study examines the structure of residual and dissolved lignins from Pinus pinaster pulps obtained at different degrees of delignification by laboratory conventional kraft pulping. The cooking H factor was varied from 85 to 8049. The residual and dissolved lignin samples were characterised by elemental analysis, residual carbohydrate content, permanganate oxidation and 13C NMR spectroscopy. The reflectance factor of the pulps was also determined in order to tentatively correlate the delignification degree and residual lignin structure with the pulp colour. The obtained results confirmed that the delignification degree increases the condensation of the lignin structure, which might have an influence upon the observed increased pulp colour. The lack of selectivity of kraft pulping process in the case of more delignified pulps was also shown.

  10. Enzymatic treatment of mechanical pulp fibers for improving papermaking properties.

    PubMed

    Wong, K K; Richardson, J D; Mansfield, S D

    2000-01-01

    Three enzyme preparations (crude cellulase, laccase, and proteinase) were evaluated for their potential to improve the papermaking properties of mechanical pulp. After treating a long fibre-rich fraction of the pulp with enzyme, the fibres were recombined with untreated fines for handsheet making and testing. None of the enzymes altered the retention of fines or the consolidation of the furnish mix during handsheet formation. All three enzymes increased tensile stiffness index, which is a measure of the initial resistance of the handsheets to strain. Only the laccase preparation, an enzyme that modifies pulp lignin, consistently increased fibre bonding to enhance other strength properties of the handsheets.

  11. Effect of Light Activation of Pulp-Capping Materials and Resin Composite on Dentin Deformation and the Pulp Temperature Change.

    PubMed

    Soares, C J; Ferreira, M S; Bicalho, A A; de Paula Rodrigues, M; Braga, Ssl; Versluis, A

    2017-10-04

    To analyze the effect of pulp-capping materials and resin composite light activation on strain and temperature development in the pulp and on the interfacial integrity at the pulpal floor/pulp-capping materials in large molar class II cavities. Forty extracted molars received large mesio-occlusal-distal (MOD) cavity bur preparation with 1.0 mm of dentin remaining at the pulp floor. Four pulp-capping materials (self-etching adhesive system, Clearfil SE Bond [CLE], Kuraray), two light-curing calcium hydroxide cements (BioCal [BIO], Biodinâmica, and Ultra-Blend Plus [ULT], Ultradent), and a resin-modified glass ionomer cement- (Vitrebond [VIT], 3M ESPE) were applied on the pulpal floor. The cavities were incrementally restored with resin composite (Filtek Z350 XT, 3M ESPE). Thermocouple (n=10) and strain gauge (n=10) were placed inside the pulp chamber in contact with the top of the pulpal floor to detect temperature changes and dentin strain during light curing of the pulp-capping materials and during resin composite restoration. Exotherm was calculated by subtracting postcure from polymerization temperature (n=10). Interface integrity at the pulpal floor was investigated using micro-CT (SkyScan 1272, Bruker). The degree of cure of capping materials was calculated using the Fourier transform infrared and attenuated total reflectance cell. Data were analyzed using one-way analysis of variance followed by the Tukey test (α=0.05). Pulpal dentin strains (μs) during light curing of CLE were higher than for other pulp-capping materials (p<0.001). During resin composite light activation, the pulpal dentin strain increased for ULT, VIT, and CLE and decreased for BIO. The pulpal dentin strain was significantly higher during pulp-capping light activation. The temperature inside the pulp chamber increased approximately 3.5°C after light curing the pulp-capping materials and approximately 2.1°C after final restoration. Pulp-capping material type had no influence temperature

  12. Preliminary study on dental pulp stem cell-mediated pulp regeneration in canine immature permanent teeth.

    PubMed

    Wang, Yuanyuan; Zhao, Yuming; Jia, Weiqian; Yang, Jie; Ge, Lihong

    2013-02-01

    The health of human teeth depends on the integrity of the hard tissue and the activity of the pulp and periodontal tissues, which are responsible for nutritional supply. Without the nourishing of the pulp tissue, the possibility of tooth fracture can increase. In immature permanent teeth, root development may be influenced as well. This study explored the potential of using autologous dental pulp stem cells (DPSCs) to achieve pulp regeneration in a canine pulpless model. The establishment of the pulpless animal model involved pulp extirpation and root canal preparation of young permanent incisor teeth in beagles. Autologous DPSCs were obtained from extracted first molars and expanded ex vivo to obtain a larger number of cells. The biological characteristics of canine DPSCs (cDPSCs) were analyzed both in vitro and in vivo by using the same method as used in human DPSCs. cDPSCs were transplanted into the pulpless root canal with Gelfoam as the scaffold, and root development was evaluated by radiographic and histologic analyses. cDPSCs with rapid proliferation, multiple differentiation capacity, and development potential were successfully isolated and identified both in vitro and in vivo. After they were transplanted into the pulpless root canal with Gelfoam as the scaffold, DPSCs were capable of generating pulp-like tissues containing blood vessels and dentin-like tissue. Thickening of the root canal wall was also observed. This study demonstrates the feasibility of using stem cell-mediated tissue engineering to realize pulp regeneration in immature teeth. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

    PubMed Central

    Lee, Y. H.; Nair, S.; Rousseau, E.; Tataranni, P. A.; Bogardus, C.; Allison, D. B.; Page, G. P.

    2006-01-01

    Aims/hypothesis: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. Methods: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25±3 kg/m2) and 19 obese (BMI 55± 8 kg/m2) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. Results: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1α. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. Conclusions/interpretation: This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity. PMID:16059715

  14. In utero and postnatal exposure to a phytoestrogen-enriched diet increases parameters of acute inflammation in a rat model of TNBS-induced colitis.

    PubMed

    Seibel, Jan; Molzberger, Almut F; Hertrampf, Torsten; Laudenbach-Leschowski, Ute; Degen, Gisela H; Diel, Patrick

    2008-12-01

    Inflammatory bowel disease (IBD) is very common in Europe and USA. Its incidence in East Asia has been traditionally low, albeit the risk of IBD increases in Asian immigrants adopting western lifestyles, suggesting a strong role of environmental/dietary factors in IBD. A lifelong exposure to phytoestrogen-rich diets has been associated with a decreased risk of developing breast cancer and might also be protective against IBD. We studied the influence of in utero and postnatal exposure to a phytoestrogen (PE)-rich diet on acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were exposed in utero and postnatally to high (genistein: 240 microg/g feed; daidzein: 232 microg/g feed) or very low levels (genistein and daidzein <10 microg/g feed) of phytoestrogen isoflavones fed to pregnant dams with the diet and throughout nursing. After weaning, the offspring had free access to these diets. At the age of 11 weeks, colitis was induced with an enema of TNBS. After 3 days, animals were sacrificed and tissues were collected for histological evaluation and analysis of molecular markers of inflammation. Animals kept on a PE-rich diet (PRD) had higher colon weights than animals on low PE-levels (PDD), suggesting enhanced acute inflammation by phytoestrogens. This result was supported by histological findings and by analysis of myeloperoxidase activity. Interestingly, relative mRNA and protein expression of cyclooxygenase-2 (COX-2) were modulated in rats on PRD, providing evidence that COX-2, the inducible isoform of the enzyme, is involved in the management of colonic inflammation. Our results suggest that early-in-life exposure to PE might not protect against the development of IBD but enhances the extent of acute inflammation.

  15. The treatment of nonunions with application of BMP-7 increases the expression pattern for angiogenic and inflammable cytokines: a matched pair analysis

    PubMed Central

    Haubruck, Patrick; Kammerer, Andreas; Korff, Sebastian; Apitz, Philipp; Xiao, Kai; Büchler, Axel; Biglari, Bahram; Zimmermann, Gerald; Daniel, Volker; Schmidmaier, Gerhard; Moghaddam, Arash

    2016-01-01

    The local application of bone morphogenetic protein-7 (BMP-7) in combination with the transplantation of autologous bone graft improves the outcome in nonunion treatment; however, the specific reasons remain unclear. In this study, we sought to determine if the local application of BMP-7 contributes to improved bone regeneration in nonunion therapy by modulation of the angiogenic and inflammable cytokine expression patterns of the early inflammation response. Therefore, we utilized the analysis of serological cytokine expression patterns. As a matched pair analysis, best-fitting patients who were treated with transplantation of autologous bone graft (G1, n=10) were compared with patients who were treated with additional application of BMP-7 (G2, n=10). The changes in the cytokine expression patterns were monitored and correlated to clinical data of bone healing. Significant differences in angiogenesis potential (vascular endothelial growth factor [VEGF] serum levels) could be found in the first days after surgery (P<0.05). Furthermore, the increase and absolute amount of VEGF levels in the BMP-7 group were considerably higher than in the control group during the first 2 weeks after surgery. The expression pattern of inflammable cytokines showed noticeable differences in the time point of significant elevated levels, in particular, inflammable cytokines showed an earlier peak in G2. Furthermore, interleukin-6 was significantly elevated within the first week only, comparing G2 to G1 (P<0.05). Our findings indicate that BMP-7 induces an early and more intense expression of VEGF via a direct and postulated indirect pathway, thereby providing a favorable environment for bone healing. Moreover, application of BMP-7 leads to an earlier expression of known proinflammatory cytokines. The results of this study show that application of BMP-7 leads to costimulatory effect on both angiogenic and inflammable cytokine expression patterns that may serve as a possible stimulus for

  16. Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats.

    PubMed

    Asghar, Mohammad; Monjok, Emmanuel; Kouamou, Ghislaine; Ohia, Sunny E; Bagchi, Debasis; Lokhandwala, Mustafa F

    2007-10-01

    Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (-)-hydroxycitric acid extracted from the dried fruit rind of the plant Garcinia cambogia, and commonly consumed as weight loss dietary supplement. In the present study, we investigated the effect of HCA-SX on inflammation, oxidative stress and insulin resistance in developing obese Zucker rats, an animal model of type II diabetes associated with inflammation and oxidative stress. Male Zucker rats (5-week old) were supplemented with vehicle (control) and HCA-SX in drinking water for 7 weeks. Oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (DNPH), and protein tyrosine nitration (tyr-NO(2)) were measured in the liver and kidney tissues using biochemical and immunoblotting techniques. Compared to controls, the levels of MDA, DNPH and tyr-NO(2) were lower in the liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive protein and interleukin-6, markers of inflammation measured by ELISA, were lower in the plasma of HCA-SX-supplemented animals compared to controls, as were levels of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin resistance did not develop in HCA-SX-supplemented rats. Food-intake and body weight gain was also lower in rats supplemented with HCA-SX compared to their control counterparts. These results suggest that HCA-SX supplementation in obese Zucker rats reduces food-intake, body weight gain, and also attenuates the increases in inflammation, oxidative stress, and insulin resistance observed in untreated animals. Therefore, HCA-SX may be used as an intervention to overcome obesity-related complications, including inflammation, oxidative stress, and insulin resistance.

  17. [Coffee hulls and pulp. XII. Effect of storage of coffee pulp on its nutritive value for calves].

    PubMed

    Cabezas, M T; Estrada, E; Murillo, B; González, J M; Bressani, R

    1976-06-01

    Coffee pulp, dehydrated and stored for 7, 13 and 17 months or ensiled for 4, 10 and 14 months, was studied in calves with a rapid growing rate. Storage of dehydrated coffee pulp did not affect its chemical composition, but ensiling reduced crude fiber and increased its nitrogen free extract content after 10 and 14 months. Three growth trials were carried out with Holstein calves averaging 95 kg in the first and second trials, and 130 kg in the third. Eighteen calves were used in the first trial and 24 in each of the other two. In each trial the animals were divided into three equal groups and randomly assigned to one of the following treatments: control, which contained 48% cottonseed hulls, and the other two, with 30% dehydrated coffee pulp or 30% ensiled coffee pulp. Basically, the difference between trials consisted in the time of storage or ensiling of coffee pulp. In all trials, weight gains of calves fed coffee pulp (1.00, 0.90 and 0.98 kg/day, and 1.06, 0.94 and 1.08 kg/day, respectively) were significantly lower (P less than 0.05) than the weight gains induced by the control ration (1.21, 1.08 and 1.19 kg/day). Feed intake was also lower, but feed conversion ratio was higher for those rations containing coffee pulp. Calf performance was better with ensiled than with deydrated coffee pulp, particularly in the third trial, where the differences in weight gains were significantly higher (P less than 0.05). It is concluded that storage time does not change nutritive value of coffee pulp; and the ensiling is an adequate process for storing pulp during coffee harvesting, and, possibly also, for improving its nutritive value.

  18. 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

  19. Increases in transient receptor potential vanilloid-1 mRNA and protein in primary afferent neurons stimulated by protein kinase C and their possible role in neurogenic inflammation

    PubMed Central

    Xu, Xijin; Wang, Peng; Zou, Xiaoju; Li, Dingge; Fang, Li; Lin, Qing

    2008-01-01

    A recent study by our group demonstrates pharmacologically that the transient receptor potential vanilloid-1 (TRPV1) is activated by intradermal injection of capsaicin to initiate neurogenic inflammation by the release of neuropeptides in the periphery. In this study, expression of TRPV1, phosphorylated protein kinase C (p-PKC) and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons were visualized using immunofluorescence, real-time PCR and Western blots to examine whether increases in TRPV1 mRNA and protein levels evoked by capsaicin injection are subject to modulation by the activation of PKC and to analyze the role of this process in the pathogenesis of neurogenic inflammation. Capsaicin injection into the hindpaw skin of anesthetized rats evoked increases in the expression of TRPV1, CGRP and p-PKC in mRNA and/or protein levels and in the number of single labeled TRPV1, p-PKC and CGRP neurons in ipsilateral L4–5 DRGs. Co-expressions of TRPV1 with p-PKC and/or CGRP in DRG neurons were also significantly increased after CAP injection. These evoked expressions both at molecular and cellular levels were significantly inhibited after TRPV1 receptors were blocked by 5′-iodoresiniferatoxin (5 μg) or PKC was inhibited by chelerythrine chloride (5 μg). Taken together, these results provide evidence that up-regulation of TRPV1 mRNA and protein levels under inflammatory conditions evoked by capsaicin injection is subject to modulation by the PKC cascade in which increased CGRP level in DRG neurons may be related to the initiation of neurogenic inflammation. Thus, up-regulation of TRPV1 receptors in DRG neurons seems critical for initiating acute neurogenic inflammation. PMID:18752301

  20. 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.

  1. 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

  2. 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.

  3. Effect of low-level laser therapy (λ780 nm) on the mechanically damaged dentin-pulp complex in a model of extrusive luxation in rat incisors.

    PubMed

    de Santana, Dandara Andrade; Fonseca, Gabriela Ferraz; Ramalho, Luciana Maria Pedreira; Rodriguez, Tânia Tavares; Aguiar, Marcio Cajazeira

    2017-08-19

    In order to regenerate the dental pulp, many strategies have been developed as phototherapy. In the pulp repair, we do not know if gallium-aluminum-arsenide (GaAlAs) laser preserves the primary odontoblasts or stimulates the formation of more dentin matrix when dental pulp is damaged. The aim of the present study was to examine the effect of laser phototherapy (λ780 nm) on vascularization, inflammation, density of the primary odontoblast layer, and formation of reactionary and reparative dentin in the dental pulp by provoking extrusion of the rat incisor. The upper incisors were extruded 3 mm and then repositioned into their original sockets followed by a laser irradiation of the palatal mucosa (λ = 780 nm; p = 70 mW; CW; 4.2 J/cm(2); 60 s) every 48 h. Non-traumatized and/or non-irradiated incisors were used as the controls. At 8 and 30 days after surgery, incisors were processed for histological and histomorphometric analysis. Morphological analysis revealed no differences in vascularization between groups, but showed discrete inflammation in some non-irradiated and injured specimens, which correlated with a more irregular reparative dentin. The density of primary odontoblasts in the groups treated with lasers was higher when compared to non-irradiated groups, but no statistically significant difference between groups (p > 0.05). The thickness of the tertiary dentin was increased in both traumatized groups with no statistically significant difference between non-irradiated and irradiated groups (p > 0.05).The present findings revealed that the GaAlAs laser induced small changes on dentin-pulp complex, with more regular dentin matrix in the irradiated dental pulps.

  4. Timber Bamboo Pulp

    Treesearch

    Troy Runge; Carl Houtman; Alberto Negri; Jackie Heinricher

    2013-01-01

    Fast-growing biomass, such as bamboo, has the potential to serve an important future role in the pulp and paper industry with potential to both lower resource costs and improve a product’s sustainability. Moso bamboo is particularly interesting due to its fast growth and size, which allows it to be handled and chipped similarly to wood resources. In this study, we will...

  5. Reducing sugar production of sweet sorghum bagasse kraft pulp

    NASA Astrophysics Data System (ADS)

    Solihat, Nissa Nurfajrin; Fajriutami, Triyani; Adi, Deddy Triyono Nugroho; Fatriasari, Widya; Hermiati, Euis

    2017-01-01

    Kraft pulping of sweet sorghum bagasse (SSB) has been used for effective delignification method for cellulose production. This study was conducted to evaluate the performance pulp kraft of SSB for reducing sugar production. The study intended to investigate the effect of active alkali and sulfidity loading variation of SSB pulp kraft on reducing sugar yield per biomass. The SSB pulp was prepared after pulping using three variations of active alkali (17, 19, and 22%) and sulfidity loading (20, 22, and 24%) at 170°C for 4 h with liquor to wood ratio of 10. A total of 9 pulps were obtained from these pretreatments. Delignification pretreatment has been succesfully removed lignin and hemicellulose more than 90% and 50%, respectively. Increasing active alkali and sulfidity loading has significantly increased lignin removal caused by disruption of the cell wall structure for releasing lignin into black liquor in the cellulose extraction. The enzymatic hydrolysis of pulp was carried out with cellulase loading of 40 FPU per g substrate in the shaking incubator at 50°C and 150 rpm for 78 h. For each 24 h, the reducing sugar yield (DNS assay) has been observed. Even though the lignin and hemicellulose loss occurred along with higher active alkali loading, this condition tends to decrease its yield. The reducing sugar concentration varied between 7-8 g/L. Increasing active alkali and sulfidity was significantly decreased the reducing sugar per biomass. Pulp delignified by 17% active alkali and 20% sulfidity has demonstrated the maximum reducing sugar yield per biomass of 45.57% resulted after 72 h enzymatic hydrolysis. These results indicated that kraft pulping was success to degrade more lignin and hemicellulose content to facilitate the enzyme for breaking down the cellulose into its sugar monomer. A high loss of lignin and hemicellulose are not single factor to improve digestibility of SSB. This sugar has potential for yeast fermented into bioethanol.

  6. Application of high-frequency radio waves to direct pulp capping.

    PubMed

    Handa, Keisuke; Koike, Toshiyuki; Hayashi, Keijiro; Saito, Takashi

    2013-09-01

    In vital pulp therapy such as direct pulp capping, clinical success rates depend on achieving hemostasis in exposed pulp tissue. For hemostasis of exposed pulp tissue, gentle pressure by cotton pellets moistened with sodium hypochlorite is most commonly used. However, more rapid and reliable methods are necessary. Therefore, we focused on high-frequency radio waves (HRW). To evaluate reparative dentin induction by HRW, we used a rat direct pulp capping model and performed hemostasis by using HRW of several strengths, covering the pulp with calcium hydroxide as a direct capping agent. After 14 or 28 days, rats were killed, and reparative dentin and pulp inflammation were investigated histologically. Radio wave-induced hemostasis required less time when compared with the control group. Reparative dentin with regularly arranged dentinal tubules was observed in the HRW group. HRW induce hemostasis and produce high-quality reparative dentin and reduced pulpal inflammation. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Anti-TNF-alpha immunotherapy is associated with increased gingival inflammation without clinical attachment loss in subjects with rheumatoid arthritis.

    PubMed

    Pers, Jacques-Olivier; Saraux, Alain; Pierre, Roselyne; Youinou, Pierre

    2008-09-01

    Because periodontitis presents many similarities with rheumatoid arthritis (RA) with regard to tumor necrosis factor-alpha (TNF-alpha)-induced bone resorption, the benefits of TNF-alpha blockade in RA prompted us to determine its efficacy in treating coexisting periodontitis. Periodontal status was evaluated in 40 subjects with RA who were divided into two groups: Group I contained 20 subjects who had received infliximab every 6 weeks for > or =22 months at the time of periodontal evaluation. The 20 subjects in group II were evaluated before their first infusion with infliximab. Nine subjects in group II had periodontitis. These subjects were reevaluated after they received nine infusions of infliximab. Infliximab tended to aggravate gingival inflammation as indicated by differences in the modified gingival and papillary bleeding indices between subjects in groups I and II with coexisting periodontitis before and after treatment. Methotrexate had no effect on periodontal status. Although the plaque index revealed that bacterial infection persisted, the probing depth was equal in groups I and II and equivalent before and after treatment in subjects with periodontitis, whereas attachment loss was decreased after infliximab treatment. Inflammation and destruction constitute two interrelated yet separate components of periodontitis in patients with RA. Therefore, TNF-alpha blockade could be beneficial in the treatment of periodontitis.

  8. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. A comparative study on dental pulp response to calcium hydroxide, white and grey mineral trioxide aggregate as pulp capping agents.

    PubMed

    Eskandarizadeh, Ali; Shahpasandzadeh, Mohammad Hossein; Shahpasandzadeh, Mahdieh; Torabi, Molok; Parirokh, Masoud

    2011-10-01

    Vital pulp therapy has been known as one of the treatment options to preserve pulp after being exposed by trauma or caries. To investigate human pulpal response to white and grey mineral trioxide aggregate (WMTA, GMTA) and Dycal (MTA) as pulp capping agents. Human volunteers were participated in this randomized clinical trial. This study was conducted on 90 intact first and second premolars of human maxillary and mandibular teeth. The teeth were randomly assigned into three groups of 30 each. Under local anesthesia, teeth were exposed and capped either with GMTA, WMTA, or Dycal. After 30, 60, and 90 days 10 teeth of each group were extracted and prepared for histologic observation. Histopathologic data were analyzed by χ(2), Kruskal Wallis and Mann Whitney tests. the calcified bridge in teeth that were capped with GMTA was significantly thicker than Dycal at 30 and 60 days (P= 0.015 and P=0.002, respectively); whereas WMTA showed significantly thicker calcified bridge than Dycal at 90 days (P=0.02). In addition, GMTA specimens showed significantly less inflammation compared to Dycal samples at 90 days interval (P=0.019). No significant difference was found between GMTA and WMTA in terms of calcified bridge thickness and pulp inflammatory response to the capping materials (P>0.05). Based on the result of this study, both types of MTA can be suggested as the materials of choice for direct pulp capping procedure instead of Dycal as hard setting calcium hydroxide cement.

  10. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-05-01

    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. 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. 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%). 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 inflammation and insulin resistance in mice as

  12. 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

  13. Molecular, cellular, and behavioral changes associated with pathological pain signaling occur after dental pulp injury

    PubMed Central

    Lee, Caroline S; Ramsey, Austin A; De Brito-Gariepy, Helaine; Michot, Benoit; Podborits, Eugene; Melnyk, Janet

    2017-01-01

    Persistent pain can occur after routine dental treatments in which the dental pulp is injured. To better understand pain chronicity after pulp injury, we assessed whether dental pulp injury in mice causes changes to the sensory nervous system associated with pathological pain. In some experiments, we compared findings after dental pulp injury to a model of orofacial neuropathic pain, in which the mental nerve is injured. After unilateral dental pulp injury, we observed increased expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY) mRNA and decreased tachykinin precursor 1 gene expression, in the ipsilateral trigeminal ganglion. We also observed an ipsilateral increase in the number of trigeminal neurons expressing immunoreactivity for ATF3, a decrease in substance P (SP) immunoreactive cells, and no change in the number of cells labeled with IB4. Mice with dental pulp injury transiently exhibit hindpaw mechanical allodynia, out to 12 days, while mice with mental nerve injury have persistent hindpaw allodynia. Mice with dental pulp injury increased spontaneous consumption of a sucrose solution for 17 days while mental nerve injury mice did not. Finally, after dental pulp injury, an increase in expression of the glial markers Iba1 and glial fibrillary acidic protein occurs in the transition zone between nucleus caudalis and interpolaris, ipsilateral to the injury. Collectively these studies suggest that dental pulp injury is associated with significant neuroplasticity that could contribute to persistent pain after of dental pulp injury. PMID:28580829

  14. Influence of dimethyl formamide pulping of bagasse on pulp properties.

    PubMed

    Rezayati-Charani, P; Mohammadi-Rovshandeh, J; Hashemi, S J; Kazemi-Najafi, S

    2006-12-01

    Organosolv pulping of bagasse was conducted following a central composite design using a two-level factorial plan involving three pulping variables (temperature: 190-210 degrees C, time: 120-180 min, organic solvent charge: 40-60% dimethyl formamide). Responses of pulp properties (yield and holocellulose, alpha-cellulose, kappa number, ash and ethanol-dichloromethane extractives contents) and the pH of the resulting wastewater to the process variables were analyzed using statistical software (MINITAB). Main factor analysis revealed that optimum pulp has the following characteristics: 82.7% (yield), 92.9 (kappa number), 95.84% (holocellulose), 83.53% (alpha-cellulose), 1.403% (ash), 2.562% (ethanol-dichloromethane extractives contents) and 6.39 (pH). These results showed that acceptable properties of pulps could be gained at 200-210 degrees C for 150 min and 40-60% DMF. Based on these results, this method could be used for pulping of bagasse equivalent NSSC concerning high yield at a fixed kappa number. In addition, bagasse could be pulped with ease to approximately 55% yield with a kappa number approximately 31. Numerical analyses showed that cooking temperature had the greatest influence on properties of obtained pulps within the DMF concentrations and cooking time as cooking variables.

  15. 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

  16. 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.

  17. Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration.

    PubMed

    Saghiri, Mohammad Ali; Asatourian, Armen; Sorenson, Christine M; Sheibani, Nader

    2015-06-01

    Dental pulp regeneration is a part of regenerative endodontics, which includes isolation, propagation, and re-transplantation of stem cells inside the prepared root canal space. The formation of new blood vessels through angiogenesis is mandatory to increase the survival rate of re-transplanted tissues. Angiogenesis is defined as the formation of new blood vessels from preexisting capillaries, which has great importance in pulp regeneration and homeostasis. Here the contribution of human dental pulp stem cells and proangiogenic and antiangiogenic factors to angiogenesis process and regeneration of dental pulp is reviewed. A search was performed on the role of angiogenesis in dental pulp regeneration from January 2005 through April 2014. The recent aspects of the relationship between angiogenesis, human dental pulp stem cells, and proangiogenic and antiangiogenic factors in regeneration of dental pulp were assessed. Many studies have indicated an intimate relationship between angiogenesis and dental pulp regeneration. The contribution of stem cells and mechanical and chemical factors to dental pulp regeneration has been previously discussed. Angiogenesis is an indispensable process during dental pulp regeneration. The survival of inflamed vital pulp and engineered transplanted pulp tissue are closely linked to the process of angiogenesis at sites of application. However, the detailed regulatory mechanisms involved in initiation and progression of angiogenesis in pulp tissue require investigation. Published by Elsevier Inc.

  18. Role of Angiogenesis in Endodontics: Contributions of Stem Cells and Proangiogenic and Antiangiogenic Factors to Dental Pulp Regeneration

    PubMed Central

    Saghiri, Mohammad Ali; Asatourian, Armen; Sorenson, Christine M.; Sheibani, Nader

    2016-01-01

    Introduction Dental pulp regeneration is a part of regenerative endodontics, which includes isolation, propagation, and re-transplantation of stem cells inside the prepared root canal space. The formation of new blood vessels through angiogenesis is mandatory to increase the survival rate of re-transplanted tissues. Angiogenesis is defined as the formation of new blood vessels from preexisting capillaries, which has great importance in pulp regeneration and homeostasis. Here the contribution of human dental pulp stem cells and proangiogenic and antiangiogenic factors to angiogenesis process and regeneration of dental pulp is reviewed. Methods A search was performed on the role of angiogenesis in dental pulp regeneration from January 2005 through April 2014. The recent aspects of the relationship between angiogenesis, human dental pulp stem cells, and proangiogenic and antiangiogenic factors in regeneration of dental pulp were assessed. Results Many studies have indicated an intimate relationship between angiogenesis and dental pulp regeneration. The contribution of stem cells and mechanical and chemical factors to dental pulp regeneration has been previously discussed. Conclusions Angiogenesis is an indispensable process during dental pulp regeneration. The survival of inflamed vital pulp and engineered transplanted pulp tissue are closely linked to the process of angiogenesis at sites of application. However, the detailed regulatory mechanisms involved in initiation and progression of angiogenesis in pulp tissue require investigation. PMID:25649306

  19. Pulp response to dentine adhesives: A study on mature human pulps

    PubMed Central

    Kouros, Pantelis; Koliniotou-Koumpia, Eugenia; Koulaouzidou, Elisabeth; Helvatjoglu-Antoniades, Maria; Tziafas, Dimitrios

    2013-01-01

    Objective: To clinically investigate the antibacterial effects of a commercially available self-etch 12-methacryloyloxy- dodecylpyridinium bromide (MDPB)-containing adhesive system in comparison with its respective non-MDPB-containing adhesive and to evaluate the pulp responses when in use on human teeth. Materials and Methods: Sixty-two viable human teeth scheduled for extraction were used. Class V cavities were prepared on the buccal surfaces of the teeth and filled with the tested materials (Protect Bond/Clearfil AP-X, SE Bond/Clearfil AP-X and Dycal/Ketac Fill Plus) as a control group, according to manufacturer's recommendations. Randomly divided to two groups teeth remained intra-orally for 4 and 8 weeks. After extraction, teeth were decalcified, sectioned and stained using the Mayer's hematoxylin and eosin, and modified Brown-Brenn's technique. Pulp responses were evaluated microscopically under a microscope and remaining dentine thickness measured under a stereomicroscope. Results: No statistically significant differences regarding pulp inflammation or bacterial infiltration were found either for the materials tested or for periods of post-operative evaluation. Conclusions: The results suggested that for a short period of evaluation there are no quantitative differences, regardless to restoring material used. PMID:24966725

  20. 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.

  1. Trends and guidelines in water pollution control in the Finnish pulp and paper industry

    SciTech Connect

    Junna, J. ); Ruonala, S. )

    1991-07-01

    There are about 50 paper and pulp mills in Finland. In this paper, their production capacities in 1988 are illustrated. Pulp and paper production has increased quite rapidly during the last few decades. The greatest increase incurred in the production of bleached kraft pulp and mechanical pulp. The production of sulfite pulp has decreased during recent years. Within paper the production of printing papers has had the biggest increase. Estimates predict that the production capacity of the finish pulp and paper industry will show an average increase of 4% per year by the middle of this decade. Final production in 1987 and one estimate of production in 1992 are given. Wastewater loadings per production output are decreasing.

  2. Increased expression of inflammation-related genes in cultured preadipocytes/stromal vascular cells from obese compared with non-obese Pima Indians

    PubMed Central

    Lee, Y. H.; Rousseau, E.; Tataranni, P. A.; Baier, L. J.; Bogardus, C.; Cam, M.; Permana, P. A.

    2006-01-01

    Aims/hypothesis: The specific contributions made by the various cell types in adipose tissue to obesity, particularly obesity-related inflammation, need to be clarified. The aim of this study was to elucidate the potential role of adipocyte precursor cells (preadipocytes/stromal vascular cells [SVC]). Methods: We performed Affymetrix oligonucleotide microarray expression profiling of cultured abdominal subcutaneous preadipocytes/SVC isolated from the adipose tissue of 14 non-obese (BMI 25±4 kg/m2) and 14 obese (55±8 kg/m2) non-diabetic Pima Indian subjects. Quantitative real-time PCR (RT-PCR) was used to verify the differential expression of several genes in an independent group of subjects. Results: We identified 218 differentially expressed genes with p values less than 0.01. Microarray expression profiling revealed that the expression of inflammation-related genes was significantly upregulated in preadipocytes/SVC of obese individuals. Quantitative RT-PCR confirmed the upregulation of IL8, CTSS, ITGB2, HLA-DRA, CD53, PLA2G7 and MMP9 in preadipocytes/SVC of obese subjects. Conclusions/interpretation: The upregulation of inflammation-related genes in preadipocytes/SVC of obese subjects may increase the recruitment of immune cells into adipose tissue and may also result in changes in the extracellular matrix (tissue remodelling) to accommodate adipose tissue expansion in obesity. PMID:16034612

  3. Ethanol-Induced Mast Cell-Mediated Inflammation Leads to Increased Susceptibility of Intestinal Tumorigenesis in the APC Δ468 Min Mouse Model of Colon Cancer

    PubMed Central

    Wimberly, Andre L.; Forsyth, Christopher B.; Khan, Mohammad Wasim; Pemberton, Alan; Khazaie, Khashayarsha; Keshavarzian, Ali

    2013-01-01

    Background Chronic and frequent ethanol (EtOH) intake has been associated with an increased incidence of several types of cancers including breast, mouth, throat, esophageal, stomach and colorectal (CRC). The underlying mechanism of this deleterious carcinogenic effect of alcohol has not been clearly established but inflammation may be one unifying feature of these cancers. We have recently shown that intestinal mast cells play a central role in intestinal carcinogenesis. In this study, we tested our hypothesis that mast cell-mediated inflammation is one underlying mechanism by which chronic alcohol promotes intestinal tumorigenesis. Methods APC Δ468 mice were fed either an alcohol containing Nanji liquid diet or isocaloric dextrose containing Nanji diet for 10 weeks and then sacrificed to collect small and large intestine samples. Assessments of tumor number and size as well as mast cell number and mast cell activity and histology score for invasion were compared between Control (dextrose fed) and Alcohol fed APCΔ468 mice. The effect of alcohol on mast cell mediated tumor migration was also assessed using an in vitro migration assay. Results Alcohol feeding increased both polyp number and size within both the small and large intestines of APCΔ468 mice. Only alcohol fed mice showed evidence of tumor invasion. Chronic alcohol feeding also resulted in an increased mast cell number and activity in tumor stroma and invading borders. In vitro migration assay showed that alcohol significantly increases mast cell mediated tumor migration in vitro. Conclusions Our data show that chronic alcohol intake promotes: (1) intestinal tumorigenesis and tumor invasion in genetically susceptible mice; (2) increases in polyp associated mast cells; (3) mast cell mediated tumor migration in vitro. Both our in vivo and in vitro studies suggest that mast cell mediated inflammation could be one mechanism by which alcohol promotes carcinogenesis. PMID:23320800

  4. Ethanol-induced mast cell-mediated inflammation leads to increased susceptibility of intestinal tumorigenesis in the APC Δ468 min mouse model of colon cancer.

    PubMed

    Wimberly, Andre L; Forsyth, Christopher B; Khan, Mohammad W; Pemberton, Alan; Khazaie, Khashayarsha; Keshavarzian, Ali

    2013-01-01

    Chronic and frequent alcohol (ethanol [EtOH]) intake has been associated with an increased incidence of several types of cancers including breast, mouth, throat, esophageal, stomach, and colorectal (CRC). The underlying mechanism of this deleterious carcinogenic effect of alcohol has not been clearly established but inflammation may be 1 unifying feature of these cancers. We have recently shown that intestinal mast cells play a central role in intestinal carcinogenesis. In this study, we tested our hypothesis that mast cell-mediated inflammation is 1 underlying mechanism by which chronic alcohol promotes intestinal tumorigenesis. APC(Δ468) mice were fed either an alcohol-containing Nanji liquid diet or isocaloric dextrose-containing Nanji diet for 10 weeks and then sacrificed to collect small and large intestine samples. Assessments of tumor number and size as well as mast cell number and mast cell activity and histology score for invasion were compared between Control (dextrose-fed) and alcohol-fed APC(∆468) mice. The effect of alcohol on mast cell-mediated tumor migration was also assessed using an in vitro migration assay. Alcohol feeding increased both polyp number and size within both the small and the large intestines of APC(∆468) mice. Only alcohol-fed mice showed evidence of tumor invasion. Chronic alcohol feeding also resulted in an increased mast cell number and activity in tumor stroma and invading borders. In vitro migration assay showed that alcohol significantly increases mast cell-mediated tumor migration in vitro. Our data show that chronic alcohol intake promotes: (i) intestinal tumorigenesis and tumor invasion in genetically susceptible mice; (ii) increases in polyp-associated mast cells; and (iii) mast cell-mediated tumor migration in vitro. Both our in vivo and in vitro studies suggest that mast cell-mediated inflammation could be 1 mechanism by which alcohol promotes carcinogenesis. Copyright © 2012 by the Research Society on Alcoholism.

  5. Kynurenine, by activating aryl hydrocarbon receptor, decreases erythropoietin and increases hepcidin production in HepG2 cells: A new mechanism for anemia of inflammation.

    PubMed

    Eleftheriadis, Theodoros; Pissas, Georgios; Antoniadi, Georgia; Liakopoulos, Vassilios; Stefanidis, Ioannis

    2016-01-01

    It is known that inadequate erythropoietin (EPO) production contributes to the pathogenesis of anemia of inflammation, although the exact molecular mechanism is unknown. Aryl hydrocarbon receptor (AhR) may compete with hypoxia-inducible factor 2α (HIF-2α), the master regulator of EPO production, for binding with HIF-1β. The effect of kynurenine, an endogenous AhR activator that increases in inflammation, on EPO and hepcidin production was evaluated. HepG2 cells were treated with the hypoxia mimetic CoCl2, kynurenine, the AhR inhibitor CH223191, and combinations of these. EPO and hepcidin production was measured with enzyme-linked immunosorbent assay. HIF-2α and CYP1A1 levels, a transcriptional target of AhR, were assessed by Western blotting. CoCl2 increased EPO production and decreased hepcidin and CYP1A1. Kynurenine exerted the opposite effects. Wherever CH223191 was added, the inhibitor overcorrected kynurenine-induced alterations in both the presence and the absence of CoCl2. Also, treatment with CH223191 alone increased EPO and decreased hepcidin, indicating that there is a degree of constitutive AhR activation, possibly by other endogenous AhR activators. In conclusion, kynurenine, by competing with HIF-2α, may contribute to anemia of inflammation by decreasing EPO and increasing hepcidin production. The fact that inactivation of AhR alone induces EPO makes this transcription factor a potential therapeutic target in situations that require increased EPO. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  6. Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

    PubMed

    Heerwagen, Margaret J R; Stewart, Michael S; de la Houssaye, Becky A; Janssen, Rachel C; Friedman, Jacob E

    2013-01-01

    Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r = 0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that

  7. Transgenic Increase in N-3/N-6 Fatty Acid Ratio Reduces Maternal Obesity-Associated Inflammation and Limits Adverse Developmental Programming in Mice

    PubMed Central

    Heerwagen, Margaret J. R.; Stewart, Michael S.; de la Houssaye, Becky A.; Janssen, Rachel C.; Friedman, Jacob E.

    2013-01-01

    Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r = 0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that

  8. Dissolving pulp industry : market trends

    Treesearch

    Irene. Durbak

    1993-01-01

    This report presents a worldwide overview of the dissolving pulp industry and highlights of this industry in Alaska. It describes trends in world markets and major end-use markets, with special emphasis on the manufacture and use of textile fibers in the United States. Figures and tables present data on production, consumption, and trade of dissolving pulp and the...

  9. [Dental pulp diseases. Ultramicroscopic studies].

    PubMed

    Conversini, A; Eramo, S; Manna, M G; Negri, P

    1998-12-01

    After the description of the anatomic and histologic aspects of the healthy dental pulp, stress is laid on pulpal pathologies and on the use of ultramicroscopic techniques to analyze the cytologic modifications in normal and pathologic dental pulp tissues. The results obtained are presented.

  10. Effect of Pioglitazone and Ramipril on Biomarkers of Low-Grade Inflammation and Vascular Function in Nondiabetic Patients with Increased Cardiovascular Risk and an Activated Inflammation: Results from the PIOace Study

    PubMed Central

    Pfützner, Andreas; Hanefeld, Markolf; Dekordi, Lida A; Müller, Jürgen; Kleine, Iris; Fuchs, Winfried; Forst, Thomas

    2011-01-01

    Aims This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk. Methods and Results Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m2, duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (−0.89 ± 1.98 mg/liter; -25%) and PIRA (−0.49 ± 2.11 mg/liter; -16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 ± 1.39 (−29%)/0.15 ± 1.03 (+5%)/ -1.44 ± 2.83 (−40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metallo-proteinase-9: -48 ± 127 (−12%)/-1 ± 224 (0%)/-60 ± 210 ng/ml (−13%), p < .05 for RAM vs PIO or PIRA in all cases]. Conclusions Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials. PMID:21880242

  11. Amino acid derivative-mediated detoxification and functionalization of dual cure dental restorative material for dental pulp cell mineralization.

    PubMed

    Minamikawa, Hajime; Yamada, Masahiro; Iwasa, Fuminori; Ueno, Takeshi; Deyama, Yoshiaki; Suzuki, Kuniaki; Yawaka, Yasutaka; Ogawa, Takahiro

    2010-10-01

    Current dental restorative materials are only used to fill the defect of hard tissues, such as dentin and enamel, because of their cytotoxicity. Therefore, exposed dental pulp tissues in deep cavities must be first covered by a pulp capping material like calcium hydroxide to form a layer of mineralized tissue. However, this tissue mineralization is based on pathological reaction and triggers long-lasting inflammation, often causing clinical problems. This study tested the ability of N-acetyl cysteine (NAC), amino acid derivative, to reduce cytotoxicity and induce mineralized tissue conductivity in resin-modified glass ionomer (RMGI), a widely used dental restorative material having dual cure mechanism. Rat dental pulp cells were cultured on untreated or NAC-supplemented RMGI. NAC supplementation substantially increased the percentage of viable cells from 46.7 to 73.3% after 24-h incubation. Cell attachment, spreading, proliferative activity, and odontoblast-related gene and protein expressions increased significantly on NAC-supplemented RMGI. The mineralization capability of cells, which was nearly suppressed on untreated RMGI, was induced on NAC-supplemented RMGI. These improved behaviors and functions of dental pulp cells on NAC-supplemented RMGI were associated with a considerable reduction in the production of intracellular reactive oxygen species and with the increased level of intracellular glutathione reserves. These results demonstrated that NAC could detoxify and functionalize RMGIs via two different mechanisms involving in situ material detoxification and antioxidant cell protection. We believe that this study provides a new approach for developing dental restorative materials that enables mineralized tissue regeneration.

  12. Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

    PubMed

    Al-Attas, Omar S; Hussain, Tajamul; Ahmed, Mukhtar; Al-Daghri, Nasser; Mohammed, Arif A; De Rosas, Edgard; Gambhir, Dikshit; Sumague, Terrance S

    2015-07-01

    Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

  13. 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

  14. 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.

  15. Simvastatin versus Calcium Hydroxide Direct Pulp Capping of Human Primary Molars: A Randomized Clinical Trial

    PubMed Central

    Asl Aminabadi, Naser; Maljaei, Ensiyeh; Erfanparast, Leila; Ala Aghbali, Amir; Hamishehkar, Hamed; Najafpour, Ebrahim

    2013-01-01

    Background and aims The aim of present study was to investigate pulp-dentin complex reactions following direct pulp capping (DPC) with calcium hydroxide [Ca(OH)2] and simvastatin as pulp-capping materials in the primary human molars. Materials and methods 120 primary molar teeth which had to be extracted for orthodontic reasons were randomly allocated into four groups. Group Ι as a control, underwent DPC with calcium hydroxide. The dental pulp in group ІІ, ІІІ and ІV were directly capped with simvastatin-based materials at concentrations of 1, 5 and 10 µM, respectively. All of the teeth were restored with stainless steel crown. After a mean period of 7.41 months teeth were extracted and processed for histological examination and categorized in terms of hard tissue formation and pulp inflammation. Results Teeth in group I had statistically favorable outcomes in hard tissue formation and pulp inflammation than did the groups ІІ, ІІІ and ІV (P < 0.001). Considering three different concentrations of simvastatin, the result showed a dose dependent trend. Teeth in group ІV showed significantly lower rates of hard tissue formation and higher rates of pulp inflammation and necrosis compared to those of groups ІІ (P < 0.05). Conclusion The findings of this study depicted that healing with no inflammation and hard tissue formation following statin treatment occurs with a lower rate than that with the calcium hydroxide. PMID:23487477

  16. Deletion of Galgt2 (B4Galnt2) Reduces Muscle Growth in Response to Acute Injury and Increases Muscle Inflammation and Pathology in Dystrophin-Deficient Mice

    PubMed Central

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

    2016-01-01

    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

  17. Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species

    PubMed Central

    2010-01-01

    Background Inappropriate responses to normal intestinal bacteria may be involved in the development of Inflammatory Bowel Diseases (IBD, e.g. Crohn's Disease (CD), Ulcerative Colitis (UC)) and variations in the host genome may mediate this process. IL-10 gene-deficient (Il10-/-) mice develop CD-like colitis mainly in the colon, in part due to inappropriate responses to normal intestinal bacteria including Enterococcus strains, and have therefore been used as an animal model of CD. Comprehensive characterization of changes in cecum gene expression levels associated with inflammation in the Il10-/- mouse model has recently been reported. Our aim was to characterize changes in colonic gene expression levels in Il10-/- and C57BL/6J (C57; control) mice resulting from oral bacterial inoculation with 12 Enterococcus faecalis and faecium (EF) strains isolated from calves or poultry, complex intestinal flora (CIF) collected from healthy control mice, or a mixture of the two (EF·CIF). We investigated two hypotheses: (1) that oral inoculation of Il10-/- mice would result in greater and more consistent intestinal inflammation than that observed in Il10-/- mice not receiving this inoculation, and (2) that this inflammation would be associated with changes in colon gene expression levels similar to those previously observed in human studies, and these mice would therefore be an appropriate model for human CD. Results At 12 weeks of age, total RNA extracted from intact colon was hybridized to Agilent 44 k mouse arrays. Differentially expressed genes were identified using linear models for microarray analysis (Bioconductor), and these genes were clustered using GeneSpring GX and Ingenuity Pathways Analysis software. Intestinal inflammation was increased in Il10-/- mice as a result of inoculation, with the strongest effect being in the EF and EF·CIF groups. Genes differentially expressed in Il10-/- mice as a result of EF or EF·CIF inoculation were associated with the following

  18. Response of autotransplanted teeth to electric pulp testing.

    PubMed

    Waikakul, Aurasa; Kasetsuwan, Julalux; Punwutikorn, Jirapun

    2002-08-01

    The purpose of this retrospective study was to assess the results of third molar autotransplantation by using electric pulp testing (EPT) and to determine the correlation of EPT response and bone formation. Fourteen patients with 22 transplanted teeth were studied. The patients had received autotransplantation of third molars and regularly came for follow-up on the third, sixth, ninth, and twelfth months. Postoperative clinical assessment included pain, inflammation of surrounding soft tissues, tooth mobility, and the EPT response. Periapical radiographs were subsequently evaluated during follow-up. The correlation between pulpal response to EPT and bone healing was analyzed. Most of the teeth had normal mobility within 3 months, which corresponded to bone formation. Bone healing at the recipient sites completely occurred within 6 months, and more than 50% had lamina dura. The teeth with EPT response increased to 95% within 12 months. There was no significant association between the EPT response and bone formation. The EPT response subsequently increased with time, and it seemed to be unchanged after 1 year.

  19. Chapter 6: Prehydrolysis Pulping with Fermentation Coproducts

    Treesearch

    T.H. Wegner; C.J. Houtman; A.W. Rudie; B.L. Illman; P.J. Ince; E.M. Bilek; T.W. Jeffries

    2013-01-01

    Although the term “integrateed biorefinery” is new, the concept has long been familiar to the pulp and paper industry, where processes include biomass boilers providing combined heat and power, and byproducts of pulping include turpentine, fatty acids and resin acids. In the dominant kraft (or sulfate) pulping process, dissolved lignin and chemicals from the pulp...

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

    PubMed

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

    2015-04-24

    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 Ser(401)-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

  1. 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

  2. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

    PubMed

    Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

    2014-07-01

    Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

  3. Micro-inflammation characterized by disturbed Treg/Teff balance with increasing sIL-2R in patients with type 2 diabetes.

    PubMed

    Cai, B; Zhang, J; Zhang, M; Li, L; Feng, W; An, Z; Wang, L

    2013-04-01

    Type 2 diabetes mellitus (T2DM) has been gradually considered as a micro- inflammatory disease. To explore the significance of peripheral CD4(+) regulatory T cells and CD4(+) effector T cells in T2DM, we analyzed inflammation, humoral and cellular immune state in patients with T2DM. 118 patients with T2DM without complications and 116 healthy volunteers were included. Serum C-reactive protein (CRP), Complement 3 (C3), Complement 4 (C4), IgG, IgA, IgM, plasma sIL-2 R and peripheral T lymphocyte subsets (including CD4(+)CD25(high) regulatory T cells (Treg) and CD4(+)CD25(low+median) effector T cells (Teff)) were analyzed by rate nephelometry immunoassay, chemiluminescence immunoassay and flow cytometry, respectively. (1) micro-inflammation state in T2DM: Serum CRP, C3, IgA and plasma sIL-2 R were all significantly higher in T2DM than those in healthy control (HC) (all P<0.05). (2) Disturbance of cellular immune in T2DM: Compared with HC, the percentage of peripheral CD3(+)CD4(+)T cells and ratio of CD3(+)CD4(+)T cells to CD3(+)CD8(+)T cells in T2DM were both significantly increased (P<0.05); and the percentage of peripheral CD4(+)CD25(+)T cells, Teff cells increased (P>0.05), Treg cells strikingly decreased in T2DM (P<0.05). A positive correlation between sIL-2R levels and peripheral CD4(+)CD25(+)T cells or Teff cell percentages, as well as a negative correlation between plasma sIL-2 R levels and serum HDL, LDL or CHOL levels in T2DM were shown (all P <0.05). Micro-inflammation state in T2DM was characterized by increased sIL-2 R, elevated CD3(+)CD4(+)T cells and the imbalance of Treg cells and Teff cells, which as one of the pathogeneses took part in inflammation reaction in T2DM. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  4. 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

  5. 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. ...

  6. Effects of topical glucocorticoid medication on collagen biosynthesis in the dental pulp.

    PubMed

    Uitto, V J; Antila, R; Ranta, R

    1975-01-01

    The aim of the study was to observe pulpal collagen synthesis in response to trauma and to glucocorticoid medication. The material consisted of 290 rabbit pulps and 76 human premolar pulps. Collagen synthesis was determined by incubating whole pulps in a medium containing [14C]proline, and measuring the formation of [14C]hydroxyproline. The effect of glucocorticoids was studied in vitro using rabbit pulps. Hydrocortisone and dexamethasone inhibited collagen synthesis, whereas prednisolone had no marked effect. Hydrocortisone was found to inhibit the synthesis of [14C]hydroxyproline in neutral salt soluble and insoluble non-dialyzable collagen fractions. [14C]hydroxyproline in the dialyzable fraction was increased, suggesting that hydrocortisone increased collagen degradation. In the human material, premolar pulps were experimentally exposed and then medicated with capping agents. The contralateral teeth were exposed and capped with other capping materials, in some cases they were left as intact controls. The exposure led to an increase in the collagen synthesis as indicated by increased [14C]hydroxyproline formation and elevated protocollagen proline hydroxylase activity in the pulp. This enzyme activity was suppressed in pulps capped with a glucocorticoid paste. In addition, the collagen synthesis rate was lower in pulps treated with another glucocorticoid containing compound, when compared to pulps capped with a calcium hydroxide preparation.

  7. Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation

    PubMed Central

    Geldenhuys, Sian; Judge, Melinda; Weeden, Clare E.; Waithman, Jason

    2016-01-01

    Skin inflammatory responses in individuals with allergic dermatitis may be suppressed by dietary vitamin D through induction and upregulation of the suppressive activity of regulatory T (TReg) cells. Vitamin D may also promote TReg cell tropism to dermal sites. In the current study, we examined the capacity of dietary vitamin D3 to modulate skin inflammation and the numbers and activity of TReg cells in skin and other sites including lungs, spleen, and blood. In female BALB/c mice, dietary vitamin D3 suppressed the effector phase of a biphasic ear swelling response induced by dinitrofluorobenzene in comparison vitamin D3-deficient female BALB/c mice. Vitamin D3 increased the percentage of TReg (CD3+CD4+CD25+Foxp3+) cells in the skin-draining lymph nodes (SDLN). The suppressive activity of TReg cells in the SDLN, mesenteric lymph nodes, spleen, and blood was upregulated by vitamin D3. However, there was no difference in the expression of the naturally occurring TReg cell marker, neuropilin, nor the expression of CCR4 or CCR10 (skin-tropic chemokine receptors) on TReg cells in skin, SDLN, lungs, and airway-draining lymph nodes. These data suggest that dietary vitamin D3 increased the percentages and suppressive activity of TReg cells in the SDLN, which are poised to suppress dermal inflammation. PMID:27672666

  8. 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

    2014-04-18

    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.

  9. 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

  10. Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice.

    PubMed

    Wu, Chia-Lung; McNeill, Jenna; Goon, Kelsey; Little, Dianne; Kimmerling, Kelly; Huebner, Janet; Kraus, Virginia; Guilak, Farshid

    2017-09-01

    To investigate whether short-term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity. CSF-1R-GFP+ macrophage Fas-induced apoptosis (MaFIA)-transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro-computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured. Macrophage-depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage-depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony-stimulating factor, interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion. Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity. © 2017, American College of Rheumatology.

  11. SGLT2 Expression is increased in Human Diabetic Nephropathy: SGLT2 Inhibition Decreases Renal Lipid Accumulation, Inflammation and the Development of Nephropathy in Diabetic Mice.

    PubMed

    Wang, Xiaoxin X; Levi, Jonathan; Luo, Yuhuan; Myakala, Komuraiah; Herman-Edelstein, Michal; Qiu, Liru; Wang, Dong; Peng, Yingqiong; Grenz, Almut; Lucia, Scott; Dobrinskikh, Evgenia; D'Agati, Vivette D; Koepsell, Hermann; Kopp, Jeffrey B; Rosenberg, Avi; Levi, Moshe

    2017-02-14

    There is very limited human renal sodium gradient dependent glucose transporter protein SGLT2 mRNA and protein expression data reported in the literature. Aim 1 of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice which had no changes in renal SGLT-2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. Aim 2 of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin and urinary thiobarbituric acid-reacting substances (TBARS). SGLT2 inhibition prevented renal lipid accumulation via inhibition of ChREBP-β, LPK, SCD-1 and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation, and expression of p65, TLR4, MCP-1 and OPN. These effects were associated with reduced mesangial expansion, accumulation of extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice.

  12. Urothelial Dysfunction and Increased Suburothelial Inflammation of Urinary Bladder Are Involved in Patients with Upper Urinary Tract Urolithiasis – Clinical and Immunohistochemistry Study

    PubMed Central

    Jiang, Yuan-Hong; Kuo, Hann-Chorng

    2014-01-01

    Objectives To investigate the urothelial dysfunction and inflammation of urinary bladder in patients with upper urinary tract (UUT) urolithiasis through the results of cystoscopic hydrodistension and immunohistochemistry study. Methods Ninety-one patients with UUT urolithiasis underwent cystoscopic hydrodistension before the stone surgery. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and TUNEL (urothelial apoptosis) were performed in 42 patients with glomerulations after hydrodistension, 10 without glomerulations, and 10 controls. Results Of the 91 patients, 62 (68.2%) developed glomerulations after hydrodistension. Lower urinary tract symptoms (LUTS) were present in 53.8% patients, in whom significantly smaller maximal anesthetic bladder capacity (MBC) was noted. Patients with middle or lower 1/3 ureteral stones had a significantly higher glomerulation rate (88.6% vs. 55.4%, p<0.01) and lower MBC (618.4±167.6 vs. 701.2±158.4 ml, p = 0.027) than those with upper 1/3 ureteral or renal stones. Patients with UUT urolithiasis had significantly lower expression of E-cadherin (26.2±14.8 vs. 42.4±16.7) and ZO-1 (5.16±4.02 vs. 11.02±5.66); and higher suburothelial mast cell (13.3±6.8 vs. 1.3±1.2) and apoptotic cell (2.6±2.5 vs. 0.1±0.3) numbers than in controls (all p<0.01). Conclusions Urothelial dysfunction and increased suburothelial inflammation and apoptosis are highly prevalent in the bladders of UUT urolithiasis patients, indicating inflammation cross-talk between UUT and urinary bladder. Patients with UUT urolithiaisis concomitant with LUTS had a smaller MBC, which may explain the presence of irritative bladder symptoms. PMID:25329457

  13. Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3β-Ser(9) phosphorylation in endothelial cells and mouse aortas.

    PubMed

    Song, Kee-Ho; Bae, Sun-Ju; Chang, Jiyeon; Park, Jung-Hyun; Jo, Inho; Cho, Kae Won; Cho, Du-Hyong

    2017-09-30

    Telmisartan, an angiotensin II type 1 receptor blocker (ARB), attenuates hyperglycemia-aggravated vascular inflammation by decreasing IκB kinase β (IKKβ) expression in endothelial cells. Because glycogen synthase 3β (GSK3β) is involved in inflammatory process by regulating nuclear factor-κB (NF-κB) activity, we investigated whether GSK3β mediates telmisartan-ameliorated vascular inflammation in hyperglycemia-treated endothelial cells and high-fat diet (HFD)-fed mice. Telmisartan remarkably induced GSK3β-Ser(9) phosphorylation in hyperglycemia-treated endothelial cells that accompanied a decrease in hyperglycemia-induced NF-κB p65-Ser(536) phosphorylation, vascular cell adhesion molecule-1 (VCAM-1) expression, and THP-1 monocyte adhesion. Ectopic expression of GSK3β-S9A, a constitutively active mutant of GSK3β, significantly restored complete telmisartan-inhibited NF-κB p65-Ser(536) phosphorylation, VCAM-1 expression, and THP-1 monocyte adhesion. In addition, it reversed telmisartan-repressed IKKβ expression. Among the ARB, including losartan and fimasartan, only telmisartan increased GSK3β-Ser(9) phosphorylation, and telmisartan-induced GSK3β-Ser(9) phosphorylation remained unchanged by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist. Finally, in the aortas of HFD-fed mice, telmisartan treatment significantly attenuated HFD-induced upregulation of NF-κB p65-Ser(536) phosphorylation, VCAM-1 expression, and IKKβ expression and downregulation of GSK3β-Ser(9) phosphorylation. Taken together, our findings demonstrated that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by inducing GSK3β-Ser(9) phosphorylation, which consequently inhibits IKKβ expression, NF-κB p65-Ser(536) phosphorylation, and VCAM-1 expression in a PPARγ-independent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

    2015-05-11

    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.

  15. 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

  16. 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

  17. Lymphatic vessels in inflamed human dental pulp.

    PubMed

    Marchetti, C; Piacentini, C; Menghini, P

    1990-01-01

    Investigation has been performed on both the light and electron microscopic characteristics of the lymphatic vessels present in the dental pulp of human teeth which have been affected by serious carious lesions. These conditions provoke a severe inflammatory response resulting in structural and functional modifications of the tissue; increase of the tissue pressure is followed by the need for a more intensive lymphatic drainage. In the inflamed pulps, dilated lymphatic vessels with distended walls and "open junctions" between endothelial cells are detectable. On the other hand they lack certain endothelial structures which characterize the morphology of these vessels under normal conditions. In the pulpal regions affected by fibrotic proliferation shrunken vessels with irregular profiles are present. From these observations it is possible to obtain other information on the mechanisms regulating the lymphatic drainage in different structural and functional conditions of the interstitium.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  19. Conversion of henequen pulp to microbial biomass by submerged fermentation

    SciTech Connect

    Blancas, A.; Alpizar, L.; Larios, G.; Saval, S.; Huitron, C.

    1982-01-01

    Mexico has cellulosic by-products that could be developed as renewable food sources for animal consumption. Sugarcane bagasse and henequen pulp are the most important of these materials because they are abundant, cheap, renewable, and nontoxic, in addition to being underutilized. A significant research and development effort has centered on the production of single-cell protein from sugarcane begasse. Nevertheless, there are no large-scale processes that utilize this substrate as a source of carbon, probably because of the extensive physical or chemical pretreatment that is needed. Henequen pulp is a by-product which is obtained in large amounts in southeastern Mexico in the process of removing fibers from the leaves of agave (sisal). A group has been working on a fermentative process that will increase the protein content of the henequen pulp by microbial conversion. The primary aim is to carry out the conversion without chemical pretreatment of the substrate and without a separation step for cells and residual substrate. A gram-negative cellulolytic bacteria has been isolated which grows well on microcrystalline cellulose, pectin, and xylane and it is able to convert an appreciable fraction of henequen pulp to microbial biomass. In this article, some results on the effect of substrate and nitrogen source concentration, on the protein enrichment of the henequen pulp, as well as the content of essential amino acids of fermented henequen pulp are presented. 4 figures.

  20. Detection of interleukin-8 in exudates from normal and inflamed human dental pulp tissues.

    PubMed

    Guo, X; Niu, Z; Xiao, M; Yue, L; Lu, H

    2000-05-01

    The purpose of this study was to investigate the level of IL-8 in exudates clinically obtained from normal and inflamed human dental pulp tissues so as to reveal the possible relationship between IL-8 and pulpitis. Samples of 2 microliters of pulpal exudate from each normal or clinically diagnosed as acute or chronic pulpitis teeth was obtained by filter paper strips and IL-8 level was measured by ELISA method. No IL-8 was detected in the samples from normal pulp, but significant amount of IL-8 appeared in inflamed pulp tissues, and the level of IL-8 in exudates of acute stage of pulpitis was higher than that of chronic stage (P < 0.01). This study demonstrates that IL-8 is produced and accumulated in pulp inflammation and may play a role in the occurrence and development of human pulpitis.

  1. Pulp development, repair, and regeneration: challenges of the transition from traditional dentistry to biologically based therapies.

    PubMed

    Schmalz, Gottfried; Smith, Anthony J

    2014-04-01

    The traditional concept of replacing diseased tooth/pulp tissues by inert materials (restoration) is being challenged by recent advances in pulp biology leading to regenerative strategies aiming at the generation of new vital tissue. New tissue formation in the pulp chamber can be observed after adequate infection control and the formation of a blood clot. However, differentiation of true odontoblasts is still more speculative, and the approach is largely limited to immature teeth with open apices. A more systematic approach may be provided by the adoption of the tissue engineering concepts of using matrices, suitable (stem) cells, and signaling molecules to direct tissue events. With these tools, pulplike constructs have already been generated in experimental animals. However, a number of challenges still remain for clinical translation of pulp regeneration (eg, the cell source [resident vs nonresident stem cells, the latter associated with cell-free approaches], mechanisms of odontoblast differentiation, the pulp environment, the role of infection and inflammation, dentin pretreatment to release fossilized signaling molecules from dentin, and the provision of suitable matrices). Transition as a process, defined by moving from one form of "normal" to another, is based not only on the progress of science but also on achieving change to established treatment concepts in daily practice. However, it is clear that the significant recent achievements in pulp biology are providing an exciting platform from which clinical translation of dental pulp regeneration can advance. Copyright © 2014. Published by Elsevier Inc.

  2. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. 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.

  4. 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.

  5. Mice lacking epidermal PPARγ exhibit a marked augmentation in photocarcinogenesis associated with increased UVB-induced apoptosis, inflammation and barrier dysfunction

    PubMed Central

    Sahu, Ravi P.; DaSilva, Sonia C.; Rashid, Badri; Martel, Kellie Clay; Jernigan, Danielle; Mehta, Shama R.; Mohamed, Deena R.; Rezania, Samin; Bradish, Joshua R.; Armstrong, Andrew B.; Warren, Simon; Konger, Raymond L.

    2012-01-01

    Recent studies suggest that peroxisome proliferator-activated receptor gamma (PPARγ) agonists may have cancer chemopreventive activity. Other studies have shown that loss of epidermal PPARγ results in enhanced chemical carcinogenesis in mice via unknown mechanisms. However, ultraviolet B (UVB) exposure represents the primary etiological agent for skin cancer formation and the role of PPARγ in photobiology and photocarcinogenesis is unknown. In previous studies, we demonstrated that UVB irradiation of cells results in the formation of oxidized glycerophosphocholines that exhibit PPARγ ligand activity. We therefore hypothesized that PPARγ would prove to be a chemopreventive target in photocarcinogenesis. We first showed that UVB irradiation of mouse skin causes generation of PPARγ agonist species in vivo. We then generated SKH-1 hairless, albino mice deficient in epidermal Pparg (Pparg−/−epi) using a cytokeratin 14 driven Cre-LoxP strategy. Using a chronic model of UVB photocarcinogenesis, we next showed that Pparg−/−epi mice exhibit an earlier onset of tumor formation, increased tumor burden, and tumor progression. Increased tumor burden in Pparg−/−epi mice was accompanied by a significant increase in epidermal hyperplasia and p53 positive epidermal cells in surrounding skin lacking tumors. Following acute UVB irradiation, Pparg−/−epi mice exhibited an augmentation of both UVB-induced caspase 3/7 activity and inflammation. Increased apoptosis and inflammation was also observed following treatment with the PPARγ antagonist GW9662. With chronic UVB irradiation, Pparg−/−epi mice exhibited a sustained increase in erythema and transepidermal water loss relative to wildtype littermates. This suggests that PPARγ agonists could have possible chemopreventive activity in non-melanoma skin cancer. PMID:22467332

  6. [Comparison of expression of transforming growth factor-β1 in rat dental pulp during direct pulp capping with 2 capping agents].

    PubMed

    Zhang, Xiao-fang; Yao, Ya-peng; Kang, Hong-ying; Dong, Pei

    2014-04-01

    To examine and compare the expression of transforming growth factor-β1(TGF-β1) in rat dental pulp after direct pulp capping with calcium hydroxide (CH) and mineral trioxide aggregate (MTA). The model of direct dental pulp capping after first molars was established in 28 female Wistar rats with CH and MTA. The rats were sacrificed 1, 3, 5, 7, 14,21 and 28 days after direct pulp capping. TGF-β1 expression in pulp tissues were measured with immunohistochemical staining. The data was analyzed by Dunnett t test and paired t test with SPSS 13.0 software package. The results showed that no TGF-β1 expression was detected in the control group. After direct pulp capping with MTA, TGF-β1 expression gradually increased and reached peak expression on 5 day. TGF-β1 expression gradually decreased afterwards and reached normal on 21 day after direct pulp. TGF-β1 was mainly expressed in neutrophils, odontoblasts cells, vascular endothelial cells and fibroblasts. The expression of TGF-β1 was significantly different between 2 capping agents 1, 3, 5, 7, 14 days after direct pulp capping (P<0.05). The results suggest that TGF-β1 expression increases at first and then decreases after direct pulp capping. The type of capping agents has an impact on the expression of TGF-β1 after direct pulp capping. MTA enhances more TGFβ-1 expression than CH 1, 3, 5, 7 and 14 days after direct pulp capping. Supported by Science and Technology Plan Project of Liaoning Province (2009225001-2).

  7. Increased βTrCP are associated with imiquimod-induced psoriasis-like skin inflammation in mice via NF-κB signaling pathway.

    PubMed

    Li, Ruilian; Wang, Juan; Wang, Xin; Zhou, Jun; Wang, Mei; Ma, Huiqun; Xiao, Shengxiang

    2016-10-30

    Psoriasis is a common inflammatory skin disease characterized by T cell-mediated hyperproliferation of keratinocytes, increased angiogenesis and inflammation. Accumulating evidence suggests that some keratinocyte differentiation events are controlled by the ubiquitin/proteasome system. β-transducin repeat-containing protein (βTrCP) serve as substrate recognition component of E3 ubiquitin ligases that control stability of important regulators of signal transduction including the nuclear factor (NF)-κB signaling, a key regulatory element in inflammatory pathways related to psoriasis, suggesting a potential role of βTrCP in psoriasis pathogenesis. However, no published study has investigated the role of βTrCP in the etiology of psoriasis. Here, we combined an in vitro cell model of tumor necrosis factor (TNF)-α-induced keratinocyte inflammation and an animal model of imiquimod (IMQ)-induced psoriasis-like inflammation to investigate the pathogenic mechanisms in psoriasis-like dermatitis and assess its βTrCP/NF-κB dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions were associated with elevated βTrCP levels, reduced inhibitor κB (IκB), and enhanced NF-κB activation in epidermal tissues. Furthermore, βTrCP knockdown via siRNA in in TNF-α-stimulated HaCaT and normal human epidermal keratinocytes (NHEK) cells significantly inhibited the over-activation of NF-κB and expression of intercellular adhesion molecule 1 (ICAM-1), demonstrating a pivotal role of βTrCP in regulation the TNF-α-activated NF-κB inflammatory pathways. Moreover, downregulation of βTrCP through lentiviral shRNA ameliorates IMQ-induced psoriasis-like skin lesions in vivo. In conclusion, βTrCP is involved in the NF-κB signaling mediated-, psoriasis-related inflammation and represent a novel target for developing agents to treat psoriasis.

  8. 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. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. Dental pulp stem cells from traumatically exposed pulps exhibited an enhanced osteogenic potential and weakened odontogenic capacity.

    PubMed

    Wang, Yanping; Yan, Ming; Wang, Zhanwei; Wu, Jintao; Wang, Zilu; Zheng, Yangyu; Yu, Jinhua

    2013-11-01

    Traumatic pulp exposure can bring about some permanent damages to tooth tissues including dental pulps. This study was designed to evaluate the effects of traumatic pulp exposure on the osteo/odontogenic capacity of dental pulp stem cells (DPSCs). Rat incisors were artificially fractured and dental pulps were exposed to the oral environment for 48 h. Then, multi-colony-derived DPSCs from the injured pulps (iDPSCs) were isolated. Their osteo/odontogenic differentiation and the involvement of NF-κB pathway were subsequently investigated. iDPSCs presented a lower proliferative capacity than normal DPSCs (nDPSCs), as indicated by MTT and FCM assay. ALP levels in iDPSCs were significantly higher (P<0.01) than those in nDPSCs. Alizarin red staining revealed that iDPSCs exhibited an increased capacity of calcium deposition. Moreover, iDPSCs expressed stronger osteogenic markers (Runx2/RUNX2 and Ocn/OCN) and less odontogenic gene/protein (Dspp/DSP) than nDPSCs in vitro. In vivo transplantation showed that nDPSCs implants generated the typical dentine-pulp complex while all iDPSCs pellets formed the osteodentin-like tissues which were immunopositive for OCN. Mechanistically, iDPSCs expressed the higher levels of cytoplasmic phosphorylated IκBα/P65 and nuclear P65 than nDPSCs, indicating an active cellular NF-κB pathway in iDPSCs. After the inhibition of NF-κB pathway, the osteogenic potential in iDPSCs was significantly down-regulated while odontogenic differentiation was up-regulated, as indicated by the decreased Alp/Runx2/Ocn and uprised Dspp expression. Pulp exposure for 48 h decreased the odontogenic capacity and enhanced the osteogenic potential of DPSCs via the NF-κB signalling pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Effect of 4-Allyl-1-hydroxy-2-methoxybenzene (Eugenol) on Inflammatory and Apoptosis Processes in Dental Pulp Fibroblasts

    PubMed Central

    Martínez-Herrera, Andrea; Ruiz-Rodríguez, Socorro; Vértiz-Hernández, Antonio

    2016-01-01

    Eugenol (mixed with zinc oxide powder) is widely used as direct capping material during pulp therapy in primary teeth. The aim of the present study was to evaluate the effect of eugenol on diverse genes involved in inflammatory and cell apoptosis processes. The regulatory effect of eugenol on the expression of inflammation and apoptotic genes was evaluated in dental pulp fibroblasts from extracted third molars, cultured under concentration of eugenol of 13 μM. Eugenol allowed the expression of inflammatory and apoptotic genes when compared with positive and negative controls. Eugenol is a proinflammatory agent when it is in direct contact with healthy tissues and behaves as an anti-inflammatory agent in tissues undergoing inflammatory/apoptotic processes, as in cases of pulp inflammation in primary teeth. These findings are relevant for dentistry, when considering the application of safer pulp treatments to grossly carious children's teeth. PMID:28044068

  11. Effect of 4-Allyl-1-hydroxy-2-methoxybenzene (Eugenol) on Inflammatory and Apoptosis Processes in Dental Pulp Fibroblasts.

    PubMed

    Martínez-Herrera, Andrea; Pozos-Guillén, Amaury; Ruiz-Rodríguez, Socorro; Garrocho-Rangel, Arturo; Vértiz-Hernández, Antonio; Escobar-García, Diana María

    2016-01-01

    Eugenol (mixed with zinc oxide powder) is widely used as direct capping material during pulp therapy in primary teeth. The aim of the present study was to evaluate the effect of eugenol on diverse genes involved in inflammatory and cell apoptosis processes. The regulatory effect of eugenol on the expression of inflammation and apoptotic genes was evaluated in dental pulp fibroblasts from extracted third molars, cultured under concentration of eugenol of 13 μM. Eugenol allowed the expression of inflammatory and apoptotic genes when compared with positive and negative controls. Eugenol is a proinflammatory agent when it is in direct contact with healthy tissues and behaves as an anti-inflammatory agent in tissues undergoing inflammatory/apoptotic processes, as in cases of pulp inflammation in primary teeth. These findings are relevant for dentistry, when considering the application of safer pulp treatments to grossly carious children's teeth.

  12. Effect of Increased Neutrophil-to-Lymphocyte Ratio (NLR) and Decreased Mean Platelet Volume (MPV) Values on Inflammation in Acute Mania

    PubMed Central

    MAYDA, Hasan; AHSEN, Ahmet; BAĞCIOĞLU, Erman; ÖZTÜRK, Ahmet; BAHÇECİ, Bülent; SOYUÇOK, Etem; BAŞPINAR, Erol; ULU, Memnune Sena

    2016-01-01

    Introduction The neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) are simple, low-cost, and useful inflammatory markers detected in routine complete blood count (CBC), and their use has recently become widespread. In this study, we aimed to investigate the presence of an inflammatory state in manic patients on the basis of NLR and MPV values. Methods This retrospective study was performed on 76 patients with acute mania who were admitted to the Inpatients Psychiatry Clinic of Afyon Kocatepe University Hospital in Turkey. Diagnoses were based on Diagnostic and Statistical Manuel of Mental disorder (DSM-IV). The control group consisted of 74 healthy individuals recruited from the community. They were age- and sex-matched with the study group. Results NLR values of the manic patient group were 2.2±1.4 and those of the control group were 1.6±0.5. NLR values were significantly higher (p=0.004) and MPV values were significantly lower in the manic patient group than in the control group (10.0±1.2 vs. 10.9±2.3, p=0.027). Conclusion Increased NLR and decreased MPV levels may reflect inflammation in manic patients, and inflammation may play a role in the complex pathophysiology of acute mania. PMID:28360805

  13. 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

  14. 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.

  15. 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 Central

    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.

    2013-01-01

    Elevated levels of cyclooxygenase (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 NSAIDs had the highest PGE-M levels. PGE-M levels were increased in association with elevated 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). Based on the current findings, PGE-M is likely to be a useful biomarker for the selection of high risk subgroups to determine the utility of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women. PMID:23531446

  16. Leptin Administration Downregulates the Increased Expression Levels of Genes Related to Oxidative Stress and Inflammation in the Skeletal Muscle of ob/ob Mice

    PubMed Central

    Sáinz, Neira; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Ramírez, Beatriz; Gómez-Ambrosi, Javier; Frühbeck, Gema

    2010-01-01

    Obese leptin-deficient ob/ob mice exhibit a low-grade chronic inflammation together with a low muscle mass. Our aim was to analyze the changes in muscle expression levels of genes related to oxidative stress and inflammatory responses in leptin deficiency and to identify the effect of in vivo leptin administration. Ob/ob mice were divided in three groups as follows: control ob/ob, leptin-treated ob/ob (1 mg/kg/d) and leptin pair-fed ob/ob mice. Gastrocnemius weight was lower in control ob/ob than in wild type mice (P < .01) exhibiting an increase after leptin treatment compared to control and pair-fed (P < .01) ob/ob animals. Thiobarbituric acid reactive substances, markers of oxidative stress, were higher in serum (P < .01) and gastrocnemius (P = .05) of control ob/ob than in wild type mice and were significantly decreased (P < .01) by leptin treatment. Leptin deficiency altered the expression of 1,546 genes, while leptin treatment modified the regulation of 1,127 genes with 86 of them being involved in oxidative stress, immune defense and inflammatory response. Leptin administration decreased the high expression of Crybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1 and Serpinb1a observed in control ob/ob mice, indicating that it improves inflammation and muscle loss. PMID:20671928

  17. 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

  18. 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. Published by Elsevier Inc.

  19. Increased Susceptibility to Staphylococcal Enterotoxin B Intoxication in Mice Primed with Actinomycin D

    DTIC Science & Technology

    1994-10-01

    blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen...pavementing and widen- flattening with villous and macrophage phagocytosis; ing of alveolar septa, with blunting; lymphocyte ne- PMN increase in the red pulp...point. Mice primed with ACT-D flattening with villous blunting (Fig. IB). and lymphocyte and injected with normal saline served as controls. Anatomical

  20. Water requirements of the pulp and paper industry

    USGS Publications Warehouse

    Mussey, Orville D.

    1955-01-01

    Water, of varied qualities, is used for several purposes in the manufacture of pulp and paper, as a vehicle for transporting the constituents of paper in the paper machines; as process water for cooking wood chips to make pulp; as a medium for heat transfer; and for washing the pulpwood, the woodpulp, and the machines that handle the pulp. About 3,200 million gallons of water was withdrawn from surface- and ground-water sources each day during 1950 for the use of the pulp and paper industry. This is about 4 percent of the total estimated industrial withdrawal of water in the Nation The paper industry in the United States has been growing at a rapid rate. It has increased about tenfold in the last 50 years and has doubled every 15 years. The 1950 production of paper was about 24 million tons, which amounts to about 85 percent of the domestic consumption. In 1950, the pulp mills of the country produced more than 14 million tons of woodpulp, which supplied about 85 percent of the demand by the paper mills and other industries. The remainder of the fiber for paper manufacture was obtained from imported woodpulp, from reclaimed wastepaper, and from other fibers including rags and straw. The nationwide paper consumption for 1955 has been estimated at 31,700,000 tons. Woodpulp is classified according to the process by which it is made. Every woodpulp has characteristics that are carried over into the many and diverse grades of paper. Groundwood pulp is manufactured by simply grinding up wood and refining the resulting product. Soda, sulfite, and sulfate pulps are manufactured by chemically breaking down the lignin that cements the cellulose of the wood together and removing, cleaning, and sometimes bleaching the resulting fibers. Some woodpulp is produced by other methods. Sulfate-pulp mills are increasing in number and in rated daily capacity and are manufacturing more than half of the present domestic production of woodpulp. Most of the newer and larger woodpulp mills

  1. 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...

  2. 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...

  3. 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

  4. 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.

  5. Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance.

    PubMed

    Yang, Hyunwon; Youm, Yun-Hee; Vandanmagsar, Bolormaa; Ravussin, Anthony; Gimble, Jeffrey M; Greenway, Frank; Stephens, Jacqueline M; Mynatt, Randall L; Dixit, Vishwa Deep

    2010-08-01

    Emerging evidence suggests that increases in activated T cell populations in adipose tissue may contribute toward obesity-associated metabolic syndrome. The present study investigates three unanswered questions: 1) Do adipose-resident T cells (ARTs) from lean and obese mice have altered cytokine production in response to TCR ligation?; 2) Do the extralymphoid ARTs possess a unique TCR repertoire compared with lymphoid-resident T cells and whether obesity alters the TCR diversity in specific adipose depots?; and 3) Does short-term elimination of T cells in epididymal fat pad without disturbing the systemic T cell homeostasis regulate inflammation and insulin-action during obesity? We found that obesity reduced the frequency of naive ART cells in s.c. fat and increased the effector-memory populations in visceral fat. The ARTs from diet-induced obese (DIO) mice had a higher frequency of IFN-gamma(+), granzyme B(+) cells, and upon TCR ligation, the ARTs from DIO mice produced increased levels of proinflammatory mediators. Importantly, compared with splenic T cells, ARTs exhibited markedly restricted TCR diversity, which was further compromised by obesity. Acute depletion of T cells from epididymal fat pads improved insulin action in young DIO mice but did not reverse obesity-associated feed forward cascade of chronic systemic inflammation and insulin resistance in middle-aged DIO mice. Collectively, these data establish that ARTs have a restricted TCR-Vbeta repertoire, and T cells contribute toward the complex proinflammatory microenvironment of adipose tissue in obesity. Development of future long-term T cell depletion protocols specific to visceral fat may represent an additional strategy to manage obesity-associated comorbidities.

  6. Obesity Increases the Production of Proinflammatory Mediators from Adipose Tissue T Cells and Compromises TCR Repertoire Diversity: Implications for Systemic Inflammation and Insulin Resistance

    PubMed Central

    Yang, Hyunwon; Youm, Yun-Hee; Vandanmagsar, Bolormaa; Ravussin, Anthony; Gimble, Jeffrey M.; Greenway, Frank; Stephens, Jacqueline M.; Mynatt, Randall L.; Dixit, Vishwa Deep

    2016-01-01

    Emerging evidence suggests that increases in activated T cell populations in adipose tissue may contribute toward obesity-associated metabolic syndrome. The present study investigates three unanswered questions: 1) Do adipose-resident T cells (ARTs) from lean and obese mice have altered cytokine production in response to TCR ligation?; 2) Do the extralymphoid ARTs possess a unique TCR repertoire compared with lymphoid-resident T cells and whether obesity alters the TCR diversity in specific adipose depots?; and 3) Does short-term elimination of T cells in epididymal fat pad without disturbing the systemic T cell homeostasis regulate inflammation and insulin-action during obesity? We found that obesity reduced the frequency of naive ART cells in s.c. fat and increased the effector-memory populations in visceral fat. The ARTs from diet-induced obese (DIO) mice had a higher frequency of IFN-γ+, granzyme B+ cells, and upon TCR ligation, the ARTs from DIO mice produced increased levels of proinflammatory mediators. Importantly, compared with splenic T cells, ARTs exhibited markedly restricted TCR diversity, which was further compromised by obesity. Acute depletion of T cells from epididymal fat pads improved insulin action in young DIO mice but did not reverse obesity-associated feed forward cascade of chronic systemic inflammation and insulin resistance in middle-aged DIO mice. Collectively, these data establish that ARTs have a restricted TCR-Vβ repertoire, and T cells contribute toward the complex proinflammatory microenvironment of adipose tissue in obesity. Development of future long-term T cell depletion protocols specific to visceral fat may represent an additional strategy to manage obesity-associated comorbidities. PMID:20581149

  7. 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

  8. 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

    Hetland, Ragna Bogen

    2015-01-01

    We have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-Apc Min/+ X C57BL/6J-Lep ob/+ 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 Apc Min/+ 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

  9. Chemotherapy Necessitates Increased Immune Control of HHVs: A Cause of Persistent Inflammation Enabling Protracted Fatigue in Breast Cancer Survivors

    DTIC Science & Technology

    2014-10-01

    found a significant increase in CRP levels between EBV + and EBV /CMV double positive subjects. Moreover, EBV /CMV double positive individuals showed...higher levels of hs-CRP. Similarly, CMV/ EBV double positive breast cancer patients undergoing chemotherapy showed higher hs-CRP levels than CMV-/ EBV ...TERMS breast cancer, chemotherapy, immunology, human herpes viruses, survivor fatigue 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

  10. 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.

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

    PubMed Central

    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

  12. Estrogens increase cystathionine-γ-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats.

    PubMed

    Zhu, Xiaoyan; Tang, Zhiping; Cong, Binhai; Du, Jiankui; Wang, Changnan; Wang, Long; Ni, Xin; Lu, Jianqiang

    2013-10-01

    Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. The objectives of the present study were to investigate the effects of estrogens on CSE expression and H2S generation in the myocardium and to examine whether serum 17β-estradiol (E2) level is associated with CSE activity and H2S generation and whether H2S or E2 level is associated with proinflammatory cytokines and oxidative stress status. Ovariectomized Sprague-Dawley rats received subcutaneous E2 (30 μg/kg/d) or vehicle for 12 weeks. At the end of the 12-week treatment, CSE expression, H2S generation, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, interleukin (IL)-6 concentration, and tumor necrosis factor-α (TNF-α) concentration in the left ventricle were determined. E2 increased CSE expression and H2S generation in the myocardium of ovariectomized rats. H2S production rate and serum E2 were positively correlated. E2 increased GSH/GSSG ratio, T-AOC, CAT, and SOD activity but decreased IL-6 and TNF-α levels. Serum E2 level was positively correlated with GSH/GSSG ratio, T-AOC, CAT, and SOD activity, and inversely correlated with IL-6 and TNF-α levels. H2S generation rate was positively correlated with T-AOC and GSH/GSSG ratio, and inversely correlated with IL-6 and TNF-α levels. E2 increases CSE expression and endogenous H2S generation in the myocardium. The effects of E2 are associated with decreased oxidative stress and inflammatory status. Our data suggest that estrogens might exert cardioprotective effects through up-regulation of CSE expression and H2S generation.

  13. 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

  14. DAAs Rapidly Reduce Inflammation but Increase Serum VEGF Level: A Rationale for Tumor Risk during Anti-HCV Treatment

    PubMed Central

    Villani, Rosanna; Facciorusso, Antonio; Bellanti, Francesco; Tamborra, Rosanna; Piscazzi, Annamaria; Landriscina, Matteo; Vendemiale, Gianluigi; Serviddio, Gaetano

    2016-01-01

    Background Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has been reported within weeks of starting treatment, but the mechanism is not known. Methods We monitored the serum level of vascular endothelial growth factor (VEGF) and changes in the pattern of circulating interleukins in 103 chronic hepatitis C patients during antiviral treatment with DAA-regimens. VEGF, epidermal growth factor (EGF), and several interleukins were assessed at baseline, during treatment, and after treatment. The biological effect of DAA-treated patient serum on human umbilical vein endothelial cell (HUVEC) proliferation was also confirmed. Results After 4 weeks of therapy, VEGF increased approximately 4-fold compared to baseline, remained elevated up to the end of treatment, and returned to the pre-treatment level after the end of therapy. In contrast, interleukin-10 and tumor necrosis factor-alpha significantly decreased during therapy, which was coincident with HCV clearance. The levels of both remained low after treatment. The addition of serum from patients collected during therapy induced HUVEC proliferation; however, this disappeared after the end of therapy. Conclusions DAA administration induces an early increase in serum VEGF and a change in the inflammatory pattern, coinciding with HCV clearance. This may alter the balance between inflammatory and anti-inflammatory processes and modify the antitumor surveillance of the host. Fortunately, such modifications return reverse to normal after the end of treatment. PMID:27997563

  15. LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro.

    PubMed

    Halvorsen, Bente; Santilli, Francesca; Scholz, Hanne; Sahraoui, Afaf; Gulseth, Hanne L; Wium, Cecilie; Lattanzio, Stefano; Formoso, Gloria; Di Fulvio, Patrizia; Otterdal, Kari; Retterstøl, Kjetil; Holven, Kirsten B; Gregersen, Ida; Stavik, Benedicte; Bjerkeli, Vigdis; Michelsen, Annika E; Ueland, Thor; Liani, Rossella; Davi, Giovanni; Aukrust, Pål

    2016-10-01

    Activation of inflammatory pathways is involved in the pathogenesis of type 2 diabetes mellitus. On the basis of its role in vascular inflammation and in metabolic disorders, we hypothesised that the TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) could be involved in the pathogenesis of type 2 diabetes mellitus. Plasma levels of LIGHT were measured in two cohorts of type 2 diabetes mellitus patients (191 Italian and 40 Norwegian). Human pancreatic islet cells and arterial endothelial cells were used to explore regulation and relevant effects of LIGHT in vitro. Our major findings were: (1) in both diabetic cohorts, plasma levels of LIGHT were significantly raised compared with sex- and age-matched healthy controls (n = 32); (2) enhanced release from activated platelets seems to be an important contributor to the raised LIGHT levels in type 2 diabetes mellitus; (3) in human pancreatic islet cells, inflammatory cytokines increased the release of LIGHT and upregulated mRNA and protein levels of the LIGHT receptors lymphotoxin β receptor (LTβR) and TNF receptor superfamily member 14 (HVEM/TNFRSF14); (4) in these cells, LIGHT attenuated the insulin release in response to high glucose at least partly via pro-apoptotic effects; and (5) in human arterial endothelial cells, glucose boosted inflammatory response to LIGHT, accompanied by an upregulation of mRNA levels of HVEM (also known as TNFRSF14) and LTβR (also known as LTBR). Our findings show that patients with type 2 diabetes mellitus are characterised by increased plasma LIGHT levels. Our in vitro findings suggest that LIGHT may contribute to the progression of type 2 diabetes mellitus by attenuating insulin secretion in pancreatic islet cells and by contributing to vascular inflammation.

  16. 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

  17. Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury.

    PubMed

    Nosrat, I V; Widenfalk, J; Olson, L; Nosrat, C A

    2001-10-01

    Interactions between ingrowing nerve fibers and their target tissues form the basis for functional connectivity with the central nervous system. Studies of the developing dental pulp innervation by nerve fibers from the trigeminal ganglion is an excellent example of nerve-target tissue interactions and will allow specific questions regarding development of the dental pulp nerve system to be addressed. Dental pulp cells (DPC) produce an array of neurotrophic factors during development, suggesting that these proteins might be involved in supporting trigeminal nerve fibers that innervate the dental pulp. We have established an in vitro culture system to study the interactions between the dental pulp cells and trigeminal neurons. We show that dental pulp cells produce several neurotrophic factors in culture. When DPC are cocultured with trigeminal neurons, they promote survival and a specific and elaborate neurite outgrowth pattern from trigeminal neurons, whereas skin fibroblasts do not provide a similar support. In addition, we show that dental pulp tissue becomes innervated when transplanted ectopically into the anterior chamber of the eye in rats, and upregulates the catecholaminergic nerve fiber density of the irises. Interestingly, grafting the dental pulp tissue into hemisected spinal cord increases the number of surviving motoneurons, indicating a functional bioactivity of the dental pulp-derived neurotrophic factors in vivo by rescuing motoneurons. Based on these findings, we propose that dental pulp-derived neurotrophic factors play an important role in orchestrating the dental pulp innervation.

  18. Increased endogenous antigen presentation in the periphery enhances susceptibility to inflammation-induced gastric autoimmunity in mice.

    PubMed

    Overall, Sarah A; Bourges, Dorothée; van Driel, Ian R; Gleeson, Paul A

    2017-01-01

    How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H(+) /K(+) ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice. However, increased presentation of endogenously derived HKα epitopes by dendritic cells (DCs) in the gastric lymph node of IE-H(+) /K(+) β transgenic mice (IEβ) reduces A23 T-cell tolerance to gastric antigens after inflammatory activation, with subsequent development of gastritis. While HKα-specific A23 T cells from immunised wild-type mice were poorly responsive to in vitro antigen specific activation, A23 T cells from immunised IEβ transgenic mice were readily re-activated, indicating loss of T-cell anergy. These findings show that DCs of gastric lymph nodes can maintain tolerance of pathogenic T cells following inflammatory stimulation and that the density of endogenous antigen presented to self-reactive T cells is critical in the balance between tolerance and autoimmunity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice.

    PubMed

    Zhang, Xiaojie; Chen, Sheng; Li, Liang; Wang, Qian; Le, Weidong

    2008-06-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by selective degeneration of motor neurons. Mutations in copper/zinc superoxide dismutase (SOD1) account for 20% cases of familial ALS (fALS), but the underlying pathogenetic mechanisms are largely unknown. Using SOD1(G93A) mice model of ALS, we demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine (Hcy). To investigate whether Hcy-lowering therapy is beneficial to this disease, we applied folic acid (FA) and vitamin B12 which are important factors involved in the Hcy metabolism to assess the neuroprotective effect of FA and B12 in the SOD1(G93A) mice. Our results showed FA or FA+B12 treatment significantly delayed the disease onset and prolonged the lifespan, accompanied by the significant reduction of motor neuron loss. Furthermore, we found that FA or FA+B12 treatment significantly attenuated the plasma Hcy level, suppressed the activation of microglia and astrocytes, and inhibited the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in spinal cord. Moreover, FA or FA+B12 treatment decreased the levels of cleaved caspase-3 and poly(ADP-ribose)polymerase (PARP) but up-regulated the level of anti-apoptotic protein Bcl-2. However, B12 treatment alone did not show any significant benefit to this disease. These results provide evidence to demonstrate that elevated Hcy is involved in the pathogenesis of fALS and FA therapy may have therapeutic potential for the treatment of the disease.

  20. 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. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. Hypoxia-increased expression of genes involved in inflammation, dedifferentiation, pro-fibrosis, and extracellular matrix remodeling of human bladder smooth muscle cells.

    PubMed

    Wiafe, Bridget; Adesida, Adetola; Churchill, Thomas; Adewuyi, Esther Ekpe; Li, Zack; Metcalfe, Peter

    2017-01-01

    Partial bladder outlet obstruction (pBOO) is characterized by exaggerated stretch, hydrodynamic pressure, and inflammation which cause significant damage and fibrosis to the bladder wall. Several studies have implicated hypoxia in its pathophysiology. However, the isolated progressive effects of hypoxia on bladder cells are not yet defined. Sub-confluent normal human bladder smooth muscle cells (hbSMC) were cultured in 3% O2 tension for 2, 24, 48, and 72 h. RNA, cellular proteins, and secreted proteins were used for gene expression analysis, immunoblotting, and ELISA, respectively. Transcription of hypoxia-inducible factor (HIF)1α and HIF2α were transiently induced after 2 h of hypoxia (p < 0.05), whereas HIF3 was upregulated after 72 h (p < 0.005). HIF1 and HIF3α proteins were significantly induced after 2 and 72 h, respectively. VEGF mRNA increased significantly after 24 and 72 h (p < 0.005). The inflammatory cytokines, TGFB (protein and mRNA), IL 1β, 1L6, and TNFα (mRNA) demonstrated a time-dependent increased expression. Furthermore, the anti-inflammatory cytokine IL-10 was downregulated after 72 h (p < 0.05). Evidence of smooth muscle cell dedifferentiation included increased αSMA, vimentin, and desmin. Evidence of pro-fibrotic changes included increased CTGF, SMAD 2, and SMAD 3 as well as collagens 1, 2, 3, and 4, fibronectin, aggrecan, and TIMP 1 transcripts (p < 0.05). Total collagen proteins also increased time-dependently (p < 0.05). Together, these results show that exposure of hbSMC to low oxygen tension results in intense hypoxic cascade, including inflammation, de-differentiation, pro-fibrotic changes, and increased extracellular matrix expression. This elucidates mechanisms of hypoxia-driven bladder deterioration in bladder cells, which is important in tailoring in vivo experiments and may ultimately translate into improved clinical outcomes.

  2. The administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to cigarette smoke.

    PubMed

    Pena, Karina Braga; Ramos, Camila de Oliveira; Soares, Nícia Pedreira; da Silva, Pamela Félix; Bandeira, Ana Carla Balthar; Costa, Guilherme de Paula; Cangussú, Sílvia Dantas; Talvani, André; Bezerra, Frank Silva

    2016-01-01

    This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflammatory response in C57BL/6 mice exposed to cigarette smoke (CS). Twenty-four male mice were divided into four groups: control group (CG), which received a standard diet; cigarette smoke group (CSG), which was exposed to CS; a high refined carbohydrate diet group (RG), which received a high refined carbohydrate diet; and a high refined carbohydrates diet and cigarette smoke group (RCSG), which received a high refined carbohydrate diet and was exposed to CS. The animals were monitored for food intake and body weight gain for 12 weeks. After this period, the CSG and RCSG were exposed to CS for five consecutive days. At the end of the experimental protocol, all animals were euthanized for subsequent analyses. There was an increase of inflammatory cells in the bronchoalveolar lavage fluid (BALF) of CSG compared to CG and RCSG compared to CG, CSG, and RG. In addition, in the BALF, there was an increase of tumor necrosis factor alpha in RCSG compared to CG, CSG, and RG; interferon gamma increase in RCSG compared to the CSG; and increase in interleukin-10 in RCSG compared to CG and RG. Lipid peroxidation increased in RCSG compared to CG, CSG, and RG. Furthermore, the oxidation of proteins increased in CSG compared to CG. The analysis of oxidative stress showed an increase in superoxide dismutase in RCSG compared to CG, CSG, and RG and an increase in the catalase activity in RCSG compared with CG. In addition, there was a decrease in the glutathione reduced/glutathione total ratio of CSG, RG, and RCSG compared to CG. Therefore, the administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to CS.

  3. The administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to cigarette smoke

    PubMed Central

    Pena, Karina Braga; Ramos, Camila de Oliveira; Soares, Nícia Pedreira; da Silva, Pamela Félix; Bandeira, Ana Carla Balthar; Costa, Guilherme de Paula; Cangussú, Sílvia Dantas; Talvani, André; Bezerra, Frank Silva

    2016-01-01

    This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflammatory response in C57BL/6 mice exposed to cigarette smoke (CS). Twenty-four male mice were divided into four groups: control group (CG), which received a standard diet; cigarette smoke group (CSG), which was exposed to CS; a high refined carbohydrate diet group (RG), which received a high refined carbohydrate diet; and a high refined carbohydrates diet and cigarette smoke group (RCSG), which received a high refined carbohydrate diet and was exposed to CS. The animals were monitored for food intake and body weight gain for 12 weeks. After this period, the CSG and RCSG were exposed to CS for five consecutive days. At the end of the experimental protocol, all animals were euthanized for subsequent analyses. There was an increase of inflammatory cells in the bronchoalveolar lavage fluid (BALF) of CSG compared to CG and RCSG compared to CG, CSG, and RG. In addition, in the BALF, there was an increase of tumor necrosis factor alpha in RCSG compared to CG, CSG, and RG; interferon gamma increase in RCSG compared to the CSG; and increase in interleukin-10 in RCSG compared to CG and RG. Lipid peroxidation increased in RCSG compared to CG, CSG, and RG. Furthermore, the oxidation of proteins increased in CSG compared to CG. The analysis of oxidative stress showed an increase in superoxide dismutase in RCSG compared to CG, CSG, and RG and an increase in the catalase activity in RCSG compared with CG. In addition, there was a decrease in the glutathione reduced/glutathione total ratio of CSG, RG, and RCSG compared to CG. Therefore, the administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to CS. PMID:28008246

  4. A PFI mill can be used to predict biomechanical pulp strength properties

    Treesearch

    Gary F. Leatham; Gary C. Myers

    1990-01-01

    Recently, we showed that a biomechanical pulping process in which aspen chips are pretreated with a white-rot fungus can give energy savings and can increase paper sheet strength. To optimize this process, we need more efficient ways to evaluate the fungal treatments. Here, we examine a method that consists of treating coarse refiner mechanical pulp, refining in a PFI...

  5. Local injections of adipose-derived mesenchymal stem cells modulate inflammation and increase angiogenesis ameliorating the dystrophic phenotype in dystrophin-deficient skeletal muscle.

    PubMed

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